Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients; (2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.

Foot ulcers are a frequent and costly problem in people with diabetes mellitus and can lead to amputations. Prevention of these ulcers is therefore of paramount importance. Claw/hammer toe deformities are commonly seen in people with diabetes. These deformities increase the risk of ulcer development specifically at the (tip of) the toe. Percutaneous needle tenotomy of the tendon of the m. flexor digitorum longus (tendon tenotomy) can be used to reduce the severity of claw/hammer toe deformity with the goal to prevent ulcer recurrence. The main objective of this randomized controlled trial is to assess the efficacy of flexor tenotomy to prevent recurrence of toe ulcers in people with diabetes and a history of toe (pre-)ulcers. Additionally, we aim to assess interphalangeal joints (IPJ) and metatarsophalangeal joint (MTPJ) angles in a weight-bearing and non-weight-bearing position, barefoot plantar pressure during walking, cost-effectiveness and quality of life before and after the intervention and compare intervention and control study groups. Sixty-six subjects with diabetes and claw/hammer toe deformity and a recent history of (pre-)ulceration on the tip of the toe will be included and randomized between flexor tenotomy of claw/hammer toes (intervention) versus standard of care including orthosis and shoe offloading (controls) in a mono-center randomized controlled trial.
UNASSIGNED: NCT05228340.

UNASSIGNED: Whether complete revascularization (CR) or incomplete revascularization (IR) may affect long-term outcomes after PCI) and coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease is unclear.
UNASSIGNED: The authors sought to assess the impact of CR or IR on 10-year outcomes after PCI or CABG for LMCA disease.
UNASSIGNED: In the PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) 10-year extended study, the authors evaluated the effect of PCI and CABG on long-term outcomes according to completeness of revascularization. The primary outcome was the incidence of major adverse cardiac or cerebrovascular events (MACCE) (composite of mortality from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization).
UNASSIGNED: Among 600 randomized patients (PCI, n = 300 and CABG, n = 300), 416 patients (69.3%) had CR and 184 (30.7%) had IR; 68.3% of PCI patients and 70.3% of CABG patients underwent CR, respectively. The 10-year MACCE rates were not significantly different between PCI and CABG among patients with CR (27.8% vs 25.1%, respectively; adjusted HR: 1.19; 95% CI: 0.81-1.73) and among those with IR (31.6% vs 21.3%, respectively; adjusted HR: 1.64; 95% CI: 0.92-2.92) (P for interaction = 0.35). There was also no significant interaction between the status of CR and the relative effect of PCI and CABG on all-cause mortality, serious composite of death, myocardial infarction, or stroke, and repeat revascularization.
UNASSIGNED: In this 10-year follow-up of PRECOMBAT, the authors found no significant difference between PCI and CABG in the rates of MACCE and all-cause mortality according to CR or IR status. (Ten-Year Outcomes of PRE-COMBAT Trial [PRECOMBAT], NCT03871127; PREmier of Randomized COMparison of Bypass Surgery Versus AngioplasTy Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT], NCT00422968).

