bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neuromuscular and multisystem features of RYR1-related malignant hyperthermia and rhabdomyolysis
Authors: van den Bersselaar Luuk R. , Kruijt Nick , Scheffer Gert-Jan , van Eijk Lucas , Malagon Ignacio , Buckens Stan , Custers José AE , Helder Leonie , Greco Anna , Joosten Leo AB , van Engelen Baziel GM , van Alfen Nens , Riazi Sheila , Treves Susan , Jungbluth Heinz , Snoeck Marc MJ , Voermans Nicol C. 
Published: August 2021

Abstract

Introduction:
Malignant hyperthermia (MH) and exertional rhabdomyolysis (ERM) have long been considered episodic phenotypes occurring in response to external triggers in otherwise healthy individuals with variants in RYR1. However, recent studies have demonstrated a clinical and histopathological continuum between patients with RYR1-related congenital myopathies and those with ERM or MH susceptibility. Furthermore, animal studies have shown non-neuromuscular features such as a mild bleeding disorder and an immunological gain-of-function associated with MH/ERM related RYR1 variants raising important questions for further research. Awareness of the neuromuscular disease spectrum and potential multisystem involvement in RYR1-related MH and ERM is essential to optimize the diagnostic work-up, improve counselling and and future treatment strategies for patients affected by these conditions. This study will examine in detail the nature and severity of continuous disease manifestations and their effect on daily life in patients with RYR1-related MH and ERM.

Methods:
The study protocol consists of four parts; an online questionnaire study, a clinical observational study, muscle imaging, and specific immunological studies. Patients with RYR1-related MH susceptibility and ERM will be included. The imaging, immunological and clinical studies will have a cross-sectional design, while the questionnaire study will be performed three times during a year to assess disease impact, daily living activities, fatigue and pain. The imaging study consists of muscle ultrasound and whole-body magnetic resonance imaging studies. For the immunological studies, peripheral mononuclear blood cells will be isolated for in vitro stimulation with toll-like receptor ligands, to examine the role of the immune system in the pathophysiology of RYR1-related MH and ERM.

Discussion:
This study will increase knowledge of the full spectrum of neuromuscular and multisystem features of RYR1-related MH and ERM and will establish a well-characterized baseline cohort for future studies on RYR1-related disorders. The results of this study are expected to improve recognition of RYR1-related symptoms, counselling and a more personalized approach to patients affected by these conditions. Furthermore, results will create new insights in the role of the immune system in the pathophysiology of MH and ERM.

Trial registration:
This study was pre-registered at ClinicalTrials.gov (ID: NCT04610619).
Efficacy and safety of tyrosine kinase inhibitors alone or in combination with radiation therapy for metastatic renal cell carcinoma
Authors: Wang Shihua , Jin Weihua , Jiang Changqing , Zhang Yiwen , Deng Kaiwen 
Published: August 2021

Abstract

Background:
Given the lack of evidence for survival benefit in patients with metastatic renal cell carcinoma from the addition of radiation therapy to tyrosine kinase inhibitor therapy, this Bayesian network meta-analysis aimed to evaluate survival outcomes in patients receiving radiation therapy plus tyrosine kinase inhibitor therapy.

Methods:
The preferred reporting items for systematic reviews and meta-analyses reporting guidelines were followed to conduct this study. The electronic databases of PubMed, Cochrane Library, EMBASE, and Web of Science were searched from the inception to August 2021. All phase III clinical trials that reported the outcomes of tyrosine kinase inhibitor with radiation therapy compared with those of tyrosine kinase inhibitor or radiation therapy alone for patients with metastatic renal cell carcinoma were considered eligible for inclusion in this meta-analysis. Overall survival as the primary outcome of interest, and adverse events as secondary outcome of interest were recorded for meta-analysis.

