bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of oclacitinib for the control of feline atopic skin syndrome: correlating plasma concentrations with clinical response
Authors: Carrasco Isaac , Ferrer Lluis , Puigdemont Anna 
Published: October 2021

Objectives The aim of this study was to assess the efficacy of a new therapeutic regimen of oclacitinib for the control of feline atopic skin syndrome (FASS) and to correlate plasma levels of this drug with clinical effects. Methods Twenty-eight client-owned cats with a clinical diagnosis of FASS were recruited. Oclacitinib was administered at 1 mg/kg q12h for 2 weeks and then at 1 mg/kg q24h for a further 2 weeks. At the study outset (D0), and 7 (D7) and 28 (D28) days after starting treatment, clinical lesions were assessed using a validated scoring system (SCORing Feline Allergic Dermatitis [SCORFAD]) and pruritus was graded via an adapted visual analogue scale (PVAS). At the same time points, plasma oclacitinib levels and haematological variables were measured. Results Among 18 cats completing the study, PVAS and SCORFAD improved by ⩾50% in 61% and 88% of animals, respectively. Mean PVAS decreased significantly between D0 and D7 and between D0 and D28 (both P <0.001) but not between D7 and D28. Likewise, mean SCORFAD values decreased significantly between D0 and D7 and between D0 and D28 (both P <0.001) but not between D7 and D28. On D7 and D28, plasma oclacitinib concentrations varied widely from 0 to 1443.2 ng/ml and from from 0 to 1177.7 ng/ml, respectively. Oclacitinib concentrations showed no correlation with clinical effects (SCORFAD and PVAS). Conclusions and relevance Oclacitinib emerged as being safe and effective to control clinical signs of FASS. A mean dose of 1 mg/kg, even without extending twice-daily treatment beyond the first 2 weeks, could be a suitable therapeutic regimen. Plasma drug levels did not seem useful to predict clinical response during treatment.
Percutaneous Transluminal Angioplasty for Below-the-Elbow Critical Hand Ischemia: A Systematic Review
Authors: Awad El-Karim Ghassan , Kennedy Sean A. , Ferraresi Roberto , Addas Jamil A.K. , Oreopoulos George D. , Jaberi Arash , Tan Kong Teng , Mafeld Sebastian 
Published: October 2021

Purpose: To perform a systematic review assessing the safety and efficacy of percutaneous transluminal angioplasty (PTA) for treatment of critical hand ischemia (CHI) due to below-the-elbow (BTE) obstructive arterial disease. Materials and Methods: MEDLINE and EMBASE systematic searches were performed from inception to December 2020 to identify studies assessing PTA for management of BTE obstructive arterial disease. Three independent reviewers performed abstract selection, data extraction, and quality assessment. The Newcastle-Ottawa Scale was used to assess individual study bias for non-randomized controlled trials. Results: Eight studies comprising 176 patients with obstructive BTE vessel disease were included. All studies had a score >5 on the Newcastle-Ottawa Scale, indicative of high quality. All studies used low-profile balloons (1.5–4 mm) for PTA of stenotic lesions or chronic total occlusions (CTOs). The weighted average technical success and clinical success rates were 89.3% (range = 82%–100%) and 69.9% (range = 19%–100%), respectively, at a mean follow-up of 29.7 ± 17.1 months. The short-term (<30 days) complication rate was low at 4.7% and most commonly included access site hematomas, pseudoaneurysms, and radial artery perforation or re-thrombosis. Nearly 20% of patients required an amputation, and most (96%) were minor (either distal phalanges or digits). Only 2 patients required above-wrist amputations. The primary and secondary patency rate at 5 years were 38% and 54%, respectively. The cumulative 5-year mortality rate was 33.1%. Conclusions: PTA for CHI due to BTE obstructive arterial disease is feasible with a high technical success rate and a low short-term complication rate. Additional long-term comparative studies are required to unequivocally establish the clinical benefit of endovascular treatment compared with conservative management or surgical bypass.
Post-Tracheostomy Vascular Injury to the Anomalous Thymic Branch Managed by Endovascular Coiling
Authors: Ray Nirmalya , Ahuja Chirag Kamal , Kumar Ajay , Panda Naresh , Singh Paramjeet 
Published: October 2021

