Journal of Clinical Medicine

13 pages, 641 KiB

Open AccessEditor’s ChoiceSystematic Review

Melatonin or Ramelteon for Delirium Prevention in the Intensive Care Unit: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Giuseppe Aiello, Micol Cuocina, Luigi La Via, Simone Messina, Giuseppe A. Attaguile, Giuseppina Cantarella, Filippo Sanfilippo and Renato Bernardini

J. Clin. Med. 2023, 12(2), 435; https://doi.org/10.3390/jcm12020435 - 05 Jan 2023

Cited by 23 | Viewed by 4026

Abstract

Melatonin modulates the circadian rhythm and has been studied as a preventive measure against the development of delirium in hospitalized patients. Such an effect may be more evident in patients admitted to the ICU, but findings from the literature are conflicting. We conducted [...] Read more.

Melatonin modulates the circadian rhythm and has been studied as a preventive measure against the development of delirium in hospitalized patients. Such an effect may be more evident in patients admitted to the ICU, but findings from the literature are conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether melatonin or ramelteon (melatonin agonist) reduce delirium incidence as compared to a placebo in ICU patients. Secondary outcomes were ICU length of stay, duration of mechanical ventilation (MV) and mortality. Estimates are presented as risk ratio (RR) or mean differences (MD) with 95% confidence interval (CI). Nine RCTs were included, six of them reporting delirium incidence. Neither melatonin nor ramelteon reduced delirium incidence (RR 0.76 (0.54, 1.07), p = 0.12; I² = 64%), although a sensitivity analysis conducted adding other four studies showed a reduction in the risk of delirium (RR = 0.67 (95%CI 0.48, 0.92), p = 0.01; I² = 67). Among the secondary outcomes, we found a trend towards a reduction in the duration of MV (MD −2.80 (−6.06, 0.47), p = 0.09; I² = 94%) but no differences in ICU-LOS (MD −0.26 (95%CI −0.89, 0.37), p = 0.42; I² = 75%) and mortality (RR = 0.85 (95%CI 0.63, 1.15), p = 0.30; I² = 0%). Melatonin and ramelteon do not seem to reduce delirium incidence in ICU patients but evidence is weak. More studies are needed to confirm this finding. Full article

(This article belongs to the Section Anesthesiology)

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10 pages, 710 KiB

Open AccessEditor’s ChoiceArticle

Unstable Total Hip Arthroplasty: Should It Be Revised Using Dual Mobility Implants? A Retrospective Analysis from the R.I.P.O. Registry

by Alberto Di Martino, Matteo Brunello, Barbara Bordini, Valentino Rossomando, Leonardo Tassinari, Claudio D’Agostino, Federico Ruta and Cesare Faldini

J. Clin. Med. 2023, 12(2), 440; https://doi.org/10.3390/jcm12020440 - 05 Jan 2023

Cited by 5 | Viewed by 1485

Abstract

Total hip arthroplasty (THA) is one of the most common surgical procedures in orthopedics; however, it is subjected to different kinds of failures, one of them being dislocation. Many different prosthetic designs have been developed to overcome this problem, such as dual mobility [...] Read more.

Total hip arthroplasty (THA) is one of the most common surgical procedures in orthopedics; however, it is subjected to different kinds of failures, one of them being dislocation. Many different prosthetic designs have been developed to overcome this problem, such as dual mobility coupling. The main purpose of this article is to determine whether there are differences regarding the revision surgery of unstable THA comparing the risk of failure between dual mobility cup (DMC) implants, standard implants, and among different head sizes. A registry-based population study has been conducted by analyzing data collected by the Emilia Romagna Registry of Orthopedic Prosthetic Implants (RIPO), including a total of 253 implants failed for dislocation and instability that were operated on by cup revision surgery between 2000 and 2019. The selected population has been divided into two groups based on the insert type: standard and DMC. The age at revision surgery was significantly lower in the standard cup group with respect to DMC (p = 0.014 t-test), with an average age of 71.2 years (33–96 years range) for the standard cups and 74.8 years (48–92 years range) for the DMC group. The cumulative survival of DMC implants was 82.0% at 5-years, decreasing to 77.5% at a 10-year follow-up, which is not significantly different from standard cups (p = 0.676, Log-Rank test). DMC implants showed a significantly lower risk of re-revision for dislocation compared to standard cups (p = 0.049). Femoral heads ≥36 mm had a higher overall survival compared to smaller femoral heads (p = 0.030). This study demonstrated that DMC or femoral heads ≥36 mm are a valid choice to manage THA instability and to reduce the revision rate for dislocation at a mid-term follow-up; in those selected and targeted patients, these options should be taken into consideration because they are associated with better outcomes. Full article

(This article belongs to the Special Issue Advances in Hip Replacement Surgery)

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10 pages, 1386 KiB

Open AccessEditor’s ChoiceArticle

Effects of Multidisciplinary Rehabilitation Program in Patients with Long COVID-19: Post-COVID-19 Rehabilitation (PCR SIRIO 8) Study

by Małgorzata Ostrowska, Alicja Rzepka-Cholasińska, Łukasz Pietrzykowski, Piotr Michalski, Agata Kosobucka-Ozdoba, Małgorzata Jasiewicz, Michał Kasprzak, Jacek Kryś and Aldona Kubica

J. Clin. Med. 2023, 12(2), 420; https://doi.org/10.3390/jcm12020420 - 04 Jan 2023

Cited by 14 | Viewed by 3004

Abstract

Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, [...] Read more.

Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, and breathing exercises), education, and group psychotherapy. After 6 weeks of rehabilitation in 97 patients with long COVID-19, body composition analysis revealed a significant decrease of abdominal fatty tissue (from 2.75 kg to 2.5 kg; p = 0.0086) with concomitant increase in skeletal muscle mass (from 23.2 kg to 24.2 kg; p = 0.0104). Almost 80% of participants reported dyspnea improvement assessed with the modified Medical Research Council scale. Patients’ physical capacity assessed with the 6 Minute Walking Test increased from 320 to 382.5 m (p < 0.0001), the number of repetitions in the 30 s Chair Stand Test improved from 13 to 16 (p < 0.0001), as well as physical fitness in the Short Physical Performance Battery Test from 14 to 16 (p < 0.0001). The impact of fatigue on everyday functioning was reduced in the Modified Fatigue Impact Scale from 37 to 27 (p < 0.0001). Cardiopulmonary exercise test did not show any change. The multidisciplinary rehabilitation program has improved body composition, dyspnea, fatigue and physical capacity in long COVID-19 patients. Full article

(This article belongs to the Special Issue 10th Anniversary of JCM— Pathophysiological Mechanisms, Diagnostics for Lung Diseases, and Therapeutic Modalities)

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18 pages, 608 KiB

Open AccessEditor’s ChoiceArticle

Breast Cancer Care Pathways for Women with Preexisting Severe Mental Disorders: Evidence of Disparities in France?

by Anna-Veera Seppänen, Fabien Daniel, Sophie Houzard, Christine Le Bihan, Magali Coldefy and Coralie Gandré

J. Clin. Med. 2023, 12(2), 412; https://doi.org/10.3390/jcm12020412 - 04 Jan 2023

Cited by 2 | Viewed by 1896

Abstract

The excess cancer mortality in persons with severe mental illness (SMI) has been well documented, and research suggests that it may be influenced by care-related factors. Our objective was to assess breast cancer care pathways in women with SMI in France, using an [...] Read more.

The excess cancer mortality in persons with severe mental illness (SMI) has been well documented, and research suggests that it may be influenced by care-related factors. Our objective was to assess breast cancer care pathways in women with SMI in France, using an exhaustive population-based data-linkage study with a matched case-control design. The cases were 1346 women with incident breast cancer in 2013/2014 and preexisting SMI who were matched with three controls without SMI presenting similar demographics, initial breast cancer type, and year of incidence. We compared cancer care pathways and their quality for cases and controls, using a consensual set of indicators covering diagnosis, treatment, follow-up, and mortality (until 2017). After adjusting for covariates, cases had lower odds to undergo the main diagnostic tests, lumpectomy, adjuvant chemotherapy, and radiotherapy, as well as hormone therapy, but higher odds for mastectomy. Suboptimal quality in cancer pathways was observed for both groups, but to a higher extent for cases, especially for not receiving timely care after diagnosis and post-treatment follow-up. Breast cancer mortality, considering competing risks of deaths, was significantly elevated in women with SMI. These findings highlight disparities in cancer care pathways for individuals with SMI, as well as specific aspects of the care continuum which could benefit from targeted actions to reach equity of outcomes. Full article

(This article belongs to the Special Issue Use of Real-World Data (RWD) to Improve Health Care and Outcomes in Patients with Mental Health Disorders)

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12 pages, 1850 KiB

Open AccessEditor’s ChoiceArticle

Segmentation-Assisted Fully Convolutional Neural Network Enhances Deep Learning Performance to Identify Proliferative Diabetic Retinopathy

by Minhaj Alam, Emma J. Zhao, Carson K. Lam and Daniel L. Rubin

J. Clin. Med. 2023, 12(1), 385; https://doi.org/10.3390/jcm12010385 - 03 Jan 2023

Cited by 7 | Viewed by 1790

Abstract

With the progression of diabetic retinopathy (DR) from the non-proliferative (NPDR) to proliferative (PDR) stage, the possibility of vision impairment increases significantly. Therefore, it is clinically important to detect the progression to PDR stage for proper intervention. We propose a segmentation-assisted DR classification [...] Read more.

With the progression of diabetic retinopathy (DR) from the non-proliferative (NPDR) to proliferative (PDR) stage, the possibility of vision impairment increases significantly. Therefore, it is clinically important to detect the progression to PDR stage for proper intervention. We propose a segmentation-assisted DR classification methodology, that builds on (and improves) current methods by using a fully convolutional network (FCN) to segment retinal neovascularizations (NV) in retinal images prior to image classification. This study utilizes the Kaggle EyePacs dataset, containing retinal photographs from patients with varying degrees of DR (mild, moderate, severe NPDR and PDR. Two graders annotated the NV (a board-certified ophthalmologist and a trained medical student). Segmentation was performed by training an FCN to locate neovascularization on 669 retinal fundus photographs labeled with PDR status according to NV presence. The trained segmentation model was used to locate probable NV in images from the classification dataset. Finally, a CNN was trained to classify the combined images and probability maps into categories of PDR. The mean accuracy of segmentation-assisted classification was 87.71% on the test set (SD = 7.71%). Segmentation-assisted classification of PDR achieved accuracy that was 7.74% better than classification alone. Our study shows that segmentation assistance improves identification of the most severe stage of diabetic retinopathy and has the potential to improve deep learning performance in other imaging problems with limited data availability. Full article

(This article belongs to the Section Ophthalmology)

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13 pages, 651 KiB

Open AccessEditor’s ChoiceSystematic Review

Clinicopathologic Profile, Management and Outcome of Sinonasal Ameloblastoma—A Systematic Review

by Vini Mehta, Gargi S. Sarode, Vishnu Teja Obulareddy, Tanvi Sharma, Shruti Kokane, Marco Cicciù and Giuseppe Minervini

J. Clin. Med. 2023, 12(1), 381; https://doi.org/10.3390/jcm12010381 - 03 Jan 2023

Cited by 8 | Viewed by 1708

Abstract

Sinonasal ameloblastoma (SNA) is considered to be a subtype of ameloblastoma. It differs from gnathic ameloblastoma in terms of clinicopathologic features, management and prognosis. Thus, the objective of the present review was to study the complications, survival, recurrence rate and outcomes following the [...] Read more.

Sinonasal ameloblastoma (SNA) is considered to be a subtype of ameloblastoma. It differs from gnathic ameloblastoma in terms of clinicopathologic features, management and prognosis. Thus, the objective of the present review was to study the complications, survival, recurrence rate and outcomes following the management of SNA. The electronic search process was conducted on PubMed-Medline, Embase, and Scopus. Google Scholar was used to search grey literature. Quality assessment of the case reports (CR) and case series (CS) was done based on CARE guidelines. The initial search resulted in 2111 articles. 15 studies (13 CR and 2 CS) were found to meet the eligibility criteria. The majority of the studies described histological features of SNA, which were consistent with ameloblastomas of gnathic origin. There were no SNA-related deaths reported in the included studies. Five studies described endoscopic surgeries to remove SNAs, and three SNAs were treated with post-surgery radiotherapy. Data from included studies suggest that sinonasal ameloblastomas are histologically similar to gnathic ameloblastomas, but their clinical presentation is different. They may cause complete or partial obstruction of the nasal cavity and the sinus. They appear to affect an older demographic, and their resection may be accompanied by the excision of a large portion of the maxilla, necessitating maxillofacial prosthetic rehabilitation. Full article

(This article belongs to the Section Oncology)

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17 pages, 1500 KiB

Open AccessEditor’s ChoiceArticle

Effect of Exercise Interventions on Irisin and Interleukin-6 Concentrations and Indicators of Carbohydrate Metabolism in Males with Metabolic Syndrome

by Karol Makiel, Agnieszka Suder, Aneta Targosz, Marcin Maciejczyk and Alon Haim

J. Clin. Med. 2023, 12(1), 369; https://doi.org/10.3390/jcm12010369 - 03 Jan 2023

Cited by 6 | Viewed by 2835

Abstract

Irisin (IR) is a biomarker that is associated with metabolic syndrome (MetS). However, the available evidence on the association of IR, physical activity, and MetS status are contradictory. Therefore, the present study aimed to investigate the effect of exercise intervention on IR and [...] Read more.

