Journal of Clinical Medicine

10 pages, 4731 KiB

Open AccessEditor’s ChoiceArticle

Prevalence of Overweight and Obesity in France: The 2020 Obepi-Roche Study by the “Ligue Contre l’Obésité”

by Annick Fontbonne, Andrew Currie, Patrick Tounian, Marie-Christine Picot, Olivier Foulatier, Marius Nedelcu and David Nocca

J. Clin. Med. 2023, 12(3), 925; https://doi.org/10.3390/jcm12030925 - 25 Jan 2023

Cited by 18 | Viewed by 13321

Abstract

Obepi-Roche 2020 by the “Ligue Contre l’Obésité” (League Against Obesity) estimated overweight and obesity prevalence in France. The adopted methodology was chosen to be as similar as possible to that of a series of quota-based surveys conducted every three years from 1997 to [...] Read more.

Obepi-Roche 2020 by the “Ligue Contre l’Obésité” (League Against Obesity) estimated overweight and obesity prevalence in France. The adopted methodology was chosen to be as similar as possible to that of a series of quota-based surveys conducted every three years from 1997 to 2012 (Obepi-Roche studies). The 2020 survey was conducted online from 24th September to 5th October 2020 by the Odoxa polling institute on a sample of metropolitan French subjects aged 18 years or over. Participants (n = 9598) self-measured their height and weight according to detailed instructions. Prevalence estimates were produced for all categories of body mass index. The prevalence of excess weight was 47.3% (17.0% of subjects with obesity), with higher values in the north and east of France. When comparing these 2020 estimates to previous Obepi-Roche estimates in order to visualize trends since 1997, it appeared that overweight fluctuated around 30%, and obesity prevalence increased steadily at a rapid pace. The increase was even steeper in the youngest age groups and for severe and complex obesity. Given the slightly different methodologies between the 1997–2012 studies and the 2020 survey, the worrying trends in obesity prevalence since 1997 must be confirmed, calling for a reedition of the Obepi-Roche series. Full article

(This article belongs to the Section General Surgery)

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10 pages, 1491 KiB

Open AccessEditor’s ChoiceReview

Introducing Machine Perfusion into Routine Clinical Practice for Liver Transplantation in the United States: The Moment Has Finally Come

by Kristopher P. Croome

J. Clin. Med. 2023, 12(3), 909; https://doi.org/10.3390/jcm12030909 - 23 Jan 2023

Cited by 11 | Viewed by 3314

Abstract

While adoption of machine perfusion technologies into clinical practice in the United States has been much slower than in Europe, recent changes in the transplant landscape as well as device availability following FDA approval have paved the way for rapid growth. Machine perfusion [...] Read more.

While adoption of machine perfusion technologies into clinical practice in the United States has been much slower than in Europe, recent changes in the transplant landscape as well as device availability following FDA approval have paved the way for rapid growth. Machine perfusion may provide one mechanism to maximize the utilization of potential donor liver grafts. Indeed, multiple studies have shown increased organ utilization with the implementation of technologies such as ex-situ normothermic machine perfusion (NMP), ex-situ hypothermic machine perfusion (HMP) and in-situ normothermic regional perfusion (NRP). The current review describes the history and development of machine perfusion utilization in the Unites States along with future directions. It also describes the differences in landscape between Europe and the United States and how this has shaped clinical application of these technologies. Full article

(This article belongs to the Special Issue (Lastest Advances) Reconditioning Strategies in Solid Organ Transplantation: Linking Theory to Clinical Practice )

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30 pages, 782 KiB

Open AccessEditor’s ChoiceReview

Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss

by Nicole Natarelli, Nimrit Gahoonia and Raja K. Sivamani

J. Clin. Med. 2023, 12(3), 893; https://doi.org/10.3390/jcm12030893 - 23 Jan 2023

Cited by 15 | Viewed by 17993

Abstract

The hair cycle is composed of four primary phases: anagen, catagen, telogen, and exogen. Anagen is a highly mitotic phase characterized by the production of a hair shaft from the hair follicle, whereas catagen and telogen describe regression and the resting phase of [...] Read more.

The hair cycle is composed of four primary phases: anagen, catagen, telogen, and exogen. Anagen is a highly mitotic phase characterized by the production of a hair shaft from the hair follicle, whereas catagen and telogen describe regression and the resting phase of the follicle, respectively, ultimately resulting in hair shedding. While 9% of hair follicles reside in telogen at any time, a variety of factors promote anagen to telogen transition, including inflammation, hormones, stress, nutritional deficiency, poor sleep quality, and cellular division inhibiting medication. Conversely, increased blood flow, direct stimulation of the hair follicle, and growth factors promote telogen to anagen transition and subsequent hair growth. This review seeks to comprehensively describe the hair cycle, anagen and telogen balance, factors that promote anagen to telogen transition and vice versa, and the clinical utility of a variety of lab testing and evaluations. Ultimately, a variety of factors impact the hair cycle, necessitating a holistic approach to hair loss. Full article

(This article belongs to the Section Dermatology)

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25 pages, 4636 KiB

Open AccessEditor’s ChoiceReview

Acute Heart Failure: Diagnostic–Therapeutic Pathways and Preventive Strategies—A Real-World Clinician’s Guide

by Ciro Mauro, Salvatore Chianese, Rosangela Cocchia, Michele Arcopinto, Stefania Auciello, Valentina Capone, Mariano Carafa, Andreina Carbone, Giuseppe Caruso, Rossana Castaldo, Rodolfo Citro, Giulia Crisci, Antonello D’Andrea, Roberta D’Assante, Maria D’Avino, Francesco Ferrara, Antonio Frangiosa, Domenico Galzerano, Vincenzo Maffei, Alberto Maria Marra, Rahul M. Mehta, Rajendra H. Mehta, Fiorella Paladino, Brigida Ranieri, Monica Franzese, Giuseppe Limongelli, Salvatore Rega, Luigia Romano, Andrea Salzano, Chiara Sepe, Olga Vriz, Raffaele Izzo, Filippo Cademartiri, Antonio Cittadini and Eduardo Bossone Show full author list Hide full author list

J. Clin. Med. 2023, 12(3), 846; https://doi.org/10.3390/jcm12030846 - 20 Jan 2023

Cited by 5 | Viewed by 6733

Abstract

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical [...] Read more.

