Journal of Clinical Medicine

16 pages, 501 KiB

Open AccessEditor’s ChoiceReview

“Heart in DRESS”: Cardiac Manifestations, Treatment and Outcome of Patients with Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome: A Systematic Review

by Milan Radovanovic, Djordje Jevtic, Andrew D. Calvin, Marija Petrovic, Margaret Paulson, Libardo Rueda Prada, Lawrence Sprecher, Ivana Savic and Igor Dumic

J. Clin. Med. 2022, 11(3), 704; https://doi.org/10.3390/jcm11030704 - 28 Jan 2022

Cited by 27 | Viewed by 3814

Abstract

Cardiac involvement in drug reaction with eosinophilia and systemic symptoms (DS) is rare but associated with high mortality. The aim of this research was to systematically review case reports by PRISMA guidelines in order to synthetize the knowledge of cardiac manifestations of DS. [...] Read more.

Cardiac involvement in drug reaction with eosinophilia and systemic symptoms (DS) is rare but associated with high mortality. The aim of this research was to systematically review case reports by PRISMA guidelines in order to synthetize the knowledge of cardiac manifestations of DS. We identified 42 cases from 36 case reports. Women were two times more affected than men. Two-thirds of patients had cardiac manifestation in the initial phase of the disease, while in one-third of cases cardiac manifestations developed later (mean time of 70 ± 63 days). The most common inciting medications were minocycline (19%) and allopurinol (12%). In 17% of patients, the heart was the only internal organ affected, while the majority (83%) had at least one additional organ involved, most commonly the liver and the kidneys. Dyspnea (55%), cardiogenic shock (43%), chest pain (38%), and tachycardia (33%) were the most common cardiac signs and symptoms reported. Patients frequently had an abnormal ECG (71.4%), and a decrease in left ventricular ejection fraction was the most common echocardiographic finding (45%). Endomyocardial biopsy or histological examination at autopsy was performed in 52.4%, with the predominant finding being fulminant eosinophilic myocarditis with acute necrosis in 70% of those biopsied. All patients received immunosuppressive therapy with intravenous steroids, while non-responders were more likely to have received IVIG, cyclosporine, mycophenolate, and other steroid-sparing agents (60%). Gender and degree of left ventricular systolic dysfunction were not associated with outcomes, but short latency between drug exposure and the first DRESS symptom onset (<15 days) and older age (above 65 years) was associated with death. This underscores the potential importance of heightened awareness and early treatment. Full article

(This article belongs to the Special Issue Myocarditis in Clinical Practice)

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26 pages, 855 KiB

Open AccessEditor’s ChoiceReview

Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review

by Jaume Alijotas-Reig, Enrique Esteve-Valverde, Ariadna Anunciación-Llunell, Joana Marques-Soares, Josep Pardos-Gea and Francesc Miró-Mur

J. Clin. Med. 2022, 11(3), 675; https://doi.org/10.3390/jcm11030675 - 28 Jan 2022

Cited by 33 | Viewed by 12217

Abstract

Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified [...] Read more.

Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified cause of recurrent pregnancy loss and late-pregnancy morbidity related to placental injury. Cases with incomplete clinical or laboratory data are classified as obstetric morbidity APS (OMAPS) and non-criteria OAPS (NC-OAPS), respectively. Inflammatory and thrombotic mechanisms are involved in the pathophysiology of OAPS. Trophoblasts, endothelium, platelets and innate immune cells are key cellular players. Complement activation plays a crucial pathogenic role. Secondary placental thrombosis appears by clot formation in response to tissue factor activation. New risk assessment tools could improve the prediction of obstetric complication recurrences or thromboses. The standard-of-care treatment consists of low-dose aspirin and prophylactic low molecular weight heparin. In refractory cases, the addition of hydroxychloroquine, low-dose prednisone or IVIG improve pregnancy outcomes. Statins and eculizumab are currently being tested for treating selected OAPS women. Finally, we revisited recent insights and concerns about the pathophysiology, diagnosis and management of OAPS. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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18 pages, 1622 KiB

Open AccessEditor’s ChoiceArticle

Identifying Predictive Bacterial Markers from Cervical Swab Microbiota on Pregnancy Outcome in Woman Undergoing Assisted Reproductive Technologies

by Annacandida Villani, Andrea Fontana, Stefano Barone, Silvia de Stefani, Mariangela Primiterra, Massimiliano Copetti, Concetta Panebianco, Cristiana Parri, Natale Sciannamè, Pasqua Anna Quitadamo, Alessandra Tiezzi, Liliana Santana, Annamaria Maglione, Federica D’Amato, Francesco Perri, Simone Palini and Valerio Pazienza

J. Clin. Med. 2022, 11(3), 680; https://doi.org/10.3390/jcm11030680 - 28 Jan 2022

Cited by 10 | Viewed by 2161

Abstract

Background and aims: Failure of the embryo to implant causes about three-fourths of lost pregnancies. Female genital tract microbiota has been associated to Assisted Reproductive Technologies (ART) outcomes. The objective of this study was to analyze the microbiota of human cervical swab and [...] Read more.

Background and aims: Failure of the embryo to implant causes about three-fourths of lost pregnancies. Female genital tract microbiota has been associated to Assisted Reproductive Technologies (ART) outcomes. The objective of this study was to analyze the microbiota of human cervical swab and to correlate these findings with the ART outcomes. Materials and Methods: In this study, 88 cervical swabs were collected from women undergoing ART cycles, with various causes of infertility, at the beginning of the ART protocols. After microbial DNA extraction, V3–V4 variable regions of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. PEnalized LOgistic Regression Analysis (PELORA) was performed to identify clusters of bacterial populations with differential abundances between patients with unfavorable and favorable pregnancy outcome groups, respectively. Results: We identified a core of microorganisms at lower taxonomic levels that were predictive of women’s pregnancy outcomes. Statistically significant differences were identified at species levels with Lactobacillus salivarius, Lactobacillus rhamnosus among others. Moreover the abundance of Lactobacillus crispatus and iners, respectively increased and decreased in favorable group as compared to unfavorable group, resulted within the core of microorganisms associated to positive ART outcome. Although the predominance of lactobacilli is generally considered to be advantageous for ART outcome, we found that also the presence of Bifidobacterium (together with the other lactobacilli) was more abundant in the favorable group. Discussion: Cervix is colonized by microorganisms which can play a role in ART outcomes as seen by an overall decrease in embryo attachment rates and pregnancy rates in both fertile and infertile women. If confirmed in a larger cohort, the abundance of these bacteria can be useful not only as a marker of unfavorable pregnancy outcome but also they may open the way to new interventional strategies based on genital tract microbiota manipulation in order to increase the pregnancy rates in woman undergoing assisted reproductive technologies. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

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24 pages, 957 KiB

Open AccessEditor’s ChoiceReview

Intestinal Inflammation and Alterations in the Gut Microbiota in Cystic Fibrosis: A Review of the Current Evidence, Pathophysiology and Future Directions

by Rachel Y. Tam, Josie M. van Dorst, Isabelle McKay, Michael Coffey and Chee Y. Ooi

J. Clin. Med. 2022, 11(3), 649; https://doi.org/10.3390/jcm11030649 - 27 Jan 2022

Cited by 23 | Viewed by 5043

Abstract

Cystic fibrosis (CF) is a life-limiting autosomal recessive multisystem disease. While its burden of morbidity and mortality is classically associated with pulmonary disease, CF also profoundly affects the gastrointestinal (GI) tract. Chronic low-grade inflammation and alterations to the gut microbiota are hallmarks of [...] Read more.