Irisin (IR) is a biomarker that is associated with metabolic syndrome (MetS). However, the available evidence on the association of IR, physical activity, and MetS status are contradictory. Therefore, the present study aimed to investigate the effect of exercise intervention on IR and interleukin-6 (IL-6) levels and indicators of carbohydrate metabolism in males with MetS. The study included 62 males with MetS (age 36.6 ± 6.9 years, BMI 33.6 ± 4.4 kg/m²) randomly assigned to: examined group 1 (EG1, n = 21) with aerobic exercise intervention, examined group 2 (EG2, n = 21) with combined aerobic and resistance exercise intervention, both for 12 weeks, and the control group (CG, n = 20) without intervention. Anthropometric measurements, body composition (body fat [BF], fat free mass [FFM]) as well as a biochemical blood analysis (irisin [IR], interleukin-6 [IL-6], insulin [INS] and glucose [GL]) were performed at baseline, 6 and 12 weeks of intervention, and 4 weeks after ending the intervention (follow-up). Intergroup and intragroup comparisons were performed. In EG1, an increase in IR level was observed as well as decreases in IL-6, BF, and GL levels in relation to the initial measurement. In EG2, decreases in IL-6, BF, and INS levels were observed as well as an increase in FFM level. In CG, no changes were found. Aerobic-resistance exercise led to a greater reduction in the concentrations of IL-6 and INS and more favorable changes in body composition (BF and FFM) than the use of aerobic training alone in males with MetS. Full article

(This article belongs to the Topic Exercise and Chronic Disease)

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11 pages, 602 KiB

Open AccessEditor’s ChoiceReview

Acute Kidney Injury: Medical Causes and Pathogenesis

by Faruk Turgut, Alaa S. Awad and Emaad M. Abdel-Rahman

J. Clin. Med. 2023, 12(1), 375; https://doi.org/10.3390/jcm12010375 - 03 Jan 2023

Cited by 17 | Viewed by 12206

Abstract

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically [...] Read more.

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically defined and staged based on serum creatinine concentration and urine output rates. The etiology of AKI is conceptually classified into three general categories: prerenal, intrarenal, and postrenal. Although this classification may be useful for establishing a differential diagnosis, AKI has mostly multifactorial, and pathophysiologic features that can be divided into different categories. Acute tubular necrosis, caused by either ischemia or nephrotoxicity, is common in the setting of AKI. The timely and accurate identification of AKI and a better understanding of the pathophysiological mechanisms that cause kidney dysfunction are essential. In this review, we consider various medical causes of AKI and summarize the most recent updates in the pathogenesis of AKI. Full article

(This article belongs to the Section Nephrology & Urology)

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23 pages, 1978 KiB

Open AccessEditor’s ChoiceReview

Prosthesis Tailoring for Patients Undergoing Transcatheter Aortic Valve Implantation

by Pier Pasquale Leone, Andrea Scotti, Edwin C. Ho, Manaf Assafin, James Doolittle, Mei Chau, Leandro Slipczuk, Matthew Levitus, Damiano Regazzoli, Antonio Mangieri and Azeem Latib

J. Clin. Med. 2023, 12(1), 338; https://doi.org/10.3390/jcm12010338 - 01 Jan 2023

Cited by 7 | Viewed by 4307

Abstract

Transcatheter aortic valve implantation (TAVI) has risen over the past 20 years as a safe and effective alternative to surgical aortic valve replacement for treatment of severe aortic stenosis, and is now a well-established and recommended treatment option in suitable patients irrespective of [...] Read more.

Transcatheter aortic valve implantation (TAVI) has risen over the past 20 years as a safe and effective alternative to surgical aortic valve replacement for treatment of severe aortic stenosis, and is now a well-established and recommended treatment option in suitable patients irrespective of predicted risk of mortality after surgery. Studies of numerous devices, either newly developed or reiterations of previous prostheses, have been accruing. We hereby review TAVI devices, with a focus on commercially available options, and aim to present a guide for prosthesis tailoring according to patient-related anatomical and clinical factors that may favor particular designs. Full article

(This article belongs to the Special Issue Transcatheter Aortic Valve Replacement: Current Status and Future Perspectives)

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12 pages, 1058 KiB

Open AccessEditor’s ChoiceReview

Osteoarthritis: New Insight on Its Pathophysiology

by Stefano Coaccioli, Piercarlo Sarzi-Puttini, Panagiotis Zis, Giuseppe Rinonapoli and Giustino Varrassi

J. Clin. Med. 2022, 11(20), 6013; https://doi.org/10.3390/jcm11206013 - 12 Oct 2022

Cited by 36 | Viewed by 11516

Abstract

Understanding of the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, as [...] Read more.

Understanding of the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, as well as the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA physiopathology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms as underlying causes of pain chronicity has been characterized. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. To this aim, this review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insights on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed. Full article

(This article belongs to the Special Issue Pain and Rheumatology)

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15 pages, 2149 KiB

Open AccessEditor’s ChoiceArticle

High Temporal Resolution Dual-Source Photon-Counting CT for Coronary Artery Disease: Initial Multicenter Clinical Experience

by Martin Soschynski, Florian Hagen, Stefan Baumann, Muhammad Taha Hagar, Jakob Weiss, Tobias Krauss, Christopher L. Schlett, Constantin von zur Mühlen, Fabian Bamberg, Konstantin Nikolaou, Simon Greulich, Matthias F. Froelich, Philipp Riffel, Daniel Overhoff, Theano Papavassiliu, Stefan O. Schoenberg, Sebastian Faby, Stefan Ulzheimer, Isabelle Ayx and Patrick Krumm

J. Clin. Med. 2022, 11(20), 6003; https://doi.org/10.3390/jcm11206003 - 11 Oct 2022

Cited by 23 | Viewed by 2555

Abstract

The aim of this paper is to evaluate the diagnostic image quality of spectral dual-source photon-counting detector coronary computed tomography angiography (PCD-CCTA) for coronary artery disease in a multicenter study. The image quality (IQ), assessability, contrast-to-noise ratio (CNR), Agatston score, and radiation exposure [...] Read more.

The aim of this paper is to evaluate the diagnostic image quality of spectral dual-source photon-counting detector coronary computed tomography angiography (PCD-CCTA) for coronary artery disease in a multicenter study. The image quality (IQ), assessability, contrast-to-noise ratio (CNR), Agatston score, and radiation exposure were measured. Stenoses were quantified and compared with invasive coronary angiography, if available. A total of 92 subjects (65% male, age 58 ± 14 years) were analyzed. The prevalence of significant coronary artery disease (CAD) (stenosis ≥ 50%) was 17% of all patients, the range of the Agatston score was 0–2965 (interquartile range (IQR) 0–135). The IQ was very good (one, IQR one–two), the CNR was very high (20 ± 10), and 5% of the segments were rated non-diagnostic. The IQ and assessability were higher in proximal coronary segments (p < 0.001). Agatston scores up to 600 did not significantly affect the assessability of the coronary segments (p = 0.3). Heart rate influenced assessability only at a high-pitch mode (p = 0.009). For the invasive coronary angiography (ICA) subgroup (n = nine), the diagnostic performance for CAD per segment was high (sensitivity 92%, specificity 96%), although the limited number of patients who underwent both diagnostic modalities limits the generalization of this finding at this stage. PCD-CCTA provides good image quality for low and moderate levels of coronary calcifications. Full article

(This article belongs to the Topic Cardiac Imaging: State of the Art)

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11 pages, 280 KiB

Open AccessEditor’s ChoiceArticle

The Burden of Carbapenem-Resistant Acinetobacter baumannii in ICU COVID-19 Patients: A Regional Experience

by Giorgia Montrucchio, Silvia Corcione, Tommaso Lupia, Nour Shbaklo, Carlo Olivieri, Miriam Poggioli, Aline Pagni, Davide Colombo, Agostino Roasio, Stefano Bosso, Fabrizio Racca, Valeria Bonato, Francesco Della Corte, Stefania Guido, Andrea Della Selva, Enrico Ravera, Nicoletta Barzaghi, Martina Cerrano, Pietro Caironi, Giacomo Berta, Cecilia Casalini, Bruno Scapino, Michele Grio, Massimiliano Parlanti Garbero, Gabriella Buono, Federico Finessi, Simona Erbetta, Paola Federica Sciacca, Gilberto Fiore, Alessandro Cerutti, Sergio Livigni, Daniela Silengo, Fulvio Agostini, Maurizio Berardino, Mauro Navarra, Silvia Vendramin, Enzo Castenetto, Marco Maria Liccardi, Emilpaolo Manno, Luca Brazzi and Francesco Giuseppe De Rosa Show full author list Hide full author list

J. Clin. Med. 2022, 11(17), 5208; https://doi.org/10.3390/jcm11175208 - 02 Sep 2022

Cited by 21 | Viewed by 1846

Abstract

Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during [...] Read more.

Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (n = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, p = 0.006 and 9.5 ± 3.6, p < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, p = 0.03), septic shock (61; 35%, p < 0.001), and in elders (66 ± 10, p < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (p = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (p < 0.001). Being colonized by CR-Ab was associated with a higher risk of developing invasive infections (p < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028–1.115) p = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572–18.988, p = 0.008). Constant infection-control measures are necessary to stop the spread of A. baumannii in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team. Full article

(This article belongs to the Special Issue Infection, Super Infection and Antimicrobial Management in ICU)

27 pages, 1318 KiB

Open AccessEditor’s ChoiceReview

Anticoagulation Strategies during Extracorporeal Membrane Oxygenation: A Narrative Review

by Sasa Rajsic, Robert Breitkopf, Dragana Jadzic, Marina Popovic Krneta, Helmuth Tauber and Benedikt Treml

J. Clin. Med. 2022, 11(17), 5147; https://doi.org/10.3390/jcm11175147 - 31 Aug 2022

Cited by 27 | Viewed by 3565

Abstract

The development of extracorporeal life support technology has added a new dimension to the care of critically ill patients who fail conventional treatment options. Extracorporeal membrane oxygenation (ECMO)—specialized temporary life support for patients with severe cardiac or pulmonary failure—plays a role in bridging [...] Read more.

The development of extracorporeal life support technology has added a new dimension to the care of critically ill patients who fail conventional treatment options. Extracorporeal membrane oxygenation (ECMO)—specialized temporary life support for patients with severe cardiac or pulmonary failure—plays a role in bridging the time for organ recovery, transplant, or permanent assistance. The overall patient outcome is dependent on the underlying disease, comorbidities, patient reaction to critical illness, and potential adverse events during ECMO. Moreover, the contact of the blood with the large artificial surface of an extracorporeal system circuit triggers complex inflammatory and coagulation responses. These processes may further lead to endothelial injury and disrupted microcirculation with consequent end-organ dysfunction and the development of adverse events like thromboembolism. Therefore, systemic anticoagulation is considered crucial to alleviate the risk of thrombosis and failure of ECMO circuit components. The gold standard and most used anticoagulant during extracorporeal life support is unfractionated heparin, with all its benefits and disadvantages. However, therapeutic anticoagulation of a critically ill patient carries the risk of clinically relevant bleeding with the potential for permanent injury or death. Similarly, thrombotic events may occur. Therefore, different anticoagulation strategies are employed, while the monitoring and the balance of procoagulant and anticoagulatory factors is of immense importance. This narrative review summarizes the most recent considerations on anticoagulation during ECMO support, with a special focus on anticoagulation monitoring and future directions. Full article

(This article belongs to the Section Intensive Care)

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11 pages, 761 KiB

Open AccessEditor’s ChoiceSystematic Review

Ureteral Access Sheaths and Its Use in the Future: A Comprehensive Update Based on a Literature Review

by Vincent De Coninck, Bhaskar Somani, Emre Tarik Sener, Esteban Emiliani, Mariela Corrales, Patrick Juliebø-Jones, Amelia Pietropaolo, Ioannis Mykoniatis, Belthangady M. Zeeshan Hameed, Francesco Esperto, Silvia Proietti, Olivier Traxer and Etienne Xavier Keller

J. Clin. Med. 2022, 11(17), 5128; https://doi.org/10.3390/jcm11175128 - 31 Aug 2022

Cited by 22 | Viewed by 3270

Abstract

Ureteral access sheaths (UASs) are part of urologist’s armamentarium when performing retrograde intrarenal surgery (RIRS). Recently, the world of RIRS has changed dramatically with the development of three game-changers: thulium fiber laser (TFL), smaller size single use digital flexible ureterosopes and intraoperative intrarenal [...] Read more.

