Activity

years 0.74 vs 0.64) arms, and there was no significant difference between the TAU and PGST arms (1 year 0.73 vs 0.72; 2 years 0.64 vs 0.62).

In this randomized clinical trial, IGST was more effective and had greater treatment retention compared with TAU and PGST. These findings suggest that IGST is the preferred ST format, with high retention and continuation of improvement in BPD severity after the completion of treatment.

trialregister.nl Identifier NTR2392.

trialregister.nl Identifier NTR2392.

Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is an autosomal recessive disorder caused by pathogenic variants in PLEC1, which encodes plectin. It is characterized by mild mucocutaneous fragility and blistering and muscle weakness. Translational readthrough-inducing drugs, such as repurposed aminoglycoside antibiotics, may represent a valuable therapeutic alternative for untreatable rare diseases caused by nonsense variants.

To evaluate whether systemic gentamicin, at a dose of 7.5 mg/kg/d for 14 consecutive days, is clinically beneficial in a patient with EBS-MD.

A single patient in Madrid, Spain, received 2 treatment courses with gentamicin on July 2019 and February 2020 with a follow-up period of 120 and 150 days, respectively.

In this case report of a woman in her 30s with EBS-MD, before gentamicin treatment, the patient had mucocutaneous involvement, skeletal and respiratory muscle weakness, and myalgia that negatively affected her quality of life. Outcomes were evaluated with exgle case report suggest that gentamicin treatment may help suppress PLEC1 premature termination codons and induce plectin expression in EBS-MD primary keratinocytes and skin. Our study suggests that gentamicin may play an important role in treating EBS-MD owing to nonsense variants.

Junctional epidermolysis bullosa (JEB) is an incurable blistering skin disorder with high infant mortality often caused by nonsense variants in the genes that encode laminin 332.

To evaluate the safety and outcomes following intravenous gentamicin readthrough therapy and subsequent laminin 332 expression in patients with JEB.

This open-label, pilot nonrandomized clinical trial assessed 1 course of low- or high-dose intravenous gentamicin, including follow-up at 30 and 90 days after treatment. Five pediatric patients with JEB (2 with intermediate JEB and 3 with severe JEB) and confirmed nonsense variants in LAMA3 or LAMB3 in 1 or 2 alleles and decreased expression of laminin 332 at the dermal-epidermal junction of their skin participated in the study, which was performed at a single institution in collaboration with physicians and home infusion services near the patients from April 1, 2019, to February 28, 2021, with follow-up until May 31, 2021.

Three patients received gentamicin at 7.5 mg/kg daily foally important differences 1 month after treatment. All 5 patients completed the study, and no ototoxic effects, nephrotoxic effects, or anti-laminin 332 antibodies were detected.

In this nonrandomized clinical trial, intravenous gentamicin therapy was associated with induced readthrough of nonsense variants in patients with JEB, restored functional laminin 332 in their skin, and wound closure during the 3-month study period. Although long-term safety and efficacy requires further evaluation, a single cycle of intravenous gentamicin may be a safe and readily available therapy in the short term for this population of patients with JEB.

ClinicalTrials.gov Identifiers NCT03526159 and NCT04140786.

ClinicalTrials.gov Identifiers NCT03526159 and NCT04140786.

To design an updated vancomycin dosing protocol for initiating therapy in patients undergoing chronic intermittent high-flux hemodialysis (iHFHD) that is congruent with the revised 2020 consensus guidelines for therapeutic drug monitoring (TDM).

Monte Carlo simulation methods were used to study vancomycin dosing for patients on iHFHD. Vancomycin regimens were constructed as intravenous infusions (for intradialytic administration) of a loading dose and maintenance doses 3 times weekly during subsequent dialysis sessions. Vancomycin plasma concentrations were simulated, and the probability of target attainment (PTA) for a 24-hour area under the time-concentration curve (AUC24) of 400 to 700 mg · h/L was determined. Standardized weight-based (ie, dose-banding) regimens were investigated, and an optimized protocol was selected based on TDM target attainment and practical considerations for use in the dialysis setting.

The proposed vancomycin dosing protocol (for intradialytic administration) specifies 3 regimens (1) a 1,500-mg loading dose and 750-mg maintenance doses for patients weighing 50 kg to 69 kg; (2) a 2,000-mg loading dose and 1,000-mg maintenance doses for patients weighing 70 kg to 89 kg; and (3) a 2,500-mg loading dose and 1,250-mg maintenance doses for patients weighing 90 kg to 110 kg. In a simulated hemodialysis population (n = 5,000), the proposed protocol delivered median (interquartile range [IQR]) loading and maintenance doses of 25.0 (23.4-26.6) mg/kg and 12.5 (11.8-13.3) mg/kg, respectively. The PTA for an AUC24 of 400 to 700 mg · h/L was 74.7% on day 1 and 70.8% on day 8, with less than 10% of values exceeding the target range.

Our proposed dosing protocol for patients undergoing iHFHD offers an updated and practical approach for initiating vancomycin therapy that can be optimized with early TDM.

