bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative Vitamin D Deficiency Is Associated With Postoperative Delirium in Critically Ill Patients
Authors: Qiu Yuwei , Sessler Daniel I. , Chen Liang , Halvorson Sven , Cohen Barak , Bravo Mauro , Ince Ilker , Maheshwari Kamal , Kurz Andrea 
Published: July 2021

Introduction: Postoperative delirium is common, with a reported incidence of 11% to 80% in critically ill patients. Delirium is an independent prognostic factor for poor hospital outcomes. Low vitamin D concentrations are associated with a decline in cognitive function. We therefore tested the hypothesis that low preoperative serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with postoperative delirium in critically ill patients. Method: We conducted a retrospective analysis of adults in a surgical intensive care unit for at least 48 hours immediately after non-cardiac and non-neurosurgical operations at Cleveland Clinic between 2013 and 2018. Delirium was assessed by trained nurses using CAM-ICU twice daily for the initial 5 postoperative days. Any positive value was considered evidence of delirium. We assessed the association between 25(OH)D concentrations within a year before surgery and the incidence of postoperative delirium using logistic regression, adjusted for potential confounders. A linear spline term with a knot at 30 ng/ml, the threshold for normal 25(OH)D concentration, was added to accommodate a nonlinear relationship between 25(OH)D concentrations and delirium. Results: We included 632 patients, who had a mean (SD) 25(OH)D concentration of 25 (15) ng/ml; 55% (346/632) experienced delirium. We observed an adjusted odds ratio of 1.4 (95% CI: [1.1, 1.8], P = 0.01) for delirium per 10 ng/ml decrease in 25(OH)D concentrations when patients’ 25(OH)D concentrations were less than 30 ng/ml. In patients whose 25(OH)D concentrations were at least 30 ng/ml, the adjusted odds ratio was 0.9 (95% CI: [0.7, 1.1], P = 0.36). Conclusion: Preoperative 25(OH)D concentrations are associated with postoperative delirium in patients whose concentrations are below the normal threshold, but not at concentrations ≥30 ng/ml. A trial will be needed to determine whether the relationship is causal, and whether vitamin D supplementation before surgery might reduce the incidence of delirium.
Usefulness of cardiac screening in patients with systemic lupus erythematosus and anti-Ro/SSA antibodies
Authors: Villuendas Roger , Martínez-Morillo Melania , Juncà Gladys , Teniente-Serra Aina , Diez Carles , Heredia Sergi , Riveros-Frutos Anne , Bayés-Genís Antoni , Olivé Alejandro 
Published: July 2021

Objectives Recent data suggest that some adult patients with autoimmune rheumatic diseases may develop cardiac conduction and repolarization abnormalities mediated by anti-Ro/SSA antibodies. We aim to investigate the utility of a cardiac screening in patients with systemic lupus erythematous (SLE) and anti-Ro/SSA positivity. Methods SLE patients who consecutively attended a Rheumatology clinic during 1 year where evaluated for the presence and levels of anti-Ro/SSA antibodies, and clinical and biological markers of organ damage and disease activity. All participants underwent a cardiovascular anamnesis and physical examination, ECG, echocardiography, and 24-hour Holter. Results Of the 145 recruited patients, 49 (32%) had anti-Ro/SSA positivity. None had any degree of atrioventricular block in the ECG or Holter monitoring. No significant differences were observed between anti-Ro/SSA–positive vs. negative patients in terms of PR, QRS or QTc intervals. No clinically significant arrhythmias were recorded during Holter monitoring and no differences in average heart rate, heart rate variability, or atrial or ventricular ectopy burden were observed. Finally, no differences were found in echocardiographic measurements. Conclusions In this study of SLE patients, anti-Ro/SSA positivity was not associated with significant alterations in ECG, echocardiography, or 24-hour Holter. These findings do not support ordinary cardiac evaluation in these patients. ( Clinicaltrials.gov registration number: NCT02162992).
Anatomic and Radiographic Safe Zone for Posterior Malleolar Screw Placement
Authors: Williams Caroline , Momenzadeh Kaveh , Michalski Max , Kwon John Y. , Nazarian Ara , Miller Christopher P. 
Published: July 2021