Ureteral access sheaths (UASs) are part of urologist’s armamentarium when performing retrograde intrarenal surgery (RIRS). Recently, the world of RIRS has changed dramatically with the development of three game-changers: thulium fiber laser (TFL), smaller size single use digital flexible ureterosopes and intraoperative intrarenal pressure (IRP) measurement devices. We aimed to clarify the impact of UASs on IRP, complications and SFRs and put its indications in perspective of these three major technological improvements. A systematic review of the literature using the Medline, Scopus and Web of Science databases was performed by two authors and relevant studies were selected according to PRISMA guidelines. Recent studies showed that using a UAS lowers IRP and intrarenal temperature by increasing irrigation outflow during RIRS. Data on the impact of a UAS on SFRs, postoperative pain, risk of infectious complications, risk of ureteral strictures and risk of bladder recurrence of urothelial carcinoma after diagnostic RIRS were inconclusive. Prestenting for at least one week resulted in ureteral enlargement, while the influence of pre-operative administration of alpha-blockers was unclear. Since TFL, smaller single use digital ureteroscopes and devices with integrated pressure-measuring and aspiration technology seemed to increase SFRs and decrease pressure and temperature related complications, indications on the use of a UAS may decrease in the near future. Full article

(This article belongs to the Section Nephrology & Urology)

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10 pages, 651 KiB

Open AccessEditor’s ChoiceArticle

Intestinal Permeability and Depression in Patients with Inflammatory Bowel Disease

by Miorita Melina Iordache, Cristina Tocia, Mariana Aschie, Andrei Dumitru, Mihaela Manea, Georgeta Camelia Cozaru, Lucian Petcu, Sabina E. Vlad, Eugen Dumitru and Anca Chisoi

J. Clin. Med. 2022, 11(17), 5121; https://doi.org/10.3390/jcm11175121 - 30 Aug 2022

Cited by 15 | Viewed by 2418

Abstract

Depression is a global health problem that requires an early and accurate diagnosis to ensure quick access to appropriate treatment. Among multiple psychopathological paths, recent attention has focused on analysing the brain–gut–microbiota axis. The intestinal barrier plays a key role, and dysfunctions occurring [...] Read more.

Depression is a global health problem that requires an early and accurate diagnosis to ensure quick access to appropriate treatment. Among multiple psychopathological paths, recent attention has focused on analysing the brain–gut–microbiota axis. The intestinal barrier plays a key role, and dysfunctions occurring at this level have implications for mental health. The aim of the present study was to investigate the role of intestinal permeability biomarkers, i.e., calprotectin, zonulin, lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FAB), in relation to depression in patients with inflammatory bowel disease (IBD). This is the first study of this kind taking place in Romania, Eastern Europe, with an emphasis on patients with Crohn’s disease and ulcerative colitis. The correlations identified between depression and calprotectin and depression and LBP have the potential to shed light on the process of rapid diagnosis of depression with the help of biomarkers. Since depression is correlated with a decrease in the quality of life in patients with IBD, the need for access to appropriate treatments must be urgent. Full article

(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)

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9 pages, 261 KiB

Open AccessEditor’s ChoiceArticle

Migraine Prevention through Ketogenic Diet: More than Body Mass Composition Changes

by Mariarosaria Valente, Riccardo Garbo, Francesca Filippi, Alice Antonutti, Veronica Ceccarini, Yan Tereshko, Cherubino Di Lorenzo and Gian Luigi Gigli

J. Clin. Med. 2022, 11(17), 4946; https://doi.org/10.3390/jcm11174946 - 23 Aug 2022

Cited by 17 | Viewed by 3466

Abstract

The ketogenic diet (KD) is gaining attention as a preventive treatment for migraine, which is sustained by many pre-clinical and clinical data. KD is also used for weight loss, and there is a relation between migraine and weight excess, but it is speculated [...] Read more.

The ketogenic diet (KD) is gaining attention as a preventive treatment for migraine, which is sustained by many pre-clinical and clinical data. KD is also used for weight loss, and there is a relation between migraine and weight excess, but it is speculated that KD efficacy on migraine may go beyond this effect. We conducted a retrospective observational study on 23 migraine patients who received a KD and were evaluated at the baseline and then after 3 months both from a neurological and a nutritional point of view, including body mass composition analysis. We observed a reduction in monthly headache days (12.5 ± 9.5 vs. 6.7 ± 8.6; p < 0.001) and in days of acute medication intake (11.06 ± 9.37 vs. 4.93 ± 7.99; p = 0.008). We also observed a reduction in patients’ weight (73.8 ± 15.2 vs. 68.4 ± 14.6; p < 0.001) and BMI (26.9 ± 6.2 vs. 23.7 ± 8.1; p < 0.001) with a decrement of the fat mass (28.6 ± 12.5 vs. 20.6 ± 9.8; p < 0.001). Patients who responded to KD and those who did not had no differences with respect to weight or fat mass loss. These data corroborate the utilization of KD as a preventive treatment for migraine and suggest that the efficacy of such an intervention is not only due to weight or fat mass loss but probably relies on other mechanisms specific to KD. Full article

(This article belongs to the Special Issue Migraine Pathophysiology and Treatment: Current Approaches and New Horizons)

18 pages, 2935 KiB

Open AccessEditor’s ChoiceReview

Subretinal Injection Techniques for Retinal Disease: A Review

by Cristina Irigoyen, Asier Amenabar Alonso, Jorge Sanchez-Molina, María Rodríguez-Hidalgo, Araceli Lara-López and Javier Ruiz-Ederra

J. Clin. Med. 2022, 11(16), 4717; https://doi.org/10.3390/jcm11164717 - 12 Aug 2022

Cited by 17 | Viewed by 5175

Abstract

Inherited retinal dystrophies (IRDs) affect an estimated 1 in every 2000 people, this corresponding to nearly 2 million cases worldwide. Currently, 270 genes have been associated with IRDs, most of them altering the function of photoreceptors and retinal pigment epithelium. Gene therapy has [...] Read more.

Inherited retinal dystrophies (IRDs) affect an estimated 1 in every 2000 people, this corresponding to nearly 2 million cases worldwide. Currently, 270 genes have been associated with IRDs, most of them altering the function of photoreceptors and retinal pigment epithelium. Gene therapy has been proposed as a potential tool for improving visual function in these patients. Clinical trials in animal models and humans have been successful in various types of IRDs. Recently, voretigene neparvovec (Luxturna^®) has been approved by the US Food and Drug Administration for the treatment of biallelic mutations in the RPE65 gene. The current state of the art in gene therapy involves the delivery of various types of viral vectors into the subretinal space to effectively transduce diseased photoreceptors and retinal pigment epithelium. For this, subretinal injection is becoming increasingly popular among researchers and clinicians. To date, several approaches for subretinal injection have been described in the scientific literature, all of them effective in accessing the subretinal space. The growth and development of gene therapy give rise to the need for a standardized procedure for subretinal injection that ensures the efficacy and safety of this new approach to drug delivery. The goal of this review is to offer an insight into the current subretinal injection techniques and understand the key factors in the success of this procedure. Full article

(This article belongs to the Special Issue Surgical Management of Vitreoretinal Diseases)

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21 pages, 3485 KiB

Open AccessEditor’s ChoiceReview

Current Options and Future Perspectives in the Treatment of Dyslipidemia

by Saverio Muscoli, Mihaela Ifrim, Massimo Russo, Francesco Candido, Angela Sanseviero, Marialucia Milite, Marco Di Luozzo, Massimo Marchei and Giuseppe Massimo Sangiorgi

J. Clin. Med. 2022, 11(16), 4716; https://doi.org/10.3390/jcm11164716 - 12 Aug 2022

Cited by 17 | Viewed by 6275

Abstract

Low-density lipoprotein cholesterol (LDL-C) plays a crucial role in the development of atherosclerosis. Statin therapy is the standard treatment for lowering LDL-C in primary and secondary prevention. However, some patients do not reach optimal LDL-C target levels or do not tolerate statins, especially [...] Read more.

Low-density lipoprotein cholesterol (LDL-C) plays a crucial role in the development of atherosclerosis. Statin therapy is the standard treatment for lowering LDL-C in primary and secondary prevention. However, some patients do not reach optimal LDL-C target levels or do not tolerate statins, especially when taking high doses long-term. Combining statins with different therapeutic approaches and testing other new drugs is the future key to reducing the burden of cardiovascular disease (CVD). Recently, several new cholesterol-lowering drugs have been developed and approved; others are promising results, enriching the pharmacological armamentarium beyond statins. Triglycerides also play an important role in the development of CVD; new therapeutic approaches are also very promising for their treatment. Familial hypercholesterolemia (FH) can lead to CVD early in life. These patients respond poorly to conventional therapies. Recently, however, new and promising pharmacological strategies have become available. This narrative review provides an overview of the new drugs for the treatment of dyslipidemia, their current status, ongoing clinical or preclinical trials, and their prospects. We also discuss the new alternative therapies for the treatment of dyslipidemia and their relevance to practice. Full article

(This article belongs to the Section Cardiovascular Medicine)

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12 pages, 985 KiB

Open AccessEditor’s ChoiceArticle

Oral Health in Breast Cancer Women with Vitamin D Deficiency: A Machine Learning Study

by Martina Ferrillo, Mario Migliario, Nicola Marotta, Lorenzo Lippi, Alessandro Antonelli, Dario Calafiore, Valerio Ammendolia, Leonzio Fortunato, Filippo Renò, Amerigo Giudice, Marco Invernizzi and Alessandro de Sire

J. Clin. Med. 2022, 11(16), 4662; https://doi.org/10.3390/jcm11164662 - 09 Aug 2022

Cited by 18 | Viewed by 3013

Abstract

Breast cancer (BC) survivors treated with aromatase inhibitors (AIs) commonly show several pathological issues, including poor oral health, bone health impairment, and vitamin D deficiency. However, to date, oral health issues in BC survivors treated with AIs have been poorly investigated and their [...] Read more.

Breast cancer (BC) survivors treated with aromatase inhibitors (AIs) commonly show several pathological issues, including poor oral health, bone health impairment, and vitamin D deficiency. However, to date, oral health issues in BC survivors treated with AIs have been poorly investigated and their relationship with vitamin D deficiency are far from being understood. This study aimed to evaluate the correlation between oral health and vitamin D status in BC survivors undergoing treatment with AIs through a machine learning approach. In this cross-sectional study, we included post-menopausal BC women with vitamin D deficiency undergoing AIs therapy. The outcome measures were the following: oral health indexes as the Decayed, Missing, and Filled Permanent Teeth Index (DMFT); serum levels of 25(OH)D₃; Bone Mineral Density (BMD); and the diagnosis of osteoporosis. We included 41 post-menopausal BC women, mean aged 66.10 ± 8.47 years, with mean serum levels of vitamin D of 14.63 ± 6.62 ng/mL. Furthermore, 56.10% of patients had a diagnosis of osteoporosis and 36.59% were osteopenic. DMFT was significantly related to smoking (p-value = 0.005) and dental floss use (p-value = 0.001). There was a significant correlation between DMFT and vitamin D levels (Pearson’s r: −0.73; p-value = 0.001). The regression machine learning model showed that vitamin D status and the use of dental floss were the most relevant variables in terms of correlation with DMFT. In conclusion, vitamin D deficiency, inadequate use of dental floss, and smoking had a negative impact on oral health in BC women. Thus, vitamin D deficiency screening and supplementation and a prompt oral rehabilitation plan should be suggested and implemented in the complex treatment framework of BC survivors undergoing treatment with AIs. Full article

(This article belongs to the Section Orthopedics)

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12 pages, 298 KiB

Open AccessEditor’s ChoiceReview

New Era in Systemic Sclerosis Treatment: Recently Approved Therapeutics

by Satoshi Ebata, Asako Yoshizaki-Ogawa, Shinichi Sato and Ayumi Yoshizaki

J. Clin. Med. 2022, 11(15), 4631; https://doi.org/10.3390/jcm11154631 - 08 Aug 2022

Cited by 18 | Viewed by 4048

Abstract

Systemic sclerosis (SSc) is a chronic autoimmune disease with a poor prognosis. Among the various complications of SSc, treatment options for the fibrotic lesions, skin sclerosis, and SSc-associated interstitial lung disease (SSc-ILD) have been limited. However, since 2019, the efficacy and safety of [...] Read more.

