Therapeutic plasma exchange in pediatric patients with acute demyelinating syndromes of the central nervous system: A single-center experience

BackgroundTherapeutic plasma exchange (TPE) is an extracorporeal treatment that can be used in adult and pediatric patients with acute demyelinating syndromes of the central nervous system. In this study, the efficacy and safety of TPE was evaluated in 10 pediatric patients who underwent TPE that were unresponsive to corticosteroid treatment.MethodsRecords of 10 pediatric patients who underwent TPE in our pediatric intensive care unit (PICU) between May 2017 and June 2020 were used. Expanded Disability Status Scale (EDSS), Gait Scale (GS), and Visual Outcome Scale (VOS) were applied to the patients before and after TPE.ResultsOf the 10 patients who underwent TPE, five were diagnosed with multiple sclerosis (MS), three with transverse myelitis (TM), and two with acute disseminated encephalomyelitis (ADEM). The median age of the patients was 13.3 years (IQR 8-15), and the median day from symptom onset to onset of TPE was 12.5 days (IQR 7-28). A total of 104 TPE sessions were performed successfully. While no complications were encountered in three patients during the sessions, the most common complication was hypofibrinogenemia. The decrease in EDSS and GS scores was found to be consistent with the clinical response of the patients. There was no statistically significant decrease in the VOS.ConclusionsWith this study, we can say that TPE is a feasible, effective, and safe treatment modality in children with acute demyelinating syndromes of the central nervous system.     

The reliability in determining the deep fascia displacement of the upper trapezius during cervical movement: A pilot study

BackgroundRestricted shoulder fascia displacement may be an etiological factor for myofascial pain syndrome. A diagnostic ultrasound video can follow deep fascia displacement during active cervical movements. Trackers can be applied to videos to convert deep fascia displacement into data points. This study reports on assessors' reliability in evaluating direction and quantifying upper trapezius' deep fascia displacement during active cervical movements.MethodsPT-Sonographer 1 recorded deep fascia displacement of upper trapezius for three sets using HS1 Konica Minolta diagnostic ultrasound. The recording sequence used was cervical flexion, extension, right lateral flexion, left lateral flexion, right rotation, and left rotation. The three assessors used the tracker to determine direction of deep fascia displacement. PT-Sonographer 1 used the tracker three times in quantifying deep fascia displacement. Intraclass correlation coefficient and Kappa determined the assessors' intra-tester and inter-tester reliability.ResultsTen participants were included in the study with a mean±(SD) age of 37±(6). All the assessors had acceptable intra-tester reliability in determining deep fascia displacement on tracker (ICC≥0.40). All assessors had clinically unacceptable inter-tester reliability in determining deep fascia displacement when tracking right rotation (ICC < 0.40). PT-Sonographer 1 had clinically unacceptable intra-tester reliability in determining deep fascia displacement when tracking left rotation (ICC<0.40).ConclusionWe report clinically acceptable assessors' reliability in determining direction and total deep fascia displacement when tracking diagnostic ultrasound videos of cervical flexion, extension, and lateral flexion. Checking for reliable deep fascia displacements may distinguish MPS from non-MPS individuals increasing the utility of diagnostic ultrasound machine and tracker in clinical practice.     

Neurologic Complications of Immune Checkpoint Inhibitors in Thoracic Malignancies

Immune checkpoint inhibitors (ICIs) have transformed the prognosis of cancers previously considered lethal. The spectrum of therapeutic indications is rapidly expanding, including the vast majority of thoracic malignancies. By enhancing the immune responses against cancer, the ICI treatments lead to the development of immune-related adverse events (irAEs) that may affect any organ. Severity varies from mild to fatal clinical manifestations. Neurologic involvement is relatively rare and highly heterogeneous, including central and peripheral nervous system diseases associated with neural-specific autoantibodies or not, central nervous system vasculitis, and granulomatous and demyelinating disorders. Symptoms often manifest within the first four cycles of treatment and can develop regardless of the class of ICI used. An unfavorable outcome is found in up to one-third of patients and is generally associated with the patients’ clinical characteristics (e.g., age, coexistence of systemic adverse events), cancer type (e.g., lung cancer versus other), and specific clinical setting (e.g., ICI treatment in patients with preexisting paraneoplastic neurologic autoimmunity, ICI rechallenge after a first neurologic irAE). Diagnosis should be suspected in patients with new-onset neurologic symptoms while on ICI treatment which are not explained by metastatic disease or other metabolic/infectious disorders. Recommended treatment is based on clinical severity and consists of ICI discontinuation with or without immunosuppressive/immunomodulatory therapy, although alternative approaches are reasonable depending on cancer status (e.g., aggressive immunosuppression without discontinuing ICI in patients with initial cancer response). Early recognition and appropriate treatment of these neurologic irAEs are crucial for improved patient outcomes and therapeutic planning.     

约束隐结构研究冠心病痰湿证的定量化辨证规则＊

目前在中医界已发布的冠心病痰湿证辨证标准是以主症、次症形式定性地给出，存在主观性较强的问题。本文引入约束隐结构分析，该方法将主症、次症的语义作为约束条件加入隐结构分析过程，得到含有主症、次症语义约束的定量化中医证候辨证规则。使用该方法对冠心病痰湿证患者556条无标签数据的分析，得到其约束隐结构模型，最后建立定量化痰湿证辨证规则，舌胖边有齿痕（3.16）、苔腻（3.12）、苔白滑（4.72）、胸闷（1.73）、脉濡或滑（6.04）；次症：肢体困重（0.48）、口黏（0.63）、体胖（0.49）、大便粘滞（1.38）、脘腹痞满（0.97）、面色晦浊（0.79）、嗜睡（1.18）、纳差（1.07）。与经典隐结构模型得到规则和中医界已发布的定性化辨证规则相比，约束隐结构得到的规则客观性强，具有可重复性。在证候类大小、规则的量化合理度上较好地反映了主症、次症的特点，得到的规则切合中医实际，为冠心病痰湿证辨证标准的定量化研究提供帮助和参考。     

Progress in Targeting the TGFβ Pathway

Signaling by the transforming growth factor-β (TGF-β) superfamily is important in the regulation of hematopoiesis and is dysregulated in myelodysplastic syndromes (MDS), contributing to ineffective hematopoiesis and clinical cytopenias. TGF-β, activins and growth differentiation factors exert inhibitory effects on red cell formation by activating canonical SMAD2/3 pathway signaling. SMAD2/3 overactivation is seen in numerous subtypes of MDS. Furthermore, reduced levels of inhibitory SMAD7 are

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Myeloid neoplasms with germline predisposition: Practical considerations and complications in the search for new susceptibility loci

Genomic research in hematological malignancies has focused far more prominently on somatic mutations than on germline variants. Although increasing numbers of germline variants are being identified, a substantial proportion of familial myeloid malignancies have no causal allele pinpointed. Here we review the biological, technological, and clinical challenges that stand in the way of the goal of establishing, implementing, and interpreting a comprehensive panel of germline variants for testing. Achieving this goal would inform care for large numbers of myeloid malignancy patients. Furthermore, knowledge of germline susceptibility variants and their corresponding genes will shed light on disease processes, potentially suggesting therapeutic strategies tailored to specific variants.