Background: The most appropriate treatment and management of posterior malleolar fractures (PMFs) lacks consensus. Indirect reduction and fixation with posterior to anterior (PA) screw shows promise by avoiding the risks associated with direct reduction or indirect anterior to posterior approaches. Some authors have raised concerns about potential risk to nearby structures with the PA technique, including hardware prominence into the syndesmosis. This study highlights use of the posteromedial vertical syndesmotic line (PVSL) as a fluoroscopic landmark, helping surgeons avoid intrasyndesmotic placement. Study aims are to evaluate PVSL correspondence with posterior border of the incisura tibialis and to define a safe zone between this line and flexor hallucis longus tendon. Methods: Indirect PA screw placement was completed on 10 cadaveric specimens, followed by fluoroscopy in mortise and lateral views. Dissection was performed to assess screw placement relative to the posteromedial border of the syndesmosis. The posterior border of the syndesmosis was marked with a radiopaque wire. Repeat imaging was completed to validate the fluoroscopic PVSL is representative of the posteromedial border of the tibial incisura. Results: On dissection, 9 out of 10 cadavers had accurate screw placement with no penetration into the syndesmosis. Corresponding imaging showed the screw head to be medial to the marker on mortise view. For the specimen with penetration into the syndesmosis, imaging confirmed that the screw head was lateral to the marker on mortise views. The radiopaque marker correlated with the PVSL for all specimens when comparing anatomic to radiographic findings. A radiographic safe zone is defined for the PA screw 12 mm medial to the PVSL to ensure no iatrogenic injury to the flexor hallucis longus tendon. Conclusion: This study demonstrated that a posterior incisura tibialis fluoroscopic landmark is unambiguous in localizing the posterior syndesmotic border and that screws medial to this line are safely out of the syndesmosis, while screws placed lateral are either in or at risk of intrasyndesmotic placement. A safe zone is defined for screw placement. Clinical Relevance: This article describes a radiographic and clinical safe zone for fixation and hardware placement during open reduction internal fixation (ORIF) of PMFs. This information will assist surgeons in avoiding intrasyndesmotic hardware placement as well as injury to deep soft tissue structures.
Immune-related myocarditis in two patients receiving camrelizumab therapy and document analysis
Authors: Zhang Chuan , Qin Shu , Zuo Zhong 
Published: July 2021

Introduction Camrelizumab is an antibody against programmed death protein 1 (PD-1) and is one of immune checkpoint inhibitors (ICI). ICI may lead to autoimmune myocarditis, which has a variety of clinical manifestations and usually has a poor prognosis. This article will discuss these clinical manifestations through 2 cases of ICI-related myocarditis caused by carrelizumab. Case report We reviewed the patients who received tumor treatment in our hospital from September 2019 to June 2020. A total of 155 patients received camrelizumab treatment. there were 2 cases of acute myocarditis, accounting for 1.29%, and 8 cases of new-onset arrhythmia. Here we present 2 cases of active myocarditis in a 69-year-old man with primary liver cancer and a 75-year-old man with non-small-cell lung cancer after treatment with camrelizumab. Management and outcome: The first patient presented with severe heart failure and died of malignant arrhythmia after being treated with glucocorticoid. The second patient presented with numbness of the extremities, weakness, and mild dyspnea. The symptoms gradually improved after treatment with glucocorticoid. The Naranjo scores of these two cases were 6 and 7, which suggested that myocarditis was probably caused by carrelizumab. Discussion ICI has been successfully used to treat a variety of malignant tumors with good results. However, blocking immune checkpoints by ICI may lead to autoimmune myocarditis with a poor prognosis. Early detection of cardiotoxicity may be possible through the patient's clinical manifestations and some commonly used cardiac examination methods.
Hypertension and hypertension severity in Hispanics/Latinx with MS
Authors: Robers Michael V , Chan Chan , Vajdi Borna , Chiong-Rivero Horacio , Martinez Andrea , Burnett Margaret E , Ramanathan Murali , Amezcua Lilyana 
Published: July 2021

