Preventive effects of pneumococcal and influenza vaccines on community-acquired pneumonia in older individuals in Japan: a case-control study

At present, there are few reports that have clarified the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia or pneumococcal pneumonia in community-acquired pneumonia (CAP) in older individuals in Japan. We conducted a hospital-based matched case-control study to investigate separately the preventive effects of PPSV23 and trivalent influenza vaccine (TIV) on all-cause CAP and pneumococcal CAP in older individuals in Japan. Cases were individuals aged 65 years or older who were newly diagnosed with CAP from October 2010 to September 2014. Two control patients with a different disease (one respiratory medicine and one non-respiratory medicine) matched for sex, age, date of outpatient visit, and medical institution were selected for each case. Odds ratios (ORs) and 95% confidence intervals (CIs) of PPSV23 and TIV for the occurrence of all-cause CAP and pneumococcal CAP were calculated using conditional and unconditional logistic regression models. The analysis included 161 cases and 308 controls from the 4-year period. The adjusted OR for the occurrence of all-cause CAP was 0.76 (95%CI = 0.44–1.32) with PPSV23 vaccination and 0.79 (95%CI = 0.50–1.25) with TIV vaccination compared with unvaccinated individuals. When the outcome index was restricted to pneumococcal CAP, the adjusted OR significantly decreased to 0.23 (95%CI = 0.08–0.66) with PPSV23 vaccination, but not with TIV vaccination (adjusted OR = 0.65, 95%CI = 0.31–1.36). PPSV23 vaccination is likely effective in reducing incidence of pneumococcal CAP in older individuals, although its preventive effect for all-cause CAP has not been achieved

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan

Objectives This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity.Design Retrospective observational study of a nationwide database.Setting The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint.Participants This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018.Main outcome measure The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis.Results The median time to surgery was 9 months (IQR 4–22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years.Conclusion ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact.Trial registration number Chiba University ID1049

Inflammation in Alzheimer’s disease: Lessons learned from microglia-depletion models

Microglia are the primary immune cell of the brain and function to protect the central nervous system (CNS) from injury and invading pathogens. In the homeostatic brain, microglia serve to support neuronal health through synaptic pruning, promoting normal brain connectivity and development, and through release of neurotrophic factors, providing support for CNS integrity. However, recent evidence indicates that the homeostatic functioning of these cells is lost in neurodegenerative disease, including Alzheimer’s disease (AD), ultimately contributing to a chronic neuroinflammatory environment in the brain. Importantly, the development of compounds and genetic models to ablate the microglial compartment has emerged as effective tools to further our understanding of microglial function in AD. Use of these models has identified roles of microglia in several pathological facets of AD, including tau propagation, synaptic stripping, neuronal loss, and cognitive decline. Although culminating evidence utilizing these microglial ablation models reports an absence of CNS-endogenous and peripheral myeloid cell involvement in Aβ phagocytosis, recent data indicates that targeting microglia-evoked neuroinflammation in AD may be essential for potential therapeutics. Therefore, identifying altered signaling pathways in the microglia-devoid brain may assist with the development of effective inflammation-based therapies in AD

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for eosinophilic granulomatosis with polyangiitis

Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1 × 109/liter (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (−3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1), and hematuria (−1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% confidence interval [95% CI] 77–91%) and the specificity was 99% (95% CI 98–100%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for EGPA demonstrate strong performance characteristics and are validated for use in research