Background Tracheostomy-related arterial haemorrhage can be devastating especially if arising from an obscure anomalous vessel which can potentially complicate treatment decision. Methods We report a case of non-Hodgkin’s lymphoma with upper airway obstruction, who had profuse bleeding, post-tracheostomy, from the stomal site. CT angiography showed presence of a pseudoaneurysm adjacent to the tracheostomy site which was confirmed on catheter angiography to be arising from anomalous thymic branch of right common carotid artery (CCA). Superselective cannulation of the anomalous thymic artery was done using a microcatheter with subsequent coil embolization. Results Post-coiling, the bleeding stopped immediately and the patient recovered. He was under oncology care till 3 months following embolization and was doing well. Conclusions The emergency physicians should be aware of this rare variation of thymic artery while performing tracheostomy. Ultrasound as point-of-care device may help mitigate these complications. Endovascular embolization is a minimally invasive and effective management option for an injured arterial branch from a tracheostomy.
Kinetics of polymerase chain reaction positivity in patients with Clostridioides difficile infection
Authors: Saha Srishti , Yadav Devvrat , Pardi Ryan , Patel Robin , Khanna Sahil , Pardi Darrell 
Published: October 2021

Background: Polymerase chain reaction (PCR) is a sensitive test for diagnosing Clostridioides difficile infection (CDI) and could remain positive following resolution of CDI. The kinetics of PCR positivity following antibiotics for CDI is unknown. We studied this and whether it predicted CDI recurrence. Methods: Adults with CDI from October 2009 to May 2017 were included. Serial stool samples within 60 days of treatment were collected. Recurrent CDI was defined as diarrhea after interim symptom resolution with positive stool PCR within 56 or 90 days of treatment completion. Contingency table analysis was used to assess the risk of recurrence. Results: Fifty patients were included [median age: 51 (range = 20–86) years, 66% women]. Treatment given was metronidazole, 50% (25); vancomycin, 44% (22); both, 4% (2); and fidaxomicin, 2% (1). Median duration of treatment for all 50 patients was 14 (range = 8–60) days. The median duration of treatment in patients who got prolonged therapy (>14 days) ( n = 10) was 47 (range = 18–60) days. Median time to negative PCR was 9 (95% CI, 7–14) days from treatment initiation, which did not differ by antibiotics given ( p = 0.5). A positive PCR during or after treatment was associated with a higher risk of recurrence at 56 days ( p = 0.02) and at 90 days ( p = 0.009). Conclusion: The median time to negative PCR in CDI was 9 days from treatment initiation. The PCR positivity during or after treatment may be useful for recurrence prediction; larger studies are needed to validate these results.
Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension
Authors: Farha Samar , Comhair Suzy , Hou Yuan , Park Margaret M. , Sharp Jacqueline , Peterson Laura , Willard Belinda , Zhang Renliang , DiFilippo Frank P. , Neumann Donald , Tang W.H. Wilson , Cheng Feixiong , Erzurum Serpil 
Published: October 2021

