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The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.(Met280Asnfs*5)) and C8B (c.1625C>T; p.(Thr542Ile)) are known individually, here, we report on a patient carrying their combination in a heterozygous form. The patient presented with a reduced general condition and suffers from a wide variety of autoimmune diseases. While no autoimmune disease-specific autoantibodies could be detected, genetic analysis revealed abnormalities in the two complement genes C2 and C8B. Therefore, we performed a comprehensive investigation of the innate immune system on a cellular and humoral level to define the functional consequences. We found slightly impaired functionality of neutrophils and monocytes regarding phagocytosis and reactive oxygen species generation and a diminished expression of the C5aR1. An extensive complement analysis revealed a declined activation potential for the alternative and classical pathway. Reconstitution with purified C2 and C8 into patient serum failed to normalize the dysfunction, whereas the addition of C3 improved the hemolytic activity. In clinical transfer, in vitro supplementation of the patient’s plasma with FFP as a complement source could fully restore full complement functionality. This study describes for the first time a combined heterozygous genetic variation in complement C2 and C8B which, however, cannot fully explain the overall dysfunctions and calls for further complement deficiency research and corresponding therapies.

The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study’s findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.

This longitudinal study investigates the psychosocial effects of long-COVID Syndrome, a domain still not extensively researched. It specifically evaluates the quality of life, coping mechanisms, anxiety and depression levels in COVID-19 survivors, differentiating between those with and without long-COVID Syndrome. Conducted at the Victor Babes Hospital for Infectious Diseases and Pulmonology in Timisoara, Romania, the study utilized a cohort of patients diagnosed with mild to moderate COVID-19. The following standardized tools: WHOQOL-BREF for quality of life, COPE-60 for coping strategies, and the Hospital Anxiety and Depression Scale (HADS), were employed for the assessment. The sample consisted of 86 patients displaying persistent post-acute symptoms and 432 asymptomatic patients at the 6-month post-discharge mark. Patients with frequent post-acute symptoms reported significantly higher levels of fatigue (8.2 ± 1.4), cognitive difficulties (7.5 ± 1.6), and respiratory challenges (7.8 ± 1.3), along with a markedly lower overall quality of life (7.0 ± 1.5) compared to their asymptomatic counterparts. HADS scores revealed elevated depression (6.8 ± 1.9) and anxiety (7.1 ± 2.3) in the symptomatic group. Quality of life, as evaluated through the use of WHOQOL-BREF, showed lower scores in the symptomatic cohort across physical (58.8 ± 15.8), mental (56.3 ± 16.4), and social domains (50.2 ± 17.5). COPE-60 findings indicated a higher prevalence of disengagement (56.4%) and emotion-focused coping strategies (61.8%) in the symptomatic group, in contrast to 30.1% and 37.0%, respectively, in the asymptomatic group. The study highlights that long-COVID Syndrome significantly deteriorates the quality of life and is associated with increased depression and anxiety levels. The prevalent use of disengagement and emotion-focused coping strategies among patients with persistent symptoms suggests a need for enhanced psychosocial support tailored to this subgroup.

Background and Objectives: This comprehensive retrospective study assesses COVID-19 outcomes in type 1 (T1D) and type 2 diabetes (T2D) patients across three years, focusing on how these outcomes varied with the evolving pandemic and changes in diabetes management. The study aims to determine if COVID-19 outcomes, including severity, intensive care unit (ICU) admission rates, duration of hospitalization, and mortality, are significantly different between these diabetes subtypes. Materials and Methods: The study analyzed data from patients admitted to the Victor Babes Hospital for Infectious Diseases and Pulmonology with confirmed COVID-19 and pre-existing diabetes, from the years 2020, 2021, and 2022. Results: Among 486 patients (200 without diabetes, 62 with T1D, 224 with T2D), T2D patients showed notably higher severity, with 33.5% experiencing severe cases, compared to 25.8% in T1D. Mortality rates were 11.6% in T2D and 8.1% in T1D. T2D patients had longer hospital stays (11.6 ± 7.0 days) compared to T1D (9.1 ± 5.8 days) and were more likely to require ICU admission (OR: 2.24) and mechanical ventilation (OR: 2.46). Hyperglycemia at admission was significantly higher in the diabetes groups, particularly in T2D (178.3 ± 34.7 mg/dL) compared to T1D (164.8 ± 39.6 mg/dL). Conclusions: The study reveals a discernible difference in COVID-19 outcomes between T1D and T2D, with T2D patients having longer hospital admissions, mechanical ventilation necessities, and mortality risks.