Results:
A Bayesian network meta-analysis is an appropriate statistical method to compare all treatment options by statistically simulating the estimated results of a comprehensive trial, and to compare treatments by common and associated comparators. In addition, Bayesian network meta-analysis can produce ranking probabilities of treatments, which may contribute to clinicians’ clinical decision-making.
Suture augmentation of acromioclavicular and coracoclavicular ligament reconstruction for acute acromioclavicular dislocation
Authors: Liu Yingliang , Zhang Xu , Yu Yadong , Ding Weifeng , Gao Yong , Wang Yanting , Yang Rong , Dhawan Vikas 
Published: August 2021

Abstract
The objective of this report was to introduce a new suture augmentation of coracoclavicular (CC) and acromioclavicular ligament reconstruction for acute Rockwood grade III to V acromioclavicular dislocations.
From January 2015 to January 2019, 43 patients with Rockwood III to VI acute acromioclavicular dislocations were retrospectively reviewed. For comparison, another series of 28 patients treated with double Endobutton technique from January 2011 to December 2014 were reviewed. A P < .05 was considered statistical significance.
The mean follow-up period of the 2 series were 39.69 ± 7.42 months (range, 24–54 months) and 37.86 ± 8.23 months (range, 26–48 months) (P > .05), respectively. There were significant differences regarding CC space (11.62 ± 2.54 mm vs 16.78 ± 5.53 mm; P < .05), CC reduction loss (5.56 ± 4.73 mm vs 26.25 ± 4.42 mm; P < .05), and acromioclavicular space (6.89 ± 1.87 mm vs 7.95 ± 2.37 mm; P < .05). There were significant differences regarding the disabilities of the arm, shoulder, and hand questionnaire (3.3 ± 2.8 vs 5.32 ± 4.37; P < .05) and University of California–Los Angeles shoulder rating scale (31.19 ± 2.48 vs 29.24 ± 2.48; P < .05). The excellent to good percentages were 100% (n = 32) and 85% (n = 23), respectively.
In conclusion, the suture augmentation of acromioclavicular and CC ligament reconstruction is a reliable technique for acute acromioclavicular dislocation with minimal complications.
Type of study/level of evidence: Therapeutic IIa.
Rectal inflammatory myofibroblastic tumor
Authors: Oh Hyung-Hoon , Joo Young-Eun 
Published: August 2021

Abstract

Rationale:
Rectal inflammatory myofibroblastic tumor (IMT) is an extremely rare mesenchymal tumor characterized by a mixture of spindle-shaped myofibroblasts or fibroblasts and inflammatory infiltration of lymphocytes and plasma cells. To date, only 8 cases of rectal IMT have been reported. Herein, we report an additional case of rectal IMT in a 28-year-old woman.

Patient concerns:
A 28-year-old woman presented with abdominal pain and hematochezia.

Diagnoses:
Colonoscopy showed a 3.0-cm subepithelial tumor with central ulceration, covered by white exudate in the rectum. Rectal magnetic resonance imaging revealed a 4.0 × 3.0-cm-sized well-defined subepithelial tumor in the right wall of the rectum, with suspicious right perirectal fat infiltration.

Interventions:
Laparoscopic anterior resection was performed. Microscopic examination of the surgical specimen revealed bland-looking spindle cells intermingled with lymphoplasma cells. Immunohistochemistry and fluorescence in situ hybridization showed anaplastic lymphoma kinase positivity and anaplastic lymphoma kinase positivity rearrangement. Rectal IMT was confirmed based on histological, immunohistochemical, and fluorescence in situ hybridization findings. The patient was doing well without evidence of tumor recurrence 1 year after the surgery.

Lessons:
Rectal IMT, despite its rarity, should be considered in the differential diagnosis of rectal cancer. Second, an accurate histopathologic diagnosis and complete surgical resection can be the most important approaches to offer a chance for the cure of rectal IMT.
Complications after native kidney biopsy: definitive data
Authors: Halimi Jean-Michel 
Published: August 2021

Purpose of review
To assess the risk of complications associated with native kidney biopsies. This review will highlight recent advances on the risk factors for major bleeding and risk management in patients with native kidney biopsy.

Recent findings
Recent studies provided new important data regarding the individualization of the risk of bleeding after kidney biopsy. A new bleeding risk score was proposed as a risk stratification tool, useful for shared decision making and procedure choice.