Cystic fibrosis (CF) is a life-limiting autosomal recessive multisystem disease. While its burden of morbidity and mortality is classically associated with pulmonary disease, CF also profoundly affects the gastrointestinal (GI) tract. Chronic low-grade inflammation and alterations to the gut microbiota are hallmarks of the CF intestine. The etiology of these manifestations is likely multifactorial, resulting from cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, a high-fat CF diet, and the use of antibiotics. There may also be a bidirectional pathophysiological link between intestinal inflammation and changes to the gut microbiome. Additionally, a growing body of evidence suggests that these GI manifestations may have significant clinical associations with growth and nutrition, quality of life, and respiratory function in CF. As such, the potential utility of GI therapies and long-term GI outcomes are areas of interest in CF. Further research involving microbial modulation and multi-omics techniques may reveal novel insights. This article provides an overview of the current evidence, pathophysiology, and future research and therapeutic considerations pertaining to intestinal inflammation and alterations in the gut microbiota in CF. Full article

(This article belongs to the Special Issue Cystic Fibrosis: Genotype, Clinical Features, and Current Comorbidities)

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27 pages, 4764 KiB

Open AccessEditor’s ChoiceReview

Molecular Genetics Overview of Primary Mitochondrial Myopathies

by Ignazio Giuseppe Arena, Alessia Pugliese, Sara Volta, Antonio Toscano and Olimpia Musumeci

J. Clin. Med. 2022, 11(3), 632; https://doi.org/10.3390/jcm11030632 - 26 Jan 2022

Cited by 13 | Viewed by 5935

Abstract

Mitochondrial disorders are the most common inherited conditions, characterized by defects in oxidative phosphorylation and caused by mutations in nuclear or mitochondrial genes. Due to its high energy request, skeletal muscle is typically involved. According to the International Workshop of Experts in Mitochondrial [...] Read more.

Mitochondrial disorders are the most common inherited conditions, characterized by defects in oxidative phosphorylation and caused by mutations in nuclear or mitochondrial genes. Due to its high energy request, skeletal muscle is typically involved. According to the International Workshop of Experts in Mitochondrial Diseases held in Rome in 2016, the term Primary Mitochondrial Myopathy (PMM) should refer to those mitochondrial disorders affecting principally, but not exclusively, the skeletal muscle. The clinical presentation may include general isolated myopathy with muscle weakness, exercise intolerance, chronic ophthalmoplegia/ophthalmoparesis (cPEO) and eyelids ptosis, or multisystem conditions where there is a coexistence with extramuscular signs and symptoms. In recent years, new therapeutic targets have been identified leading to the launch of some promising clinical trials that have mainly focused on treating muscle symptoms and that require populations with defined genotype. Advantages in next-generation sequencing techniques have substantially improved diagnosis. So far, an increasing number of mutations have been identified as responsible for mitochondrial disorders. In this review, we focused on the principal molecular genetic alterations in PMM. Accordingly, we carried out a comprehensive review of the literature and briefly discussed the possible approaches which could guide the clinician to a genetic diagnosis. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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18 pages, 1557 KiB

Open AccessEditor’s ChoiceArticle

Comparison between Two Different Scanners for the Evaluation of the Role of ¹⁸F-FDG PET/CT Semiquantitative Parameters and Radiomics Features in the Prediction of Final Diagnosis of Thyroid Incidentalomas

by Francesco Dondi, Nadia Pasinetti, Roberto Gatta, Domenico Albano, Raffaele Giubbini and Francesco Bertagna

J. Clin. Med. 2022, 11(3), 615; https://doi.org/10.3390/jcm11030615 - 26 Jan 2022

Cited by 12 | Viewed by 3209

Abstract

The aim of this study was to compare two different tomographs for the evaluation of the role of semiquantitative PET/CT parameters and radiomics features (RF) in the prediction of thyroid incidentalomas (TIs) at ¹⁸F-FDG imaging. A total of 221 patients with the [...] Read more.

The aim of this study was to compare two different tomographs for the evaluation of the role of semiquantitative PET/CT parameters and radiomics features (RF) in the prediction of thyroid incidentalomas (TIs) at ¹⁸F-FDG imaging. A total of 221 patients with the presence of TIs were retrospectively included. After volumetric segmentation of each TI, semiquantitative parameters and RF were extracted. All of the features were tested for significant differences between the two PET scanners. The performances of all of the features in predicting the nature of TIs were analyzed by testing three classes of final logistic regression predictive models, one for each tomograph and one with both scanners together. Some RF resulted significantly different between the two scanners. PET/CT semiquantitative parameters were not able to predict the final diagnosis of TIs while GLCM-related RF (in particular GLCM entropy_log2 e GLCM entropy_log10) together with some GLRLM-related and GLZLM-related features presented the best predictive performances. In particular, GLCM entropy_log2, GLCM entropy_log10, GLZLM SZHGE, GLRLM HGRE and GLRLM HGZE resulted the RF with best performances. Our study enabled the selection of some RF able to predict the final nature of TIs discovered at ¹⁸F-FDG PET/CT imaging. Classic semiquantitative and volumetric PET/CT parameters did not reveal these abilities. Furthermore, a good overlap in the extraction of RF between the two scanners was underlined. Full article

(This article belongs to the Special Issue PET/CT Imaging in Oncology: Clinical Updates and Perspectives)

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13 pages, 651 KiB

Open AccessEditor’s ChoiceReview

The Rationale and Current Status of Endotoxin Adsorption in the Treatment of Septic Shock

by Jakub Śmiechowicz

J. Clin. Med. 2022, 11(3), 619; https://doi.org/10.3390/jcm11030619 - 26 Jan 2022

Cited by 12 | Viewed by 3781

Abstract

Lipopolysaccharide, the main component of the outer membrane of Gram-negative bacteria is a highly potent endotoxin responsible for organ dysfunction in sepsis. It is present in the blood stream not only in Gram-negative infections, but also in Gram-positive and fungal infections, presumably due [...] Read more.

Lipopolysaccharide, the main component of the outer membrane of Gram-negative bacteria is a highly potent endotoxin responsible for organ dysfunction in sepsis. It is present in the blood stream not only in Gram-negative infections, but also in Gram-positive and fungal infections, presumably due to sepsis-related disruption of the intestinal barrier. Various pathways, both extra- and intracellular, are involved in sensing endotoxin and non-canonical activation of caspase-mediated pyroptosis is considered to have a major role in sepsis pathophysiology. Endotoxin induces specific pathological alterations in several organs, which contributes to poor outcomes. The adverse consequences of endotoxin in the circulation support the use of anti-endotoxin therapies, yet more than 30 years of experience with endotoxin adsorption therapies have not provided clear evidence in favor of this treatment modality. The results of small studies support timely endotoxin removal guided by measuring the levels of endotoxin; unfortunately, this has not been proven in large, randomized studies. The presence of endotoxemia can be demonstrated in the majority of patients with COVID-19, yet only case reports and case series describing the effects of endotoxin removal in these patients have been published to date. The place of blood purification therapies in the treatment of septic shock has not yet been determined. Full article

(This article belongs to the Special Issue Management of Endotoxemia and Sepsis)

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13 pages, 2387 KiB

Open AccessEditor’s ChoiceArticle

Hyaluronic Acid/Collagenase Ointment in the Treatment of Chronic Hard-to-Heal Wounds: An Observational and Retrospective Study

by Francesco De Francesco, Marialuisa De Francesco and Michele Riccio

J. Clin. Med. 2022, 11(3), 537; https://doi.org/10.3390/jcm11030537 - 21 Jan 2022

Cited by 13 | Viewed by 4562

Abstract

Background: Wound bed preparation is an important concept in clinical practice and is related to adequate debridement. The use of proteolytic enzymes is an established method of enzymatic wound debridement, especially in hard-to-heal ulcers that are unresponsive to normal healing procedures and progress. [...] Read more.

Background: Wound bed preparation is an important concept in clinical practice and is related to adequate debridement. The use of proteolytic enzymes is an established method of enzymatic wound debridement, especially in hard-to-heal ulcers that are unresponsive to normal healing procedures and progress. The TIME framework (tissue, inflammation/infection, moisture balance, and edge of wound) offers an appropriate strategy to eliminate resistance to healing, as well as maximizing the healing process. Maintenance debridement, as opposed to sporadic debridement, may be proposed in preserving an adequate wound bed towards complete recovery. Collagenase has been effective in debridement due to its ability to degrade collagen and elastin. In this clinical context, collagenase taken from Vibrio alginolitycus is the most favorably expressed enzymatic debriding agent. Methods: This retrospective observational study evaluates the efficacy of an ointment based on hyaluronic acid and collagenase (Bionect Start^®), considering a reduced healing time and greater healing quality. We included 70 patients with chronic wounds of different etiologies, including diabetes mellitus (20), post-traumatic ulcers (35), chronic burns of degrees I and II (10), and pressure ulcers (5). We analyzed wound characteristics using the wound bed score (WBS) concept, healing time, as well as operator and patient satisfaction. Results: Frequency of debridement efficacy in terms of wound bed cleansing varied from 26% after 2 weeks to 93% after 4 weeks. We observed complete healing in 62 patients within an eight-week period. The overall operator and patient satisfaction after 8 weeks were 100% and 90%, respectively. Moreover, all patients reported less pain. Conclusions: A combined action of hyaluronic acid and collagenase ointment demonstrated a reduction in healing time while improving healing quality, with a decrease in pain. Full article

(This article belongs to the Special Issue Chronic Wounds or Hard to Heal Ulcers: Updating Epidemiology, Physiopathology, and Therapies)

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9 pages, 1254 KiB

Open AccessEditor’s ChoiceArticle

Microwave Therapy for Cellulite: An Effective Non-Invasive Treatment

by Luigi Bennardo, Irene Fusco, Cristina Cuciti, Claudia Sicilia, Benedetta Salsi, Giovanni Cannarozzo, Klaus Hoffmann and Steven Paul Nisticò

J. Clin. Med. 2022, 11(3), 515; https://doi.org/10.3390/jcm11030515 - 20 Jan 2022

Cited by 13 | Viewed by 4648

Abstract

Background: Cellulite represents a common cosmetic problem that affects nearly all women. This study aimed to evaluate microwave therapy’s effectiveness for cellulite treatment. Methods: In this study, 26 women showing severe or moderate cellulite underwent four sessions of microwave therapy on the buttocks [...] Read more.

