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Background The objective of this systematic review and meta-analysis is to investigate whether nocturnal blood pressure fall, expressed by dipping patterns according to 24 h ambulatory blood pressure monitoring (ABPM), is associated with abnormal cognitive function (cognitive impairment or dementia). Methods We systematically searched PubMed, Embase, and Cochrane databases to identify original articles through December 2022. We included any study with at least ten participants reporting on all-cause dementia or cognitive impairment incidence (primary outcome) or validated cognitive tests (secondary outcome) among ABPM patterns. We assessed risk of bias using Newcastle–Ottawa Quality Assessment Scale. We pooled odds ratios (OR) and standardized mean differences (SMD) using random-effect models for primary and secondary outcome, respectively. Results In the qualitative synthesis, 28 studies examining 7595 patients were included. The pooled analysis of 18 studies showed that dippers had a 51% [OR 0.49(0.35–0.69)] lower risk of abnormal cognitive function and a 63% [OR 0.37(0.23–0.61)] lower risk of dementia alone, compared to non-dippers. Reverse dippers presented an up to sixfold higher risk [OR 6.06(3.15–11.64)] of abnormal cognitive function compared to dippers and an almost twofold higher risk [OR 1.81(1.26–2.6)] compared to non-dippers. Reverse dippers performed worse in global function neuropsychological tests compared with both dippers [SMD − 0.66(− 0.93 to − 0.39)] and non-dippers [SMD − 0.35(− 0.53 to − 0.16)]. Conclusion Dysregulation of the normal circadian BP rhythm, specifically non-dipping and reverse dipping is associated with abnormal cognitive function. Further studies are required to determine potential underlying mechanisms and possible prognostic or therapeutic implications. Protocol registration PROSPERO database (ID: CRD42022310384).

The objective of this systematic review and meta‐analysis is to determine whether nocturnal blood pressure fall, expressed by dipping patterns according to ambulatory blood pressure monitoring (ABPM), is a risk factor for cardiovascular events (CVEs) in untreated hypertensives. Α thorough systematic literature search at MEDLINE, Embase, Cochrane Library, and gray literature was conducted through March 2020. Two reviewers screened studies and assessed dipping patterns of untreated hypertensives using ABPM with a follow‐up >6 months. Newcastle‐Ottawa scale was used for risk of bias assessment. We initially identified 463 reports; of which, seven cohort studies were eligible for meta‐analysis enrolling 10 438 untreated hypertensives. Untreated patients classified as dippers at baseline (n = 7081) had significant lower risk of CVEs and total mortality compared to non‐dippers (n = 3,357) [RR = 0.67, 95% CI (0.49, 0.92); RR = 0.71, 95% CI (0.59, 0.86)]. However, when patients were further classified into four dipping groups, only reverse dippers, yet not extreme dippers or non‐dippers, were at increased risk for CVEs compared to dippers [RR = 0.47, 95% CI (0.33, 0.66)]. Likewise, only reverse dippers had a higher stroke risk than dippers [RR = 0.39, 95% CI (0.22, 0.72)]. When compared with the whole group of dippers (including extreme dippers), non‐dipping alone (excluding reverse dipping) was not a significant risk factor for CVEs [RR = 0.84, 95% CI (0.61, 1.16)] or total mortality [RR = 0.84, 95% CI (0.61, 1.16); RR = 0.78, 95% CI (0.53, 1.13), respectively]. Untreated hypertensives may benefit more from the evaluation of reverse dipping rather than the non‐dipping phenomenon in general.

Accumulating evidence points toward a protective role of intestinal microbiota diversity in allogeneic hematopoietic cell transplantation (allo-HCT). The purpose of this systematic review and meta-analysis is to determine the effect of antibiotic-mediated disruption of microbiota on main allo-HCT outcomes (graft-versus-host disease [GVHD], treatment-related mortality [TRM], overall survival [OS]). Following literature search, 2 reviewers screened eligible studies and assessed risk of bias (RoB). Meta-analysis was performed using Review Manager Software. Among 443 screened references, 18 were eligible for meta-analysis. In studies with genomic markers, grade II to IV acute GVHD was significantly reduced in patients not receiving gut decontamination (GD) (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.20 to 2.04). In subgroup analysis, prophylaxis with systemic antibiotics conferred an increased risk of acute GVHD (OR, 1.65; 95% CI, 1.08 to 2.53). When we incorporated RoB, we found a positive correlation of intestinal GVHD with GD (OR, 1.77; 95% CI, 1.29 to 2.44). Patients with higher microbiota diversity presented increased OS (risk ratio [RR], 1.58; 95% CI, 1.19 to 2.09) and lower TRM (RR, 0.45; 95% CI, 0.26 to 0.76). Our findings confirm that GD and prophylaxis with systemic antibiotics increase acute and intestinal GVHD. Importantly, our meta-analysis was the first to show a significant effect of microbiota diversity on TRM and OS.