Summary
The risk of complications is low (<1%) in most patients but varies widely. Risk factors include Charlson index, frailty index, female gender, dyslipidemia, anemia, thrombocytopenia, cancer, abnormal kidney function, glomerular disease, autoimmune disease, vasculitis, hematologic disease, and thrombotic microangiopathy. A new bleeding score can help physicians and patients to assess the risk of bleeding enabling informed consent, and decide to perform it or not, and to prefer transjugular vs percutaneous route.
Current management of skull base osteomyelitis
Authors: Auinger Alice B. , Arnoldner Christoph 
Published: August 2021

Purpose of review
Skull base osteomyelitis (SBO) is a life-threatening condition. Due to an aging and increasingly multimorbid population, clinicians are more often challenged with this disease. Yet, there is no consensus on the optimal diagnostic and follow-up management. This review should aid clinicians in decision-making for their patients.

Recent findings
Treatment-resistant otalgia or headache is suspicious of SBO. Pseudomonas aeruginosa remains the most common pathogen but clinicians are challenged with increasing rates of sterile or fungal cultures due to previously applied antibiotics/steroids. No single imaging modality is able to detect the full extent of the disease. Whereas functional nuclear imaging with gallium-67 or methylene diphosphonate-technetium-99m was once advocated, its actual benefit is questionable. Newer modalities such as fluoro-D-glucose-positron emission tomography (PET)/computed tomography, PET/magnetic resonance imaging (MRI), or diffusion-weighted MRI seem to be promising in diagnosis and follow-up. Finding the causative pathogen is of utmost importance followed by long-term intravenous antibiotics until the disease has completely resolved. Surgery plays a minor role in treatment but can be helpful in selected cases.

Summary
The numerous challenges in SBO render management difficult, but with a clear work-up including regular clinical, laboratory and imaging examinations, outcome can be improved.
Risk Factors for Loss to Follow-Up in the Lower Extremity Limb Salvage Population
Authors: Sharif-Askary Banafsheh , Zolper Elizabeth G. , Deldar Romina , Tefera Eshetu , Tirrell Abigail R. , Abu El Hawa Areeg A. , Attinger Christopher E. , Evans Karen K. , Fan Kenneth L. 
Published: August 2021

Background:
Limb salvage for chronic lower extremity wounds requires long-term care best delivered by specialized multidisciplinary centers. This optimizes function, reduces amputation rates, and improves mortality. These centers may be limited to urban/academic settings, making access and appropriate follow-up challenging. Therefore, the authors hypothesize that both system- and patient-related factors put this population at exceedingly high risk for loss to follow-up.

Methods:
Records were reviewed retrospectively for 200 new patients seen at the Georgetown Center for Wound Healing in 2013. The primary outcome was loss to follow-up, defined as three consecutive missed appointments despite explicit documentation indicating the need for return visits. Demographic, clinical, and geographic data were compared. Multivariate logistic regression analysis for loss to follow-up status controlled for variables found significant in the bivariate analysis. Spatial dependency was evaluated using variograms.

Results:
Over a 6.5-year-period, 49.5 percent of patients followed were lost to follow-up. Male sex and increased driving distance to the limb salvage center were risk factors for loss to follow-up. Wound-specific characteristics including ankle and knee/thigh location were also associated with higher rates of loss to follow-up. There was no spatial dependency or discrete clustering of at-risk patients.

Conclusions:
This study is the first of its kind to investigate the demographic and clinical characteristics that predispose chronic lower extremity wound patients to loss to follow-up. These findings inform stakeholders of the high rates of loss to follow-up and support decentralized specialty care, in the form of telemedicine, satellite facilities, and/or dedicated case managers. Future work will focus on targeting vulnerable populations through focused interventions to reduce patient and system burden.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study
Authors: Biousse Valérie , Newman Nancy J. , Yu-Wai-Man Patrick , Carelli Valerio , Moster Mark L. , Vignal-Clermont Catherine , Klopstock Thomas , Sadun Alfredo A. , Sergott Robert C. , Hage Rabih , Esposti Simona , La Morgia Chiara , Priglinger Claudia , Karanja Rustum , Blouin Laure , Taiel Magali , Sahel José-Alain ,   for the LHON Study Group
Published: August 2021

Background:
RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials.