Systemic sclerosis (SSc) is a chronic autoimmune disease with a poor prognosis. Among the various complications of SSc, treatment options for the fibrotic lesions, skin sclerosis, and SSc-associated interstitial lung disease (SSc-ILD) have been limited. However, since 2019, the efficacy and safety of nintedanib, tocilizumab, and rituximab for SSc or SSc-ILD have been demonstrated in double-blind, randomized, placebo-controlled trials, respectively. The antifibrotic agent nintedanib was approved for SSc-ILD in all regions of the United States, Europe, and Japan after the SENSCIS study confirmed that it suppressed the reduction in forced vital capacity (FVC), a measure of SSc-ILD. Tocilizumab, an anti-interleukin-6 receptor antibody, was approved for the treatment of SSc-ILD in the United States after the FocuSSced study showed that it inhibited the decrease in FVC. Rituximab, an anti-CD20 antibody, showed improvement in both modified Rodnan skin score, a measure of skin sclerosis, and FVC in the DESIRES study, and was approved in Japan for the treatment of SSc itself. With the development of these three drugs, SSc treatment is entering a new era. This paper outlines the latest advances in SSc therapeutics, focusing on nintedanib, tocilizumab, and rituximab. Full article

(This article belongs to the Special Issue 10th Anniversary of JCM – New Era in Dermatology)

17 pages, 1038 KiB

Open AccessEditor’s ChoiceSystematic Review

The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review

by Aikaterini Tsiogka, Maria Kyriazopoulou, George Kontochristopoulos, Electra Nicolaidou, Alexander Stratigos, Dimitris Rigopoulos and Stamatios Gregoriou

J. Clin. Med. 2022, 11(15), 4431; https://doi.org/10.3390/jcm11154431 - 29 Jul 2022

Cited by 26 | Viewed by 7026

Abstract

In recent years, the broadening understanding of the pathogenesis of atopic dermatitis (AD) has led to the development of novel therapeutic molecules, that target core inflammatory components of the disease. The Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway constitutes the [...] Read more.

In recent years, the broadening understanding of the pathogenesis of atopic dermatitis (AD) has led to the development of novel therapeutic molecules, that target core inflammatory components of the disease. The Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway constitutes the principal signaling cascade for a large number of cytokines and growth factors and is involved in intracellular signal transduction and subsequent regulation of gene transcription. Current knowledge suggests that the robust activation of the T-helper (Th)-2 [interleukin (IL)-4, IL-5, IL-13, IL-31] and Th22 (IL-22) immune responses in both skin and serum plays a pivotal role in the immunopathogenesis of AD especially at the acute stage, followed by a variable degree of Th1 (interferon-γ, tumor necrosis factor alpha) and Th17 (IL-17) activation in chronic disease. Of note, most of the aforementioned inflammatory cytokines utilize the JAK/STAT pathway for downstream signal transduction, explaining the emerging role of JAK inhibitors in the therapeutic armamentarium of AD. The present systematic review aims to discuss the involvement of JAK/STAT pathway in the pathogenesis of AD and summarize the clinical data available on the efficacy and safety of JAK inhibitors which have been used in the treatment of AD thus far. Full article

(This article belongs to the Section Dermatology)

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12 pages, 1383 KiB

Open AccessEditor’s ChoiceArticle

The Feasibility of Liver Biopsy for Undefined Nodules in Patients under Surveillance for Hepatocellular Carcinoma: Is Biopsy Really a Useful Tool?

by Matteo Renzulli, Anna Pecorelli, Nicolò Brandi, Stefano Brocchi, Francesco Tovoli, Alessandro Granito, Gianpaolo Carrafiello, Anna Maria Ierardi and Rita Golfieri

J. Clin. Med. 2022, 11(15), 4399; https://doi.org/10.3390/jcm11154399 - 28 Jul 2022

Cited by 18 | Viewed by 1574

Abstract

Background: The aim of the present study is to determine the feasibility of biopsy for atypical liver nodules in patients under surveillance for hepatocellular carcinoma (HCC), assessing which factors influence the decision to perform it. Methods: A total of 128 atypical [...] Read more.

Background: The aim of the present study is to determine the feasibility of biopsy for atypical liver nodules in patients under surveillance for hepatocellular carcinoma (HCC), assessing which factors influence the decision to perform it. Methods: A total of 128 atypical liver nodules in 108 patients under surveillance for HCC, who underwent CT between September 2018 and September 2019, were included. All the images were saved digitally (on CD-ROM) and the two most representative images in the arterial and delayed phases were selected for each lesion and inserted into a digital atlas (on PDF). Two experienced radiologists (Readers 1 and 2) reviewed both the CD-ROM and the PDF to define the feasibility of biopsy in both scenarios, specifying the reasons for the unfeasibility of biopsy. The intra-observer variability and inter-observer variability were assessed. Results: When reviewing the PDF, 76 (59.4%) and 68 (53.1%) nodules were deemed unfeasible for biopsy by the less experienced radiologist (Reader 1) and the more experienced radiologist (Reader 2), respectively (p = 0.604). When reviewing the entire CT study, both percentages decreased slightly (Reader 1 = 70/128 (54.7%); Reader 2 = 61/128 (47.6%); p = 0.591). The intra-reader agreement on the PDF was substantial (k = 0.648 (95% CI = 0.513–0.783)). The inter-reader agreement on the PDF was slight (k = 0.185 (95% CI = 0.021–0.348)) and moderate on the entire CT study (k = 0.424 (95% CI = 0.269–0.579)). When assessing the PDF, the nodule size (10–20 mm) and location in segments six and eight were negatively and positively associated with the feasibility of liver biopsy, respectively. When assessing the CD-ROM, only the nodule dimension was associated with the unfeasibility of liver biopsy. Conclusions: The unfeasibility of liver biopsy is mainly due to the small size of the lesions and their location. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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30 pages, 20527 KiB

Open AccessEditor’s ChoiceReview

Macrophages, Low-Grade Inflammation, Insulin Resistance and Hyperinsulinemia: A Mutual Ambiguous Relationship in the Development of Metabolic Diseases

by Gerhard Paul Püschel, Julia Klauder and Janin Henkel

J. Clin. Med. 2022, 11(15), 4358; https://doi.org/10.3390/jcm11154358 - 27 Jul 2022

Cited by 29 | Viewed by 4611

Abstract

Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated with chronic low-grade inflammation and hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play a key role in the maintenance of normal tissue homeostasis, but functional alterations in the [...] Read more.

Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated with chronic low-grade inflammation and hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play a key role in the maintenance of normal tissue homeostasis, but functional alterations in the resident macrophage pool as well as newly recruited monocyte-derived macrophages are important drivers in the development of low-grade inflammation. While metabolic dysfunction, insulin resistance and tissue damage may trigger or advance pro-inflammatory responses in macrophages, the inflammation itself contributes to the development of insulin resistance and the resulting hyperinsulinemia. Macrophages express insulin receptors whose downstream signaling networks share a number of knots with the signaling pathways of pattern recognition and cytokine receptors, which shape macrophage polarity. The shared knots allow insulin to enhance or attenuate both pro-inflammatory and anti-inflammatory macrophage responses. This supposedly physiological function may be impaired by hyperinsulinemia or insulin resistance in macrophages. This review discusses the mutual ambiguous relationship of low-grade inflammation, insulin resistance, hyperinsulinemia and the insulin-dependent modulation of macrophage activity with a focus on adipose tissue and liver. Full article

(This article belongs to the Special Issue The Connection between Liver Disease and Diabetes Mellitus)

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36 pages, 3127 KiB

Open AccessEditor’s ChoiceSystematic Review

Real-World Evidence of the Effectiveness and Safety of Ustekinumab for the Treatment of Crohn’s Disease: Systematic Review and Meta-Analysis of Observational Studies

by Cristina Rubín de Célix, María Chaparro and Javier P. Gisbert

J. Clin. Med. 2022, 11(14), 4202; https://doi.org/10.3390/jcm11144202 - 20 Jul 2022

Cited by 18 | Viewed by 2846

Abstract

(1) Background: Evidence on the outcomes of ustekinumab treatment in real-world Crohn’s disease (CD) patients is needed. Our aim was to evaluate the effectiveness and safety of ustekinumab in CD, reported by observational studies. (2) Methods: bibliographical searches were performed (PubMed, EMBASE). Selection: [...] Read more.

(1) Background: Evidence on the outcomes of ustekinumab treatment in real-world Crohn’s disease (CD) patients is needed. Our aim was to evaluate the effectiveness and safety of ustekinumab in CD, reported by observational studies. (2) Methods: bibliographical searches were performed (PubMed, EMBASE). Selection: observational studies assessing the effectiveness and safety of ustekinumab in CD. Exclusion criteria: studies using ustekinumab as a prophylaxis for postoperative recurrence or perianal disease. Data synthesis: effectiveness by intention-to-treat (random-effects model). Data were stratified by study design, population included, administered dose, and prior biologic exposure. (3) Results: A total of 63 studies (8529 patients) were included. Response was achieved in 60% (95% CI, 54–67%) in the short term (8–14 weeks); 64% (57–71%) in the medium term (16–24 weeks); and 64% (52–74%) in the long term (48–52 weeks). Remission was achieved in 37% (28–46%) in the short term; 42% (36–49%) in the medium term; and 45% (37–53%) in the long term. The endoscopic remission rate was 33% (25–40%) in the long term. Eighteen percent of patients lost response during follow-up. Nearly one-third of the patients needed dose optimisation, and in 59% of them it was effective. Twenty-five percent of patients developed adverse events, leading to treatment withdrawal in seven percent of the cases. (4) Conclusions: Ustekinumab is an effective and safe therapy in real-world refractory CD patients. Dose optimisation is frequently required, being effective in a high percentage of cases. Full article

(This article belongs to the Special Issue Crohn’s Disease: Advances in Diagnosis and Treatment)

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33 pages, 1809 KiB

Open AccessEditor’s ChoiceReview

Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases

by Manuele Biazzo and Gabriele Deidda

J. Clin. Med. 2022, 11(14), 4119; https://doi.org/10.3390/jcm11144119 - 15 Jul 2022

Cited by 27 | Viewed by 7472

Abstract

The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota [...] Read more.

The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient’s gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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15 pages, 914 KiB

Open AccessEditor’s ChoiceReview

Influenza Myopericarditis and Pericarditis: A Literature Review

by Milan Radovanovic, Marija Petrovic, Michel K. Barsoum, Charles W. Nordstrom, Andrew D. Calvin, Igor Dumic, Dorde Jevtic and Richard D. Hanna

J. Clin. Med. 2022, 11(14), 4123; https://doi.org/10.3390/jcm11144123 - 15 Jul 2022

Cited by 18 | Viewed by 3219

Abstract

Myopericarditis is a rare complication of influenza infection. The presentation may range from mild and frequently unrecognized, to fulminant and potentially complicated by cardiogenic and/or obstructive shock (tamponade), which is associated with high mortality. We performed a review of literature on all influenza [...] Read more.

Myopericarditis is a rare complication of influenza infection. The presentation may range from mild and frequently unrecognized, to fulminant and potentially complicated by cardiogenic and/or obstructive shock (tamponade), which is associated with high mortality. We performed a review of literature on all influenza pericarditis and myopericarditis cases according to PRISMA guidelines using the PubMed search engine of the Medline database. Seventy-five cases of influenza myopericarditis and isolated pericarditis were identified from 1951 to 2021. Influenza A was reported twice as often as influenza B; however, influenza type did not correlate with outcome. Men and elderly patients were more likely to have isolated pericarditis, while women and younger patients were more likely to have myopericarditis. All included patients had pericardial effusion, while 36% had tamponade. Tamponade was more common in those with isolated pericarditis (41.2%) than myopericarditis (13.8%). Cardiogenic shock was more common in patients with myopericarditis (64%), with an overall mortality rate of 14.7%. Nearly 88% of the recovered patients remained without long-term complications reported. Conclusion: Influenza A appears a more common cause of pericarditis and myopericarditis. Isolated pericarditis was more commonly associated with tamponade but without reported deaths, whereas myopericarditis was more commonly associated with cardiogenic shock and death (19%). Full article

(This article belongs to the Section Cardiology)

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12 pages, 552 KiB

Open AccessEditor’s ChoiceArticle

Incidence of Sleep Bruxism in Different Phenotypes of Obstructive Sleep Apnea

by Joanna Smardz, Mieszko Wieckiewicz, Anna Wojakowska, Monika Michalek-Zrabkowska, Rafal Poreba, Pawel Gac, Grzegorz Mazur and Helena Martynowicz

J. Clin. Med. 2022, 11(14), 4091; https://doi.org/10.3390/jcm11144091 - 14 Jul 2022

Cited by 11 | Viewed by 2972

Abstract

(1) Background: Sleep bruxism (SB) is a common sleep behavior. Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder with potential long-term major neurocognitive and cardiovascular sequelae. Although the co-occurrence of SB and OSA has been described previously, the exact relationship remains [...] Read more.