Este estudo objetiva apresentar, por meio da análise de cocitações, a estrutura da produção científica que fornece base para estudos sobre mercados de agricultores e sistemas agroalimentares locais. O método utilizado foi exploratório e os dados para as análises foram constituídos de artigos científicos recuperados na base Web of Science. Os resultados revelaram que os estudos sobre esse tema se iniciaram na década de 1940, mais precisamente em 1944, mas só a partir de 2000 ocorreu aumento significativo nas pesquisas. A Análise Fatorial Exploratória (AFE) revela que a estrutura da produção científica sobre mercados de agricultores e sistemas agroalimentares locais é explicada, em 72,24% dos casos, por 84 artigos, para os quais foi possível fazer um agrupamento em cinco dimensões: as definições constitutivas das economias locais alimentares alternativas; as características dos sistemas alimentares locais; a diversidade das redes alimentícias alternativas; a busca por práticas inovadoras e melhorias de gestão nas redes agroalimentares locais alternativas; e locus da dinâmica de redes alternativas agroalimentares onde a relação consumidor/produtor é priorizada. Este estudo reforça a necessidade de continuidade de investigações visando à busca de um entendimento progressivo a respeito do importante papel dos mercados de agricultores e dos sistemas agroalimentares locais na sociedade. Futuras pesquisas poderiam explorar as formas e as possibilidades de aproximação entre produtor e consumidor na cadeia de circuitos curtos de abastecimento de alimentos nos mercados de agricultores.

Background: Carotid artery intraluminal thrombus (ILT), or free-floating thrombus, is an uncommon cerebrovascular entity with considerable equipoise regarding its clinical management. Likewise, in patients treated with medical management (MM), distal embolization and/or intracranial hemorrhage (ICH) may still occur., Methods: All patients with symptomatic ILT from 2016 to 2023 were identified from our tertiary care institution. Patients with MM failure (recurrent cerebral ischemia and/or symptomatic ICH) were compared with patients with MM non-failure. Differences in ILT volume and length were calculated. Receiver operator characteristic (ROC) curve analysis was used to identify the cut-off volume and length for risk of MM failure., Results: In total, 45 patients with ILT were identified with 41 treated with frontline MM. Of these 41 patients treated with MM, seven (17%) had MM failure with six (14.6%) having new embolic stroke and one (2.3%) with symptomatic ICH. Patients with MM failure had a significantly higher mean thrombus volume than MM non-failure patients (257 mm 3 vs 59.6 mm 3 , P=0.0006). Likewise, patients with MM failure had significantly longer thrombus on average (21 mm vs 6.6 mm, P=0.0009). ROC curve analysis showed that an ILT volume of 90 mm 3 resulted in a sensitivity of 71.4% and specificity of 85.3% for MM failure (AUC 0.775; CI 0.55 to 1.0, P=0.023)., Conclusions: Carotid ILTs that fail MM are significantly larger and longer. These findings suggest that a thrombus volume of 90 mm 3 may serve as a guide for intervention with good sensitivity and specificity for risk of MM failure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Infection of astrocytes by Human Immunodeficiency Virus (HIV-1) remains a topic of debate, with conflicting data, yet instances of astrocytes containing viral DNA have been observed in vivo . In this study, we aimed to elucidate potential routes through which astrocytes could be infected and their ability to produce infectious particles using primary human astrocytes., Methods: We infected primary astrocytes derived from either neuroprogenitor cells (NPCs) or induced pluripotent stem cells (iPSCs) that express both C-X-C chemokine receptor type 4 (CXCR4) and the C-C chemokine receptor type 5 (CCR5) coreceptors, using either cell-free HIV-1 virus directly or cell-associated virus indirectly through infected macrophages and microglia., Results: Low-level infectivity by cell-free viruses was primarily attributed to a defect in the entry process. Bypassing HIV-specific receptor-mediated entry using pseudotyped viruses resulted in productive infection and the release of infectious particles., Conclusions: These findings suggest that astrocytes may be one of the potential sources of neurotoxicity in HIV-associated neurocognitive disorders (HAND) and could possibly act as reservoirs for HIV in the central nervous system (CNS)., (© 2024 The Author(s). Published by IMR Press.)