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed. Full article

(This article belongs to the Special Issue New Advances in Pharmacologic and Non-pharmacologic Therapy in Heart Failure and Heart Transplant)

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18 pages, 1327 KiB

Open AccessEditor’s ChoiceSystematic Review

Non-Alcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome: A Systematic Review, Meta-Analysis, and Meta-Regression

by Ramiro Manzano-Nunez, Marta Santana-Dominguez, Jesus Rivera-Esteban, Clara Sabiote, Elena Sena, Juan Bañares, Frank Tacke and Juan M. Pericàs

J. Clin. Med. 2023, 12(3), 856; https://doi.org/10.3390/jcm12030856 - 20 Jan 2023

Cited by 9 | Viewed by 3187

Abstract

Background: The metabolic effects of polycystic ovary syndrome (PCOS) may increase the risk of non-alcoholic fatty liver disease (NAFLD). However, the burden of NAFLD in PCOS has not been unequivocally defined. This systematic review (SR), meta-analysis (MA) assessed NAFLD’s prevalence, and risk factors [...] Read more.

Background: The metabolic effects of polycystic ovary syndrome (PCOS) may increase the risk of non-alcoholic fatty liver disease (NAFLD). However, the burden of NAFLD in PCOS has not been unequivocally defined. This systematic review (SR), meta-analysis (MA) assessed NAFLD’s prevalence, and risk factors in patients with PCOS. Methods: A literature search was performed in MEDLINE, Scopus, and Scielo. First, we performed a MA of proportions to estimate the prevalence of NAFLD in PCOS. Second, we performed meta-analyses of precalculated adjusted odds ratios to examine NAFLD risk factors. Finally, we performed a meta-regression to model how the estimated prevalence changed with changes in prespecified variables. Results: We identified 817 articles from the database searches. Thirty-six were included. MA of proportions found a pooled NAFLD prevalence of 43% (95% CI, 35–52%) with high heterogeneity (I² = 97.2%). BMI, waist circumference, ALT values, HOMA-IR values, free androgen index levels, hyperandrogenism, and triglycerides were associated with significantly higher risk-adjusted odds of NAFLD among patients with PCOS. Meta-regression showed that rises in NAFLD prevalence were mediated through increases in metabolic syndrome prevalence and higher levels of HOMA-IR, free androgen index, and total testosterone. Conclusion: The prevalence of NAFLD (43%) among PCOS patients is high despite their average young age, with several metabolic and PCOS-specific factors influencing its occurrence. Screening programs may aid in detecting metabolic-associated fatty liver disease and prevent its consequences. Further work is required to establish the burden of liver-related outcomes once NAFLD has progressed in the PCOS population. Full article

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

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8 pages, 1131 KiB

Open AccessEditor’s ChoiceArticle

Epidemiology of Inflammatory Bowel Diseases: A Population Study in a Healthcare District of North-West Italy

by Gian Paolo Caviglia, Angela Garrone, Chiara Bertolino, Riccardo Vanni, Elisabetta Bretto, Anxhela Poshnjari, Elisa Tribocco, Simone Frara, Angelo Armandi, Marco Astegiano, Giorgio Maria Saracco, Luciano Bertolusso and Davide Giuseppe Ribaldone

J. Clin. Med. 2023, 12(2), 641; https://doi.org/10.3390/jcm12020641 - 13 Jan 2023

Cited by 8 | Viewed by 4456

Abstract

The burden of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. The aim of the present study was to investigate the clinical characteristics and the changing in epidemiology of IBD in the Healthcare District Bra, an [...] Read more.

The burden of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. The aim of the present study was to investigate the clinical characteristics and the changing in epidemiology of IBD in the Healthcare District Bra, an area of North-West Italy accounting for 57,615 inhabitants as of 31 December 2021. Clinical and demographic data were retrieved from administrative databases and the medical records of general practitioners (n = 39) at Verduno Hospital. Prevalence and incidence rates were calculated for the time span 2016–2021 and compared to the 2001–2006 period. IBD prevalence was 321.2 per 100,000 population in 2021 and, compared with 2006 (200 per 100,000 population), the prevalence has increased at a rate of +46%. Similarly, the average incidence has increased from the period 2001–2006 (6.7 per 100,000 population/year) to the period 2016–2021 (18.0 per 100,000 population/year) at a rate of +169%; such an increase was greater for CD than UC. In the 2016–2021 period, the mean age at diagnosis was 42.0 ± 17.4 years and 30.9% required at least one hospitalization, while 10.9% of patients underwent at least one surgery. In conclusion, the prevalence and incidence of IBD distinctly increased over a two decade period in the Healthcare District Bra paralleling the results of previous surveys from other Italian regions. These data warrant specific interventions to improve patients’ management and resources’ allocation. Full article

(This article belongs to the Special Issue Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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15 pages, 1500 KiB

Open AccessEditor’s ChoiceSystematic Review

Future of Orthodontics—A Systematic Review and Meta-Analysis on the Emerging Trends in This Field

by Mohammad Khursheed Alam, Huda Abutayyem, Bushra Kanwal and Maher A. L. Shayeb

J. Clin. Med. 2023, 12(2), 532; https://doi.org/10.3390/jcm12020532 - 09 Jan 2023

Cited by 8 | Viewed by 3719

Abstract

Technology is rapidly evolving in the modern world, and the accompanying developments due to its influence are shaping each and every aspect of our life, with the field of orthodontics being no exception. This systematic review and meta-analysis aimed to examine such trends [...] Read more.

Technology is rapidly evolving in the modern world, and the accompanying developments due to its influence are shaping each and every aspect of our life, with the field of orthodontics being no exception. This systematic review and meta-analysis aimed to examine such trends in orthodontics and hypothesize which ones would emerge and continue in the near future. After a thorough search of online journals using keywords such as “3D printing,” “Aligners,” “Artificial intelligence,” “Future trends,” “Orthodontics,” and “Teleorthodontics” across databases of PubMed-MEDLINE, Web of Science, Cochrane, and Scopus, a total of 634 papers were initially recovered. Technological advancements in 3D printing, Computer-aided design and Computer-aided manufacturing (CAD/CAM), biopolymers and Teleorthodontics were the most important categories of development seen across the 17 studies that we selected for our review. All the investigations selected for this systematic review depicted aspects of orthodontics that were influenced by rapid technological changes and could potentially become mainstream in the coming times. However, caution was sought to be observed in the usage/adoption of some of these trends, with social media usage amongst both patients as well as orthodontists being a prime example of this. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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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 1509

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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Graphical abstract

17 pages, 1414 KiB

Open AccessEditor’s ChoiceReview

Global Incidence and Prevalence of Gaucher Disease: A Targeted Literature Review

by Genaro Castillon, Shun-Chiao Chang and Yola Moride

J. Clin. Med. 2023, 12(1), 85; https://doi.org/10.3390/jcm12010085 - 22 Dec 2022

Cited by 13 | Viewed by 3477

Abstract

Incidence and prevalence estimates for Gaucher disease (GD) are scarce for this rare disease and can be variable within the same region. This review provides a qualitative synthesis of global GD incidence and prevalence estimates, GD1–3 type-specific and overall, published in the last [...] Read more.