Background: Cellulite represents a common cosmetic problem that affects nearly all women. This study aimed to evaluate microwave therapy’s effectiveness for cellulite treatment. Methods: In this study, 26 women showing severe or moderate cellulite underwent four sessions of microwave therapy on the buttocks and posterior thighs. The following assessments were performed at baseline and the three-month follow-up after the last treatment: the Cellulite Severity Scale (CSS), Nürnberger–Müller classification scale, photographic evaluation, and buttocks/posterior thighs circumference measurements. A Likert scale questionnaire was used to assess patient satisfaction at the 3-month follow-up. Results: The treatment positively affected the cellulite severity as confirmed by the Cellulite Severity Scale (CSS) and Nürnberger–Müller classification scale results. CSS showed a significant amelioration in cellulite severity between the initial assessment and the 3-month follow-up for the buttocks and posterior thighs, with total average scores that ranged from 10.7 ± 3.1 to 4.5 ± 1.8 (p < 0.01). The treatment also resulted in a remarkable improvement in comfort/satisfaction and a buttocks and posterior thighs circumference reduction. No serious adverse events were observed. Conclusions: Microwave therapy has proven to be a safe treatment for improving cellulite appearance and reducing body circumferences. Full article

(This article belongs to the Special Issue The 10th Anniversary of JCM-Post-bariatric Plastic Surgery: The State of the Art of Body Contouring for 'Plastic, Reconstructive and Aesthetic Surgery/Aesthetic Medicine' Section)

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12 pages, 1966 KiB

Open AccessEditor’s ChoiceArticle

The Acute Effects of an Ultramarathon on Atrial Function and Supraventricular Arrhythmias in Master Athletes

by Luna Cavigli, Alessandro Zorzi, Veronica Spadotto, Giulia Elena Mandoli, Andrea Melani, Chiara Fusi, Antonello D’Andrea, Marta Focardi, Serafina Valente, Matteo Cameli, Marco Bonifazi and Flavio D’Ascenzi

J. Clin. Med. 2022, 11(3), 528; https://doi.org/10.3390/jcm11030528 - 20 Jan 2022

Cited by 14 | Viewed by 2834

Abstract

Background. Endurance sports practice has significantly increased over the last decades, with a growing proportion of master athletes. However, concerns exist regarding the potential proarrhythmic effects induced by ultra-endurance sports. This study aimed to analyse the acute effects of an ultramarathon race on [...] Read more.

Background. Endurance sports practice has significantly increased over the last decades, with a growing proportion of master athletes. However, concerns exist regarding the potential proarrhythmic effects induced by ultra-endurance sports. This study aimed to analyse the acute effects of an ultramarathon race on atrial remodelling and supraventricular arrhythmias in a population of master athletes. Methods. Master athletes participating in an ultramarathon (50 km, 600 m of elevation gain) with no history of heart disease were recruited. A single-lead ECG was recorded continuously from the day before to the end of the race. Echocardiography and 12-lead resting ECG were performed before and immediately at the end of the race. Results. The study sample consisted of 68 healthy non-professional master athletes. Compared with baseline, P wave voltage was higher after the race (p < 0.0001), and more athletes developed ECG criteria for right atrial enlargement (p < 0.0001). Most of the athletes (97%) had ≥1 premature atrial beats (PAB) during the 24-h monitoring, also organised in triplets (17%) and non-sustained supraventricular tachycardias (NSSVTs) (19%). In contrast, exercise-induced PABs, triplets, and NSSVTs were rare. One athlete developed acute atrial fibrillation during the race. After the race, no significant differences were found in biatrial dimensions. Biatrial function, estimated by peak atrial longitudinal and contraction strains, were normal both before and after the race. Conclusions. In master athletes running an ultramarathon, acute exercise-induced atrial dysfunction was not detected, and exercise-induced supraventricular arrhythmias were uncommon. These results did not confirm the hypothesis of an acute atrial dysfunction induced by ultra-endurance exercise. Full article

(This article belongs to the Section Cardiology)

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18 pages, 558 KiB

Open AccessEditor’s ChoiceArticle

Family-Centered Early Intervention (FCEI) Involving Fathers and Mothers of Children Who Are Deaf or Hard of Hearing: Parental Involvement and Self-Efficacy

by Evelien Dirks and Amy Szarkowski

J. Clin. Med. 2022, 11(3), 492; https://doi.org/10.3390/jcm11030492 - 19 Jan 2022

Cited by 15 | Viewed by 3729

Abstract

(1) Background: Studies related to family-centered early intervention (FCEI) for children who are deaf or hard of hearing (DHH) have largely focused on mothers, at the exclusion of fathers. Yet, understanding fathers’ experiences with FCEI is also important and may inform service delivery. [...] Read more.

(1) Background: Studies related to family-centered early intervention (FCEI) for children who are deaf or hard of hearing (DHH) have largely focused on mothers, at the exclusion of fathers. Yet, understanding fathers’ experiences with FCEI is also important and may inform service delivery. The present study explores self-efficacy and involvement with FCEI in both fathers and mothers. (2) Methods: Dutch fathers and mothers completed questionnaires about their parental self-efficacy, involvement in FCEI, perceived support from their primary EI provider, and the impact of raising a child who is DHH on parenting. (3) Results: Both fathers and mothers reported relatively high levels of self-efficacy. Mothers reported higher levels than fathers on some domains of self-efficacy and tended to be more involved in their child’s FCEI than fathers. In fathers, but not mothers, higher levels of self-efficacy were related to higher levels of involvement and higher levels of perceived support. (4) Conclusions: Similarities and differences were found between fathers and mothers in their perspectives on self-efficacy and involvement. This points to potential differences related to their FCEI needs. EI providers need to address both the needs of fathers and mothers to promote optimal development among child who are DHH. Full article

(This article belongs to the Special Issue Early Intervention for Hearing Loss in Children: Drafting from Theory to Clinical Practice)

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16 pages, 594 KiB

Open AccessEditor’s ChoiceArticle

Treatment-Resistant Depression in Poland—Epidemiology and Treatment

by Piotr Gałecki, Jerzy Samochowiec, Magdalena Mikułowska and Agata Szulc

J. Clin. Med. 2022, 11(3), 480; https://doi.org/10.3390/jcm11030480 - 18 Jan 2022

Cited by 15 | Viewed by 2869

Abstract

(1) Background: Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. Although several antidepressant drugs have been developed, up to 30% of patients fail to achieve remission, and acute remission rates decrease with the number of treatment steps required. [...] Read more.