(1) Background: Sleep bruxism (SB) is a common sleep behavior. Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder with potential long-term major neurocognitive and cardiovascular sequelae. Although the co-occurrence of SB and OSA has been described previously, the exact relationship remains unclear. The present study aimed to evaluate the incidence of SB in different phenotypes of OSA. (2) Methods: The participants of this study were adult patients referred to the Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology at the Wroclaw Medical University. They underwent a single-night video polysomnography in a sleep laboratory. The data related to common OSA phenotypes were analyzed in two separate groups of patients: body position related (n = 94) and rapid eye movement (REM) related (n = 85). (3) Results: The obtained results showed that the incidence of SB and severe SB was higher for body position-related OSA phenotype (p < 0.05 for all comparisons). No statistically significant differences were observed for REM-related OSA phenotype (p > 0.05 for all comparisons). (4) Conclusions: Body position-related OSA phenotype seems to be associated with higher SB and severe SB incidence, but the relationship is not independent. However, in the light of the unclear relationship between SB and sleep-disordered breathing, the topic needs further study. Full article

(This article belongs to the Section Epidemiology & Public Health)

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27 pages, 1316 KiB

Open AccessEditor’s ChoiceReview

Pathogenesis of Human Adenomyosis: Current Understanding and Its Association with Infertility

by Khaleque N. Khan, Akira Fujishita and Taisuke Mori

J. Clin. Med. 2022, 11(14), 4057; https://doi.org/10.3390/jcm11144057 - 13 Jul 2022

Cited by 17 | Viewed by 5233

Abstract

The aim of this review article was to summarize our current understanding on the etiologies and pathogenesis of human adenomyosis and to clarify the relative association between adenomyosis and infertility. The exact pathogenesis of adenomyosis is still elusive. Among different reported concepts, direction [...] Read more.

The aim of this review article was to summarize our current understanding on the etiologies and pathogenesis of human adenomyosis and to clarify the relative association between adenomyosis and infertility. The exact pathogenesis of adenomyosis is still elusive. Among different reported concepts, direction invagination of gland cells from the basalis endometrium deep into myometrium is the most widely accepted opinion on the development of adenomyosis. According to this concept, endometrial epithelial cells and changed fibroblasts, abnormally found in the myometrium in response to repeated tissue injury and/or disruption at the endometrium-myometrium interface (EMI), elicit hyperplasia and hypertrophy of the surrounding smooth muscle cells. In this review, a comprehensive review was performed with a literature search using PubMed for all publications in English and Japanese (abstract in English), related to adenomyosis and infertility, from inception to April 2021. As an estrogen-regulated factor, hepatocyte growth factor (HGF) exhibits multiple functions in endometriosis, a disease commonly believed to arise from the functionalis endometrium. As a mechanistic basis of gland invagination, we investigated the role of HGF, either alone or in combination with estrogen, in the occurrence of epithelial-mesenchymal transition (EMT) in adenomyosis. Aside from microtrauma at the EMI, metaplasia of displaced Müllerian remnants, differentiation of endometrial stem/progenitor cells within the myometrium and somatic mutation of some target genes have been put forward to explain how adenomyosis develops. In addition, the possible role of microRNAs in adenomyosis is also discussed. Besides our knowledge on the conventional classification (focal and diffuse), two recently proposed classifications (intrinsic and extrinsic) of adenomyosis and the biological differences between them have been described. Although the mechanistic basis is unclear, the influence of adenomyosis on fertility outcome is important, especially considering the recent tendency to delay pregnancy among women. Besides other proposed mechanisms, a recent transmission election microscopic (TEM) study indicated that microvilli damage and an axonemal alteration in the apical endometria of human adenomyosis, in response to endometrial inflammation, may be involved in negative fertility outcomes. We present a critical analysis of the literature data concerning the mechanistic basis of infertility in women with adenomyosis and its impact on fertility outcome. Full article

(This article belongs to the Special Issue Cracking the Enigma of Adenomyosis)

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14 pages, 532 KiB

Open AccessEditor’s ChoiceReview

Artificial Intelligence in Cardiology—A Narrative Review of Current Status

by George Koulaouzidis, Tomasz Jadczyk, Dimitris K. Iakovidis, Anastasios Koulaouzidis, Marc Bisnaire and Dafni Charisopoulou

J. Clin. Med. 2022, 11(13), 3910; https://doi.org/10.3390/jcm11133910 - 05 Jul 2022

Cited by 23 | Viewed by 4184

Abstract

Artificial intelligence (AI) is an integral part of clinical decision support systems (CDSS), offering methods to approximate human reasoning and computationally infer decisions. Such methods are generally based on medical knowledge, either directly encoded with rules or automatically extracted from medical data using [...] Read more.

Artificial intelligence (AI) is an integral part of clinical decision support systems (CDSS), offering methods to approximate human reasoning and computationally infer decisions. Such methods are generally based on medical knowledge, either directly encoded with rules or automatically extracted from medical data using machine learning (ML). ML techniques, such as Artificial Neural Networks (ANNs) and support vector machines (SVMs), are based on mathematical models with parameters that can be optimally tuned using appropriate algorithms. The ever-increasing computational capacity of today’s computer systems enables more complex ML systems with millions of parameters, bringing AI closer to human intelligence. With this objective, the term deep learning (DL) has been introduced to characterize ML based on deep ANN (DNN) architectures with multiple layers of artificial neurons. Despite all of these promises, the impact of AI in current clinical practice is still limited. However, this could change shortly, as the significantly increased papers in AI, machine learning and deep learning in cardiology show. We highlight the significant achievements of recent years in nearly all areas of cardiology and underscore the mounting evidence suggesting how AI will take a central stage in the field. Full article

(This article belongs to the Special Issue 10th Anniversary of JCM—Evidence-Based Medicine, Research and Education in Integrative and Personalized Medicine for Cardiovascular Medicine Section)

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26 pages, 1780 KiB

Open AccessEditor’s ChoiceSystematic Review

Autonomic Dysfunction during Acute SARS-CoV-2 Infection: A Systematic Review

by Irene Scala, Pier Andrea Rizzo, Simone Bellavia, Valerio Brunetti, Francesca Colò, Aldobrando Broccolini, Giacomo Della Marca, Paolo Calabresi, Marco Luigetti and Giovanni Frisullo

J. Clin. Med. 2022, 11(13), 3883; https://doi.org/10.3390/jcm11133883 - 04 Jul 2022

Cited by 16 | Viewed by 3299

Abstract

Although autonomic dysfunction (AD) after the recovery from Coronavirus disease 2019 (COVID-19) has been thoroughly described, few data are available regarding the involvement of the autonomic nervous system (ANS) during the acute phase of SARS-CoV-2 infection. The primary aim of this review was [...] Read more.

Although autonomic dysfunction (AD) after the recovery from Coronavirus disease 2019 (COVID-19) has been thoroughly described, few data are available regarding the involvement of the autonomic nervous system (ANS) during the acute phase of SARS-CoV-2 infection. The primary aim of this review was to summarize current knowledge regarding the AD occurring during acute COVID-19. Secondarily, we aimed to clarify the prognostic value of ANS involvement and the role of autonomic parameters in predicting SARS-CoV-2 infection. According to the PRISMA guidelines, we performed a systematic review across Scopus and PubMed databases, resulting in 1585 records. The records check and the analysis of included reports’ references allowed us to include 22 articles. The studies were widely heterogeneous for study population, dysautonomia assessment, and COVID-19 severity. Heart rate variability was the tool most frequently chosen to analyze autonomic parameters, followed by automated pupillometry. Most studies found ANS involvement during acute COVID-19, and AD was often related to a worse outcome. Further studies are needed to clarify the role of autonomic parameters in predicting SARS-CoV-2 infection. The evidence emerging from this review suggests that a complex autonomic nervous system imbalance is a prominent feature of acute COVID-19, often leading to a poor prognosis. Full article

(This article belongs to the Special Issue Clinical Health Care during the COVID-19 Pandemic: Therapeutic and Management Strategies)

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16 pages, 1169 KiB

Open AccessEditor’s ChoiceReview

Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias

by Clarice Gareri, Alberto Polimeni, Salvatore Giordano, Laura Tammè, Antonio Curcio and Ciro Indolfi

J. Clin. Med. 2022, 11(13), 3884; https://doi.org/10.3390/jcm11133884 - 04 Jul 2022

Cited by 25 | Viewed by 4060

Abstract

The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides [...] Read more.

The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides and small interfering RNAs (siRNAs) that operate upstream, blocking the mRNA translation of the proteins specifically involved in lipid metabolism. In this review, we briefly explain the mechanisms of action of these molecules and discuss the difficulties related to their in vivo use as therapeutical agents. We go over the oligonucleotides tested in clinical trials that could potentially revolutionize the care of patients by acting on proteins involved in the lipoprotein metabolism and regulation, namely: angiopoietin-like protein 3 (ANGPTL3); lipoprotein a (Lp(a)); apolipoprotein B (Apo B); apolipoprotein C III (Apo C-III); and proprotein convertase subtilisin–kexin type 9 (PCSK9). Finally, the differences between ASOs and siRNAs, their future possible clinical applications, and the role of Inclisiran, a siRNA direct against PCSK9 to reduce LDL-C, were reviewed in detail. Full article

(This article belongs to the Special Issue PCSK9 Inhibitors and Cardiovascular Diseases: A New Era of Lipid Lowering Therapy)

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15 pages, 1049 KiB

Open AccessEditor’s ChoiceReview

Current Effective Therapeutics in Management of COVID-19

by Kavya Atluri, Iris Aimlin and Shitij Arora

J. Clin. Med. 2022, 11(13), 3838; https://doi.org/10.3390/jcm11133838 - 01 Jul 2022

Cited by 22 | Viewed by 4020

Abstract

The current pandemic due to the SARS-CoV-2 virus has caused irreparable damage globally. High importance is placed on defining current therapeutics for Coronavirus Disease 2019 (COVID-19). In this review, we discuss the evidence from pivotal trials that led to the approval of effective [...] Read more.

The current pandemic due to the SARS-CoV-2 virus has caused irreparable damage globally. High importance is placed on defining current therapeutics for Coronavirus Disease 2019 (COVID-19). In this review, we discuss the evidence from pivotal trials that led to the approval of effective therapeutics in the treatment and prevention of COVID-19. We categorize them as effective outpatient and inpatient management strategies The review also attempts to contextualize the efficacy of therapeutics to the emerging variants. Vaccines, which remain the most effective prevention against hospitalization and deaths is not included in this review. Full article

(This article belongs to the Special Issue COVID-19: Clinical Advances and Challenges)

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10 pages, 1358 KiB

Open AccessEditor’s ChoiceArticle

Efficacy of Oxybrasion in the Treatment of Acne Vulgaris: A Preliminary Report

by Karolina Chilicka, Aleksandra M. Rogowska, Renata Szyguła, Monika Rusztowicz and Danuta Nowicka

J. Clin. Med. 2022, 11(13), 3824; https://doi.org/10.3390/jcm11133824 - 01 Jul 2022

Cited by 20 | Viewed by 3891

Abstract

There are many cosmetic methods to reduce skin eruptions in people with acne vulgaris. As oxybrasion is a safe method of exfoliating dead epidermis, our objective was to investigate its effectiveness in young women with acne vulgaris. The Global Acne Grading System (GAGS) [...] Read more.