Incidence and prevalence estimates for Gaucher disease (GD) are scarce for this rare disease and can be variable within the same region. This review provides a qualitative synthesis of global GD incidence and prevalence estimates, GD1–3 type-specific and overall, published in the last 10 years. A targeted literature search was conducted across multiple databases from January 2011 to September 2020, including web-based sources and congress proceedings to May 2021. Searches yielded 490 publications, with 31 analyzed: 20 cohort studies (15 prospective, 5 retrospective), 6 cross-sectional studies, 5 online reports (most from Europe (n = 11) or North America (n = 11); one multiregional). Across all GD types, incidence estimates ranged 0.45–25.0/100,000 live births (16 studies), lowest for Asia-Pacific. Incidence of GD1: 0.45–22.9/100,000 live births (Europe and North America) and GD3: 1.36/100,000 live births (Asia-Pacific only). GD type-specific prevalence estimates per 100,000 population were GD1: 0.26–0.63; GD2 and GD3: 0.02–0.08 (Europe only); estimates for GD type unspecified or overall ranged 0.11–139.0/100,000 inhabitants (17 studies), highest for North America. Generalizability was assessed as “adequate”or “intermediate” for all regions with data. GD incidence and prevalence estimates for the last 10 years varied considerably between regions and were poorly documented outside Europe and North America. Data for GD2 and GD3 were limited. Full article

(This article belongs to the Topic Advances in Gaucher Disease: A Model for Rare Lysosomal Disorders)

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21 pages, 1333 KiB

Open AccessEditor’s ChoiceReview

Osteoarthritis: Pathogenesis, Animal Models, and New Regenerative Therapies

by Tomasz Szponder, Michał Latalski, Anna Danielewicz, Katarzyna Krać, Aleksandra Kozera, Beata Drzewiecka, Dominika Nguyen Ngoc, Dominika Dobko and Joanna Wessely-Szponder

J. Clin. Med. 2023, 12(1), 5; https://doi.org/10.3390/jcm12010005 - 20 Dec 2022

Cited by 20 | Viewed by 3400

Abstract

Osteoarthritis (OA) is a chronic, progressive, multifactorial disease resulting in a progressive loss of articular cartilage structure and function that is most common in middle-aged and older patients. OA is involved in the loss of extracellular matrix and cartilage as well as cell [...] Read more.

Osteoarthritis (OA) is a chronic, progressive, multifactorial disease resulting in a progressive loss of articular cartilage structure and function that is most common in middle-aged and older patients. OA is involved in the loss of extracellular matrix and cartilage as well as cell number decreases within the matrix, especially in the further stages of the disease. The immune system plays a pivotal role in the pathomechanism of this condition. Both humoral and cellular mediators contribute to cartilage destruction, abnormal bone remodeling, synovitis, and joint effusion. The increasing prevalence of this disease has led to a growing interest in using animal models as the primary way to broaden the knowledge of the pathogenesis of OA and possible therapies at each stage of disease development. This review aims to describe the signs, pathogenesis, and classification of OA as well as discuss the advantages and disadvantages of some animal models. The currently used treatment methods include mesenchymal stem cells, exosomes, gene therapies, and blood-derived products. In addition, exogenous growth factors, platelet-rich plasma (PRP), platelet lysate, and autologous conditioned serum (ACS) are discussed with the application of tissue engineering techniques and biomaterials. Full article

(This article belongs to the Special Issue Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease)

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12 pages, 2120 KiB

Open AccessEditor’s ChoiceReview

The Assessment of Immune Fitness

by Joris C. Verster, Aletta D. Kraneveld and Johan Garssen

J. Clin. Med. 2023, 12(1), 22; https://doi.org/10.3390/jcm12010022 - 20 Dec 2022

Cited by 13 | Viewed by 1615

Abstract

Immune fitness (i.e., adequate functioning of the immune system) is essential to maintain health, prevent and resolve disease, and improve quality of life. This article provides an overview of how to assess immune fitness. It discusses how a single-item rating scale can be [...] Read more.

Immune fitness (i.e., adequate functioning of the immune system) is essential to maintain health, prevent and resolve disease, and improve quality of life. This article provides an overview of how to assess immune fitness. It discusses how a single-item rating scale can be used to assess immune fitness. The scale can be used in conjunction with a single “yes” or “no” question asking whether the individual is experiencing reduced immune fitness. Retrospective assessments can be complemented with the Immune Status Questionnaire (ISQ) to provide more insight into the type and frequency of experiencing specific immune-related complaints. Momentary assessments of immune fitness can be complemented with biomarker measurements in body fluids. As individuals may be unaware of systemic inflammation (e.g., biomarker concentrations outside the normal range), it remains critical to combine immune fitness assessments with biomarker measurements of immune functioning. Full article

(This article belongs to the Section Immunology)

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11 pages, 1120 KiB

Open AccessEditor’s ChoiceArticle

Cystic Fibrosis Patients with F508del/Minimal Function Genotype: Laboratory and Nutritional Evaluations after One Year of Elexacaftor/Tezacaftor/Ivacaftor Treatment

by Vincenzo Carnovale, Filippo Scialò, Monica Gelzo, Paola Iacotucci, Felice Amato, Federica Zarrilli, Assunta Celardo, Giuseppe Castaldo and Gaetano Corso

J. Clin. Med. 2022, 11(23), 6900; https://doi.org/10.3390/jcm11236900 - 22 Nov 2022

Cited by 13 | Viewed by 1453

Abstract

The last ten years have been characterized by an enormous step forward in the therapy and management of patients with Cystic Fibrosis (CF), thanks to the development and combination of Cystic Fibrosis Transmembrane Receptor (CFTR) correctors and potentiators. Specifically, the last [...] Read more.