(1) Background: Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. Although several antidepressant drugs have been developed, up to 30% of patients fail to achieve remission, and acute remission rates decrease with the number of treatment steps required. The aim of the current project was to estimate and describe the population of treatment-resistant depression (TRD) patients in outpatient clinics in Poland. (2) Methods: The project involved a representative sample of psychiatrists working in outpatient clinics, chosen through a process of quota random sampling. The doctors completed two questionnaires on a consecutive series of patients with MDD, which captured the patients’ demographics, comorbidities, and medical histories. TRD was defined as no improvement seen after a minimum of two different antidepressant drug therapies applied in sufficient doses for a minimum of 4 weeks each. The data were weighted and extrapolated to the population of TRD outpatients in Poland. (3) Results: A total of 76 psychiatrists described 1781 MDD patients, out of which 396 fulfilled the criteria of TRD. The TRD patients constituted 25.2% of all MDD patients, which led to the number of TRD outpatients in Poland being estimated at 34,800. The demographics, comorbidities, medical histories, and histories of treatment of Polish TRD patients were described. In our sample of the TRD population (mean age: 45.6 ± 13.1 years; female: 64%), the patients had experienced 2.1 ± 1.6 depressive episodes (including the current one), and the mean duration of the current episode was 4.8 ± 4.4 months. In terms of treatment strategies, most patients (around 70%) received monotherapy during the first three therapies, while combination antidepressant drugs (ADs) were applied more often from the fourth line of treatment. The use of additional medications and augmentation was reported in only up to one third of the TRD patients. During all of the treatment steps, patients most often received a selective serotonin reuptake inhibitor (SSRI) and a serotonin norepinephrine reuptake inhibitor (SNRI). (4) Conclusions: TRD is a serious problem, affecting approximately one fourth of all depressive patients and nearly 35,000 Poles. Full article

(This article belongs to the Section Mental Health)

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16 pages, 3121 KiB

Open AccessEditor’s ChoiceArticle

Unraveling the Signaling Secretome of Platelet-Rich Plasma: Towards a Better Understanding of Its Therapeutic Potential in Knee Osteoarthritis

by Cristina Del Amo, Arantza Perez-Valle, Leire Atilano and Isabel Andia

J. Clin. Med. 2022, 11(3), 473; https://doi.org/10.3390/jcm11030473 - 18 Jan 2022

Cited by 14 | Viewed by 2694

Abstract

Platelets and their secretory products play an important role in determining the balance between tissue repair and tissue damage. To obtain novel insights into the molecular composition of platelet-rich plasma (PRP) and contextualize them in knee osteoarthritis (OA), two different plasma formulations, namely [...] Read more.

Platelets and their secretory products play an important role in determining the balance between tissue repair and tissue damage. To obtain novel insights into the molecular composition of platelet-rich plasma (PRP) and contextualize them in knee osteoarthritis (OA), two different plasma formulations, namely PRP and platelet-poor plasma (PPP), were prepared from six healthy donors following a biobank-automated protocol. Inter-donor differences were analyzed, and pools were created before performing multiplexing protein arrays. In addition, PRP and PPP were prepared from six patients following our in-house protocols. Supernatants from PRP and PPP were harvested one hour after calcium chloride activation. Multiplexing protein arrays were performed in parallel for all plasma formulations. Results were normalized to fold change in relation to PPP and examined using Ingenuity Pathway Analysis Software. Bioinformatic predictions showed that PRPs constitute a signaling system with interrelated networks of inflammatory and angiogenic proteins, including but not limited to interleukin-6 and -8 (IL-6, IL-8), insulin like growth factor 1 (IGF-1), transforming growth factor beta, (TGF-b), and vascular endothelial growth factor (VEGF) signaling, underlying biological actions. Predictions of canonical systems activated with PRP molecules include various inflammatory pathways, including high-mobility group box protein (HMGB1) and interleukin 17 (IL-17) signaling, neuroinflammation, and nuclear factor-kappa b (NF-κB) pathways. Eventually, according to these predictions and OA evolving knowledge, selected PRP formulations should be tailored to modulate different inflammatory phenotypes, i.e., meta-inflammation, inflame-aging or posttraumatic inflammatory osteoarthritis. However, further research to discriminate the peculiarities of autologous versus allogeneic formulations and their effects on the various OA inflammatory phenotypes is needed to foster PRPs. Full article

(This article belongs to the Special Issue New Insights into Osteoarthritis: Pathophysiology, Diagnosis, and Treatment Options)

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34 pages, 797 KiB

Open AccessEditor’s ChoiceReview

A Review of Current and Emerging Trends in Donor Graft-Quality Assessment Techniques

by Natalia Warmuzińska, Kamil Łuczykowski and Barbara Bojko

J. Clin. Med. 2022, 11(3), 487; https://doi.org/10.3390/jcm11030487 - 18 Jan 2022

Cited by 13 | Viewed by 3589

Abstract

The number of patients placed on kidney transplant waiting lists is rapidly increasing, resulting in a growing gap between organ demand and the availability of kidneys for transplantation. This organ shortage has forced medical professionals to utilize marginal kidneys from expanded criteria donors [...] Read more.

The number of patients placed on kidney transplant waiting lists is rapidly increasing, resulting in a growing gap between organ demand and the availability of kidneys for transplantation. This organ shortage has forced medical professionals to utilize marginal kidneys from expanded criteria donors (ECD) to broaden the donor pool and shorten wait times for patients with end-stage renal disease. However, recipients of ECD kidney grafts tend to have worse outcomes compared to those receiving organs from standard criteria donors (SCD), specifically increased risks of delayed graft function (DGF) and primary nonfunction incidence. Thus, representative methods for graft-quality assessment are strongly needed, especially for ECDs. Currently, graft-quality evaluation is limited to interpreting the donor’s recent laboratory tests, clinical risk scores, the visual evaluation of the organ, and, in some cases, a biopsy and perfusion parameters. The last few years have seen the emergence of many new technologies designed to examine organ function, including new imaging techniques, transcriptomics, genomics, proteomics, metabolomics, lipidomics, and new solutions in organ perfusion, which has enabled a deeper understanding of the complex mechanisms associated with ischemia-reperfusion injury (IRI), inflammatory process, and graft rejection. This review summarizes and assesses the strengths and weaknesses of current conventional diagnostic methods and a wide range of new potential strategies (from the last five years) with respect to donor graft-quality assessment, the identification of IRI, perfusion control, and the prediction of DGF. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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22 pages, 1084 KiB

Open AccessEditor’s ChoiceReview

XR (Extended Reality: Virtual Reality, Augmented Reality, Mixed Reality) Technology in Spine Medicine: Status Quo and Quo Vadis

by Tadatsugu Morimoto, Takaomi Kobayashi, Hirohito Hirata, Koji Otani, Maki Sugimoto, Masatsugu Tsukamoto, Tomohito Yoshihara, Masaya Ueno and Masaaki Mawatari

J. Clin. Med. 2022, 11(2), 470; https://doi.org/10.3390/jcm11020470 - 17 Jan 2022

Cited by 75 | Viewed by 15717

Abstract

In recent years, with the rapid advancement and consumerization of virtual reality, augmented reality, mixed reality, and extended reality (XR) technology, the use of XR technology in spine medicine has also become increasingly popular. The rising use of XR technology in spine medicine [...] Read more.

In recent years, with the rapid advancement and consumerization of virtual reality, augmented reality, mixed reality, and extended reality (XR) technology, the use of XR technology in spine medicine has also become increasingly popular. The rising use of XR technology in spine medicine has also been accelerated by the recent wave of digital transformation (i.e., case-specific three-dimensional medical images and holograms, wearable sensors, video cameras, fifth generation, artificial intelligence, and head-mounted displays), and further accelerated by the COVID-19 pandemic and the increase in minimally invasive spine surgery. The COVID-19 pandemic has a negative impact on society, but positive impacts can also be expected, including the continued spread and adoption of telemedicine services (i.e., tele-education, tele-surgery, tele-rehabilitation) that promote digital transformation. The purpose of this narrative review is to describe the accelerators of XR (VR, AR, MR) technology in spine medicine and then to provide a comprehensive review of the use of XR technology in spine medicine, including surgery, consultation, education, and rehabilitation, as well as to identify its limitations and future perspectives (status quo and quo vadis). Full article

(This article belongs to the Section Clinical Neurology)

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14 pages, 37643 KiB

Open AccessEditor’s ChoiceReview

Diagnosis of Mitral Valve Prolapse: Much More than Simple Prolapse. Multimodality Approach to Risk Stratification and Therapeutic Management

by Ali Alenazy, Abdalla Eltayeb, Muteb K. Alotaibi, Muhammah Kashif Anwar, Norah Mulafikh, Mohammed Aladmawi and Olga Vriz

J. Clin. Med. 2022, 11(2), 455; https://doi.org/10.3390/jcm11020455 - 17 Jan 2022

Cited by 12 | Viewed by 3434

Abstract

Mitral valve prolapse (MVP) is the most common valvular disease with a prevalence of 2%. It has generally a benign course; however, recent findings suggested an association between MVP and complex arrhythmias and eventually cardiac arrest and for this reason, it is also [...] Read more.