Diabetic nephropathy causes cardiovascular complications among individuals with diabetes which results in decreased kidney function and overall physical decline. The objective of this systematic review was to determine effects of exercise on various renal function parameters amond individuals with type 2 diabetes and nephropathy. It was registered with PROSPERO (CRD42020198754). Total 6 databases (PubMed/Medline, Scopus, Web of Science, CINAHL, ProQuest, and Cochrane) were searched. Among 1734 records, only four randomized controlled trials were included. The review included a total of 203 participants (103 in the intervention group and 100 in the control/standard group) with type 2 diabetic nephropathy or stage 2,3, or 4 of chronic kidney disease. The meta-analysis showed no effects of exercise on serum creatinine, serum cystatin c and varied eGFR equations. However, exercise decreased urinary albumin to creatinine ratio, urinary protein to creatinine ratio, serum urea nitrogen, creatinine clearance, and urinary protein excretion while increasing urea clearance. Limited evidence on the reno-protective role of exercise demands future research in this direction.
UNASSIGNED: يسبب اعتلال الكلية السكري مضاعفات في القلب والأوعية الدموية لدى الأفراد المصابين بداء السكري، مما يؤدي إلى انخفاض وظائف الكلى والتدهور الجسدي العام. كان الهدف من هذه المراجعة المنهجية هو تحديد تأثير التمرين على متغيرات وظائف الكلى المختلفة بين الأفراد المصابين بداء السكري من النوع الثاني واعتلال الكلية.
UNASSIGNED: تم تسجيل المراجعة المنهجية في قاعدة بيانات \"بروسبيرو\"، وتم البحث في قواعد البيانات التالية: ميدلاين، وسكوبس، وشبكة العلوم، وسيناهل، وبروكويست، وكوكران. من بين 1734 سجل وجدت فقط أربع تجارب معشاة ذات شواهد، وتم تضمينها في التوليف النوعي والكمي بعد فحص أهلية الدراسة في مرحلة العنوان والملخص والنص الكامل.
UNASSIGNED: تضمنت المراجعة ما مجموعه 203 شخصا (103 في مجموعة التدخل و 100 في المجموعة الضابطة / القياسية) مصابين باعتلال الكلية السكري من النوع 2 أو مرض الكلى المزمن في المراحل 2 و 3 و 4. استخدمت ثلاث من الدراسات الأربع مبدأ \"فيت\" (التكرار، والشدة، والوقت، والنوع) في تدريب التمرينات والوصفات الطبية. تلقت مجموعة التدخل تمارين هوائية ومقاومة، منزلية، خاضعة للإشراف، ومنظمة. أظهر التحليل التلوي عدم وجود تأثير للتمرين على كرياتينين المصل، وسيستاتين المصل، ومعادلة الكرياتينين، ومعادلة سيستاتين، ومعادلة الكرياتينين-سيستاتين. ومع ذلك ، فقد أدت التمارين الرياضية إلى خفض نسبة الألبومين البولي إلى نسبة الكرياتينين، ونسبة البروتين البولي إلى نسبة الكرياتينين، ونتروجين اليوريا في الدم، وإزالة الكرياتينين، وإفراز البروتين في البول مع زيادة تصفية اليوريا.
UNASSIGNED: هناك دليل محدودة على دور التمارين في وقاية الكلى وتغيير معايير وظائف الكلى بين مرضى السكري من النوع الثاني المصابين باعتلال الكلية.

UNASSIGNED: Few large-scale, real-world studies have compared the efficacy and safety of non-antivitamin K anticoagulants (NOACs) with that of warfarin in catheter ablation (CA) for atrial fibrillation (AF).
UNASSIGNED: This retrospective, cross-sectional study used a nationwide administrative claims database, to compare complication-incidence rates following CA for AF between NOAC-treated patients and warfarin-treated matched cohorts in the real-world. Among the 32,797,540 records between June 2011 and August 2020 from 426 hospitals, 41,347 patients (38,065 on NOACs and 3,282 on Warfarin) were considered eligible. After performing propensity matching, 6,564 patients (3,282 per group) were analyzed.
UNASSIGNED: The overall complication incidence was significantly lower in the NOACs group than in the warfarin group (2.3 % vs. 4.0 %; P < 0.001, odds ratio [OR]: 0.55, 95 % confidence interval [CI]: 0.41-0.74). Although no significant differences in the incidence of cardiac tamponade (1.0 % vs. 1.1 %; P = 0.90, OR: 0.97, 95 % CI: 0.60-1.56) and major bleeding (0.6 % vs. 0.7 %; P = 0.54, OR: 0.83, 95 % CI: 0.44-1.52) were noted, blood transfusion requirements (0.6 % vs. 1.2 %; P = 0.02, OR: 0.52, 95 % CI: 0.30-0.88) and vascular complications (0.2 % vs. 0.5 %; P = 0.02, OR: 0.33, 95 % CI: 0.12-0.79) were significantly lower in the NOACs group than in the warfarin group. Furthermore, the thromboembolic event incidence was significantly lower in the NOACs group than in the warfarin group (0.5 % vs. 1.2 %; P < 0.001, OR: 0.36, 95 % CI: 0.19-0.64).
UNASSIGNED: NOACs should be considered as a first-line therapy for periprocedural anticoagulation in patients undergoing CA for AF.

UNASSIGNED: Primary biliary cholangitis (PBC) is an autoimmune liver disease involving the small intrahepatic bile ducts; when untreated or undertreated, it may evolve to liver fibrosis and cirrhosis. Ursodeoxycholic Acid (UDCA) is the standard of care treatment, Obeticholic Acid (OCA) has been approved as second-line therapy for those non responder or intolerant to UDCA. However, due to moderate rate of UDCA-non responders and to warnings recently issued against OCA use in patients with cirrhosis, further therapies are needed.Areas covered. Deep investigations into the pathogenesis of PBC is leading to proposal of new therapeutic agents, among which peroxisome proliferator-activated receptor (PPAR) ligands seem to be highly promising given the preliminary, positive results in Phase 2 and 3 trials. Bezafibrate, the most evaluated, is currently used in clinical practice in combination with UDCA in referral centers. We herein describe completed and ongoing trials involving PPAR agonists use in PBC, analyzing pits and falls.
UNASSIGNED: Testing new therapeutic opportunities in PBC is challenging due to its low prevalence and slow progression. However, new drugs including PPAR agonists, are currently under investigation and should be considered for at-risk PBC patients.

