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Introduction Hidradenitis suppurativa (HS) is a frequently debilitating, inflammatory skin condition. Patients may have a limited response to adalimumab, currently the only Food and Drug Administration (FDA)-approved biologic treatment for HS. Ustekinumab is an interleukin-12/23 inhibitor that has been utilized in HS, but there is a lack of an updated systematic review on its efficacy and safety. The aim of this study is to perform a systematic review and meta-analysis of the literature on the efficacy and safety of ustekinumab for HS. Methods In October 2022, MEDLINE and Embase databases were searched for articles on ustekinumab in HS. Data extraction was performed on relevant articles by two reviewers. The primary study outcome was the pooled response rate of HS to ustekinumab. A fixed-effects meta-analysis was performed, and Cochran’s Q statistic and I squared index were used to assess heterogeneity. Statistical significance was determined at p  < 0.05. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Results From 2012 to 2022, ten articles (nine case series and one prospective trial) with 88 patients met the inclusion criteria. Patients with reported disease severity had Hurley stage II (17.6%, 12/68) or III (82.4%, 56/68) disease. The majority (80.7%, 71/88) had previously failed at least one biologic treatment. A meta-analysis of all ten studies showed a pooled response rate of 67% (95% CI 0.57–0.76). Study limitations include a small number of patients and randomized controlled trials (RCTs). Conclusions Ustekinumab may be a helpful treatment option to consider for HS that is recalcitrant to first-line biologic therapies, but RCTs are needed to determine optimal dosing regimens and the specific patient populations that would benefit the most from this agent.

Background Microglia responses to Aβ and tau pathology and the dysregulation of the microglial role in synaptic function may determine the onset and course of Alzheimer’s disease (AD). While significant work has been performed in mouse models, we still lack a complete understanding of physiological and pathological microglial states and functions in human AD brain. Method For immunoblotting of brain homogenates against multiple microglial markers, and flow cytometry (FC) analysis of synaptosomal fractions (SNAP25/CD47/Aβ(10G4)/phospho‐tau(AT8)), 49 cryopreserved human parietal cortex samples were categorized into four groups: low pathology control (LPC), high Aβ control (HAC), high pathology control (HPC), and AD. Selected microglia markers were assessed in the snRNAseq dataset (Rexach et al., 2023, bioRxiv) and validated by immunohistochemistry (IHC) analysis. Result In the LPC group, only 22.5% of Aβ‐positive (+)/p‐tau‐negative (‐) synaptosomes expressed CD47 on their surface, with a significant progressive increase in the percentage (%) of CD47+ events in the Aβ+/p‐tau‐ group across disease stages, reaching 53.4% in the AD group. Surprisingly, Aβ+/tau+ synaptosomes expressed the highest CD47 levels, suggesting protection from elimination. Higher levels of P2ry12 and CD206 were found in the LPC group compared to all other groups in brain homogenates. Interestingly, the levels of P2ry12, CD206, and Axl1 were significantly higher, and the level of Clec7a was significantly lower in the HPC group compared to the AD group. Linear regression modeling revealed a significant negative association between P2ry12 and synaptic tau pathology, as well as CD47 expression in p‐tau‐positive synaptosomes. Interestingly, in primary tauopathy microglia (but not AD microglia), IKFZ1‐regulated genes, including P2ry12, were upregulated according to snRNAseq and around p‐tau‐bearing neurons by IHC. Conclusion Our data suggest that in normal aging, synaptic Aβ accumulation leads to a diminishing of synaptic CD47 (‘don’t eat me’) signal, accelerating the clearance of malfunctioning Aβ but not p‐tau positive synapses. Upregulation of P2ry12 and CD206, accompanied by downregulation of Clec7a, may represent an early and potentially protective response to pre‐tangle tau pathology. Later in disease progression, P2ry12 reduction may drive a more reactive, phagocytic phenotype in response to tau pathology, leading to an increase in synaptic CD47 levels and synaptic pathology accumulation.

Microglia responses to Aβ and tau pathology and the dysregulation of the microglial role in synaptic function may determine the onset and course of Alzheimer's disease (AD). While significant work has been performed in mouse models, we still lack a complete understanding of physiological and pathological microglial states and functions in human AD brain. For immunoblotting of brain homogenates against multiple microglial markers, and flow cytometry (FC) analysis of synaptosomal fractions (SNAP25/CD47/Aβ(10G4)/phospho-tau(AT8)), 49 cryopreserved human parietal cortex samples were categorized into four groups: low pathology control (LPC), high Aβ control (HAC), high pathology control (HPC), and AD. Selected microglia markers were assessed in the snRNAseq dataset (Rexach et al., 2023, bioRxiv) and validated by immunohistochemistry (IHC) analysis. In the LPC group, only 22.5% of Aβ-positive (+)/p-tau-negative (-) synaptosomes expressed CD47 on their surface, with a significant progressive increase in the percentage (%) of CD47+ events in the Aβ+/p-tau- group across disease stages, reaching 53.4% in the AD group. Surprisingly, Aβ+/tau+ synaptosomes expressed the highest CD47 levels, suggesting protection from elimination. Higher levels of P2ry12 and CD206 were found in the LPC group compared to all other groups in brain homogenates. Interestingly, the levels of P2ry12, CD206, and Axl1 were significantly higher, and the level of Clec7a was significantly lower in the HPC group compared to the AD group. Linear regression modeling revealed a significant negative association between P2ry12 and synaptic tau pathology, as well as CD47 expression in p-tau-positive synaptosomes. Interestingly, in primary tauopathy microglia (but not AD microglia), IKFZ1-regulated genes, including P2ry12, were upregulated according to snRNAseq and around p-tau-bearing neurons by IHC. Our data suggest that in normal aging, synaptic Aβ accumulation leads to a diminishing of synaptic CD47 ('don't eat me') signal, accelerating the clearance of malfunctioning Aβ but not p-tau positive synapses. Upregulation of P2ry12 and CD206, accompanied by downregulation of Clec7a, may represent an early and potentially protective response to pre-tangle tau pathology. Later in disease progression, P2ry12 reduction may drive a more reactive, phagocytic phenotype in response to tau pathology, leading to an increase in synaptic CD47 levels and synaptic pathology accumulation.