Mitral valve prolapse (MVP) is the most common valvular disease with a prevalence of 2%. It has generally a benign course; however, recent findings suggested an association between MVP and complex arrhythmias and eventually cardiac arrest and for this reason, it is also called arrhythmogenic MVP. Subjects who experience this complication are in general young women, with thickened mitral leaflets or bileaflet prolapse not necessarily associated with severe mitral regurgitation (MR). The nature of the relation between MVP and cardiac arrest is not clearly understood. Actually, the challenging task is to find the cluster of prognostic factors including T-wave inversion, polymorphic premature ventricular contractions, bileaflet prolapse, MR severity, but most importantly, those parameters of hypercontractility, mitral annulus disjunction (MAD), and myocardial fibrosis using a multimodality approach. Transthoracic echocardiography is the first-line imaging modality for the diagnosis of MVP, but also for detecting MAD and hypercontractility, followed by cardiac magnetic resonance for tissue characterization and detection of myocardial and papillary muscle fibrosis, using either late gadolinium enhancement (at the basal segment of the inferolateral wall and papillary muscles) (macro-fibrosis), or diffuse fibrosis by T1 mapping (native and post contrast T1). Moreover, there are also preliminary data on positron emission tomography utilizing ¹⁸F-fluorodeoxyglucose as a tool for providing evidence of early myocardial inflammation. The objective of this review article is to provide the clinician with an overview and a practical clinical approach to MVP for risk stratification and treatment guidance. Full article

(This article belongs to the Special Issue State of the Art of Cardiac Multimodality Imaging)

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20 pages, 1339 KiB

Open AccessEditor’s ChoiceReview

Multi-Level Processes and Retina–Brain Pathways of Photic Regulation of Mood

by Julia Maruani and Pierre A. Geoffroy

J. Clin. Med. 2022, 11(2), 448; https://doi.org/10.3390/jcm11020448 - 16 Jan 2022

Cited by 18 | Viewed by 5353

Abstract

Light exerts powerful biological effects on mood regulation. Whereas the source of photic information affecting mood is well established at least via intrinsically photosensitive retinal ganglion cells (ipRGCs) secreting the melanopsin photopigment, the precise circuits that mediate the impact of light on depressive [...] Read more.

Light exerts powerful biological effects on mood regulation. Whereas the source of photic information affecting mood is well established at least via intrinsically photosensitive retinal ganglion cells (ipRGCs) secreting the melanopsin photopigment, the precise circuits that mediate the impact of light on depressive behaviors are not well understood. This review proposes two distinct retina–brain pathways of light effects on mood: (i) a suprachiasmatic nucleus (SCN)-dependent pathway with light effect on mood via the synchronization of biological rhythms, and (ii) a SCN-independent pathway with light effects on mood through modulation of the homeostatic process of sleep, alertness and emotion regulation: (1) light directly inhibits brain areas promoting sleep such as the ventrolateral preoptic nucleus (VLPO), and activates numerous brain areas involved in alertness such as, monoaminergic areas, thalamic regions and hypothalamic regions including orexin areas; (2) moreover, light seems to modulate mood through orexin-, serotonin- and dopamine-dependent pathways; (3) in addition, light activates brain emotional processing areas including the amygdala, the nucleus accumbens, the perihabenular nucleus, the left hippocampus and pathways such as the retina–ventral lateral geniculate nucleus and intergeniculate leaflet–lateral habenula pathway. This work synthetizes new insights into the neural basis required for light influence mood Full article

(This article belongs to the Special Issue Sleep and Circadian Rhythms in Psychiatric Disorders)

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13 pages, 2331 KiB

Open AccessEditor’s ChoiceReview

Artificial Intelligence-Based Approaches to Reflectance Confocal Microscopy Image Analysis in Dermatology

by Ana Maria Malciu, Mihai Lupu and Vlad Mihai Voiculescu

J. Clin. Med. 2022, 11(2), 429; https://doi.org/10.3390/jcm11020429 - 14 Jan 2022

Cited by 19 | Viewed by 2942

Abstract

Reflectance confocal microscopy (RCM) is a non-invasive imaging method designed to identify various skin diseases. Confocal based diagnosis may be subjective due to the learning curve of the method, the scarcity of training programs available for RCM, and the lack of clearly defined [...] Read more.

Reflectance confocal microscopy (RCM) is a non-invasive imaging method designed to identify various skin diseases. Confocal based diagnosis may be subjective due to the learning curve of the method, the scarcity of training programs available for RCM, and the lack of clearly defined diagnostic criteria for all skin conditions. Given that in vivo RCM is becoming more widely used in dermatology, numerous deep learning technologies have been developed in recent years to provide a more objective approach to RCM image analysis. Machine learning-based algorithms are used in RCM image quality assessment to reduce the number of artifacts the operator has to view, shorten evaluation times, and decrease the number of patient visits to the clinic. However, the current visual method for identifying the dermal-epidermal junction (DEJ) in RCM images is subjective, and there is a lot of variation. The delineation of DEJ on RCM images could be automated through artificial intelligence, saving time and assisting novice RCM users in studying the key DEJ morphological structure. The purpose of this paper is to supply a current summary of machine learning and artificial intelligence’s impact on the quality control of RCM images, key morphological structures identification, and detection of different skin lesion types on static RCM images. Full article

(This article belongs to the Special Issue Novel Imaging Techniques in Skin Diseases)

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19 pages, 1347 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Advances in Diabetic Nephropathy

by Hanny Sawaf, George Thomas, Jonathan J. Taliercio, Georges Nakhoul, Tushar J. Vachharajani and Ali Mehdi

J. Clin. Med. 2022, 11(2), 378; https://doi.org/10.3390/jcm11020378 - 13 Jan 2022

Cited by 49 | Viewed by 13280

Abstract

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD) in the United States. Risk factor modification, such as tight control of blood glucose, management of hypertension and hyperlipidemia, and the use of renin–angiotensin–aldosterone system (RAAS) blockade have been [...] Read more.

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD) in the United States. Risk factor modification, such as tight control of blood glucose, management of hypertension and hyperlipidemia, and the use of renin–angiotensin–aldosterone system (RAAS) blockade have been proven to help delay the progression of DKD. In recent years, new therapeutics including sodium-glucose transport protein 2 (SGLT2) inhibitors, endothelin antagonists, glucagon like peptide-1 (GLP-1) agonists, and mineralocorticoid receptor antagonists (MRA), have provided additional treatment options for patients with DKD. This review discusses the various treatment options available to treat patients with diabetic kidney disease. Full article

(This article belongs to the Special Issue Update on Diabetic Nephropathy: Recent Progress and Future Perspective)

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15 pages, 3595 KiB

Open AccessEditor’s ChoiceArticle

Regular Intake of Green Tea Polyphenols Suppresses the Development of Nonmelanoma Skin Cancer through miR-29-Mediated Epigenetic Modifications

by Vikash Kansal, Anshu Agarwal, Angela Harbour, Humaira Farooqi, Vijay Kumar Singh and Ram Prasad

J. Clin. Med. 2022, 11(2), 398; https://doi.org/10.3390/jcm11020398 - 13 Jan 2022

Cited by 10 | Viewed by 2380

Abstract

Previously, we and others have shown that the regular intake of green tea polyphenols (GTPs) reduces ultraviolet B (UVB) radiation-induced skin cancer by targeting multiple signaling pathways, including DNA damage, DNA repair, immunosuppression, and inflammation. Here, we determine the effect of GTPs on [...] Read more.