Alterations in metabolism and bioenergetics are hypothesized in the mechanisms leading to pulmonary vascular remodeling and heart failure in pulmonary hypertension (PH). To test this, we performed metabolomic analyses on 30 PH individuals and 12 controls. Furthermore, using 2‐[18F]fluoro‐2‐deoxy‐D‐glucose positron emission tomography, we dichotomized PH patients into metabolic phenotypes of high and low right ventricle (RV) glucose uptake and followed them longitudinally. In support of metabolic alterations in PH and its progression, the high RV glucose group had higher RV systolic pressure (p < 0.001), worse RV function as measured by RV fractional area change and peak global longitudinal strain (both p < 0.05) and may be associated with poorer outcomes (33% death or transplantation in the high glucose RV uptake group compared to 7% in the low RV glucose uptake group at five years follow‐up, log‐ranked p = 0.07). Pathway enrichment analysis identified key metabolic pathways including fructose catabolism, arginine‐nitric oxide metabolism, tricarboxylic acid cycle, and ketones metabolism. Integrative human protein‐protein interactome network analysis of metabolomic and transcriptomic data identified key pathobiological pathways: arginine biosynthesis, tricarboxylic acid cycle, purine metabolism, hypoxia‐inducible factor 1, and apelin signaling. These findings identify a PH metabolomic endophenotype, and for the first time link this to disease severity and outcomes.
Third-party type 2 innate lymphoid cells prevent and treat GI tract GvHD
Authors: Bruce Danny W. , Kolupaev Oleg , Laurie Sonia J. , Bommiasamy Hemamalini , Stefanski Heather , Blazar Bruce R. , Coghill James M. , Serody Jonathan S. 
Published: October 2021

AbstractAcute graft-versus-host disease (aGVHD), mediated by the recognition of host major histocompatibility complex/peptide polymorphisms by donor T cells, remains a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). aGVHD most commonly involves the gastrointestinal tract, liver, and skin; symptomatic aGVHD is treated with corticosteroids. Steroid-nonresponsive aGVHD is a significant problem for patients undergoing allo-HSCT, with &lt;15% of these patients alive 1 year after diagnosis. Previously, we found that the infusion of donor innate lymphoid type 2 (ILC2) cells could prevent and treat aGVHD of the lower gastrointestinal tract with no effect on the graft-versus-leukemia response. This approach for clinical translation is cumbersome, as it would require the generation of donor-derived ILC2 cells for each recipient. Thus, the ability to use third-party ILC2 cells would provide an “off-the-shelf” reagent that could be used to treat and/or prevent aGVHD. Here, we show that third-party ILC2 cells enhance the survival of allo-HSCT recipients. Treatment required at least 4 weekly infusions of ILC2 cells. Mechanistically, we show that ILC2 cell function was completely lost if the cells could not express both interleukin-13 (IL-13) and amphiregulin. Finally, we show that the activity of IL-13 has a greater dependence on the expression of the IL-13R on host rather than donor bone marrow cells. The ability to generate third-party ILC2 cells offers a new avenue for the prevention of aGVHD.
Vemurafenib acts as a molecular on-off switch governing systemic inflammation in Langerhans cell histiocytosis
Authors: Eder Sebastian K. , Schwentner Raphaela , Ben Soussia Philipp , Abagnale Giulio , Attarbaschi Andishe , Minkov Milen , Halbritter Florian , Hutter Caroline 
Published: October 2021

Abstract
Langerhans cell histiocytosis (LCH) is a neoplasm marked by the accumulation of CD1A+CD207+ cells. It is most commonly driven by a somatic, activating mutation in the BRAF serine-threonine kinase (BRAFV600E). Multisystem disease with risk-organ involvement requires myelotoxic chemotherapy, making BRAF-inhibitors an attractive treatment option. Here, we present a comprehensive analysis of the course of an LCH patient treated with the combination of vemurafenib and salvage chemotherapy who achieved sustained clinical and molecular remission. We show that there is no relationship between peripheral blood BRAFV600E levels and clinical presentation during treatment with vemurafenib, but that vemurafenib leads to a fast, efficient, but reversible inhibition of clinical manifestations of systemic inflammation. In line, serum levels of inflammatory cytokines exactly mirror vemurafenib administration. Genotyping analysis identified the BRAFV600E mutation in multiple hematopoietic cell types, including NK cells and granulocytes. Single-cell transcriptome analyses of peripheral blood and bone marrow cells at time of diagnosis and during treatment indicate that RAF-inhibition abrogates the expression of inflammatory cytokines previously implicated in LCH such as IL1B and CXCL8. Together, our data suggest that while the CD1A+CD207+ histiocytes are the hallmark of LCH, other BRAF-mutated cell populations may contribute significantly to morbidity in patients with multisystem LCH.
A p.Arg127Gln variant in GPIbα LRR5 allosterically enhances affinity for VWF: a novel form of platelet-type VWD
Authors: Bury Loredana , Falcinelli Emanuela , Kuchi Bhotla Haripriya , Mezzasoma Anna Maria , Guglielmini Giuseppe , Tischer Alexander , Moon-Tasson Laurie , Auton Matthew , Gresele Paolo 
Published: October 2021