The last ten years have been characterized by an enormous step forward in the therapy and management of patients with Cystic Fibrosis (CF), thanks to the development and combination of Cystic Fibrosis Transmembrane Receptor (CFTR) correctors and potentiators. Specifically, the last approved triple combination elexacaftor/tezacaftor/ivacaftor has been demonstrated to improve lung function in CF patients with both homozygous Phe508del and Phe508del/minimal function genotypes. Here we have assessed the effect of elexacaftor/tezacaftor/ivacaftor in patients carrying the Phe508del/minimal function genotype (n = 20) after one year of treatments on liver function and nutrient absorption with a focus on lipid metabolism. We show that weight, BMI, and albumin significantly increase, suggesting a positive impact of the treatment on nutrient absorption. Furthermore, cholesterol levels as a biomarker of lipid metabolism increased significantly after one year of treatment. Most importantly, we suggest that these results were not dependent on the diet composition, possibly indicating that the drug improves the hepatic synthesis and secretion of proteins and cholesterol. Full article

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

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11 pages, 5104 KiB

Open AccessEditor’s ChoiceArticle

No Significant Differences in Clinical and Radiographic Outcomes between PCL Retained or Sacrificed Kinematic Aligned Medial Pivot Total Knee Arthroplasty in Varus Knee

by Fortunato Giustra, Francesco Bosco, Giorgio Cacciola, Salvatore Risitano, Marcello Capella, Alessandro Bistolfi, Alessandro Massè and Luigi Sabatini

J. Clin. Med. 2022, 11(21), 6569; https://doi.org/10.3390/jcm11216569 - 05 Nov 2022

Cited by 15 | Viewed by 1717

Abstract

In the last decades, several surgical techniques, such as medial pivot (MP) philosophy and kinematic alignment (KA), have been introduced in total knee arthroplasty (TKA) to improve patients’ outcomes. This retrospective study aims to evaluate the clinical, radiographic, and functional results of PCL [...] Read more.

In the last decades, several surgical techniques, such as medial pivot (MP) philosophy and kinematic alignment (KA), have been introduced in total knee arthroplasty (TKA) to improve patients’ outcomes. This retrospective study aims to evaluate the clinical, radiographic, and functional results of PCL preservation or sacrifice in KA MP-TKA. A consecutive series of 147 patients older than 60, with a minimum follow-up of two years, were treated with TKA for severe primary knee osteoarthritis (OA) at the Department of Orthopedics and Traumatology between 1 January 2019, and 1 July 2020. After excluding those not meeting the inclusion criteria, 64 patients were included in the study analysis. Regarding radiographic outcomes, no statistically significant difference was observed between patients with preserved or sacrificed PCL (p > 0.05). A slight improvement in Knee Society Score (KSS), knee and function score, and FJS was observed for the PCL-preserved group, although this superiority tendency was not statistically significant (p > 0.05). PCL-preserved MA MP-TKA reported a statistically significant result in only two questions on the FJS questionnaire (p < 0.05). A slight, non-statistically significant improvement in active ROM was found in the PCL-sacrificed group (p > 0.05). No interventions or revisions were reported in this case series for all treated patients at the final follow-up. No significant differences were described in clinical, radiographic, and functional outcomes in preserved or sacrificed PCL KA MP-TKA. Although not significant, a slight trend toward better clinical outcomes was reported in PCL-preserved KA MP-TKA. Full article

(This article belongs to the Special Issue New Frontiers in Orthopedic Surgery)

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11 pages, 1670 KiB

Open AccessEditor’s ChoiceArticle

Efficacy of Hydrogen Purification and Cosmetic Acids in the Treatment of Acne Vulgaris: A Preliminary Report

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

J. Clin. Med. 2022, 11(21), 6269; https://doi.org/10.3390/jcm11216269 - 25 Oct 2022

Cited by 18 | Viewed by 2505

Abstract

Acne and skin lesions that appear in its course deteriorate the quality of life of patients, cause depression and the emergence of suicidal thoughts. Cosmetic treatments can have a positive effect on improving skin condition by cleaning up skin eruptions, thus improving the [...] Read more.

Acne and skin lesions that appear in its course deteriorate the quality of life of patients, cause depression and the emergence of suicidal thoughts. Cosmetic treatments can have a positive effect on improving skin condition by cleaning up skin eruptions, thus improving the well-being of affected people. Hydrogen purification is a treatment that uses alkaline water generated by a device, which reduces sebum from the surface of the epidermis. This is a novel treatment that has recently been introduced to beauty salons. On the other hand, cosmetic acids have been used for many years for treating people with acne vulgaris and give spectacular results in terms of improving the skin condition. In this study, skin condition was evaluated with a Derma Unit SSC 3 device. The Global Acne Grading System (GAGS) was used to check acne severity. Twenty-four women aged 19–21 years (M = 20.13, SD = 0.80) diagnosed with mild acne vulgaris and a high sebum level participated in the study. Group A underwent a hydrogen purification treatment using an H2jet manipulator, which ejected alkaline water from the manipulator under pressure. Group B underwent a hydrogen purification treatment with the use of a phytic, pyruvic, lactic and ferulic acids at 40% mixture (pH 1.4). A series of four treatments was performed at 14-day intervals in both groups. Skin parameters were measured before and 30 days after the series of treatment. Very good results were obtained in both groups. The skin eruptions in patients were reduced and we also observed lower amounts of sebum on the surface of the epidermis, and an improvement in skin hydration. However, in group B, the results were better than in group A. The study showed that the synergy of the treatments produced much better effects than those obtained by completing the hydrogen purification treatment alone. Full article

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

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17 pages, 1241 KiB

Open AccessEditor’s ChoiceReview

Bruton’s Tyrosine Kinase Inhibitors: The Next Frontier of B-Cell-Targeted Therapies for Cancer, Autoimmune Disorders, and Multiple Sclerosis

by Neeta Garg, Elizabeth Jordan Padron, Kottil W. Rammohan and Courtney Frances Goodman

J. Clin. Med. 2022, 11(20), 6139; https://doi.org/10.3390/jcm11206139 - 18 Oct 2022

Cited by 13 | Viewed by 4165

Abstract

Bruton’s tyrosine kinase (BTK) is an important protein belonging to the tyrosine kinase family that plays a key role in the intracellular signaling and proliferation, migration, and survival of normal and malignant B-lymphocytes and myeloid cells. Understanding the role of BTK in the [...] Read more.

