Citations

Post-acute sequelae of SARS-CoV-2 (PASC) is defined as persistent symptoms after apparent recovery from acute COVID-19 infection, also known as COVID-19 long-haul. We performed a retrospective review of electronic health records (EHR) from the University of California COvid Research Data Set (UC CORDS), a de-identified EHR of PCR-confirmed SARS-CoV-2-positive patients in California. The purposes were to (1) describe the prevalence of PASC, (2) describe COVID-19 symptoms and symptom clusters, and (3) identify risk factors for PASC. Data were subjected to non-negative matrix factorization to identify symptom clusters, and a predictive model of PASC was developed. PASC prevalence was 11% (277/2,153), and of these patients, 66% (183/277) were considered asymptomatic at days 0–30. Five PASC symptom clusters emerged and specific symptoms at days 0–30 were associated with PASC. Women were more likely than men to develop PASC, with all age groups and ethnicities represented. PASC is a public health priority.

Background Flow diverters have been widely used in clinical practice for more than a decade. However, most outcome data are limited to 1 year timepoints. This study aims to offer meta-analysis data on long-term (>1 year) safety and effectiveness results for patients with aneurysms treated with flow diverters. Methods PubMed, Web of Science, Embase, and SCOPUS were searched up to February 24, 2022 using the AutoLit platform. We included primary studies assessing the long-term outcomes for flow diverter devices to manage unruptured internal carotid artery aneurysms with a follow-up period of >1 year. The meta-analysis was carried out using Comprehensive Meta-Analysis software (CMA). Results Eleven studies were included in the meta-analysis. The pooled occlusion rates after flow diversion treatment for unruptured intracranial brain aneurysms were 77%, 87.4%, 84.5%, 89.4%, 96% for 1 year, 1–2 years, 2 years, 3 years, and 5 years follow-up, respectively. The in-stent stenosis rate was 4.8% and the retreatment rate for the long-term follow-up period was 5%. No delayed rupture of the aneurysm was reported, and there was one case of delayed ischemic stroke. The sensitivity analysis of the prospective studies showed a complete occlusion rate of 83.5% and 85.2% for 1 and 3 years of follow-up, respectively. Conclusion Flow diverters are safe and effective in short- and long-term follow-up and rarely cause serious delayed side effects.

Background. The Banff classification scheme provides a framework for interpreting transplant kidney biopsies and has undergone various updates in the past 2 decades especially related to antibody-mediated rejection. The clinical significance of early glomerulitis seen within 4 mo on protocol biopsies has received limited attention. We hypothesized that early glomerulitis seen on protocol biopsies will lead to significant adverse outcomes as assessed by histopathology and allograft outcome. Methods. A single-center retrospective study of a cohort of patients who underwent protocol biopsies within 4 mo after transplantation with timely follow-up protocol biopsies were assessed. Patients with recurrent glomerulonephritis were excluded. Results. We calculated glomerulitis (g) scores for 2212 biopsy specimens and identified 186 patients with glomerulitis (g > 0) and 2026 patients without glomerulitis (g = 0). The progression to chronic transplant glomerulopathy at 1 and 2 y was higher in patients with g > 0 as compared with g = 0 (year 1, 10.7% versus 2.3% [P < 0.001]‚ respectively; year 2, 17.2% versus 4.3% [P < 0.001], respectively) with no difference in other chronic lesions. The death-censored graft failure rate was higher in patients with g > 0 as compared with g = 0 (hazard ratio, 1.68 [95% CI, 1.07-2.65]; P = 0.02). We did not find any difference in outcomes in glomerulitis group based on donor-specific antibody. Conclusion. Our findings suggest that early glomerulitis (seen within 4 mo after transplantation) may lead to clinically significant long-term changes and thus could be a target for early intervention therapies.

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5–17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 μg/mL (SD 67) and a median of 22 μg/mL (interquartile range 12–38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

This webinar is the first of a new series that brings together international experts to discuss ongoing developments in cancer research. This webinar focusses on emerging therapeutics, with speakers covering areas including immunotherapy, metabolic targets, and the treatment of lung and colorectal cancers. Our panellists discuss these developments, their ongoing challenges, and their global perspectives.

TREM2 is exclusively expressed by microglia in the brain and is strongly linked to the risk for Alzheimer’s disease (AD). As microglial responses modulated by TREM2 are central to AD pathogenesis, enhancing TREM2 signaling has been explored as an AD therapeutic strategy. However, the effective therapeutic window targeting TREM2 is unclear. Here, by using microglia-specific inducible mouse models overexpressing human wild-type TREM2 (TREM2-WT) or R47H risk variant (TREM2-R47H), we show that TREM2-WT expression reduces amyloid deposition and neuritic dystrophy only during the early amyloid seeding stage, whereas TREM2-R47H exacerbates amyloid burden during the middle amyloid rapid growth stage. Single-cell RNA sequencing reveals suppressed disease-associated microglia (DAM) signature and reduced DAM population upon TREM2-WT expression in the early stage, whereas upregulated antigen presentation pathway is detected with TREM2-R47H expression in the middle stage. Together, our findings highlight the dynamic effects of TREM2 in modulating AD pathogenesis and emphasize the beneficial effect of enhancing TREM2 function in the early stage of AD development.