Methods:
In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a period of up to 52 months after onset of vision loss. A locally estimated scatterplot smoothing regression model was used to analyze changes in BCVA over time. Vision-related quality of life was reported using the visual function questionnaire-25 (VFQ-25).

Results:
The population of MT-ND4 subjects enrolled in RESTORE was representative of the combined cohorts of RESCUE and REVERSE for mean age (35.1 years) and gender distribution (79% males). There was a progressive and sustained improvement of BCVA up to 52 months after the onset of vision loss. The final mean BCVA was 1.26 logarithm of the minimal angle of resolution 48 months after the onset of vision loss. The mean VFQ-25 composite score increased by 7 points compared with baseline.

Conclusion:
The treatment effect of lenadogene nolparvovec on BCVA and vision-related quality of life observed 96 weeks (2 years) after treatment in RESCUE and REVERSE was sustained at 3 years in RESTORE, with a maximum follow-up of 52 months (4.3 years) after the onset of vision loss.
Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals
Authors: Luo Chun Huai , Morris C. Paul , Sachithanandham Jaiprasath , Amadi Adannaya , Gaston David , Li Maggie , Swanson Nicholas J. , Schwartz Matthew , Klein Eili Y. , Pekosz Andrew , Mostafa Heba H. 
Published: August 2021

AbstractBackgroundThe emerging SARS-CoV-2 variant of concern (VOC) B.1.6.17.2 (Delta) quickly displaced the B.1.1.7 (Alpha) and is associated with increases in COVID-19 cases nationally. The Delta variant has been associated with greater transmissibility and higher viral RNA loads in both unvaccinated and fully vaccinated individuals. Data is lacking regarding the infectious virus load in Delta infected individuals and how that compares to individuals infected with other SARS-CoV-2 lineages.MethodsWhole genome sequencing of 2,785 clinical isolates was used to characterize the prevalence of SARS-CoV-2 lineages circulating in the National Capital Region between January and July 2021. Clinical chart reviews were performed for the Delta, Alpha, and B.1.2 (a control predominant lineage prior to both VOCs) variants to evaluate disease severity and outcome and Cycle threshold values (Cts) were compared. The presence of infectious virus was determined using Vero-TMPRSS2 cells and anti-SARS-CoV-2 IgG levels were determined from upper respiratory specimen. An analysis of infection in unvaccinated and fully vaccinated populations was performed.ResultsThe Delta variant displaced the Alpha variant to constitute 88.2% of the circulating lineages in the National Capital Region by July, 2021. The Delta variant associated with increased breakthrough infections in fully vaccinated individuals that were mostly symptomatic when compared to the Alpha breakthrough infections, though it is important to note there was a significantly longer period of time between vaccination and infection with Delta infections. The recovery of infectious virus on cell culture was significantly higher with the Delta variant compared to Alpha in both vaccinated and unvaccinated groups. The impact of vaccination on reducing the recovery of infectious virus from clinical samples was only observed with Alpha variant infections but was strongly associated with low localized SARS-CoV-2 IgG for both variants. A comparison of Ct values showed a significant decrease in the Delta compared to Alpha with no significant differences between unvaccinated and vaccinated groups.ConclusionsOur data indicate that the Delta variant is associated with increased infectious virus loads when compared to the Alpha variant and decreased upper respiratory antiviral IgG levels. Measures to reduce transmission in addition to increasing vaccinations rates have to be implemented to reduce Delta variant spread.FundingNIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department of health, Centers for Disease Control and Prevention contract 75D30121C11061.
Association of COVID-19 vaccination with risks of hospitalization due to cardiovascular and other diseases: A study of the UK
Authors: Xiang Yong , Feng Yaning , Qiu Jinghong , Zhang Ruoyu , So Hon-Cheong 
Published: August 2021