Abstract
Gain-of-function (GOF) variants in GP1BA cause platelet-type von Willebrand disease (PT-VWD), a rare inherited autosomal dominant bleeding disorder characterized by enhanced platelet GPIbα to von Willebrand factor (VWF) interaction, and thrombocytopenia. To date, only 6 variants causing PT-VWD have been described, 5 in the C-terminal disulfide loop of the VWF-binding domain of GPIbα and 1 in the macroglycopeptide. GOF GP1BA variants generate a high-affinity conformation of the C-terminal disulfide loop with a consequent allosteric conformational change on another region of GPIbα, the leucine-rich-repeat (LRR) domain. We identified a novel GP1BA variant (p.Arg127Gln) affecting the LRR5 domain of GPIbα in a boy with easy bruising and laboratory test results suggestive of PT-VWD. We thus aimed to investigate the impact of the p.Arg127Gln variant on GPIbα affinity for VWF and GPIbα structure. Chinese hamster ovary cells expressing p.Arg127Gln GPIbα showed increased binding of VWF induced by ristocetin and enhanced tethering on immobilized VWF as compared with cells expressing wild-type GPIbα. Surface plasmon resonance confirmed that p.Arg127Gln enhances the binding affinity of GPIbα for VWF. Hydrogen-deuterium exchange mass spectrometry showed that p.Arg127Gln of LRR, while having little effect on the dynamics of the LRR locally, enhances the conformational dynamics of the GPIbα C-terminal disulfide loop structure. Our data demonstrate for the first time that GOF variants outside the GPIbα C-terminal disulfide loop may be pathogenic and that aminoacidic changes in the LRR may cause allosterically conformational changes in the C-terminal disulfide loop of GPIbα, inducing a conformation with high affinity for VWF.
Use of Singing for Lung Health as an alternative training modality within pulmonary rehabilitation for COPD: a randomised controlled trial
Authors: Kaasgaard Mette , Rasmussen Daniel Bech , Andreasson Karen Hjerrild , Hilberg Ole , Løkke Anders , Vuust Peter , Bodtger Uffe 
Published: October 2021

BackgroundPulmonary rehabilitation (PR) is a cornerstone in chronic obstructive pulmonary disease (COPD) management. However, PR adherence is generally low, and barriers include availability, economic issues, motivation and an inability to attend or perform physical training. Therefore, alternative, evidence-based PR activities are required. Singing may have benefits for quality of life (QoL), respiratory control and well-being in COPD, but the impact on the PR key outcome, physical exercise capacity, is uncertain.MethodsIn this randomised controlled trial (NCT03280355), we investigated the effectiveness of 10 weeks of PR, including either “Singing for Lung Health” (SLH) training or standard physical exercise training (PExT). The primary outcome was a change in exercise capacity (6-min walk distance (6MWD)) from baseline to post-PR. Secondary outcomes were changes in QoL (St George's Respiratory Questionnaire (SGRQ)), Hospital Anxiety and Depression Score (HADS), lung function, dyspnoea and adherence.ResultsWe included 270 COPD patients, and 195 completed the study. Demographics across groups were comparable, and both groups improved significantly in 6MWD and SGRQ score. SLH was non-inferior to PExT in improving 6MWD (mean±sd13.1±36.3 mversus14.1±32.3 m, p=0.81; difference 1.0 m, 95% CI −7.3–9.3 m) with 21.8% and 25.0%, respectively (p=0.57), reaching the 6MWD minimal important difference of 30 m. We found no significant between-group differences concerning SGRQ, HADS, lung function, dyspnoea or adherence.ConclusionOur study suggests that SLH is non-inferior to PExT in improving 6MWD during a 10-week PR programme. Future studies addressing reproducibility, long-term effects and health economics are needed.
Chronic cough in Germany: results from a general-population survey
Authors: Virchow J. Christian , Li Vicky W. , Fonseca Eileen , Salmen Helena , Martin Ashley , Brady Joanne , Jannowitz Christina , Schelfhout Jonathan 
Published: October 2021