Bruton’s tyrosine kinase (BTK) is an important protein belonging to the tyrosine kinase family that plays a key role in the intracellular signaling and proliferation, migration, and survival of normal and malignant B-lymphocytes and myeloid cells. Understanding the role of BTK in the B-cell signaling pathway has led to the development of BTK inhibitors (BTKi) as effective therapies for malignancies of myeloid origin and exploration as a promising therapeutic option for other cancers. Given its central function in B-cell receptor signaling, inhibition of BTK is an attractive approach for the treatment of a wide variety of autoimmune diseases that involve aberrant B-cell function including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Here, we review the role of BTK in different cell signaling pathways, the development of BTKi in B-cell malignancies, and their emerging role in the treatment of MS and other autoimmune disorders. Full article

(This article belongs to the Section Immunology)

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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 12003

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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22 pages, 1122 KiB

Open AccessEditor’s ChoiceReview

The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review

by Marcin Sochal, Marta Ditmer, Agata Gabryelska and Piotr Białasiewicz

J. Clin. Med. 2022, 11(20), 6023; https://doi.org/10.3390/jcm11206023 - 12 Oct 2022

Cited by 19 | Viewed by 2893

Abstract

Brain-derived neurotrophic factor (BDNF) is a neurotrophin regulating synaptic plasticity, neuronal excitability, and nociception. It seems to be one of the key molecules in interactions between the central nervous system and immune-related diseases, i.e., diseases with an inflammatory background of unknown etiology, such [...] Read more.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin regulating synaptic plasticity, neuronal excitability, and nociception. It seems to be one of the key molecules in interactions between the central nervous system and immune-related diseases, i.e., diseases with an inflammatory background of unknown etiology, such as inflammatory bowel diseases or rheumatoid arthritis. Studies show that BDNF levels might change in the tissues and serum of patients during the course of these conditions, e.g., affecting cell survival and modulating pain severity and signaling pathways involving different neurotransmitters. Immune-related conditions often feature psychiatric comorbidities, such as sleep disorders (e.g., insomnia) and symptoms of depression/anxiety; BDNF may be related as well to them as it seems to exert an influence on sleep structure; studies also show that patients with psychiatric disorders have decreased BDNF levels, which increase after treatment. BDNF also has a vital role in nociception, particularly in chronic pain, hyperalgesia, and allodynia, participating in the formation of central hypersensitization. In this review, we summarize the current knowledge on BDNF’s function in immune-related diseases, sleep, and pain. We also discuss how BDNF is affected by treatment and what consequences these changes might have beyond the nervous system. Full article

(This article belongs to the Section Clinical Neurology)

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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 2608

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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30 pages, 474 KiB

Open AccessEditor’s ChoiceReview

Current Insights on Biomarkers in Lupus Nephritis: A Systematic Review of the Literature

by Leonardo Palazzo, Julius Lindblom, Chandra Mohan and Ioannis Parodis

J. Clin. Med. 2022, 11(19), 5759; https://doi.org/10.3390/jcm11195759 - 28 Sep 2022

Cited by 14 | Viewed by 4551

Abstract

Lupus nephritis (LN) is a major cause of morbidity and mortality among patients with systemic lupus erythematosus (SLE). However, promising emerging biomarkers pave the way toward an improved management of patients with LN. We have reviewed the literature over the past decade, and [...] Read more.

Lupus nephritis (LN) is a major cause of morbidity and mortality among patients with systemic lupus erythematosus (SLE). However, promising emerging biomarkers pave the way toward an improved management of patients with LN. We have reviewed the literature over the past decade, and we herein summarise the most relevant biomarkers for diagnosis, monitoring, and prognosis in LN. An initial systematic search of Medline was conducted to identify pertinent articles. A total of 104 studies were selected to be included in this review. Several diagnostic biomarkers, including MCP-1, TWEAK, NGAL, and uric acid, exhibited good ability to differentiate LN patients from non-renal SLE patients. Several cytokines and chemokines, including IL-10, IL-17, MCP-1, and IP-10, hold promise for assessing LN disease activity, as do cell adhesion molecules (CAMs). Angiogenesis-related and haemostasis-related proteins have also displayed potential for monitoring disease activity. Biomarkers of responses to therapy include Axl, CD163, and BAFF, whereas VCAM-1, ALCAM, and ANCAs have been reported as prognostic markers, along with traditional markers. In addition, novel renal tissue biomarkers may prove to be a useful complement to histological evaluations. The overall heterogeneity of the inclusion criteria and outcome measures across different studies, along with a lack of validation in multi-centre cohorts, call for future collaborative efforts. Nevertheless, we foresee that several biomarkers hold promise toward optimisation of the management of LN, with the use of integrated omics and panels of less invasive biomarkers paving the way towards personalised medicine. Full article

(This article belongs to the Special Issue Clinical Advances in Lupus Nephritis)

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 3649

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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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 16 | Viewed by 2466

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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23 pages, 4133 KiB

Open AccessEditor’s ChoiceSystematic Review

DNA Methylation in Offspring Conceived after Assisted Reproductive Techniques: A Systematic Review and Meta-Analysis

by Rossella Cannarella, Andrea Crafa, Laura M. Mongioì, Loredana Leggio, Nunzio Iraci, Sandro La Vignera, Rosita A. Condorelli and Aldo E. Calogero

J. Clin. Med. 2022, 11(17), 5056; https://doi.org/10.3390/jcm11175056 - 28 Aug 2022

Cited by 13 | Viewed by 2058

Abstract

Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all [...] Read more.

Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. Results. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of H19 CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD −0.81 (−1.53; −0.09), I² = 89%, p = 0.03). In contrast, H19 CCCTC-binding factor 6 (CTCF6), Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1OT1), Paternally-expressed gene 3 (PEG3), and Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) were not differently methylated in ART vs. SC offspring. Conclusion: The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring. Full article

(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)

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23 pages, 865 KiB

Open AccessEditor’s ChoiceArticle

Ocular Inflammation Induced by Immune Checkpoint Inhibitors

by Florence Chaudot, Pascal Sève, Antoine Rousseau, Alexandre Thibault Jacques Maria, Pierre Fournie, Pierre Lozach, Jeremy Keraen, Marion Servant, Romain Muller, Baptiste Gramont, Sara Touhami, Habeeb Mahmoud, Pierre-Antoine Quintart, Stéphane Dalle, Olivier Lambotte, Laurent Kodjikian and Yvan Jamilloux

J. Clin. Med. 2022, 11(17), 4993; https://doi.org/10.3390/jcm11174993 - 25 Aug 2022

Cited by 13 | Viewed by 1852

Abstract

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients [...] Read more.