Acute injuries trigger an intense activation of the body's defense mechanisms aiming to limit damage and initiate healing. Among the crucial components of the intravascular immune system, the complement system plays a significant role in traumatic injuries, albeit often negatively. It has been suggested that excessive activation of the complement system, transitioning from a localized and timed response to a systemic one, can lead to a loss of its host-protective characteristics. Complement activation products have been associated with the severity of injuries, which sometimes serve as predictors for the onset of organ dysfunctions. Animal studies utilizing complement-targeting agents have provided the basis for considering complement in the management of traumatic injuries in humans. However, numerous studies suggest that the spatial and temporal aspects of complement inhibition are crucial for its efficacy. Understanding the underlying mechanism of the injury is essential to determine where, when, and whether complement inhibition is warranted. Despite the detrimental effects of uncontrolled complement activation, its regulated activation may contribute to essential aspects of healing, such as waste removal and regeneration. This review focuses on the beneficial roles of complement activation in trauma, which are often overlooked or given less consideration but are of immense importance., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

HIV stigma has a negative influence on antiretroviral therapy (ART) initiation and persistence and viral suppression. Immediate access to ART (RAPID ART) has been shown to accelerate viral suppression (VS) that is sustained up to one year after HIV diagnosis. Little is known about the role of RAPID ART in reducing individual-level stigma. We explored how stigma manifests in RAPID ART encounters and whether RAPID ART interventions influence individual-level HIV stigma during and in the time immediately after the diagnosis experience. We conducted in-depth interviews with 58 RAPID ART patients from three health clinics in San Francisco, CA, and Chicago, IL. Interviews were transcribed, coded, and thematically analyzed. In the results, we discuss three main themes. First, Pre-Diagnosis HIV Beliefs, which included three sub-themes: HIV is "gross" and only happens to other people; HIV (Mis)education; and People are "living long and strong" with HIV. Second, Positive and Reassuring Messages During the RAPID Experience, which included two sub-themes: Correcting Misinformation and Early Interactions with People Living with HIV. Third, The RAPID ART Process Can Disrupt Stigma. RAPID ART encounters served as a potent mechanism to disrupt internalized stigma by providing accurate information and dispelling unhelpful myths through verbal and nonverbal messages. Reducing internalized stigma and misinformation about HIV at this early stage has the potential to reduce the effect of HIV stigma on ART initiation and adherence over time.

The role of the complement system in schizophrenia (Sz) is inconclusive due to heterogeneity of the disease and study designs. Here, we assessed the levels of complement activation products and functionality of the classical pathway in acutely ill unmedicated Sz patients at baseline and after 6 weeks of treatment versus matched controls. The study included analyses of the terminal complement complex (sTCC) and C5a in plasma from 96 patients and 96 controls by enzyme-linked immunosorbent assay. Sub-group analysis of serum was conducted for measurement of C4 component and activity of the classical pathway (28 and 24 cases per cohort, respectively). We found no differences in levels of C5a, C4 and classical pathway function in patients versus controls. Plasma sTCC was significantly higher in patients [486 (392-659) ng/mL, n = 96] compared to controls [389 (304-612) ng/mL, n = 96] (p = 0.027, δ = 0.185), but not associated with clinical symptom ratings or treatment. The differences in sTCC between Sz and controls were confirmed using an Aligned Rank Transformation model considering the covariates age and sex (p = 0.040). Additional analysis showed that sTCC was significantly associated with C-reactive protein (CRP; p = 0.006). These findings suggest that sTCC plays a role in Sz as a trait marker of non-specific chronic immune activation, as previously described for CRP. Future longitudinal analyses with more sampling time points from early recognition centres for psychoses may be helpful to better understand the temporal dynamics of innate immune system changes during psychosis development., (© 2024. The Author(s).)

Bilateral adrenal infarction is an extremely rare disease, and it has been reported that some coagulation abnormalities, including essential thrombocythemia (ET), exist in the background. We herein report a 76-year-old patient in whom the platelet count had been in the normal range at the onset of adrenal infarction but subsequently increased to 102×10 4 /μL at 7 months later, leading to the diagnosis of JAK2V617F-positive ET. As the presence of the JAK2V617F mutation increases the risk of thrombosis, Janus kinase 2 (JAK2) genetic testing should be considered in some cases of nonspecific unknown thrombosis, even if there are no obvious hematological findings, such as clonal hematopoiesis of indeterminate potential (CHIP).