The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis.
UNASSIGNED: A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.

UNASSIGNED: Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson\'s disease patients across 54 weeks. Evidence on CLES\'s long-term effectiveness on patterns of motor-symptom control throughout the day remains limited.
UNASSIGNED: We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients\' motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states\' durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD).
UNASSIGNED: Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58-65 min; wk54: 60-78 min; all P < 0.0001) and reductions in OFF (wk4: 50-61 min; wk54: 56-68 min; all P < 0.0001). At weeks 4 and 54, patients\' motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001).
UNASSIGNED: CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day.

UNASSIGNED: There are limited data regarding comparative prognosis and medical cost between fractional flow reserve (FFR)-based and angiography-based percutaneous coronary intervention (PCI) among revascularized patients.
UNASSIGNED: This study evaluates prognosis and medical cost of FFR use in revascularized patients by PCI.
UNASSIGNED: Using the National Health Insurance Service database, stable or unstable angina patients who underwent PCI from 2011 to 2017 were evaluated. Eligible patients were divided into 2 groups according to use of FFR in PCI. Primary outcome was a composite of all-cause death or spontaneous myocardial infarction (MI). Secondary outcomes included individual components of the primary outcome, unplanned revascularization, and medical costs.
UNASSIGNED: Among 134,613 eligible patients, PCI was performed based on angiography (n = 129,497) and FFR (n = 5,116). During the study period, both the annual number and proportion of use of FFR in PCI increased (all P for trend <0.001). The FFR group showed significantly lower risk of the primary outcome (7.0% vs 9.5%; P < 0.001), all-cause death (5.8% vs 7.7%; P = 0.001), and spontaneous MI (1.6% vs 2.2%; P = 0.022) than the angiography group. Although the FFR group showed higher medical cost during index admission than angiography group (median: $6,265.10 vs $5,385.60; P < 0.001), cumulative medical cost after index admission was significantly lower ($2,696.50 vs. $3,142.10; P < 0.001).
UNASSIGNED: Use of FFR in PCI in stable or unstable angina patients showed significantly lower risk of all-cause death and spontaneous MI compared to angiography-based PCI. Although the FFR group had higher initial medical cost than the angiography group, cumulative medical cost after index admission was significantly lower.

UNASSIGNED: Assess the feasibility of a virtually-delivered, physiotherapist-guided knee health program (SOAR) that targets self-management of knee health and osteoarthritis risk after an activity-related knee injury.
UNASSIGNED: In this quasi-experimental feasibility study, individuals with varied lived experience of knee trauma completed a 4-week SOAR program. This included: 1) Knee Camp (group education, 1:1 exercise and activity goal-setting); 2) weekly home-based exercise and activity program with tracking, and; 3) weekly 1:1 physiotherapy-guided action-planning. SOAR program feasibility was assessed with implementation (attrition, adherence, intervention fidelity), practicality (adverse events, goal completion), acceptability and efficacy (change in Knee injury and Osteoarthritis Outcome Score subscales, Patient Specific Functional Scale (PSFS), Godin Leisure-Time Exercise Questionnaire (GLTEQ), Partner in Health Scale (PHS)) outcomes. Descriptive statistics, disaggregated by gender, were calculated.
UNASSIGNED: Thirty participants (60% women, median (min-max) age 30 years (19-50), time from injury 5.6 years (1.2-25.2)) were enrolled. No participant attrition or adverse events were reported, and 90% of mandatory program components were completed. Participants rated their adherence at 80%, and 96% of exercise-therapy and 95% of activity goals were fully or partially achieved. Both women and men reported significant group mean (95%CI) improvements in GLTEQ scores (women: 22 METS (6,37), men: 31 METS (8,54)), while women alone reported improvements in PHS (-7 (-11,-3) and PSFS (1.7 (0.6,2.8) scores.
UNASSIGNED: The SOAR program is feasible for persons at various timepoints post-knee trauma, and gender may be an important consideration for SOAR implementation and assessment. A randomized controlled trial to assess intervention efficacy is warranted.