Previously, we and others have shown that the regular intake of green tea polyphenols (GTPs) reduces ultraviolet B (UVB) radiation-induced skin cancer by targeting multiple signaling pathways, including DNA damage, DNA repair, immunosuppression, and inflammation. Here, we determine the effect of GTPs on UVB-induced epigenetic changes, emphasizing DNA hypermethylation in UV-exposed skin and tumors and their association with miR-29, a key regulator of DNA methyltransferases (DNMTs). Skin cancer was induced in SKH-1 hairless mice following repeated exposures of UVB radiation (180 mJ/cm², three times/week, 24 weeks) with or without GTPs supplementation (0.2%) in drinking water. Regular intake of GTPs inhibited tumor growth by hindering the cascade of DNA hypermethylation events. GTPs supplementation significantly blocked UVB-induced DNA hypermethylation in the skin (up to 35%; p < 0.0001) and in tumors (up to 50%; p < 0.0001). Experimental results showed that the levels of DNA hypermethylation were higher in GTPs-treated mice than in the control group. The expressions of miR-29a, miR-29b, and miR-29c were markedly decreased in UV-induced skin tumors, and GTPs administration blocked UVB-induced miR-29s depletion. Furthermore, these observations were verified using the in vitro approach in human skin cancer cells (A431) followed by treatment with GTPs or mimics of miR-29c. Increased levels of miR-29 were observed in GTPs-treated A431 cells, resulting in increased TET activity and decreased DNA hypermethylation. In conclusion, UVB-mediated miR-29 depletion promotes DNA hypermethylation and leads to enhanced tumor growth by silencing tumor suppressors. Regular intake of GTPs rescued UVB-induced miR-29 depletion and prevented tumor growth by maintaining reduced DNA hypermethylation and activating tumor suppressors. Our observations suggest that miR-based strategies and regular consumption of GTPs could minimize the risk of UVB-induced skin cancers and contribute to better management of NMSCs. Full article

(This article belongs to the Special Issue Molecular Targets and Chemoprevention (Tumor Growth and Metastasis))

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15 pages, 1629 KiB

Open AccessEditor’s ChoiceReview

The Role of Innate and Adaptive Immune Cells in the Pathogenesis and Development of the Inflammatory Response in Ulcerative Colitis

by Aleksandra Kałużna, Paweł Olczyk and Katarzyna Komosińska-Vassev

J. Clin. Med. 2022, 11(2), 400; https://doi.org/10.3390/jcm11020400 - 13 Jan 2022

Cited by 60 | Viewed by 9743

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease with an underlying excessive immune response directed against resident microbiota and/or dietary antigens. Both innate and adaptive immune cells play a crucial role in the pathogenesis of UC. In the case of innate immune response [...] Read more.

Ulcerative colitis (UC) is a chronic inflammatory disease with an underlying excessive immune response directed against resident microbiota and/or dietary antigens. Both innate and adaptive immune cells play a crucial role in the pathogenesis of UC. In the case of innate immune response cells, neutrophils, dendritic cells, macrophages have a crucial impact on the development of the disease, as well as innate lymphoid cells, which have received a particular attention in recent years. On the other hand, mechanisms of the adaptive immune response involve cells such as: cytotoxic lymphocytes, regulatory lymphocytes Treg, or helper lymphocytes Th–Th2, Th9, Th17, Th22, among which significant discoveries about Th9 and Th17 lymphocytes have been made in recent years. Due to the presence of antibodies directed against resident microbiota or one’s own tissues, the influence of B lymphocytes on the development of UC is also highlighted. Additionally, the impact of cytokines on shaping the immune response as well as sustaining inflammation seems to be crucial. This review briefly describes the current state of knowledge about the involvement of the innate and adaptive immune systems in the pathogenesis of UC. The review is based on personal selection of literature that were retrieved by a selective search in PubMed using the terms “ulcerative colitis” and “pathogenesis of ulcerative colitis”. It included systematic reviews, meta-analyses and clinical trials. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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10 pages, 2663 KiB

Open AccessEditor’s ChoiceArticle

Association between C-Reactive Protein Velocity and Left Ventricular Function in Patients with ST-Elevated Myocardial Infarction

by Ariel Banai, Dana Levit, Samuel Morgan, Itamar Loewenstein, Ilan Merdler, Aviram Hochstadt, Yishay Szekely, Yan Topilsky, Shmuel Banai and Yacov Shacham

J. Clin. Med. 2022, 11(2), 401; https://doi.org/10.3390/jcm11020401 - 13 Jan 2022

Cited by 11 | Viewed by 1390

Abstract

C-reactive protein velocity (CRPv), defined as the change in wide-range CRP concentration divided by time, is an inflammatory biomarker associated with increased morbidity and mortality in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI). However, data regarding CRPv [...] Read more.

C-reactive protein velocity (CRPv), defined as the change in wide-range CRP concentration divided by time, is an inflammatory biomarker associated with increased morbidity and mortality in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI). However, data regarding CRPv association with echocardiographic parameters assessing left ventricular systolic and diastolic function is lacking. Echocardiographic parameters and CRPv values were analyzed using a cohort of 1059 patients admitted with STEMI and treated with primary PCI. Patients were stratified into tertiles according to their CRPv. A receiver operating characteristic (ROC) curve was used to evaluate CRPv optimal cut-off values for the prediction of severe systolic and diastolic dysfunction. Patients with high CRPv tertiles had lower left ventricular ejection fraction (LVEF) (49% vs. 46% vs. 41%, respectively; p < 0.001). CRPv was found to independently predict LVEF ≤ 35% (HR 1.3 CI 95% 1.21–1.4; p < 0.001) and grade III diastolic dysfunction (HR 1.16 CI 95% 11.02–1.31; p = 0.02). CRPv exhibited a better diagnostic profile for severe systolic dysfunction as compared to CRP (area under the curve 0.734 ± 0.02 vs. 0.608 ± 0.02). In conclusion, For STEMI patients treated with primary PCI, CRPv is a marker of both systolic and diastolic dysfunction. Further larger studies are needed to support this finding. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Biomarkers-Guided Therapy and Clinical Management)

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13 pages, 1057 KiB

Open AccessEditor’s ChoiceArticle

Adherence to Eye Drops Usage in Dry Eye Patients and Reasons for Non-Compliance: A Web-Based Survey

by Miki Uchino, Norihiko Yokoi, Jun Shimazaki, Yuichi Hori, Kazuo Tsubota and on behalf of the Japan Dry Eye Society

J. Clin. Med. 2022, 11(2), 367; https://doi.org/10.3390/jcm11020367 - 12 Jan 2022

Cited by 23 | Viewed by 4543

Abstract

This study aimed to investigate the actual use of eye drops for dry eye disease (DED), the reasons for instillation behavior, and the relationship between instillation behavior and subjective symptoms. This web-based cross-sectional study collected data on instillation behavior, medication instruction, reasons for [...] Read more.

This study aimed to investigate the actual use of eye drops for dry eye disease (DED), the reasons for instillation behavior, and the relationship between instillation behavior and subjective symptoms. This web-based cross-sectional study collected data on instillation behavior, medication instruction, reasons for instillation behavior, and subjective symptoms. In total, 2645 participants were enrolled. The proportion of participants who instilled at the frequency specified in the package insert (the specified frequency) was 10.2%. The most common reason for not instilling at the prescribed frequency was as-needed instillation to alleviate subjective symptoms, and 61.3% of participants instilled when feeling symptoms. The improvement in the subjective symptoms score was significantly greater in the group that regularly instilled at the specified frequency than the other group (p = 0.0027), and patients in the other group were younger and had a higher rate of contact lens use and over-the-counter eye drops use. In conclusion, most participants did not instill the DED eye drops at the specified frequency to alleviate symptoms. In order to obtain the appropriate effect of eye drops, ophthalmologists need to impress upon patients the importance of regular instillation at the frequency specified in the package insert, while taking into account patient characteristics. Full article

(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)

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14 pages, 1337 KiB

Open AccessEditor’s ChoiceArticle

Fluid Overload Phenotypes in Critical Illness—A Machine Learning Approach

by Anna S. Messmer, Michel Moser, Patrick Zuercher, Joerg C. Schefold, Martin Müller and Carmen A. Pfortmueller

J. Clin. Med. 2022, 11(2), 336; https://doi.org/10.3390/jcm11020336 - 11 Jan 2022

Cited by 12 | Viewed by 2035

Abstract

Background: The detrimental impact of fluid overload (FO) on intensive care unit (ICU) morbidity and mortality is well known. However, research to identify subgroups of patients particularly prone to fluid overload is scarce. The aim of this cohort study was to derive “FO [...] Read more.