Background: Vascular comorbidities (VCs) including hypertension (HTN) are associated with worse multiple sclerosis (MS) outcomes. HTN is common in Latinx, but the prevalence and relationship with disability are unknown in Latinx with MS. Methods: Latinx ( n = 451) from the Alliance for Research in Hispanic MS (ARHMS) seen between 2007 and 2019 were included. HTN, diabetes (DM), hyperlipidemia (HLD), ischemic events, and smoking were considered VC. Blood pressures (BPs) were classified using the American Heart Association (AHA) criteria. Logistic regression determined associations between VC and ambulatory disability accounting for age, sex, and disease duration. Results: Medical comorbidities were found in 41.9% and VC in 24.2%. Smoking (13.6%) and HTN (7.3%) were the most common. HTN was the most common over the age of 40 (12.6%). The odds of having severe disability were three times higher for those with HTN (odds ratio [OR], 3.12; 95% confidence interval (CI), 1.37–7.12). Stage II HTN according to AHA also tripled the odds (OR, 2.89; 95%CI, 1.11–7.55). AHA BP confirmed HTN in 27.5% (compared to 7.3% with established diagnosis). Conclusion: HTN diagnosis and stage II HTN defined by AHA were independently associated with severe ambulatory disability in Latinx with MS. HTN was underdiagnosed. Future studies should assess whether HTN treatment control would prevent disability in MS.
Social workers’ perceptions of their peers’ unprofessional behavior
Authors: Gricus Michelle , Wysiekierski Lili 
Published: July 2021

Summary This article explores social workers’ perceptions of their colleagues’ professional mistakes, and the influences of those opinions. Vignettes in a factorial survey helped to determine whether certain variables related to the social worker or the situation influenced the perception of others’ professional errors and ethical violations. The changed variables included personal characteristics of the offending social worker such as perceived race, gender, and sexual orientation of the social worker, and characteristics of the situation, such as the length of time involved in unprofessional behavior. Findings Licensed social workers in six U.S. states ( n = 5596) read vignettes based on real cases brought before licensing boards ( n = 22,127) and assigned levels of seriousness and importance to discipline. The vignettes rated most highly involved perceived harm to a client or other vulnerable individual. Those on the lower end of seriousness and importance to discipline were those violations against the profession of social work. Analysis of changed variables indicated respondents’ ratings were influenced by several situational factors, but not by personal characteristics of the social worker involved in the vignette. Applications Our findings provide some insight into the decision-making factors important to social workers. The results may be helpful to licensing boards considering the contextual factors of unprofessional behavior and whether to discipline certain actions.
Launching support groups for informal caregivers of people living with dementia within participatory action research
Authors: Varik Merle , Medar Marju , Saks Kai 
Published: July 2021

Support groups are one possibility to empower informal carers and accordingly have spread across many countries because of their informal, inexpensive nature and because of their effectiveness. This paper aims to reflect on the viewpoints and experiences of the lessons learned from the participatory action research (PAR) conducted from 2016 to 2019. During PAR, several support groups in different regions of Estonia were launched to empower the informal caregivers. In the study, the stakeholders and researchers participated as partners and developed new knowledge and 17 support groups were launched in different regions of Estonia. In conclusion, our experiences highlighted the stakeholders’ collaboration which resulted in creating the knowledge needed to launch support groups. Based on our experience, we recommend launching support groups in countries where they do not exist yet, and to apply participatory action research.
SOX11, CD70, and Treg cells configure the tumor immune microenvironment of aggressive mantle cell lymphoma
Authors: Balsas Patricia , Veloza Luis , Clot Guillem , Sureda-Gómez Marta , Rodríguez Marta-Leonor , Masaoutis Christos , Frigola Gerard , Navarro Alba , Beà Silvia , Nadeu Ferran , Giné Eva , López-Guillermo Armando , Martínez Antonio , Ribera-Cortada Inmaculada , Engel Pablo , Quintanilla-Martínez Leticia , Klapper Wolfram , Campo Elias , Amador Virginia 
Published: July 2021