Hidradenitis suppurativa (HS) is a chronic, debilitating skin condition that requires multimodal treatment. Adherence remains a significant challenge for many patients due to complex nature of treatment, thus presenting a barrier to management success. This review summarizes the current literature on the factors associated with adherence to medications, and lifestyle behaviors in patients with HS and proposes strategies to improve adherence. In February 2023, a systematic literature search was conducted by two independent authors on PubMed and EMBASE for articles from 2000 to 2023 on hidradenitis suppurativa adherence. A total of 21 articles met inclusion/exclusion criteria for this review. Of the studies, 11 addressed systemic medication adherence, 3 addressed topical medication adherence, 2 addressed both systemic and topical medication adherence, and 5 addressed lifestyle/behavioral modification adherence. The generalizability of results was limited by differences in study design, outcome measures, and sample size. English-only articles with full texts were used. The most reported reasons for non-adherence included presence of side effects, cost of medications, low efficacy, and unclear instructions. Proposed strategies to improve adherence in HS patients include management of side effects, use of reminder systems, improved patient education, patient support groups, aid of family and caregivers, personalization of the medication regimen, and regular follow-ups with patients. PROSPERO Registration Number : CRD42023488549.

BackgroundLong-COVID is a condition post SARS-CoV-2 infection with persistent or recurring symptoms affecting multiple organs, and may involve viral persistence, changes to the microbiome, coagulopathies, and alterations to neuro-immune interactions. These factors can disrupt the Gut-Brain Axis, which is a complex system involving bidirectional communication between the central nervous system and the gastrointestinal (GI) system. As a result of these disruptions, individuals with long-COVID may develop post-infectious functional GI disorders, which can cause a range of symptoms affecting the digestive system.AimTo understand frequency of GI manifestations of Long-COVID and to determine association with sleep or neurological symptoms in a predominantly minority population.MethodsWe included patients with positive SARS-CoV-2 PCR (n = 747) who were hospitalized from Feb. 2020 to May 2021 at Howard University Hospital and followed between 6 and 12 months from discharge. GI, sleep, and neurological symptoms (via the Montreal Cognitive Assessment (MoCA) scoring system) were assessed using a standardized questionnaire. Linear regression analysis, χ2 and Fisher's exact test were utilized to determine the statistical significance of correlations of GI/Neuro/COVID.ResultsThe mean age of patients was 58, with 51.6% females and a predominant African American ethnicity (73.6%, n = 550). A total of 108 patients died during their initial hospital stay, with the remaining 639 patients followed-up. Three hundred fifty (350) patients responded to the questionnaire (57 patients died during the follow-up period). Overall, 39 (13.3%) patients reported GI-related symptoms, out of which 19 (6.4%) had persistent symptoms and 20 (6.8%) developed new onset GI symptoms. Nausea and vomiting were the most common 24/39 (61.5%), followed by abdominal pain 7/39 (18%), diarrhea 5/39 (12.8%), and others 3/39 (7.6%). Patients who presented with vomiting during acute SARS-CoV-2 infection were more likely to have Long-COVID GI manifestations (P = 0.023). Use of ACE inhibitors, abnormal lymphocyte count and elevated ferritin are other variables that showed significant associations with Long-COVID GI manifestations (P = 0.03, 0.006 and 0.03, respectively). During follow-up, a total of 28 (9.5%) patients reported difficulty with sleep and 79 (27%) patients had abnormal MoCA assessment. With further analysis, there was a trend between presentation of GI symptoms on admission with abnormal MoCA assessment, and an association between abnormal LFTs and history of liver disease during hospitalization with subsequent sleep problems. Baseline characteristics, clinical comorbidities, other laboratory values, hospital length of stay, mechanical ventilation, medications during hospitalization, re-admission and Flu or COVID-19 vaccination have not shown any association with Long-COVID GI symptoms in our cohort.ConclusionDyspeptic symptoms were common GI manifestations in the acute and post COVID periods. GI symptoms, abnormal LFTs and a history of liver disease during the acute infectious phase associates with abnormal MoCA and sleep problems during follow-up. Further large population studies are needed to determine if COVID-19 leads to a GI symptoms-associated Long-COVID phenotypes and other symptoms through the Gut–Brain-Axis.