Our proposed dosing protocol for patients undergoing iHFHD offers an updated and practical approach for initiating vancomycin therapy that can be optimized with early TDM.

Clopidogrel monotherapy after short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has not yet been fully investigated in patients with acute coronary syndrome (ACS).

To test the hypothesis of noninferiority of 1 to 2 months of DAPT compared with 12 months of DAPT for a composite end point of cardiovascular and bleeding events in patients with ACS.

This multicenter, open-label, randomized clinical trial enrolled 4169 patients with ACS who underwent successful PCI using cobalt-chromium everolimus-eluting stents at 96 centers in Japan from December 2015 through June 2020. These data were analyzed from June to July 2021.

Patients were randomized either to 1 to 2 months of DAPT followed by clopidogrel monotherapy (n = 2078) or to 12 months of DAPT with aspirin and clopidogrel (n = 2091).

The primary end point was a composite of cardiovascular (cardiovascular death, myocardial infarction [MI], any stroke, or definite stent thrombosis) or bleeding (Thrombolysis in MI majorPT group (absolute difference, 0.90% [95% CI, -0.02% to 1.82%]; HR, 1.50 [95% CI, 0.99-2.26]). The major secondary bleeding end point occurred in 11 patients (0.5%) in the 1- to 2-month DAPT group and 24 patients (1.2%) in the 12-month DAPT group (absolute difference, -0.63% [95% CI, -1.20% to -0.06%]; HR, 0.46 [95% CI, 0.23-0.94]).

In patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events. The directionally different efficacy and safety outcomes indicate the need for further clinical trials.

ClinicalTrials.gov Identifiers NCT02619760 and NCT03462498.

ClinicalTrials.gov Identifiers NCT02619760 and NCT03462498.

Decision-making on management of proximal femoral fractures in frail patients with limited life expectancy is challenging, but surgical overtreatment needs to be prevented. Current literature provides limited insight into the true outcomes of nonoperative management and operative management in this patient population.

To investigate the outcomes of nonoperative management vs operative management of proximal femoral fractures in institutionalized frail older patients with limited life expectancy.

This multicenter cohort study was conducted between September 1, 2018, and April 25, 2020, with a 6-month follow-up period at 25 hospitals across the Netherlands. Eligible patients were aged 70 years or older, frail, and institutionalized and sustained a femoral neck or pertrochanteric fracture. The term frail implied at least 1 of the following characteristics was present malnutrition (body mass index [calculated as weight in kilograms divided by height in meters squared] <18.5) or cachexia, severe comorbidiould not be a foregone conclusion for this patient population.

Results of this study indicated that nonoperative management of proximal femoral fractures (selected through an SDM process) was a viable option for frail institutionalized patients with limited life expectancy, suggesting that surgery should not be a foregone conclusion for this patient population.

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute myocardial infarction enriched among individuals with early-onset myocardial infarction but is of unclear etiology.

To assess which genes contribute to the development of SCAD.

To prioritize genes influencing risk for SCAD, whole-exome sequencing was performed among individuals with SCAD in the discovery and replication cohorts from a tertiary care hospital outpatient specialty clinic, and gene set enrichment analyses were also performed for disruptive coding variants. All patients were sequentially enrolled beginning July 2013. Aggregate prevalence of rare disruptive variants for prioritized gene sets was compared between individuals with SCAD with population-based controls comprising 46 468 UK Biobank participants with whole-exome sequencing. Complementary mice models were used for in vivo validation. Analysis took place between June 2020 and January 2021.

The frequency and identity of rare size of arterial diameters especially in female mice, with resulting changes in collagen fibril organization and diameter.

Unbiased gene discovery in patients with SCAD with independent human and murine validation highlights the role of the extracellular matrix dysfunction in SCAD.

Unbiased gene discovery in patients with SCAD with independent human and murine validation highlights the role of the extracellular matrix dysfunction in SCAD.We read with great interest, in the December 2021 issue of the journal, three papers by Clorinda Panebianco, Ari Cantuária Vilela et al., and Tamara Borger et al. concerning musculoskeletal complaints in musicians. These authors have successfully addressed the topic of the highly prevalent complaints and disorders among musicians that impact their wellbeing and performance abilities. Unfortunately, even if musculoskeletal disorders are among the most frequent and painful, we must also remember other occupational disorders that affect musicians, often overlooked and underestimated, can have the same clinical and performance impact. Among these “forgotten” diseases, it seems important to remember the microcirculation disorders.Groin pain is a cause of mobility impairment, and its diverse presentation can make the diagnosis difficult. Quadratus femoris muscle tendinopathy is a poorly described etiology, but its diagnosis is important for the success of the therapeutic program. The authors present the case of an 18-year-old woman who complained of chronic pain in the left inguinal region due to regular ballet practice. Physical examination revealed restriction in the left hip medial rotation. Ultrasound and radiographic studies were normal. Magnetic resonance imaging showed asymmetry in the signal intensity of the quadratus femoris muscle. The patient improved significantly after a rehabilitation program that included quadratus femoris muscle-specific exercises. Diagnostic accuracy and an understanding of segmental biomechanics ensure greater effectiveness in the therapeutic approach.