Objective: Surgery performed at night and on weekends is thought to be associated with increased complications. However, the impact of time of day on outcomes has not been studied within cranial neurosurgery. We aim to determine if there are differences in outcomes for cranial neurosurgery performed after hours (AH) compared with during hours (DH)., Methods: We performed a single-center retrospective study of cranial neurosurgery patients who underwent emergent surgery from January 2015 through December 2019. Surgery was considered DH if the incision occurred between 8 am and 5 pm Monday through Friday. We assessed outcome measures for differences between operations performed DH or AH., Results: Three-hundred and ninety-three patients (114 DH, 279 AH) underwent surgery. There was a lower rate of return to the operating room within 30 days for AH (8.6%) compared with DH (14.0%), P = 0.03, on multivariate analysis. There were no significant differences in length of operation, estimated blood loss, improvement in Glasgow Coma Scale, intensive care unit and total hospital length of stay, 30-day readmission, 30-day mortality, and in-hospital mortality for cases performed DH compared with AH. Further subgroup analyses were performed for patients who underwent immediate surgery for subdural hematomas, with no differences noted in outcomes on multivariate analysis., Conclusions: This study suggests that operating AH does not appear to negatively impact outcomes when compared with operating DH, in cases of cranial neurosurgical emergencies. Further study assessing the impact on elective neurosurgical cases is required., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This cross-sectional study aimed to investigate the risk factors for low levels of subjective well-being (SWB) in the general population of Japan, specifically, the impact of the number of teeth and self-rated mastication. The surveyed population consisted of individuals aged between 40 and 79 years from Yamagata prefecture, Japan. A postal self-administered questionnaire survey of respondents lifestyles, medical history, oral health, and dietary intake, was conducted from 2017 to 2021. We included 6846 participants to confirm the independent associations between SWB and several parameters using multivariate ordinal logistic regression analysis to estimate adjusted odds ratios and 95% confidence intervals. Individuals with < 20 teeth and poor mastication ability had a 1.3-fold risk for low levels of SWB compared with individuals with ≥ 20 teeth with good mastication ability (adjusted odds ratios = 1.300, 95% confidence intervals = 1.043-1.621, P = .020). There were no differences between individuals with good mastication ability, regardless of the number of remaining teeth. Our study emphasizes not only the importance of having ≥ 20 teeth and good mastication ability for high levels of SWB but also the importance of restoring mastication ability using some form of prosthesis, to facilitate a high level of SWB when the number of remaining teeth is < 20., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: This cross-sectional study investigated the factors associated with weight gain ≥ 10 kg after 20 years of age in the general Japanese population, with a focus on the number of teeth., Materials and Methods: We included individuals aged ≥ 40 years from Yamagata prefecture, Japan from 2017-2021. A postal survey was conducted using a self-administered questionnaire; 5,940 participants were included in the final analysis. The questionnaire included items on lifestyle factors, medical history, physical and mental conditions, oral health, and dietary intake. A multivariate logistic regression analysis was used to identify independent associations between weight gain ≥ 10 kg after 20 years of age and various parameters; adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated., Results: Less than 20 teeth, male sex, drinking habit frequency, eating very fast or fast, and a higher frequency of eating-away-from-home were significant factors associated with weight gain ≥ 10 kg after 20 years of age; individuals with < 20 versus > 20 teeth exhibited a 1.35-fold higher OR (95% CI 1.15-1.59; p < 0.01)., Conclusions: Our results suggest that having < 20 teeth may affect weight gain ≥ 10 kg after 20 years of age. However, owing to the cross-sectional study design, causality could not be determined. Therefore, maintaining healthy lifestyle behaviors to avoid tooth loss may also affect weight gain ≥ 10 kg after 20 years of age., Clinical Relevance: Having < 20 teeth has the potential to affect long-term weight gain after 20 years of age., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: We aimed to verify the usefulness of targeted next-generation sequencing (NGS) technology for diagnosing monogenic diabetes in a single center., Methods: We designed an amplicon-based NGS panel targeting 34 genes associated with known monogenic diabetes and performed resequencing in 56 patients with autoantibody-negative diabetes mellitus diagnosed at < 50 years who had not been highly obese. By bioinformatic analysis, we filtered significant variants based on allele frequency (< 0.005 in East Asians) and functional prediction. We estimated the pathogenicity of each variant upon considering the family history., Results: Overall, 16 candidate causative variants were identified in 16 patients. Among them, two previously known heterozygous nonsynonymous single-nucleotide variants associated with monogenic diabetes were confirmed as causative variants: one each in the GCK and WFS1 genes. The former was found in two independent diabetes-affected families. Two novel putatively deleterious heterozygous variants were also assumed to be causative from the family history: one frameshift and one nonsynonymous single-nucleotide variant in the HNF4A