Introduction:COVID-19 pandemic caused a major disruption to healthcare system. A year after COVID-19 outbreak, the question remains to what extent the lockdowns changed the volume of non-infected patients who were admitted to the Neurologic Department (ND). To determine the impact of the pandemic´s first year on a tertiary ND. Methods:non-infected patients admitted to ND between March 2020 and February 2021 were examined. A control group was generated for the same time interval starting from March 2019. Primary outcomes were the number of patients presenting with neurologic complaint who were admitted to the hospital and the diagnosis type. Secondary outcomes were hospitalization length and patients´ outcome. Results:overall, 816 patients (49.4% females) were admitted during the predetermined periods. Median age was 55 years. Median length of hospitalization was six days. We observed a 47.2% reduction in our department´s admissions during pandemic (n=282). None of the examined variables (type of neurologic diagnosis, age, gender, hospitalization length and outcome) changed significantly during pandemic. However, the number of patients admitted during the pandemic with a diagnosis categorized as “other” was statistically significant lower compared to the year before COVID-19 (p=0.007). Hospitalization length was associated only with patients´ age. Conclusion:our study examined for the first-time the consequences of the first year of COVID-19 pandemic on ND admissions. COVID-19 outbreak resulted in decreased admissions. Delays in seeking medical consultation for urgent or undiagnosed neurologic conditions require rigorous long-term monitoring to fully understand the impact of COVID-19 pandemic on patients with neurologic diseases.

Evidence for nusinersen administration in adult 5q spinal muscular atrophy (5q-SMA) patients is scarce and based on real-world observational data. The present systematic review and meta-analysis aimed to explore the efficacy and safety of nusinersen in patients older than 12 years of age with 5q-SMA. We searched MEDLINE, EMBASE, the Cochrane Library, and grey literature through April 2021. Cross-sectional studies, case reports, review articles, and studies with follow-up less than 6 months were excluded. We included 12 records (seven case-series, five cohorts) representing 11 population cohorts and enrolling 428 SMA patients. We observed statistically significant improvements on motor function Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores at the longest follow-up assessments [SMD = 0.17(95% CI 0.01–0.33), SMD = 0.22(95% CI 0.06–0.38), respectively]. HFMSE and RULM significant improvements were also detected at the subgroup analysis during 10 and 14 months. HFMSE and RULM amelioration occurred earlier in patients with SMA type 3 or 4 during short-term analysis (≤ 6 months). 6-min walk tests (6MWT) and pulmonary function tests did not change. Minimal clinically important differences in HFMSE and RULM were observed in 43.3% (95% CI 34.5–52.3) and 38.9% (95% CI 27.7–50.7), respectively. Severe adverse events were reported in 2% (95% CI 0–5.8). Treatment withdrawal rate was 3% (95% CI 0.5–6.6). Despite the low quality of evidence and the unmet need for randomized data to establish the safety and efficacy of nusinersen in adults, our meta-analysis confirms that nusinersen is a valuable treatment option for older patients with longer-disease duration. Trial registration: PROSPERO database CRD42020223109. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01200-3.

Limited and conflicting data exist on outcomes of patients with extramedullary relapses (EMRs) after allogeneic hematopoietic cell transplantation (allo-HCT) for acute leukemias. We retrospectively reviewed charts of consecutive allo-HCT recipients who underwent transplantation in our center with the indication of acute leukemia (July 1990 to July 2018). Incidences of isolated EMR (iEMR) and bone marrow relapse (BMR) were calculated using cumulative incidence (CI) analysis, with each and treatment-related mortality considered a competing risk. We studied 554 allo-HCT recipients for 1.8 years (range, .04 to 27.75). Ten-year CI of 10.5% for iEMR was associated only with advanced disease phase at transplantation, whereas 10-year CI of 34.8% for BMR was independently associated with pretransplant disease phase, lines of treatment, and fungal infections. Most iEMR and BMR patients (75% and 81%, respectively) received systemic treatment combined with local radiation for iEMR (26%) and donor lymphocyte infusions (16% and 28%, respectively) when feasible. Extensive chronic graft-versus-host disease (GVHD) was recorded in 47% of iEMR and 48% of BMR patients. Outcomes were poor both in iEMR (10-year overall survival [OS], 18.3%) and BMR (10-year OS, 19.1%). Independent predictors of OS were disease phase, type of donor, acute and chronic GVHD, fungal infections, iEMR, and BMR. In a large population with long-term follow-up, incidence of iEMR was relatively high, developed at the late post-transplant period, and was associated only with disease phase at transplantation. Furthermore, iEMR and BMR conferred similarly poor outcomes despite systemic treatment or extensive chronic GVHD.

Immunotherapy with chimeric antigen receptor T (CAR-T cells) has been recently approved for patients with relapsed/refractory B-lymphoproliferative neoplasms. Along with great efficacy in patients with poor prognosis, CAR-T cells have been also linked with novel toxicities in a significant portion of patients. Cytokine release syndrome (CRS) and neurotoxicity present with unique clinical phenotypes that have not been previously observed. Nevertheless, they share similar characteristics with endothelial injury syndromes developing post hematopoietic cell transplantation (HCT). Evolution in complement therapeutics has attracted renewed interest in these life-threatening syndromes, primarily concerning transplant-associated thrombotic microangiopathy (TA-TMA). The immune system emerges as a key player not only mediating cytokine responses but potentially contributing to endothelial injury in CAR-T cell toxicity. The interplay between complement, endothelial dysfunction, hypercoagulability, and inflammation seems to be a common denominator in these syndromes. As the indications for CAR-T cells and patient populations expand, there in an unmet clinical need of better understanding of the pathophysiology of CAR-T cell toxicity. Therefore, this review aims to provide state-of-the-art knowledge on cellular therapies in clinical practice (indications and toxicities), endothelial injury syndromes and immunity, as well as potential therapeutic targets.