There are many cosmetic methods to reduce skin eruptions in people with acne vulgaris. As oxybrasion is a safe method of exfoliating dead epidermis, our objective was to investigate its effectiveness in young women with acne vulgaris. The Global Acne Grading System (GAGS) and Derma Unit SSC 3 device (Sebumeter SM 815, Corneometer CM 825) were used to assess acne vulgaris and skin properties. Twenty-four women aged 19–21 years (M = 19.50, SD = 0.66) with diagnosed mild acne vulgaris and a high level of sebum (more than 100 μg/cm²) participated in the study. Women on any dermatological treatment within the last 12 months and/or hormonal contraception were excluded. Probands were randomly assigned to two equal groups. Group A (experimental) was oxybrased with 0.9% sodium chloride solution simultaneously with compressed oxygen. Group B (placebo) was the group treated with non-carbonated mineral water and oxygen from the device (not pure). A series of five treatments was performed at 10-day intervals. Skin parameters were measured before and 30 days after the end of treatment. As a result, in group A (experimental), skin hydration and GAGS improved, while sebum on the epidermis was reduced. No side effects were noted. We concluded that oxybrasion is effective in women with acne and safe, as it improved skin parameters; however, further research is needed. Full article

(This article belongs to the Special Issue New Insights on Acne, Rosacea, and Hidradenitis Suppurativa: Etiology and Treatment)

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29 pages, 2515 KiB

Open AccessEditor’s ChoiceSystematic Review

Effectiveness of Home-Based Cardiac Rehabilitation, Using Wearable Sensors, as a Multicomponent, Cutting-Edge Intervention: A Systematic Review and Meta-Analysis

by Varsamo Antoniou, Constantinos H. Davos, Eleni Kapreli, Ladislav Batalik, Demosthenes B. Panagiotakos and Garyfallia Pepera

J. Clin. Med. 2022, 11(13), 3772; https://doi.org/10.3390/jcm11133772 - 29 Jun 2022

Cited by 45 | Viewed by 3824

Abstract

Exercise-based cardiac rehabilitation is a highly recommended intervention towards the advancement of the cardiovascular disease (CVD) patients’ health profile; though with low participation rates. Although home-based cardiac rehabilitation (HBCR) with the use of wearable sensors is proposed as a feasible alternative rehabilitation model, [...] Read more.

Exercise-based cardiac rehabilitation is a highly recommended intervention towards the advancement of the cardiovascular disease (CVD) patients’ health profile; though with low participation rates. Although home-based cardiac rehabilitation (HBCR) with the use of wearable sensors is proposed as a feasible alternative rehabilitation model, further investigation is needed. This systematic review and meta-analysis aimed to evaluate the effectiveness of wearable sensors-assisted HBCR in improving the CVD patients’ cardiorespiratory fitness (CRF) and health profile. PubMed, Scopus, Cinahl, Cochrane Library, and PsycINFO were searched from 2010 to January 2022, using relevant keywords. A total of 14 randomized controlled trials, written in English, comparing wearable sensors-assisted HBCR to center-based cardiac rehabilitation (CBCR) or usual care (UC), were included. Wearable sensors-assisted HBCR significantly improved CRF when compared to CBCR (Hedges’ g = 0.22, 95% CI 0.06, 0.39; I² = 0%; p = 0.01), whilst comparison of HBCR to UC revealed a nonsignificant effect (Hedges’ g = 0.87, 95% CI −0.87, 1.85; I² = 96.41%; p = 0.08). Effects on physical activity, quality of life, depression levels, modification of cardiovascular risk factors/laboratory parameters, and adherence were synthesized narratively. No significant differences were noted. Technology tools are growing fast in the cardiac rehabilitation era and promote exercise-based interventions into a more home-based setting. Wearable-assisted HBCR presents the potential to act as an adjunct or an alternative to CBCR. Full article

(This article belongs to the Special Issue New Insights from Cardiopulmonary Exercise Testing and Cardiac Rehabilitation)

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14 pages, 771 KiB

Open AccessEditor’s ChoiceReview

Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin

by Susanna Campo, Antonio Lacquaniti, Domenico Trombetta, Antonella Smeriglio and Paolo Monardo

J. Clin. Med. 2022, 11(13), 3759; https://doi.org/10.3390/jcm11133759 - 28 Jun 2022

Cited by 29 | Viewed by 4256

Abstract

Biocompatibility in hemodialysis (HD) has considerably improved in recent decades, but remains an open issue to be solved, appearing essential to reduce systemic inflammation and enhance patients’ clinical outcomes. Clotting prevention, reduction in complement and leukocyte activation, and improvement of antioxidant effect represent [...] Read more.

Biocompatibility in hemodialysis (HD) has considerably improved in recent decades, but remains an open issue to be solved, appearing essential to reduce systemic inflammation and enhance patients’ clinical outcomes. Clotting prevention, reduction in complement and leukocyte activation, and improvement of antioxidant effect represent the main goals. This review aims to analyze the different pathways involved in HD patients, leading to immune system dysfunction and inflammation. In particular, we mostly review the evidence about thrombogenicity, which probably represents the most important characteristic of bio-incompatibility. Platelet activation is one of the first steps occurring in HD patients, determining several events causing chronic sub-clinical inflammation and immune dysfunction involvement. Moreover, oxidative stress processes, resulting from a loss of balance between pro-oxidant factors and antioxidant mechanisms, have been described, highlighting the link with inflammation. We updated both innate and acquired immune system dysfunctions and their close link with uremic toxins occurring in HD patients, with several consequences leading to increased mortality. The elucidation of the role of immune dysfunction and inflammation in HD patients would enhance not only the understanding of disease physiopathology, but also has the potential to provide new insights into the development of therapeutic strategies. Full article

(This article belongs to the Special Issue Clinical Management of Hemodialyzed Patients: From Pharmacological Interventions to Advanced Technologies)

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13 pages, 1321 KiB

Open AccessEditor’s ChoiceArticle

The Risk of Developing Alzheimer’s Disease and Parkinson’s Disease in Patients with Inflammatory Bowel Disease: A Meta-Analysis

by Marta Szandruk-Bender, Benita Wiatrak and Adam Szeląg

J. Clin. Med. 2022, 11(13), 3704; https://doi.org/10.3390/jcm11133704 - 27 Jun 2022

Cited by 16 | Viewed by 2216

Abstract

Recently, a growing body of research has linked gut microbiota dysbiosis to central nervous system diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has suggested that AD and PD pathology may take its origin from chronic inflammation in the gastrointestinal [...] Read more.

Recently, a growing body of research has linked gut microbiota dysbiosis to central nervous system diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has suggested that AD and PD pathology may take its origin from chronic inflammation in the gastrointestinal tract. Thus, this study aimed to elucidate whether inflammatory bowel disease (IBD) is associated with a higher risk of developing AD and PD as compared to the non-IBD population by conducting a meta-analysis. A thorough search of Pubmed and Embase databases was performed to identify all relevant articles. The quality of included studies was assessed using the Newcastle-Ottawa Scale. The odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed using a fixed-effect model. To assess publication bias and heterogeneity among the studies, Egger’s test and L’Abbé plots were used, respectively. A total of eight eligible studies were included in this meta-analysis. No significant heterogeneity or significant publication bias was detected. The risk of developing AD in IBD patients was higher than in non-IBD patients (OR = 0.37; 95% CI = 0.14–1.00; p = 0.05), and there was a relationship between the occurrence of AD and Crohn’s disease or ulcerative colitis (OR = 0.11; 95% CI = 0.04–0.30; p < 0.0001, OR = 0.14; 95% CI = 0.04–0.49; p = 0.0024, respectively). The risk of developing both of the most common neurodegenerative diseases, AD and PD, was also significantly higher in patients diagnosed with Crohn’s disease or ulcerative colitis (OR = 0.21; 95% CI = 0.09–0.49; p = 0.0003, OR = 0.25; 95% CI = 0.13–0.51; p = 0.0001, respectively). This meta-analysis revealed a higher risk of AD and PD among CD and UC patients compared to the general population. It may suggest a key role for the gut microbiota in the pathogenesis of not only Crohn’s disease and ulcerative colitis but also AD and PD. The identification of this potential risk may provide earlier preventive measures to be implemented to reduce comorbidity and mortality rate. Full article

(This article belongs to the Special Issue Prevention of Alzheimer's Disease: The Impact of Modifiable Risk Factors)

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23 pages, 3359 KiB

Open AccessEditor’s ChoiceReview

The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications

by Rossella Palma, Annamaria Pronio, Mario Romeo, Flavia Scognamiglio, Lorenzo Ventriglia, Vittorio Maria Ormando, Antonietta Lamazza, Stefano Pontone, Alessandro Federico and Marcello Dallio

J. Clin. Med. 2022, 11(13), 3649; https://doi.org/10.3390/jcm11133649 - 24 Jun 2022

Cited by 20 | Viewed by 3710

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome’s extrahepatic components has suggested the nature of the systemic metabolic-related disorder based on the interplay between [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome’s extrahepatic components has suggested the nature of the systemic metabolic-related disorder based on the interplay between genetic, nutritional, and environmental factors, creating a complex network of yet-unclarified pathogenetic mechanisms in which the role of insulin resistance (IR) could be crucial. This review detailed the clinical and pathogenetic evidence involved in the NAFLD–IR relationship, presenting both the classic and more innovative models. In particular, we focused on the reciprocal effects of IR, oxidative stress, and systemic inflammation on insulin-sensitivity disruption in critical regions such as the hepatic and the adipose tissue, while considering the impact of genetics/epigenetics on the regulation of IR mechanisms as well as nutrients on specific insulin-related gene expression (nutrigenetics and nutrigenomics). In addition, we discussed the emerging capability of the gut microbiota to interfere with physiological signaling of the hormonal pathways responsible for maintaining metabolic homeostasis and by inducing an abnormal activation of the immune system. The translation of these novel findings into clinical practice could promote the expansion of accurate diagnostic/prognostic stratification tools and tailored pharmacological approaches. Full article

(This article belongs to the Special Issue Clinical Research Advances in Non-alcoholic Fatty Liver Disease)

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13 pages, 1292 KiB

Open AccessEditor’s ChoiceArticle

Lipid Peroxidation Levels in Saliva and Plasma of Patients Suffering from Periodontitis

by Tanja Veljovic, Milanko Djuric, Jelena Mirnic, Ivana Gusic, Aleksandra Maletin, Bojana Ramic, Isidora Neskovic, Karolina Vukoje and Snezana Brkic

J. Clin. Med. 2022, 11(13), 3617; https://doi.org/10.3390/jcm11133617 - 23 Jun 2022

Cited by 15 | Viewed by 1748

Abstract

Lipid peroxidation (LPO) participates in the development of various diseases, including periodontitis, and malondialdehyde (MDA) is its terminal product. Therefore, in the present study, salivary and plasma MDA levels in 30 periodontitis patients were compared to those in 20 healthy controls, as well [...] Read more.

Lipid peroxidation (LPO) participates in the development of various diseases, including periodontitis, and malondialdehyde (MDA) is its terminal product. Therefore, in the present study, salivary and plasma MDA levels in 30 periodontitis patients were compared to those in 20 healthy controls, as well as in relation to periodontal therapy in order to assess its effectiveness. Periodontal status was assessed via plaque index, gingival index, papilla bleeding index, probing depth and clinical attachment level, while salivary and plasma MDA levels were determined by the ELISA method. The periodontitis group had a significantly greater salivary (2.99 pmol/µL) and plasma (0.50 pmol/µL) MDA levels relative to the healthy controls (1.33 pmol/µL and 0.40 pmol/µL, respectively). Three months after the periodontal therapy completion, although salivary MDA levels were significantly lower than those measured at the baseline (p < 0.001), the reduction in plasma MDA was not statistically significant (p > 0.05). These findings indicate that, while inflammatory processes in periodontium may increase local and systemic lipid peroxidation, periodontal therapy can result in a significant decrease in salivary, but not plasma, MDA levels. Full article

(This article belongs to the Special Issue Periodontitis: Current Status and the Future)

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9 pages, 246 KiB

Open AccessEditor’s ChoiceArticle

Nutritional Status and Potentially Inappropriate Medications in Elderly

by Simona Loddo, Francesco Salis, Samuele Rundeddu, Luca Serchisu, Maria Monica Peralta and Antonella Mandas

J. Clin. Med. 2022, 11(12), 3465; https://doi.org/10.3390/jcm11123465 - 16 Jun 2022

Cited by 15 | Viewed by 2001

Abstract

(1) Background: The association between polypharmacy and malnutrition has been investigated in several studies; however, few of these specifically deepened the relationship between potentially inappropriate medication and malnutrition. With a descriptive approach, the primary aim of our study was to evaluate the impact [...] Read more.

