Citations

SummaryThe phase I/II AU‐003 study in patients with treatment‐naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow‐up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response at 3 years was reported in 85·7%. The ORR in patients with del(17p)/tumour protein p53 mutation was 87·5% (CR 16·7%). The 2‐ and 3‐year progression‐free survival estimates were 90% (TN, 90%; R/R, 91%) and 83% (TN, 81%; R/R, 83%) respectively. The most reported Grade ≥3 adverse events were neutropenia (15·4%), pneumonia (9·8%), hypertension (8·9%) and anaemia (6·5%). The annual incidence of atrial fibrillation, major haemorrhage, Grade ≥3 neutropenia and Grade ≥3 infection decreased over time. With a median follow‐up of ~4 years, responses remain clinically meaningful and durable and long‐term tolerability to zanubrutinib therapy continues.

Summary The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long‐term video‐electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using the PRISMA (Preferred Reporting Items for Systematic Review and Meta‐Analysis) statement. We found limited high‐level evidence aimed at specific aspects of diagnosis for LTVEM performed to evaluate patients with seizures and nonepileptic events. For classification of evidence, we used the Clinical Practice Guideline Process Manual of the American Academy of Neurology. We formulated recommendations for the indications, technical requirements, and essential practice elements of LTVEM to derive minimum standards used in the evaluation of patients with suspected epilepsy using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Further research is needed to obtain evidence about long‐term outcome effects of LTVEM and to establish its clinical utility.

BACKGROUND Thoracic spinal epidural lipomatosis (SEL) involves the pathological overgrowth of histologically normal, unencapsulated adipose tissue that can compress the spinal cord and cause myelopathy. SEL has been associated with multiple medical conditions, including Scheuermann kyphosis (SK). Optimal treatment strategies for SEL, especially in the setting of a sagittal spinal deformity, remain unclear. OBSERVATIONS In this report, the authors discussed surgical management of a patient with thoracic SEL and SK using skip hemilaminotomies for resection of the epidural adipose tissue. To the authors’ knowledge, only one other report described a similar surgical technique in a patient who did not have a spinal deformity. LESSONS When conservative efforts fail, thoracic SEL may require surgical treatment. Surgical planning must account for co-medical conditions such as SK. The described approach involving skip laminotomies, which minimizes spine destabilization, is a viable option to treat SEL spanning multiple spinal segments. Prognosis after surgical treatment varies and is impacted by multiple factors, including severity of preoperative neurological deficits.

Four groups of children were studied over periods of 1 to 14 years. Group 1 included 402 children who had been born after prolonged labor. Follow-up studies were made of 321 of the 402 children. Twelve children (3.7%) were noted to have convulsions, but only one child had a recurring convulsive disorder (epilepsy). The remainder had so-called febrile convulsions. No other persistent neurologic difficulties were found. Group 3 included 236 children who had asphyxia (anoxia) or delayed respiration at birth. Follow-up data were available on 180 children. The only resulting neurologic difficulties noted were febrile convulsions in two children. None had persistent convulsive disorders (epilepsy). Group 5 included 124 babies whose mothers had had toxemia of pregnancy. Fourteen were stillborn or died in early infancy. Four of the remaining 110 (3.6%) had a febrile convulsion at some time, but to our knowledge persistent convulsions did not develop. Groups 2 and 4 were control groups and included a total of 633 children, who were born after relatively short uncomplicated deliveries. Follow-up data were available for 498 of the children; among them 16 children (3.2%) had convulsions at some time, and 13 of the 16 had convulsions at some time between the ages of 8 and 14 years. No other persistent neurologic conditions were found. Four children had recurring convulsive disorders and four others had a single convulsion or occasional convulsion of unknown etiology. Eight others had so-called febrile convulsions. No other persistent neurologic conditions were found. The findings of the present study reinforce the conclusions in the previous report from this clinic—that prolonged labor, asphyxia, or delayed respiration at birth did not cause any neurologic abnormality in children who survive the early months of life, and that convulsions of any type are not commoner among children who had difficulty at birth than among children who did not have difficulty at birth.

Records of 34 hyperventilating children aged 18 years or younger seen at the Mayo Clinic over a 25-year period were reviewed. Five different clinical subtypes were identified. Evaluation and treatment varied considerably. At follow-up, 40% were still hyperventilating as adults, and many had signs and symptoms of chronic anxiety. Hyperventilation in childhood can be a signal that the child is experiencing severe anxiety, which may persist into adulthood.

AbstractAmyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is an aggressive motor neuron degenerative disease characterized by selective loss of both upper and lower motor neurons. The mechanisms underlying disease initiation and progression are poorly understood. The involvement of nonmotor neuraxis emphasizes the contribution of glial cells in disease progress. Microglia comprise a unique subset of glial cells and are the principal immune cells in the central nervous system (CNS). Triggering receptor expressed on myeloid cell 2 (TREM2) is a surface receptor that, within the CNS, is exclusively expressed on microglia and plays crucial roles in microglial proliferation, migration, activation, metabolism, and phagocytosis. Genetic evidence has linked TREM2 to neurodegenerative diseases including ALS, but its function in ALS pathogenesis is largely unknown. In this review, we summarize how microglial activation, with a specific focus on TREM2 function, affects ALS progression clinically and experimentally. Understanding microglial TREM2 function will help pinpoint the molecular target for ALS treatment.

Abstract Background Severe acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course. Methods We evaluated coronavirus disease 2019 (COVID-19) vaccine–related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes. Results A total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P < .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age <50 years, female sex, vaccine type, and antitumor necrosis factor and vedolizumab use were associated with severe systemic reactions to dose 2. Overall rates (2%) of IBD flare were low following vaccination. Conclusions Our findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.

SummaryBackgroundTofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open‐label, long‐term extension study.AimsThe primary objective of OCTAVE Open was to assess the safety and tolerability of long‐term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective.MethodsEligible patients included OCTAVE Induction 1&2 non‐responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient‐years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit).ResultsIn OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient‐years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09‐0.54); serious infections, 1.61 (1.14‐2.20); herpes zoster (non‐serious and serious), 3.16 (2.47‐3.97); opportunistic infections, 0.87 (0.54‐1.33); major adverse cardiovascular events, 0.16 (0.04‐0.42); malignancies (excluding non‐melanoma skin cancer), 1.03 (0.67‐1.52); non‐melanoma skin cancer, 0.75 (0.45‐1.19); deep vein thrombosis, 0.04 (0.00‐0.23); pulmonary embolism, 0.21 (0.07‐0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively.ConclusionTofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long‐term efficacy beyond the 52‐week maintenance study.