AbstractMantle cell lymphoma (MCL) is a mature B-cell neoplasm with a heterogeneous clinical and biological behavior. SOX11 oncogenic expression contributes to the aggressiveness of these tumors by different mechanisms, including tumor and stromal cell interactions. However, the precise composition of the immune cell microenvironment of MCL, its possible relationship to SOX11 expression, and how it may contribute to tumor behavior is not well known. Here, we performed an integrative transcriptome analysis of 730 immune-related genes combined with the immune cell phenotype analysis by immunohistochemistry in SOX11+ and SOX11− primary nodal MCL cases and non-neoplastic reactive lymph nodes. SOX11+ MCL had a significant lower T-cell intratumoral infiltration compared with negative cases. A reduced expression of MHCI/II-like and T-cell costimulation and signaling activation related transcripts was significantly associated with poor clinical outcome. Moreover, we identified CD70 as a SOX11 direct target gene, whose overexpression was induced in SOX11+, but not SOX11− tumor cells by CD40L in vitro. CD70 was overexpressed in primary SOX11+ MCL and it was associated with an immune unbalance of the tumor microenvironment characterized by increased number of effector regulatory T (Treg) cell infiltration, higher proliferation, and aggressive clinical course. CD27 was expressed with moderate to strong intensity in 76% of cases. Overall, our results suggest that SOX11 expression in MCL is associated with an immunosuppressive microenvironment characterized by CD70 overexpression in tumor cells, increased Treg cell infiltration and downmodulation of antigen processing, and presentation and T-cell activation that could promote MCL progression and represent a potential target for tailored therapies.
Incidence and prognosis of clonal hematopoiesis in patients with chronic idiopathic neutropenia
Authors: Tsaknakis Grigorios , Gallì Anna , Papadakis Stavros , Kanellou Peggy , Elena Chiara , Todisco Gabriele , Bono Elisa , Rizzo Ettore , Molteni Elisabetta , Fragiadaki Irene , Mavroudi Irene , Pontikoglou Charalampos , Batas Anastasios , Maxouri Stella , Linardaki Emmanouela , Tavernarakis Nektarios , Malcovati Luca , Papadaki Helen A. 
Published: July 2021

Abstract
The incidence and prognosis of clonal hematopoiesis in patients with isolated neutropenia among patients with idiopathic cytopenia of undetermined significance (ICUS), known as ICUS-N or chronic idiopathic neutropenia (CIN) patients, is poorly defined. The current study sought to investigate the frequency and clinical significance of mutations of genes implicated in myeloid malignancies using next-generation sequencing in patients with CIN (n = 185) with a long follow-up. We found that 21 (11.35%) of 185 patients carried a total of 25 somatic mutations in 6 genes with a median variant allele frequency of 12.75%. The most frequently mutated genes were DNMT3A and TET2 involving &gt;80% of patients, followed by IDH1/2, SRSF2, and ZRSR2. The frequency of transformation to a myeloid malignancy was low in the total group of patients (5 of 185 patients [2.70%]). However, from the transformed patients, 4 belonged to the clonal group (4 of 21 [19.05%]) and 1 to the nonclonal group (1 of 164 [0.61%]), indicating that the presence of mutation(s) confers a relative risk for transformation of 31.24 (P = .0017). The variant allele frequency of the mutant clones in the transformed patients was &gt;10% in all cases, and the genes most frequently associated with malignant transformation were SRSF2 and IDH1. No significant differences were identified between the clonal and nonclonal groups in the severity of neutropenia. Patients with clonal disease were older compared with nonclonal patients. These data contribute to the better understanding of the heterogeneous entities underlying ICUS and highlight the importance of mutation analysis for the diagnosis and prognosis of patients with unexplained neutropenias.
Functional characterization of 105 factor H variants associated with aHUS: lessons for variant classification
Authors: Martín Merinero Hector , Zhang Yuzhou , Arjona Emilia , del Angel Guillermo , Goodfellow Renee , Gomez-Rubio Elena , Ji Rui-Ru , Michelena Malkoa , Smith Richard J. H. , Rodríguez de Córdoba Santiago 
Published: July 2021