BackgroundChronic cough (CC) which is defined ≥8 weeks is a common condition in clinical practice. However, estimates of prevalence and associated comorbidities in German adults and key subgroups of age and gender are lacking.MethodsCross-sectional study based on a representative panel of 15 020 adult subjects of the general population who completed the German National Health and Wellness Survey, reporting CC and questions about comorbidities. Lifetime and 12-month prevalence are presented as unweighted estimates.ResultsThe lifetime CC prevalence was 6.5% (range across age groups 5.1%–8.3%) and the 12-month prevalence was 4.9% (range 3.7–5.7%). The prevalence of diagnosed CC was 2.8% (range 0.9–4.1%) and the prevalence of persons currently on any prescription to treat CC was 0.6% (range 0.2–1.4%). Respondents who experienced CC were 52.0±17.0 years old, with a higher prevalence in those aged 50 years and older. Persons with CC had higher morbidity scores and were diagnosed with an increased number of comorbidities, most frequently diagnoses of the respiratory system (71.0%), followed by digestive tract disorders (34.0%) and sleep disorders (37.6%).ConclusionsIn a broadly representative sample of German adults, lifetime and 12-month prevalence of CC was greatest in current and former smokers and those older ≥50 years of age. Comorbidities are frequent and may complicate management of these patients.
The risk of respiratory tract infections and antibiotic use in a general population and among people with asthma
Authors: Kisiel Marta A. , Zhou Xingwu , Björnsson Eythor , Holm Mathias , Dahlman-Höglund Anna , Wang Juan , Svanes Cecilie , Norbäck Dan , Franklin Karl A. , Malinovschi Andrei , Johannessen Ane , Schlünssen Vivi , Janson Christer 
Published: October 2021

AimThe aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals.MethodThis study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25–54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations.ResultsIn the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53–3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18–4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood.ConclusionIn this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.
Sarcoidosis in Iceland: a nationwide study of epidemiology, clinical picture and environmental exposure
Authors: Haraldsdóttir Sigríður Ólína , Jonasson Jon Gunnlaugur , Jorundsdottir Kristin Bara , Hannesson Haraldur Jon , Gislason Thorarinn , Gudbjornsson Bjorn 
Published: October 2021

BackgroundThis nationwide study aimed to elucidate the incidence and clinical characteristics of tissue-verified sarcoidosis in Iceland. A secondary aim was to analyse sex differences and identify possible environmental factors contributing to the pathological process.Materials and methodsThis is a descriptive study covering 36 years (January 1, 1981 through December 31, 2016). Histopathological reports and electronic hospital discharge registries were reviewed in context for granulomas and/or sarcoidosis. National data were used for comparison regarding smoking habits and occupation, adjusted for age, sex and year of diagnosis. The data were stored in FileMaker and calculations were made by extracting data from this database to the statistical software package R.ResultsA total of 418 patients (54% females) were diagnosed with tissue-verified sarcoidosis. The incidence rate was 4.15/100 000/year, similar among females and males. The mean age at diagnosis was higher among females (53.0±14.2 years) than males (48.2±13.8 years). Fatigue was the most frequent single symptom (49.7%), but when all respiratory symptoms were grouped, they were the most frequent symptoms (60%). No significant difference was found between smoking status and sarcoidosis. Possible hazardous exposure in the workplace was reported by 19.4% of the cases.ConclusionThe incidence of sarcoidosis in Iceland was higher than in an Asian population where the same inclusion criteria were applied. The clinical picture diverges partly from that in the Asian population but resembles that among other Caucasians. Fatigue and respiratory symptoms were predominant. The biphasic pattern of age at disease debut seen elsewhere among females was not evident in Iceland.