Background: The detrimental impact of fluid overload (FO) on intensive care unit (ICU) morbidity and mortality is well known. However, research to identify subgroups of patients particularly prone to fluid overload is scarce. The aim of this cohort study was to derive “FO phenotypes” in the critically ill by using machine learning techniques. Methods: Retrospective single center study including adult intensive care patients with a length of stay of ≥3 days and sufficient data to compute FO. Data was analyzed by multivariable logistic regression, fast and frugal trees (FFT), classification decision trees (DT), and a random forest (RF) model. Results: Out of 1772 included patients, 387 (21.8%) met the FO definition. The random forest model had the highest area under the curve (AUC) (0.84, 95% CI 0.79–0.86), followed by multivariable logistic regression (0.81, 95% CI 0.77–0.86), FFT (0.75, 95% CI 0.69–0.79) and DT (0.73, 95% CI 0.68–0.78) to predict FO. The most important predictors identified in all models were lactate and bicarbonate at admission and postsurgical ICU admission. Sepsis/septic shock was identified as a risk factor in the MV and RF analysis. Conclusion: The FO phenotypes consist of patients admitted after surgery or with sepsis/septic shock with high lactate and low bicarbonate. Full article

(This article belongs to the Special Issue Critical Care Update: Innovations in Diagnostic & Treatment)

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14 pages, 1118 KiB

Open AccessEditor’s ChoiceArticle

Avoidable Blood Loss in Critical Care and Patient Blood Management: Scoping Review of Diagnostic Blood Loss

by Philipp Helmer, Sebastian Hottenrott, Andreas Steinisch, Daniel Röder, Jörg Schubert, Udo Steigerwald, Suma Choorapoikayil and Patrick Meybohm

J. Clin. Med. 2022, 11(2), 320; https://doi.org/10.3390/jcm11020320 - 10 Jan 2022

Cited by 17 | Viewed by 3867

Abstract

Background: Anemia remains one of the most common comorbidities in intensive care patients worldwide. The cause of anemia is often multifactorial and triggered by underlying disease, comorbidities, and iatrogenic factors, such as diagnostic phlebotomies. As anemia is associated with a worse outcome, especially [...] Read more.

Background: Anemia remains one of the most common comorbidities in intensive care patients worldwide. The cause of anemia is often multifactorial and triggered by underlying disease, comorbidities, and iatrogenic factors, such as diagnostic phlebotomies. As anemia is associated with a worse outcome, especially in intensive care patients, unnecessary iatrogenic blood loss must be avoided. Therefore, this scoping review addresses the amount of blood loss during routine phlebotomies in adult (>17 years) intensive care patients and whether there are factors that need to be improved in terms of patient blood management (PBM). Methods: A systematic search of the Medline Database via PubMed was conducted according to PRISMA guidelines. The reported daily blood volume for diagnostics and other relevant information from eligible studies were charted. Results: A total of 2167 studies were identified in our search, of which 38 studies met the inclusion criteria (9 interventional studies and 29 observational studies). The majority of the studies were conducted in the US (37%) and Canada (13%). An increasing interest to reduce iatrogenic blood loss has been observed since 2015. Phlebotomized blood volume per patient per day was up to 377 mL. All interventional trials showed that the use of pediatric-sized blood collection tubes can significantly reduce the daily amount of blood drawn. Conclusion: Iatrogenic blood loss for diagnostic purposes contributes significantly to the development and exacerbation of hospital-acquired anemia. Therefore, a comprehensive PBM in intensive care is urgently needed to reduce avoidable blood loss, including blood-sparing techniques, regular advanced training, and small-volume blood collection tubes. Full article

(This article belongs to the Special Issue Patient Blood Management in Critical Care Medicine)

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22 pages, 431 KiB

Open AccessEditor’s ChoiceReview

Managing Neovascular Age-Related Macular Degeneration in Clinical Practice: Systematic Review, Meta-Analysis, and Meta-Regression

by Daniele Veritti, Valentina Sarao, Valentina Soppelsa, Carla Danese, Jay Chhablani and Paolo Lanzetta

J. Clin. Med. 2022, 11(2), 325; https://doi.org/10.3390/jcm11020325 - 10 Jan 2022

Cited by 14 | Viewed by 3365

Abstract

The use of anti-vascular endothelial growth factor (VEGF) agents has profoundly changed the prognosis of neovascular age-related macular degeneration (nAMD). As clinical experiences have accumulated, it has become mandatory to summarize data to give information that can be useful in everyday practice. We [...] Read more.

The use of anti-vascular endothelial growth factor (VEGF) agents has profoundly changed the prognosis of neovascular age-related macular degeneration (nAMD). As clinical experiences have accumulated, it has become mandatory to summarize data to give information that can be useful in everyday practice. We conducted a systematic review to identify randomized controlled trials (RCTs) and observational studies that reported 12-month changes in best-corrected visual acuity (BCVA) in patients with nAMD on anti-VEGF monotherapy. Data were analyzed in a random-effects meta-analysis with BCVA change as the primary outcome. Meta-regression was conducted to evaluate the impact of multiple covariates. Four hundred and twelve heterogeneous study populations (109,666 eyes) were included. Anti-VEGFs induced an overall improvement of +5.37 ETDRS letters at 12 months. Meta-regression showed that mean BCVA change was statistically greater for RCTs (p = 0.0032) in comparison with observational studies. Populations following a proactive regimen had better outcomes than those following a reactive treatment regimen. Mean BCVA change was greater in younger populations, with lower baseline BCVA and treated with a higher number of injections (p < 0.001). Our results confirm that anti-VEGFs may produce a significant functional improvement at 12 months in patients with nAMD. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Age-Related Macular Degeneration)

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16 pages, 1214 KiB

Open AccessEditor’s ChoiceReview

Scleral Buckling: A Review of Clinical Aspects and Current Concepts

by Matteo Fallico, Pietro Alosi, Michele Reibaldi, Antonio Longo, Vincenza Bonfiglio, Teresio Avitabile and Andrea Russo

J. Clin. Med. 2022, 11(2), 314; https://doi.org/10.3390/jcm11020314 - 09 Jan 2022

Cited by 21 | Viewed by 7221

Abstract

Scleral buckling represents a valuable treatment option for rhegmatogenous retinal detachment repair. The surgery is based on two main principles: the closure of retinal breaks and the creation of a long-lasting chorioretinal adhesion. Buckles are placed onto the sclera with the purpose of [...] Read more.

Scleral buckling represents a valuable treatment option for rhegmatogenous retinal detachment repair. The surgery is based on two main principles: the closure of retinal breaks and the creation of a long-lasting chorioretinal adhesion. Buckles are placed onto the sclera with the purpose of sealing retinal breaks. Cryopexy is usually performed to ensure a long-lasting chorioretinal adhesion. Clinical outcomes of scleral buckling have been shown to be more favorable in phakic eyes with uncomplicated or medium complexity retinal detachment, yielding better anatomical and functional results compared with vitrectomy. Several complications have been described following scleral buckling surgery, some of which are sight-threatening. Expertise in indirect ophthalmoscopy is required to perform this type of surgery. A great experience is necessary to prevent complications and to deal with them. The use of scleral buckling surgery has declined over the years due to increasing interest in vitrectomy. Lack of confidence in indirect ophthalmoscopy and difficulties in teaching this surgery have contributed to limiting its diffusion among young ophthalmologists. The aim of this review is to provide a comprehensive guide on technical and clinical aspects of scleral buckling, focusing also on complications and their management. Full article

(This article belongs to the Section Ophthalmology)

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15 pages, 832 KiB

Open AccessEditor’s ChoiceArticle

Clinical Characteristics of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Korean Children: A Multicenter Retrospective Study

by Yun Jung Choi, Eun Hee Chung, Eun Lee, Chul-Hong Kim, Yong Ju Lee, Hyo-Bin Kim, Bong-Seong Kim, Hyung Young Kim, Yoojung Cho, Ju-Hee Seo, In Suk Sol, Myongsoon Sung, Dae Jin Song, Young Min Ahn, Hea Lin Oh, Jinho Yu, Sungsu Jung, Kyung Suk Lee, Ju Suk Lee, Gwang Cheon Jang, Yoon-Young Jang, Hai Lee Chung, Sung-Min Choi, Man Yong Han, Jung Yeon Shim, Jin Tack Kim, Chang-Keun Kim, Hyeon-Jong Yang and Dong In Suh Show full author list Hide full author list

J. Clin. Med. 2022, 11(2), 306; https://doi.org/10.3390/jcm11020306 - 08 Jan 2022

Cited by 18 | Viewed by 2773

Abstract

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early [...] Read more.