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients (36 ocular IRAEs), occurring after an average of 17 weeks (±19). Forty-six percent of patients were treated for metastatic melanoma. Anti-PD1 agents were responsible for 57% of the IRAEs. Anterior uveitis was the most common (44%), followed by panuveitis (28%). Of 25 uveitis cases, 80% were bilateral and 60% were granulomatous. We found one case with complete Vogt-Koyanagi–Harada syndrome and one case of birdshot retinochoroidopathy. The other IRAEs were eight ocular surface disorders, one optic neuropathy, and one inflammatory orbitopathy. Seventy percent of the IRAEs were grade 3 according to the common terminology of AEs. ICPIs were discontinued in 60% of patients and 50% received local corticosteroids alone. The literature review included 230 uveitis cases, of which 7% were granulomatous. The distributions of ICPIs, cancer, and type of uveitis were similar to our cohort. Ocular IRAEs appeared to be easily controlled by local or systemic corticosteroids and did not require routine discontinuation of ICPIs. Further work is still warranted to define the optimal management of ocular IRAEs. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

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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 3501

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)

24 pages, 1359 KiB

Open AccessEditor’s ChoiceSystematic Review

Clinical Outcomes of Second- versus First-Generation Carotid Stents: A Systematic Review and Meta-Analysis

by Adam Mazurek, Krzysztof Malinowski, Kenneth Rosenfield, Laura Capoccia, Francesco Speziale, Gianmarco de Donato, Carlo Setacci, Christian Wissgott, Pasqualino Sirignano, Lukasz Tekieli, Andrey Karpenko, Waclaw Kuczmik, Eugenio Stabile, David Christopher Metzger, Max Amor, Adnan H. Siddiqui, Antonio Micari, Piotr Pieniążek, Alberto Cremonesi, Joachim Schofer, Andrej Schmidt and Piotr Musialek Show full author list Hide full author list

J. Clin. Med. 2022, 11(16), 4819; https://doi.org/10.3390/jcm11164819 - 17 Aug 2022

Cited by 26 | Viewed by 3253

Abstract

Background: Single-cohort studies suggest that second-generation stents (SGS; “mesh stents”) may improve carotid artery stenting (CAS) outcomes by limiting peri- and postprocedural cerebral embolism. SGS differ in the stent frame construction, mesh material, and design, as well as in mesh-to-frame position (inside/outside). Objectives: [...] Read more.

Background: Single-cohort studies suggest that second-generation stents (SGS; “mesh stents”) may improve carotid artery stenting (CAS) outcomes by limiting peri- and postprocedural cerebral embolism. SGS differ in the stent frame construction, mesh material, and design, as well as in mesh-to-frame position (inside/outside). Objectives: To compare clinical outcomes of SGS in relation to first-generation stents (FGSs; single-layer) in CAS. Methods: We performed a systematic review and meta-analysis of clinical studies with FGSs and SGS (PRISMA methodology, 3302 records). Endpoints were 30-day death, stroke, myocardial infarction (DSM), and 12-month ipsilateral stroke (IS) and restenosis (ISR). A random-effect model was applied. Results: Data of 68,422 patients from 112 eligible studies (68.2% men, 44.9% symptomatic) were meta-analyzed. Thirty-day DSM was 1.30% vs. 4.11% (p < 0.01, data for SGS vs. FGS). Among SGS, both Casper/Roadsaver and CGuard reduced 30-day DSM (by 2.78 and 3.03 absolute percent, p = 0.02 and p < 0.001), whereas the Gore stent was neutral. SGSs significantly improved outcomes compared with closed-cell FGS (30-day stroke 0.6% vs. 2.32%, p = 0.014; DSM 1.3% vs. 3.15%, p < 0.01). At 12 months, in relation to FGS, Casper/Roadsaver reduced IS (−3.25%, p < 0.05) but increased ISR (+3.19%, p = 0.04), CGuard showed a reduction in both IS and ISR (−3.13%, −3.63%; p = 0.01, p < 0.01), whereas the Gore stent was neutral. Conclusions: Pooled SGS use was associated with improved short- and long-term clinical results of CAS. Individual SGS types, however, differed significantly in their outcomes, indicating a lack of a “mesh stent” class effect. Findings from this meta-analysis may provide clinically relevant information in anticipation of large-scale randomized trials. Full article

(This article belongs to the Section Cardiovascular Medicine)

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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 5304

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 6372

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 3055

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, 638 KiB

Open AccessEditor’s ChoiceReview

Atopic Dermatitis: Striving for Reliable Biomarkers

by Styliani Mastraftsi, Georgia Vrioni, Michail Bakakis, Electra Nicolaidou, Dimitrios Rigopoulos, Alexander J. Stratigos and Stamatios Gregoriou

J. Clin. Med. 2022, 11(16), 4639; https://doi.org/10.3390/jcm11164639 - 09 Aug 2022

Cited by 17 | Viewed by 3484

Abstract

Atopic dermatitis (AD) is a highly heterogeneous inflammatory disease regarding both its pathophysiology and clinical manifestations. However, it is treated according to the “one-size-fits-all” approach, which may restrict response to treatment. Thus, there is an unmet need for the stratification of patients with [...] Read more.

Atopic dermatitis (AD) is a highly heterogeneous inflammatory disease regarding both its pathophysiology and clinical manifestations. However, it is treated according to the “one-size-fits-all” approach, which may restrict response to treatment. Thus, there is an unmet need for the stratification of patients with AD into distinct endotypes and clinical phenotypes based on biomarkers that will contribute to the development of precision medicine in AD. The development of reliable biomarkers that may distinguish which patients with AD are most likely to benefit from specific targeted therapies is a complex procedure and to date none of the identified candidate biomarkers for AD has been validated for use in routine clinical practice. Reliable biomarkers in AD are expected to improve diagnosis, evaluate disease severity, predict the course of disease, the development of comorbidities, or the therapeutic response, resulting in effective and personalized treatment of AD. Among the studied AD potential biomarkers, thymus and activation-regulated chemokine/C-C motif ligand 17 (TARC/CCL17) has the greatest evidence-based support for becoming a reliable biomarker in AD correlated with disease severity in both children and adults. In this review, we present the most prominent candidate biomarkers in AD and their suggested use. Full article

(This article belongs to the Section Dermatology)

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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 4120

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)

28 pages, 378 KiB

Open AccessEditor’s ChoiceReview

Second-Generation Antipsychotics’ Effectiveness and Tolerability: A Review of Real-World Studies in Patients with Schizophrenia and Related Disorders

by Michele Fabrazzo, Salvatore Cipolla, Alessio Camerlengo, Francesco Perris and Francesco Catapano

J. Clin. Med. 2022, 11(15), 4530; https://doi.org/10.3390/jcm11154530 - 03 Aug 2022

Cited by 14 | Viewed by 3565

Abstract

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics’ (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles [...] Read more.