AbstractBackgroundVaccines for COVID-19 represent a major breakthrough. However, worries about adverse effects led to vaccine hesitancy in some people. On the other hand, as COVID-19 may be associated with various sequelae, vaccination may protect against such sequelae via prevention of infections and severe disease.MethodsWe leveraged the UK-Biobank (UKBB) and studied associations of at least one dose of COVID-19 vaccination (BioNTech-BNT162b2 or Oxford-AstraZeneca-ChAdOx1) with short-term hospitalizations from cardiovascular and other selected diseases (N=393,544; median follow-up=54 days among vaccinated). Multivariable Cox and Poisson regression analyses were performed. We also performed adjustment using prescription-time distribution matching (PTDM) and prior-event rate ratio (PERR). PERR minimizes unmeasured confounding by comparing event hazards before introduction of vaccination.ResultsWe observed that COVID-19 vaccination(at least one dose), when compared to no vaccination, was associated with reduced short-term risks of hospitalizations from stroke(hazard ratio[HR]=0.178, 95% CI: 0.127-0.250,P=1.50e-23), venous thromboembolism (VTE) (HR=0.426, CI: 0.270-0.673,P=2.51e-4), dementia(HR=0.114, CI: 0.060-0.216;P=2.24e-11), non-COVID-19 pneumonia(NCP) (HR=0.108, CI: 0.080-0.145;P=2.20e-49), coronary artery disease (CAD) (HR=0.563, CI: 0.416-0.762;P=2.05e-4), chronic obstructive pulmonary disease (COPD) (HR=0.212, CI: 0.126-0.357;P=4.92e-9), type-2 diabetes (T2DM) (HR=0.216, CI: 0.096-0.486,P=2.12e-4), heart failure (HR=0.174, CI: 0.118-0.256,P=1.34e-18) and renal failure (HR=0.415, CI: 0.255-0.677,P=4.19e-4), based on Cox regression models. Among the above results, reduced hospitalizations for stroke, heart failure, NCP and dementia were consistently observed across all analyses, including regression/PTDM/PERR.ConclusionsTaken together, this study provides further support to the safety and benefits of COVID-19 vaccination, and such benefits may extend beyond reduction of infection risk or severity per se. However, causal relationships cannot be concluded and further studies are required to verify the findings.
COVID-19 ASSOCIATED MUCORMYCOSIS: A CASE-CONTROL STUDY
Authors: Gupta Dulari , Kulkarni Rahul , Pujari Shripad , Mulay Atul 
Published: August 2021

AbstractBackgroundIndia has seen a surge in COVID-19 associated mucormycosis (CAM) cases during the second wave of the pandemic. We conducted a study to determine independent risk factors for CAM.MethodsWe performed a retrospective case control study in a tertiary care private hospital in Pune, India. Fifty-two cases of CAM were compared with 166 concurrent controls randomly selected from the COVID-19 admissions during the same time period. Association of demographic factors, comorbidities, cumulative steroid dose used (calculated as dexamethasone equivalent), maximum respiratory support required, use of injectable/oral anticoagulation, and use of aspirin with CAM was assessed by univariate and multivariate logistic regression.ResultsA total of 218 subjects (52 cases; 166 controls) were studied. Any diabetes (pre-existing diabetes and new onset diabetes during COVID-19) was noted in a significantly higher proportion of cases (73·1%, 45·8% P<0.001) and cumulative dexamethasone dose used in cases was significantly greater (97·72 mg vs 60 mg; P=0·016). In a multivariate regression analysis cumulate dexamethasone dose >120 mg (OR 9·03, confidence interval 1·75-46·59, P=0·009) and any diabetes (OR 4·78, confidence interval 1·46-15·65, P=0·01) were found to be risk factors for CAM. While use of anticoagulation (OR 0·01, confidence interval 0·00-0·09, P<0·001) and use of aspirin (OR 0·02, confidence interval 0·01-0·07, P<0·001) were found to be protective against CAM.ConclusionDiabetes mellitus and cumulative dose of dexamethasone greater than 120 mg (or equivalent dose of other corticosteroid) were associated with an increased risk of CAM while use of aspirin and anticoagulation were associated with a lower risk.