(1) Background: The association between polypharmacy and malnutrition has been investigated in several studies; however, few of these specifically deepened the relationship between potentially inappropriate medication and malnutrition. With a descriptive approach, the primary aim of our study was to evaluate the impact of the nutritional status, assessed with the Mini Nutritional Assessment (MNA), on potentially inappropriate medications (PIM), estimated 10-year survival, and the risk of adverse drug reactions in elderly patients; the secondary aim was to evaluate how the Screening Tool of Older People’s Prescriptions (STOPP), Screening Tool to Alert to Right Treatment (START), and BEERS 2019 criteria identify PIM compared to nutritional status. (2) Methods: In this study, 3091 subjects were enrolled, of whom 2748 (71.7%) were women; the median age was 80 years, with an interquartile range between 75 and 85 years of age. The subjects were assessed at the outpatient service for frail older people of the University Hospital of Cagliari. The study population was evaluated for their: MNA, Charlson Comorbidity Index, 10-year survival estimation, BEERS 2019, STOPP and START criteria, and ADR Risk scores. (3) Results: We divided the study population into three groups: MNA1 (MNA score ≥ 24), MNA2 (23.5–17), and MNA3 (<17): the severity of comorbidities, STOPP and START alerts, and BEERS 2019 criteria were significantly worse in both MNA2 and MNA3 compared to MNA1—with the exception of BEERS “non-anti-infective medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults”. Moreover, the estimated 10-year survival was significantly higher in MNA1 than in MNA2 and MNA3, and also in MNA2 compared to MNA3. Finally, the ADR risk scores were significantly lower in MNA1 than in MNA2 and MNA3. (4) Conclusions: Our study demonstrated the association between nutritional status and PIM checked with the BEERS 2019 criteria, and, for the first time, with the STOPP and START criteria. Full article

(This article belongs to the Section Epidemiology & Public Health)

16 pages, 2004 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Clinical Characterisation of Brain Fog in Adults Reporting Long COVID Symptoms

by Glenn Jennings, Ann Monaghan, Feng Xue, Eoin Duggan and Román Romero-Ortuño

J. Clin. Med. 2022, 11(12), 3440; https://doi.org/10.3390/jcm11123440 - 15 Jun 2022

Cited by 35 | Viewed by 8184

Abstract

(1) Introduction: A subset of individuals experiencing long COVID symptoms are affected by ‘brain fog’, a lay term that often refers to general cognitive dysfunction but one that is still poorly characterised. In this study, a comprehensive clinical characterisation of self-reported brain fog [...] Read more.

(1) Introduction: A subset of individuals experiencing long COVID symptoms are affected by ‘brain fog’, a lay term that often refers to general cognitive dysfunction but one that is still poorly characterised. In this study, a comprehensive clinical characterisation of self-reported brain fog was conducted vis-à-vis other long COVID symptoms and parameters of mental, cognitive, and physical health. (2) Methodology: Adult participants reporting long COVID symptoms were recruited from hospital clinics and as self-referrals. Participants completed a battery of questionnaires and clinical assessments, including COVID-19 history, symptomatology, self-reported scales (Chalder Fatigue Scale [CFQ], Center for Epidemiological Studies Depression Scale, and Impact of Events Scale–Revised), computer-based cognitive assessments (simple response time and choice reaction time tasks), physical performance tests (gait velocity and muscle strength assessments), and an orthostatic active stand test. A systematic comparison between participants with and without self-reported brain fog was conducted, and a backwards binary logistic regression model was computed to identify the strongest independent associations with brain fog. This was complemented by an automatic cluster analysis to rank the importance of associations. Finally, a structural equation model was postulated with a causal model of key symptomatic indicators and functional consequences of brain fog as a latent variable. (3) Results: Of 108 participants assessed, brain fog was a self-reported symptom in 71 (65.7%) participants. Those with brain fog were at a longer point in time since COVID-19 onset and reported longer duration of low activity during the acute illness. When assessed, those with brain fog had higher frequencies of subjective memory impairment, word-finding difficulties, dizziness, myalgia, arthralgia, hyperhidrosis, cough, voice weakness, throat pain, visual and hearing problems, dysosmia, paraesthesia, chest pain, skin rashes, and hair loss; mean scores in fatigue, depression, and post-traumatic stress scales were higher; performance in both computer-based cognitive tasks was poorer; and measured gait speed and grip strength were lower. The logistic regression suggested that the best independent associations with brain fog were memory impairment, CFQ, and myalgia. The cluster analysis suggested that the most important associations with brain fog were CFQ, dizziness, myalgia, reduced gait speed, word-finding difficulties, reduced grip strength, and memory impairment. The SEM was consistent with key indicators of brain fog being CFQ, dizziness, myalgia, word-finding difficulties, and memory impairment; and reduced grip strength, gait speed, and cognitive response times its functional consequences. (4) Conclusions: The findings indicate that self-reported brain fog in long COVID is a recognisable symptom cluster primarily characterised by fatigue, dizziness, myalgia, word-finding difficulties, and memory impairment and has adverse psychological and psychomotor correlates. In long COVID, brain fog should be regarded as a wide-ranging symptom and addressed holistically with medical, psychological, and rehabilitative supports as guided by individual needs. Full article

(This article belongs to the Topic Infectious Diseases)

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36 pages, 529 KiB

Open AccessEditor’s ChoiceReview

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

by Enrico Zelin, Carlo Alberto Maronese, Arianna Dri, Ludovica Toffoli, Nicola Di Meo, Gianluca Nazzaro and Iris Zalaudek

J. Clin. Med. 2022, 11(12), 3364; https://doi.org/10.3390/jcm11123364 - 11 Jun 2022

Cited by 18 | Viewed by 2360

Abstract

Background: Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The [...] Read more.

Background: Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The majority of NMSCs can be successfully treated with surgery or radiotherapy, but advanced and metastatic stages may require systemic approaches such as immunotherapy with immune checkpoint inhibitors (ICIs). Summary: Since immunotherapy is not effective in all patients and can potentially lead to severe adverse effects, an important clinical question is how to properly identify those who could be suitable candidates for this therapeutic choice. In this paper, we review the potential features and biomarkers used to predict the outcome of ICIs therapy for NMSCs. Moreover, we analyze the role of immunotherapy in special populations, such as the elderly, immunocompromised patients, organ transplant recipients, and subjects suffering from autoimmune conditions. Key messages: Many clinical, serum, histopathological, and genetic features have been investigated as potential predictors of response in NMSCs treated with ICIs. Although this field of research is very promising, definitive, cost-effective, and reproducible biomarkers are still lacking and further efforts are needed to validate the suggested predictors in larger cohorts. Full article

(This article belongs to the Section Dermatology)

21 pages, 10302 KiB

Open AccessEditor’s ChoiceSystematic Review

A Comprehensive Systematic Review and Meta-Analysis of the Association between the Neutrophil-to-Lymphocyte Ratio and Adverse Outcomes in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

by Angelo Zinellu, Elisabetta Zinellu, Maria Carmina Pau, Ciriaco Carru, Pietro Pirina, Alessandro G. Fois and Arduino A. Mangoni

J. Clin. Med. 2022, 11(12), 3365; https://doi.org/10.3390/jcm11123365 - 11 Jun 2022

Cited by 12 | Viewed by 2295

Abstract

The neutrophil-to-lymphocyte ratio (NLR) predicts adverse outcomes in stable chronic obstructive pulmonary disease (COPD); however, its prognostic role in acute exacerbations (AECOPD) is less clear. We conducted a systematic review and meta-analysis of the association between the NLR on admission and adverse outcomes [...] Read more.

The neutrophil-to-lymphocyte ratio (NLR) predicts adverse outcomes in stable chronic obstructive pulmonary disease (COPD); however, its prognostic role in acute exacerbations (AECOPD) is less clear. We conducted a systematic review and meta-analysis of the association between the NLR on admission and adverse outcomes (mortality, need for mechanical ventilation, transfer to the intensive care unit, length of stay, pulmonary hypertension, or their combination) in AECOPD by searching PubMed, Web of Science, and Scopus from inception to April 2022. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation, respectively. In 15 studies (n = 10,038 patients), the NLR was significantly associated with the risk of adverse outcomes (odds ratio = 1.054, 95% CI 1.016 to 1.093, p = 0.005; low certainty of evidence; standard mean difference = 0.82, 95% CI 0.57 to 1.06, p < 0.001; high certainty of evidence). Pooled sensitivity, specificity, and area under the curve were 0.71 (95% CI 0.64 to 0.77), 0.73 (95% CI 0.65 to 0.80), and 0.78 (95% CI 0.74 to 0.81), respectively. In our study, the NLR on admission was significantly associated with adverse outcomes in AECOPD patients, suggesting the potential utility of this biomarker for early risk stratification and management in this group. Full article

(This article belongs to the Special Issue Pathophysiology, Diagnosis and Novel Treatment of Obstructive Lung Diseases)

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35 pages, 1602 KiB

Open AccessEditor’s ChoiceSystematic Review

Uterine Septum with or without Hysteroscopic Metroplasty: Impact on Fertility and Obstetrical Outcomes—A Systematic Review and Meta-Analysis of Observational Research

by Marco Noventa, Giulia Spagnol, Matteo Marchetti, Carlo Saccardi, Giulio Bonaldo, Antonio Simone Laganà, Francesco Cavallin, Alessandra Andrisani, Guido Ambrosini, Salvatore Giovanni Vitale, Luis Alonso Pacheco, Sergio Haimovich, Attilio Di Spiezio Sardo, Jose Carugno, Marco Scioscia, Simone Garzon, Stefano Bettocchi, Giovanni Buzzaccarini, Roberto Tozzi and Amerigo Vitagliano

J. Clin. Med. 2022, 11(12), 3290; https://doi.org/10.3390/jcm11123290 - 08 Jun 2022

Cited by 15 | Viewed by 3646

Abstract

Objective: we performed a systematic review/meta-analysis to evaluate the impact of septate uterus and hysteroscopic metroplasty on pregnancy rate-(PR), live birth rate-(LBR), spontaneous abortion-(SA) and preterm labor (PL) in infertile/recurrent miscarriage-(RM) patients. Data sources: a literature search of relevant papers was conducted using [...] Read more.

Objective: we performed a systematic review/meta-analysis to evaluate the impact of septate uterus and hysteroscopic metroplasty on pregnancy rate-(PR), live birth rate-(LBR), spontaneous abortion-(SA) and preterm labor (PL) in infertile/recurrent miscarriage-(RM) patients. Data sources: a literature search of relevant papers was conducted using electronic bibliographic databases (Medline, Scopus, Embase, Science direct). Study eligibility criteria: we included in this meta-analysis all types of observational studies that evaluated the clinical impact of the uterine septum and its resection (hysteroscopic metroplasty) on reproductive and obstetrics outcomes. The population included were patients with a diagnosis of infertility or recurrent pregnancy loss. Study appraisal and synthesis methods: outcomes were evaluated according to three subgroups: (i) Women with untreated uterine septum versus women without septum (controls); (ii) Women with treated uterine septum versus women with untreated septum (controls); (iii) Women before and after septum removal. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the outcome measures. A p-value < 0.05 was considered statistically significant. Subgroup analysis was performed according to the depth of the septum. Sources of heterogeneity were explored by meta-regression analysis according to specific features: assisted reproductive technology/spontaneous conception, study design and quality of papers included Results: data from 38 studies were extracted. (i) septum versus no septum: a lower PR and LBR were associated with septate uterus vs. controls (OR 0.45, 95% CI 0.27–0.76; p < 0.0001; and OR 0.21, 95% CI 0.12–0.39; p < 0.0001); a higher proportion of SA and PL was associated with septate uterus vs. controls (OR 4.29, 95% CI 2.90–6.36; p < 0.0001; OR 2.56, 95% CI 1.52–4.31; p = 0.0004). (ii) treated versus untreated septum: PR and PL were not different in removed vs. unremoved septum(OR 1.10, 95% CI 0.49–2.49; p = 0.82 and OR 0.81, 95% CI 0.35–1.86; p = 0.62); a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.47, 95% CI 0.21–1.04; p = 0.001); (iii) before-after septum removal: the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93–82.13; p < 0.0001) and the proportion of SA and PL was lower after the removal of the septum (OR 0.02, 95% CI 0.02–0.04; p < 0.000 and OR 0.05, 95% CI 0.03–0.08; p < 0.0001) Conclusions: the results show the detrimental effect of the uterine septum on PR, LBR, SA and PL. Its treatment reduces the rate of SA. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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17 pages, 1868 KiB

Open AccessEditor’s ChoiceReview

Colistin Monotherapy versus Colistin plus Meropenem Combination Therapy for the Treatment of Multidrug-Resistant Acinetobacter baumannii Infection: A Meta-Analysis

by Chienhsiu Huang, Ihung Chen and Tiju Tang

J. Clin. Med. 2022, 11(11), 3239; https://doi.org/10.3390/jcm11113239 - 06 Jun 2022

Cited by 10 | Viewed by 4164

Abstract

(1) Introduction: Colistin combination therapy with other antibiotics is a way to enhance colistin activity. The purpose of this meta-analysis was to compare the efficacy and safety of treatment with colistin monotherapy versus colistin plus meropenem combination therapy in patients with drug-resistant Acinetobacter [...] Read more.