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics’ (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles of second-generation antipsychotics (SGAs) from real-world studies to aid clinicians and researchers in selecting the proper treatment for patients with schizophrenia and related disorders. The present review evidenced that SGAs demonstrated superior effectiveness over first-generation antipsychotics (FGAs) in relapse-free survival and psychiatric hospitalization rate and for treating negative symptoms. Persistence and adherence to therapy were higher in SGAs than FGAs. Most studies concluded that switching to long-acting injectables (LAIs) was significantly associated with a lower treatment failure rate than monotherapy with oral SGAs. Considerable improvements in general functionality, subjective well-being, and total score on global satisfaction tests, besides improved personal and social performance, were reported in some studies on patients treated with LAI SGAs. Clozapine was also associated with the lowest rates of treatment failure and greater effectiveness over the other SGAs, although with more severe side effects. Effectiveness on primary negative symptoms and cognitive deficits was rarely measured in these studies. Based on the data analyzed in the present review, new treatments are needed with better tolerability and improved effectiveness for negative, affective, and cognitive symptoms. Full article

(This article belongs to the Special Issue Schizophrenia Research and Care—Advancements and Challenges)

14 pages, 2337 KiB

Open AccessEditor’s ChoiceReview

PCOS Physiopathology and Vitamin D Deficiency: Biological Insights and Perspectives for Treatment

by Giuseppe Morgante, Ilenia Darino, Amelia Spanò, Stefano Luisi, Alice Luddi, Paola Piomboni, Laura Governini and Vincenzo De Leo

J. Clin. Med. 2022, 11(15), 4509; https://doi.org/10.3390/jcm11154509 - 02 Aug 2022

Cited by 23 | Viewed by 8785

Abstract

Recent literature has stressed the importance of vitamin D (VD) in polycystic ovary syndrome (PCOS). Women with PCOS are deficient in VD, particularly those with a higher weight. Hypovitaminosis is a risk factor for glucose intolerance, and reduced levels of VD is associated [...] Read more.

Recent literature has stressed the importance of vitamin D (VD) in polycystic ovary syndrome (PCOS). Women with PCOS are deficient in VD, particularly those with a higher weight. Hypovitaminosis is a risk factor for glucose intolerance, and reduced levels of VD is associated with insulin resistance and increased diabetes risk. Since women with PCOS and hirsutism seem to have lower levels of VD than women with PCOS without hirsutism, a correlation between VD deficiency and hyperandrogenism may be suggested. Interestingly, VD is crucial for many human physiological functions, including to counteract inflammation and oxidative stress. Some studies evaluated effects of VD supplementation on glucose homeostasis variables, hormonal status, lipid concentrations, and biomarkers of inflammation and oxidative stress among VD-deficient women. Moreover, VD has been shown to play a role in egg quality and fertility. This review aims to show the relationship between VD and the endocrine and metabolic profile of PCOS patients, as well as its implications for their fertility. The supplement of VD to the common therapy can lead to an improvement of the insulin resistance and lipid metabolism, a reduction of circulating androgens, as well as a better response to the induction of ovulation in PCOS women. Full article

(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)

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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 1589

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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18 pages, 3854 KiB

Open AccessEditor’s ChoiceArticle

Ulva pertusa, a Marine Green Alga, Attenuates DNBS-Induced Colitis Damage via NF-κB/Nrf2/SIRT1 Signaling Pathways

by Alessio Ardizzone, Alessia Filippone, Deborah Mannino, Sarah Adriana Scuderi, Giovanna Casili, Marika Lanza, Laura Cucinotta, Michela Campolo and Emanuela Esposito

J. Clin. Med. 2022, 11(15), 4301; https://doi.org/10.3390/jcm11154301 - 25 Jul 2022

Cited by 16 | Viewed by 2136

Abstract

Inflammatory bowel diseases (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) represent gastrointestinal (GI) disorders associated with varied responses to microbial and environmental agents. Natural compounds have been suggested as a valid approach to the management of various GI diseases, particularly the [...] Read more.

Inflammatory bowel diseases (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) represent gastrointestinal (GI) disorders associated with varied responses to microbial and environmental agents. Natural compounds have been suggested as a valid approach to the management of various GI diseases, particularly the green alga Ulva pertusa, belonging to the Ulvaceae family, which showed powerful biological properties. Here, we aimed to evaluate the effect and the mechanism of Ulva pertusa treatments in a murine model of DNBS-induced colitis. Colitis was induced by DNBS intrarectal installation (4 mg in 100 μL of 50% ethanol), while Ulva pertusa treatments (doses of 10, 50 and 100 mg/kg) were administered orally daily. Ulva pertusa, at the higher doses of 50 and 100 mg/kg, significantly reduced tissue damage DNBS-induced and the consequent inflammatory cascade via NF-κB inhibition. Furthermore, we demonstrated, for the first time, Ulva pertusa action on the SIRT1/Nrf2 axis, enhancing antioxidant response and the modulation of the apoptosis pathway colitis-induced, regulating the expression of p53, Bax, Bcl-2, and Caspases. Taken together, Ulva pertusa could be considered a valid approach for counteracting and blocking the progression of IBDs through modulation of the NF-κB/SIRT1/Nrf2 axis. Full article

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

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15 pages, 1259 KiB

Open AccessEditor’s ChoiceReview

Atopic Dermatitis and Food Allergy: A Complex Interplay What We Know and What We Would Like to Learn

by Niki Papapostolou, Paraskevi Xepapadaki, Stamatis Gregoriou and Michael Makris

J. Clin. Med. 2022, 11(14), 4232; https://doi.org/10.3390/jcm11144232 - 21 Jul 2022

Cited by 15 | Viewed by 5261

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus, eczematous lesions, and relapsing course. It presents with great clinical heterogeneity, while underlying pathogenetic mechanisms involve a complex interplay between a dysfunctional skin barrier, immune dysregulation, microbiome dysbiosis, genetic and [...] Read more.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus, eczematous lesions, and relapsing course. It presents with great clinical heterogeneity, while underlying pathogenetic mechanisms involve a complex interplay between a dysfunctional skin barrier, immune dysregulation, microbiome dysbiosis, genetic and environmental factors. All these interactions are shaping the landscape of AD endotypes and phenotypes. In the “era of allergy epidemic”, the role of food allergy (FA) in the prevention and management of AD is a recently explored “era”. Increasing evidence supports that AD predisposes to FA and not vice versa, while food allergens are presumed as one of the triggers of AD exacerbations. AD management should focus on skin care combined with topical and/or systemic treatments; however, in the presence of suspected food allergy, a thorough allergy evaluation should be performed. Food-elimination diets in food-allergic cases may have a beneficial effect on AD morbidity; however, prolonged, unnecessary diets are highly discouraged since they can lead to loss of tolerance and potentially increase the risk of IgE-mediated food allergy. Preventive AD strategies with the use of topical emollients and anti-inflammatory agents as well as early introduction of food allergens in high-risk infants seem promising in managing and preventing food allergy in AD patients. The current review aims to overview data on the complex AD/FA relationship and provide the most recent developments on whether food allergy interventions change the AD course and vice versa. Full article