BACKGROUND: Current literature has identified textbook outcome (TO) as a quality metric after cancer surgery. We studied whether TO after pancreatic resection has a stronger association with long-term survival than individual hospital case volume. STUDY DESIGN: Patients undergoing surgery for pancreatic adenocarcinoma from 2010 to 2015 were identified from the National Cancer Database. Hospitals were stratified by volume (low less than 6, medium 6 to 19, and high 20 cases or more per year), and overall survival data were abstracted. We defined TO as adequate lymph node count, negative margins, length of stay less than the 75th percentile, appropriate systemic therapy, timely systemic therapy, and without a mortality event or readmission within 30 days. The association of TO and case volume was assessed using a multivariable Cox regression model for survival. RESULTS: Overall, 7270 patients underwent surgery, with 30.7%, 48.7%, and 20.6% performed at low-, medium-, and high-volume hospitals, respectively. Patients treated at low-volume hospitals were more likely to be Black, be uninsured or on Medicaid, have higher Charlson comorbidity scores, and be less likely to achieve TO (23.4% TO achievement vs 37.5% achievement at high-volume hospitals). However, high hospital volume was no longer associated with overall survival once TO was added to the multivariable model stratified by volume status. Achievement of TO corresponded to a 31% decrease in mortality (hazard ratio 0.69; p < 0.001), independent of hospital volume. CONCLUSIONS: Improved long-term survival after pancreatic resection was associated with TO rather than high hospital volume. Quality improvement efforts focused on TO criteria have the potential to improve outcomes irrespective of case volume.

Abstract Background Hidradenitis suppurativa (HS) is associated with substantial morbidity. Few studies have addressed the natural history and mortality rates associated with HS. A higher risk of cardiovascular death in patients with HS has been reported. We investigated whether patients with HS have an increased overall risk of death compared with age‐ and gender‐matched referents. Methods We performed a retrospective cohort study of residents of Olmsted County, Minnesota, with incident HS between January 1, 1980, and December 31, 2008, and age‐ and gender‐matched referents. The main outcomes and measures were the overall and cause‐specific risks of death. Results We identified 226 incident cases of HS and 678 age‐ and gender‐matched referents among Olmsted County residents during the study period. Compared to referents, patients with HS had a significantly higher risk of all‐cause death (hazard ratio [HR, 2.48; 95% CI, 1.53–4.03, P < 0.001) and cardiovascular‐ or cerebrovascular‐related death (HR, 2.85; 95% CI, 1.10–7.40, P = 0.03). However, these risks were attenuated by adjusting for smoking history: all‐cause HR, 1.65 (95% CI, 0.97–2.82, P = 0.07) and cardiovascular‐ or cerebrovascular‐related HR, 2.03 (95% CI, 0.71–5.81, P = 0.18). The 71% of patients were former or current smokers at the time of HS diagnosis. Conclusions Hidradenitis suppurativa patients have a substantially increased risk of death from any cause, including cardiovascular or cerebrovascular causes; the risk is especially dependent on smoking history.

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system that is manifested as secondary myelin loss. Oligodendrocyte progenitor cells (OPCs) are the principal source of myelinating oligodendrocytes (OLs) and are abundant in demyelinated regions of NMOSD patients, thus possibly representing a cellular target for pharmacological intervention. To explore the therapeutic compounds that enhance myelination due to endogenous OPCs, we screened the candidate drugs in mouse neural progenitor cell (NPC)‐derived OPCs. We identified drug edaravone, which is approved by the Food and Drug Administration (FDA), as a promoter of OPC differentiation into mature OLs. Edaravone enhanced remyelination in organotypic slice cultures and in mice, even when edaravone was administered following NMO‐IgG‐induced demyelination, and ameliorated motor impairment in a systemic mouse model of NMOSD. The results of mechanistic studies in NMO‐IgG‐treated mice and the biopsy samples of the brain tissues of NMOSD patients indicated that the mTORC1 signaling pathway was significantly inhibited, and edaravone promoted OPC maturation and remyelination by activating mTORC1 signaling. Furthermore, pharmacological activation of mTORC1 signaling significantly enhanced myelin regeneration in NMOSD. Thus, edaravone is a potential therapeutic agent that promotes lesion repair in NMOSD patients by enhancing OPC maturation.