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides. Full article

(This article belongs to the Section Pulmonology)

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10 pages, 1050 KiB

Open AccessEditor’s ChoiceArticle

The Effects of Wearing a Medical Mask on the Masticatory and Neck Muscle Activity in Healthy Young Women

by Michał Ginszt, Grzegorz Zieliński, Jacek Szkutnik, Marcin Wójcicki, Michał Baszczowski, Monika Litko-Rola, Ingrid Rózyło-Kalinowska and Piotr Majcher

J. Clin. Med. 2022, 11(2), 303; https://doi.org/10.3390/jcm11020303 - 07 Jan 2022

Cited by 11 | Viewed by 1826

Abstract

The objective of this study was to analyze the influence of wearing a medical mask on masticatory and neck muscle activity in healthy young women. We recruited 66 healthy women aged from 18 to 30 years (mean 23.6 ± 2.3 years). The temporalis [...] Read more.

The objective of this study was to analyze the influence of wearing a medical mask on masticatory and neck muscle activity in healthy young women. We recruited 66 healthy women aged from 18 to 30 years (mean 23.6 ± 2.3 years). The temporalis anterior (TA), the superficial part of the masseter muscle (MM), the anterior bellies of the digastric muscle (DA), and the middle part of the sternocleidomastoid muscle (SCM) potentials were recorded at rest and during functional activity using an eight-channel device for surface electromyography—BioEMG III^TM. There was a statistically significant decrease in mean TA activity during medical mask measurement compared to no mask examination at rest (2.16 µV vs. 2.58 µV; p = 0.05; ES = 0.2). Significant decreases in resting RMS values were also observed during the medical mask phase in comparison to no mask examination concerning the left MM (1.75 µV vs. 2.17 µV; p = 0.01; ES = 0.3), and mean bioelectrical activity of the MM (1.81 µV vs. 2.15 µV; p = 0.02; ES = 0.2). The differences between the two conditions did not reach the assumed significance level (p > 0.05) in terms of other indices. Wearing a medical mask has a small effect on decreasing the resting potentials of the temporalis anterior and masseter muscles without changing the parameters of activity and asymmetry within the stomatognathic system. Full article

(This article belongs to the Special Issue Clinical Features of COVID-19 in Elderly Patients)

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12 pages, 1544 KiB

Open AccessEditor’s ChoiceArticle

Platelet-Rich Plasma Releasate versus Corticosteroid for the Treatment of Discogenic Low Back Pain: A Double-Blind Randomized Controlled Trial

by Koji Akeda, Kohshi Ohishi, Norihiko Takegami, Takao Sudo, Junichi Yamada, Tatsuhiko Fujiwara, Rui Niimi, Takeshi Matsumoto, Yuki Nishimura, Toru Ogura, Satoshi Tamaru and Akihiro Sudo

J. Clin. Med. 2022, 11(2), 304; https://doi.org/10.3390/jcm11020304 - 07 Jan 2022

Cited by 18 | Viewed by 2405

Abstract

Clinical application of platelet-rich plasma is gaining popularity in treating low back pain (LBP). This study investigated the efficacy and safety of platelet-rich plasma releasate (PRPr) injection into degenerated discs of patients with discogenic LBP. A randomized, double-blind, active-controlled clinical trial was conducted. [...] Read more.

Clinical application of platelet-rich plasma is gaining popularity in treating low back pain (LBP). This study investigated the efficacy and safety of platelet-rich plasma releasate (PRPr) injection into degenerated discs of patients with discogenic LBP. A randomized, double-blind, active-controlled clinical trial was conducted. Sixteen patients with discogenic LBP received an intradiscal injection of either autologous PRPr or corticosteroid (CS). Patients in both groups who wished to have PRPr treatment received an optional injection of PRPr eight weeks later. The primary outcome was change in VAS from baseline at eight weeks. Secondary outcomes were pain, disability, quality of life (QOL), image analyses of disc degeneration, and safety for up to 60 weeks. The VAS change at eight weeks did not significantly differ between the two groups. Fifteen patients received the optional injection. Compared to the CS group, the PRPr group had a significantly improved disability score at 26 weeks and walking ability scores at four and eight weeks. Radiographic disc height and MRI grading score were unchanged from baseline. PRPr caused no clinically important adverse events. PRPr injection showed clinically significant improvements in LBP intensity equal to that of CS. PRPr treatment relieved pain, and improved disability and QOL during 60 weeks of observation. Full article

(This article belongs to the Special Issue Minimally Invasive Spinal Treatment: State of the Art)

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12 pages, 933 KiB

Open AccessEditor’s ChoiceReview

Newborn Hearing Screening Benefits Children, but Global Disparities Persist

by Katrin Neumann, Philipp Mathmann, Shelly Chadha, Harald A. Euler and Karl R. White

J. Clin. Med. 2022, 11(1), 271; https://doi.org/10.3390/jcm11010271 - 05 Jan 2022

Cited by 17 | Viewed by 3857

Abstract

There is substantial evidence that newborn hearing screening (NHS) reduces the negative sequelae of permanent childhood hearing loss (PCHL) if performed in programs that aim to screen all newborns in a region or nation (often referred to as Universal Newborn Hearing Screening or [...] Read more.

There is substantial evidence that newborn hearing screening (NHS) reduces the negative sequelae of permanent childhood hearing loss (PCHL) if performed in programs that aim to screen all newborns in a region or nation (often referred to as Universal Newborn Hearing Screening or UNHS). The World Health Organization (WHO) has called in two resolutions for the implementation of such programs and for the collection of large-scale data. To assess the global status of NHS programs we surveyed individuals potentially involved with newborn and infant hearing screening (NIHS) in 196 countries/territories (in the following text referred to as countries). Replies were returned from 158 countries. The results indicated that 38% of the world’s newborns and infants had no or minimal hearing screening and 33% screened at least 85% of the babies (hereafter referred to as UNHS). Hearing screening programs varied considerably in quality, data acquisition, and accessibility of services for children with PCHL. In this article, we summarize the main results of the survey in the context of several recent WHO publications, particularly the World Report on Hearing, which defined advances in the implementation of NHS programs in the Member States as one of three key indicators of worldwide progress in ear and hearing care (EHC). Full article

(This article belongs to the Special Issue Newborn Hearing Loss: Detection and Intervention)

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15 pages, 2491 KiB

Open AccessEditor’s ChoiceReview

Histology of Cardiac Sarcoidosis with Novel Considerations Arranged upon a Pathologic Basis

by Shu Kato, Yasuhiro Sakai, Asako Okabe, Yoshiaki Kawashima, Kazuhiko Kuwahara, Kazuya Shiogama, Masato Abe, Hiroyasu Ito and Shin’ichiro Morimoto

J. Clin. Med. 2022, 11(1), 251; https://doi.org/10.3390/jcm11010251 - 04 Jan 2022

Cited by 14 | Viewed by 2859

Abstract

Sarcoidosis is a rare disease of isolated or diffuse granulomatous inflammation. Although any organs can be affected by sarcoidosis, cardiac sarcoidosis is a fatal disorder, and it is crucial to accurately diagnose it to prevent sudden death due to dysrhythmia. Although endomyocardial biopsy [...] Read more.

Sarcoidosis is a rare disease of isolated or diffuse granulomatous inflammation. Although any organs can be affected by sarcoidosis, cardiac sarcoidosis is a fatal disorder, and it is crucial to accurately diagnose it to prevent sudden death due to dysrhythmia. Although endomyocardial biopsy is invasive and has limited sensitivity for identifying granulomas, it is the only modality that yields a definitive diagnosis of cardiac sarcoidosis. It is imperative to develop novel pathological approaches for the precise diagnosis of cardiac sarcoidosis. Here, we aimed to discuss commonly used diagnostic criteria for cardiac sarcoidosis and to summarize useful and novel histopathologic criteria of cardiac sarcoidosis. While classical histologic observations including noncaseating granulomas and multinucleated giant cells (typically Langhans type) are the most important findings, others such as microgranulomas, CD68⁺ CD163⁻ pro-inflammatory (M1) macrophage accumulation, CD4/CD8 T-cell ratio, Cutibacterium acnes components, lymphangiogenesis, confluent fibrosis, and fatty infiltration may help to improve the sensitivity of endomyocardial biopsy for detecting cardiac sarcoidosis. These novel histologic findings are based on the pathology of cardiac sarcoidosis. We also discussed the principal histologic differential diagnoses of cardiac sarcoidosis, such as tuberculosis myocarditis, fungal myocarditis, giant cell myocarditis, and dilated cardiomyopathy. Full article

(This article belongs to the Special Issue New Frontiers in the Diagnosis of Sarcoidosis)

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