(This article belongs to the Section Dermatology)

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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 2890

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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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 3288

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 3047

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 18 | Viewed by 5334

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 4247

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 17 | Viewed by 3341

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 4144

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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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 46 | Viewed by 3868

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 4288

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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12 pages, 408 KiB

Open AccessEditor’s ChoiceArticle

Achilles Tendon Rupture and Dysmetabolic Diseases: A Multicentric, Epidemiologic Study

by Francesco Oliva, Emanuela Marsilio, Giovanni Asparago, Alessio Giai Via, Carlo Biz, Johnny Padulo, Marco Spoliti, Calogero Foti, Gabriella Oliva, Stefania Mannarini, Alessandro Alberto Rossi, Pietro Ruggieri and Nicola Maffulli

J. Clin. Med. 2022, 11(13), 3698; https://doi.org/10.3390/jcm11133698 - 27 Jun 2022

Cited by 15 | Viewed by 2036

Abstract

Introduction: Achilles tendon ruptures are common. Metabolic disorders, such as diabetes mellitus, hypercholesterolemia, thyroid disorders, and obesity, impair tendons health, leading to Achilles tendinopathy and likely predisposing patients to Achilles tendon ruptures. Materials and methods: Patients who visited the Orthopedic Outpatient Clinics and [...] Read more.

Introduction: Achilles tendon ruptures are common. Metabolic disorders, such as diabetes mellitus, hypercholesterolemia, thyroid disorders, and obesity, impair tendons health, leading to Achilles tendinopathy and likely predisposing patients to Achilles tendon ruptures. Materials and methods: Patients who visited the Orthopedic Outpatient Clinics and the Accident and Emergency Departments of five different hospitals in Italy were recruited. Through telephone interviews, we administered a questionnaire to all the patients who had undergone surgical ATR repair, evaluating their past medical history, sport- and work-related activities, drug use, and post-operative rehabilitation outcomes. Results: “Return to work activities/sport” was negatively predicted by the presence of a metabolic disorder (β = −0.451; OR = 0.637) and ‘open’ surgery technique (β = −0.389; OR = 0.678). “Medical complications” were significantly predicted by metabolic disorders (β = 0.600 (0.198); OR = 1.822) and was negatively related to ‘mini-invasive’ surgery (i.e., not ‘open’ nor ‘percutaneous’) (β = −0.621; OR = 0.537). “Immediate weightbearing” and “immediate walking without assistance” were negatively predicted by ‘open’ technique (β = −0.691; OR = 0.501 and β = −0.359 (0.174; OR = 0.698)). Conclusions: Metabolic conditions can strongly affect post-operative outcomes following surgical repair of acute Achilles tendon tears. Full article

(This article belongs to the Special Issue Achilles Tendon Ailments: From the Bedside to the Bench)

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 17 | Viewed by 2248

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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16 pages, 3971 KiB

Open AccessEditor’s ChoiceArticle

Novel Noninvasive Spinal Neuromodulation Strategy Facilitates Recovery of Stepping after Motor Complete Paraplegia

by Ricardo Siu, Edward H. Brown, Samineh Mesbah, Federica Gonnelli, Tanvi Pisolkar, V. Reggie Edgerton, Alexander V. Ovechkin and Yury P. Gerasimenko

J. Clin. Med. 2022, 11(13), 3670; https://doi.org/10.3390/jcm11133670 - 25 Jun 2022

Cited by 14 | Viewed by 2061

Abstract

It has been suggested that neuroplasticity-promoting neuromodulation can restore sensory-motor pathways after spinal cord injury (SCI), reactivating the dormant locomotor neuronal circuitry. We introduce a neuro-rehabilitative approach that leverages locomotor training with multi-segmental spinal cord transcutaneous electrical stimulation (scTS). We hypothesized that scTS [...] Read more.

It has been suggested that neuroplasticity-promoting neuromodulation can restore sensory-motor pathways after spinal cord injury (SCI), reactivating the dormant locomotor neuronal circuitry. We introduce a neuro-rehabilitative approach that leverages locomotor training with multi-segmental spinal cord transcutaneous electrical stimulation (scTS). We hypothesized that scTS neuromodulates spinal networks, complementing the neuroplastic effects of locomotor training, result in a functional progression toward recovery of locomotion. We conducted a case-study to test this approach on a 27-year-old male classified as AIS A with chronic SCI. The training regimen included task-driven non-weight-bearing training (1 month) followed by weight-bearing training (2 months). Training was paired with multi-level continuous and phase-dependent scTS targeting function-specific motor pools. Results suggest a convergence of cross-lesional networks, improving kinematics during voluntary non-weight-bearing locomotor-like stepping. After weight-bearing training, coordination during stepping improved, suggesting an important role of afferent feedback in further improvement of voluntary control and reorganization of the sensory-motor brain-spinal connectome. Full article

(This article belongs to the Section Clinical Rehabilitation)

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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 21 | Viewed by 3908

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 1771

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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13 pages, 1150 KiB

Open AccessEditor’s ChoiceArticle

Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan

by Ichiro Morioka, Yasumasa Kakei, Takashi Omori, Kandai Nozu, Kazumichi Fujioka, Naoto Takahashi, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Yoshinori Ito and Akira Oka

J. Clin. Med. 2022, 11(13), 3582; https://doi.org/10.3390/jcm11133582 - 21 Jun 2022

Cited by 13 | Viewed by 2886

Abstract

Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in [...] Read more.

Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the whole blood CMV load before and after treatment. The secondary endpoint was the change in the auditory brainstem response (ABR) before and after treatment. Changes in ABR were assessed between the younger and older age groups (≤ and >30 days at treatment initiation). Of the 25 patients, one was excluded owing to epilepsy before VGCV administration. The median change in the CMV DNA level in whole blood was −246.0 IU/mL. The best ear and total ear assessments based on ABR were categorized as (improved + unchanged) after treatment for 100% and 93.8%, respectively. No differences in hearing efficacy were observed between the younger and older age groups. Oral VGCV is a potential therapeutic option for treating infants aged ≤2 months with congenital CMV disease. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics, and Therapeutics in Neonatal and Pediatric Diseases: Prospective and Retrospective Clinical Studies)

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