(1) Introduction: Colistin combination therapy with other antibiotics is a way to enhance colistin activity. The purpose of this meta-analysis was to compare the efficacy and safety of treatment with colistin monotherapy versus colistin plus meropenem combination therapy in patients with drug-resistant Acinetobacter baumannii infection. (2) Methods: All studies were included if they reported one or more of the following outcomes: clinical improvement, complete microbiological response, 14-day mortality, hospital mortality, or nephrotoxicity. (3) Results: Three randomized controlled trials and seven retrospective studies were included in the meta-analysis. Colistin monotherapy has similar rates of clinical improvement, 14-day mortality, hospital mortality, and nephrotoxicity as colistin plus meropenem combination therapy. Regarding complete microbiological response, the colistin plus meropenem combination was better than colistin monotherapy. (4) Discussion: Previous meta-analyses demonstrated heterogeneity in study quality and a lack of evidence supporting the use of colistin-based combination therapy. Our meta-analysis clearly showed that colistin combined with meropenem was not superior to colistin monotherapy for the treatment of Acinetobacter baumannii infection. (5) Conclusions: The efficacy and safety of treatment with colistin monotherapy and that of colistin plus meropenem combination therapy in patients with drug-resistant Acinetobacter baumannii infection were comparable. The majority of the evidence was obtained from nonrandomized studies, and high-quality randomized controlled trials are needed to confirm the role of colistin plus meropenem combination therapy in the treatment of multidrug-resistant Acinetobacter baumannii infection. Full article

(This article belongs to the Topic Infectious Diseases)

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18 pages, 1666 KiB

Open AccessEditor’s ChoiceReview

Pediatric Infective Endocarditis: A Literature Review

by Lourdes Vicent, Raquel Luna and Manuel Martínez-Sellés

J. Clin. Med. 2022, 11(11), 3217; https://doi.org/10.3390/jcm11113217 - 05 Jun 2022

Cited by 18 | Viewed by 4889

Abstract

Infective endocarditis in children is a rare entity that poses multiple challenges. A history of congenital heart disease is the most common risk factor, although in recent years, other emerging predisposing conditions have gained relevance, such as central venous catheters carriers or children [...] Read more.

Infective endocarditis in children is a rare entity that poses multiple challenges. A history of congenital heart disease is the most common risk factor, although in recent years, other emerging predisposing conditions have gained relevance, such as central venous catheters carriers or children with chronic debilitating conditions; cases in previously healthy children with no medical history are also seen. Diagnosis is complex, although it has improved with the use of multimodal imaging techniques. Antibiotic treatment should be started early, according to causative microorganism and risk factors. Complications are frequent and continue to cause significant morbidity. Most studies have been conducted in adults and have been generalized to the pediatric population, with subsequent limitations. Our manuscript presents a comprehensive review of pediatric infective endocarditis, including recent advances in diagnosis and management. Full article

(This article belongs to the Topic Infectious Diseases)

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29 pages, 1288 KiB

Open AccessEditor’s ChoiceReview

An Overview of Healthcare Associated Infections and Their Detection Methods Caused by Pathogen Bacteria in Romania and Europe

by Sándor Szabó, Bogdan Feier, Denisa Capatina, Mihaela Tertis, Cecilia Cristea and Adina Popa

J. Clin. Med. 2022, 11(11), 3204; https://doi.org/10.3390/jcm11113204 - 04 Jun 2022

Cited by 19 | Viewed by 10084

Abstract

Healthcare-associated infections can occur in different care units and can affect both patients and healthcare professionals. Bacteria represent the most common cause of nosocomial infections and, due to the excessive and irrational use of antibiotics, resistant organisms have appeared. The most important healthcare-associated [...] Read more.

Healthcare-associated infections can occur in different care units and can affect both patients and healthcare professionals. Bacteria represent the most common cause of nosocomial infections and, due to the excessive and irrational use of antibiotics, resistant organisms have appeared. The most important healthcare-associated infections are central line-associated bloodstream infections, catheter-associated urinary tract infections, surgical site, soft tissue infections, ventilator-associated pneumonia, hospital acquired pneumonia, and Clostridioides difficile colitis. In Europe, some hospitalized patients develop nosocomial infections that lead to increased costs and prolonged hospitalizations. Healthcare-associated infection prevalence in developed countries is lower than in low-income and middle-income countries such as Romania, an Eastern European country, where several factors contribute to the occurrence of many nosocomial infections, but official data show a low reporting rate. For the rapid identification of bacteria that can cause these infections, fast, sensitive, and specific methods are needed, and they should be cost-effective. Therefore, this review focuses on the current situation regarding healthcare-associated infections in Europe and Romania, with discussions regarding the causes and possible solutions. As a possible weapon in the fight against the healthcare-associated infections, the diagnosis methods and tests used to determine the bacteria involved in healthcare-associated infections are evaluated. Full article

(This article belongs to the Special Issue Clinical Research on Infectious Diseases: State of the Art)

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28 pages, 1298 KiB

Open AccessEditor’s ChoiceReview

Vector-Borne Viral Diseases as a Current Threat for Human and Animal Health—One Health Perspective

by Wojciech Socha, Malgorzata Kwasnik, Magdalena Larska, Jerzy Rola and Wojciech Rozek

J. Clin. Med. 2022, 11(11), 3026; https://doi.org/10.3390/jcm11113026 - 27 May 2022

Cited by 25 | Viewed by 4856

Abstract

Over the last decades, an increase in the emergence or re-emergence of arthropod-borne viruses has been observed in many regions. Viruses such as dengue, yellow fever, or zika are a threat for millions of people on different continents. On the other hand, some [...] Read more.

Over the last decades, an increase in the emergence or re-emergence of arthropod-borne viruses has been observed in many regions. Viruses such as dengue, yellow fever, or zika are a threat for millions of people on different continents. On the other hand, some arboviruses are still described as endemic, however, they could become more important in the near future. Additionally, there is a group of arboviruses that, although important for animal breeding, are not a direct threat for human health. Those include, e.g., Schmallenberg, bluetongue, or African swine fever viruses. This review focuses on arboviruses and their major vectors: mosquitoes, ticks, biting midges, and sandflies. We discuss the current knowledge on arbovirus transmission, ecology, and methods of prevention. As arboviruses are a challenge to both human and animal health, successful prevention and control are therefore only possible through a One Health perspective. Full article

(This article belongs to the Section Infectious Diseases)

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26 pages, 2258 KiB

Open AccessEditor’s ChoiceReview

Novel Therapies for the Treatment of Neuropathic Pain: Potential and Pitfalls

by Pottathil Shinu, Mohamed A. Morsy, Anroop B. Nair, Abdulaziz K. Al Mouslem, Katharigatta N. Venugopala, Manoj Goyal, Monika Bansal, Shery Jacob and Pran Kishore Deb

J. Clin. Med. 2022, 11(11), 3002; https://doi.org/10.3390/jcm11113002 - 26 May 2022

Cited by 19 | Viewed by 7177

Abstract

Neuropathic pain affects more than one million people across the globe. The quality of life of people suffering from neuropathic pain has been considerably declining due to the unavailability of appropriate therapeutics. Currently, available treatment options can only treat patients symptomatically, but they [...] Read more.

Neuropathic pain affects more than one million people across the globe. The quality of life of people suffering from neuropathic pain has been considerably declining due to the unavailability of appropriate therapeutics. Currently, available treatment options can only treat patients symptomatically, but they are associated with severe adverse side effects and the development of tolerance over prolonged use. In the past decade, researchers were able to gain a better understanding of the mechanisms involved in neuropathic pain; thus, continuous efforts are evident, aiming to develop novel interventions with better efficacy instead of symptomatic treatment. The current review discusses the latest interventional strategies used in the treatment and management of neuropathic pain. This review also provides insights into the present scenario of pain research, particularly various interventional techniques such as spinal cord stimulation, steroid injection, neural blockade, transcranial/epidural stimulation, deep brain stimulation, percutaneous electrical nerve stimulation, neuroablative procedures, opto/chemogenetics, gene therapy, etc. In a nutshell, most of the above techniques are at preclinical stage and facing difficulty in translation to clinical studies due to the non-availability of appropriate methodologies. Therefore, continuing research on these interventional strategies may help in the development of promising novel therapies that can improve the quality of life of patients suffering from neuropathic pain. Full article

(This article belongs to the Special Issue Neuropathic Pain: From Prevention to Diagnosis and Treatment)

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13 pages, 1481 KiB

Open AccessEditor’s ChoiceSystematic Review

Efficacy of Liraglutide in Non-Diabetic Obese Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Joshuan J. Barboza, Mariella R. Huamán, Beatriz Melgar, Carlos Diaz-Arocutipa, German Valenzuela-Rodriguez and Adrian V. Hernandez

J. Clin. Med. 2022, 11(11), 2998; https://doi.org/10.3390/jcm11112998 - 25 May 2022

Cited by 10 | Viewed by 3649

Abstract

Objective: We systematically assessed the efficacy of liraglutide in non-diabetic obese adults. Methods: Six databases were searched up to July 2021 for randomized controlled trials (RCTs) assessing liraglutide versus placebo in obese adults. Primary outcomes were body weight and body mass index (BMI). [...] Read more.

Objective: We systematically assessed the efficacy of liraglutide in non-diabetic obese adults. Methods: Six databases were searched up to July 2021 for randomized controlled trials (RCTs) assessing liraglutide versus placebo in obese adults. Primary outcomes were body weight and body mass index (BMI). Secondary outcomes were treatment-emergent adverse events (TEAEs), hypoglycemic episodes, HbA1c, and blood pressure. Effect measures were risk ratio (RR) or mean difference (MD) with their confidence interval (95%CI). Random-effects models and inverse variance meta-analyses were used. Quality of evidence was assessed using GRADE. Results: Twelve RCTs (n = 8249) were included. In comparison to placebo, liraglutide reduced body weight (MD −3.35 kg; 95%CI −4.65 to −2.05; p < 0.0001), and BMI (MD −1.45 kg/m²; 95%CI −1.98 to −0.91; p < 0.0001). Liraglutide did not reduce TEAEs (RR 1.08; 95%CI 0.92 to 1.27; p = 0.25), and Hb1Ac (MD −0.76%; 95%CI −2.24 to 0.72; p = 0.31). Furthermore, it did not increase hypoglycemic episodes (RR 2.01; 95%CI 0.37 to 11.02; p = 0.28). Finally, liraglutide reduced systolic blood pressure (MD −3.07 mmHg; 95%CI −3.66 to −2.48; p < 0.0001) and diastolic blood pressure (MD −1.01 mmHg; 95%CI −1.55 to −0.47; p = 0.0003). Seven RCTs had a high risk of bias. Subgroup analyses by length of treatment and doses had effects similar to the overall analyses. Quality of evidence was low or very low for most outcomes. Conclusions: In non-diabetic obese adults, liraglutide reduced body weight, BMI and blood pressure in comparison to placebo. Adverse events, Hb1Ac levels and hypoglycemic episodes were not different than placebo. Full article

(This article belongs to the Special Issue Clinical Research on Type 2 Diabetes and Its Complications)

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14 pages, 3609 KiB

Open AccessEditor’s ChoiceReview

Current Status and Future Perspectives of Artificial Intelligence in Colonoscopy

by Yu Kamitani, Kouichi Nonaka and Hajime Isomoto

J. Clin. Med. 2022, 11(10), 2923; https://doi.org/10.3390/jcm11102923 - 22 May 2022

Cited by 14 | Viewed by 3559

Abstract

The early endoscopic identification, resection, and treatment of precancerous adenoma and early-stage cancer has been shown to reduce not only the prevalence of colorectal cancer but also its mortality rate. Recent advances in endoscopic devices and imaging technology have dramatically improved our ability [...] Read more.

The early endoscopic identification, resection, and treatment of precancerous adenoma and early-stage cancer has been shown to reduce not only the prevalence of colorectal cancer but also its mortality rate. Recent advances in endoscopic devices and imaging technology have dramatically improved our ability to detect colorectal lesions and predict their pathological diagnosis. In addition to this, rapid advances in artificial intelligence (AI) technology mean that AI-related research and development is now progressing in the diagnostic imaging field, particularly colonoscopy, and AIs (i.e., devices that mimic cognitive abilities, such as learning and problem-solving) already approved as medical devices are now being introduced into everyday clinical practice. Today, there is an increasing expectation that sophisticated AIs will be able to provide high-level diagnostic performance irrespective of the level of skill of the endoscopist. In this paper, we review colonoscopy-related AI research and the AIs that have already been approved and discuss the future prospects of this technology. Full article

(This article belongs to the Special Issue Latest Advances in Endoscopic Imaging and Therapy—Part I)

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