Abstract
Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy that can progress, when untreated, to end-stage renal disease. Most frequently, aHUS is caused by complement dysregulation due to pathogenic variants in genes that encode complement components and regulators. Among these genes, the factor H (FH) gene, CFH, presents with the highest frequency (15% to 20%) of variants and is associated with the poorest prognosis. Correct classification of CFH variants as pathogenic or benign is essential to clinical care but remains challenging owing to the dearth of functional studies. As a result, significant numbers of variants are reported as variants of uncertain significance. To address this knowledge gap, we expressed and functionally characterized 105 aHUS-associated FH variants. All FH variants were categorized as pathogenic or benign and, for each, we fully documented the nature of the pathogenicity. Twenty-six previously characterized FH variants were used as controls to validate and confirm the robustness of the functional assays used. Of the remaining 79 uncharacterized variants, only 29 (36.7%) alter FH expression or function in vitro and, therefore, are proposed to be pathogenic. We show that rarity in control databases is not informative for variant classification, and we identify important limitations in applying prediction algorithms to FH variants. Based on structural and functional data, we suggest ways to circumvent these difficulties and, thereby, improve variant classification. Our work highlights the need for functional assays to interpret FH variants accurately if clinical care of patients with aHUS is to be individualized and optimized.
Single-cell ATAC-seq reveals GATA2-dependent priming defect in myeloid and a maturation bottleneck in lymphoid lineages
Authors: Avagyan Serine , Weber Margaret C. , Ma Sai , Prasad Meera , Mannherz William P. , Yang Song , Buenrostro Jason D. , Zon Leonard I. 
Published: July 2021

Abstract
Germline heterozygous mutations in GATA2 are associated with a syndrome characterized by cytopenias, atypical infections, and increased risk of hematologic malignancies. Here, we generated a zebrafish mutant of gata2b that recapitulated the myelomonocytopenia and B-cell lymphopenia of GATA2 deficiency syndrome. Using single-cell assay for transposase accessible chromatin with sequencing of marrow cells, we showed that loss of gata2b led to contrasting alterations in chromosome accessibility in early myeloid and lymphoid progenitors, associated with defects in gene expression. Within the myeloid lineage in gata2b mutant zebrafish, we identified an attenuated myeloid differentiation with reduced transcriptional priming and skewing away from the monocytic program. In contrast, in early lymphoid progenitors, gata2b loss led to accumulation of B-lymphoid transcription factor accessibility coupled with increased expression of the B-cell lineage-specification program. However, gata2b mutant zebrafish had incomplete B-cell lymphopoiesis with loss of lineage-specific transcription factor accessibility in differentiating B cells, in the context of aberrantly reduced oxidative metabolic pathways. Our results establish that transcriptional events in early progenitors driven by Gata2 are required to complete normal differentiation.
A retrospective cohort study of idiopathic diaphragmatic palsy: a diagnostic triad, natural history and prognosis
Authors: Nafisa Syeda , Messer Ben , Downie Beatrice , Ehilawa Patience , Kinnear William , Algendy Sherif , Sovani Milind 
Published: July 2021

BackgroundIsolated diaphragmatic palsy in the absence of progressive neuromuscular disease is uncommon. It poses diagnostic challenges and limited data are available regarding prognosis. We present retrospective cohort data from two large teaching hospitals in the United Kingdom.Method60 patients who were assessed either as inpatients or outpatients were included in this study. Patients with progressive neuromuscular disease were excluded. Clinical presentation, tests of respiratory muscle function (sitting/supine vital capacity, maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP) and sniff nasal inspiratory pressure (SNIP)) and outcomes were recorded.ResultsFor patients with diaphragmatic palsy, mean±sdseated and supine vital capacity pre-noninvasive ventilation (NIV) were reduced at 1.7±1.2 L and 1.1±0.9 L, respectively, with a mean±sdpostural fall in vital capacity of 42±0.16%. The mean MEP/MIP and MEP/SNIP ratios for diaphragmatic palsy were 3 and 3.5, respectively. After a year of treatment with NIV, mean±sdupright and supine vital capacity had increased to 2.1±0.9 L and 1.8±1 L, respectively, and the mean±sdfall in vital capacity from sitting to supine reduced to 29±0.17%. MEP/MIP and MEP/SNIP ratios reduced to 2.6 and 2.9, respectively, from the pre-NIV values. The values of postural fall in vital capacity correlated (p<0.05) with MEP/MIP and MEP/SNIP ratio (r2=0.86 and r2=0.7, respectively).ConclusionTests of respiratory muscle strength are valuable in the diagnostic workup of patients with unexplained dyspnoea. A triad of 1) orthopnoea, with 2) normal lung imaging and 3) MEP/MIP and/or MEP/SNIP ratio ≥2.7 points towards isolated diaphragmatic palsy. This needs to be confirmed by prospective studies.