gene. Twelve variants remained as candidates associated with the development of diabetes., Conclusion: Targeted NGS panel testing was useful to diagnose various forms of monogenic diabetes in combination with familial analysis, but additional ingenuity would be needed for practice., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00669-3., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Japan Diabetes Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Rapid antiretroviral therapy initiation (R-ART) for treatment of HIV has been recommended since 2017, however it has not been adopted widely across the US., Purpose: The study purpose was to understand facilitators and barriers to R-ART implementation in the U.S., Research Design: This was a qualitative design involving semi-structured interviews., Study Sample: The study sample was comprised of the medical leadership of nine US HIV clinics that were early implementers of R-ART., Data Collection and Analysis: In-depth, semi-structured interviews were performed. The Consolidated Framework for Implementation Research (CFIR) was used to guide thematic analysis., Results: We identified three main content areas: strong scientific rationale for R-ART, buy-in from multiple key stakeholders, and the condensed timeline of R-ART. The CFIR construct of Evidence Strength and Quality was cited as an important factor in R-ART implementation. Buy-in from key stakeholders and immediate access to medications ensured the success of R-ART implementation. Patient acceptance of the condensed timeline for ART initiation was facilitated when presented in a patient-centered manner, including empathetic communication and addressing other patient needs concurrently. The condensed timeline of R-ART presented logistical challenges and opportunities for the development of intense patient-provider relationships., Conclusions: Results from the analysis showed that R-ART implementation should address the following: 1) logistical planning to implement HIV treatment with a condensed timeline 2) patients' mixed reactions to a new HIV diagnosis and 3) the high cost of HIV medications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Spinal injuries, whether mechanical or neurological, frequently require urgent intervention. Superior outcomes are associated with earlier intervention, which often requires operating overnight and on weekends. However, operating after hours has been associated with increased risks of complications in selected studies. The authors sought to determine whether there are differences in outcomes for "after hours" surgery compared with "during hours" surgery for spinal emergencies., Methods: This is a single-center retrospective cohort study of spine surgery patients who underwent urgent surgery within 6 hours, from January 2015 through December 2019. Surgery was considered during hours if it started between 8 am and 5 pm Monday through Friday. After hours was defined as from 5 pm through 8 am on a weekday or Saturday or Sunday. We assessed 30-day outcome measures for differences between operations performed during hours or after hours., Results: There were 241 spine procedures performed (49 during hours and 192 after hours). There was no significant difference between the length of operation (145.3 vs 129.8 minutes, P = 0.29), estimated blood loss (303.9 vs 274.4 mL, P = 0.61), improvement in American Spinal Injury Association scale (0.26 vs 0.24 grade, P = 0.85), 30-day return to the operating room (OR; 14.3% vs 6.8%, P = 0.09), 30-day readmission (2.0% vs 6.3% P = 0.24), intensive care unit length of stay (4.6 vs 6.3 days, P = 0.27), hospital length of stay (13.5 days vs 14.2 days, P = 0.72), or 30-day mortality (4.1% vs 7.3%, P = 0.42) for cases performed during hours compared with those after hours, respectively. On multivariate analysis, prior malignancy ( P = 0.008) and blue immediate status ( P = 0.004) were predictors of 30-day mortality. However, "after hours" surgery was not a predictor of 30-day return to the OR, readmission, or mortality in either univariate or multivariate analysis., Conclusions: Spine surgery must often be performed after hours. However, the time of day does not significantly impact the 30-day outcomes for emergent spine surgery., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Offering antiretroviral therapy (ART) to patients directly following an HIV diagnosis ("Rapid ART") improves clinical outcomes and is feasible and acceptable for patients and providers. Despite this, implementation of Rapid ART is not yet standard practice in the USA. Structural-level implementation guidance is available, but research at the individual provider level that explores the patient-provider interaction itself remains scarce. The Consolidated Framework for Implementation Research (CFIR) provides a nuanced guide to investigating the less visible, more social elements of implementation like the knowledge and feelings of people, and the influences of culture and resources on individual approaches., Methods: We conducted a multi-site qualitative study, exploring intervention commonalities across three HIV clinic environments: an HIV primary care clinic; an HIV/STI testing, treatment, and prevention clinic; and a large federally qualified health center (FQHC). Qualitative data were gathered from 27 provider informants-Rapid ART program staff and clinicians-using an interview guide developed using the CFIR. An experienced qualitative team conducted a comprehensive thematic analysis and identified cross-cutting themes in how providers approach and engage in the Rapid interaction, as well as longer-form narratives from providers that describe more fully what this interaction looks like for them., Results: Three main themes represent the range and content of individual provider approaches to the Rapid interaction: (1) patient-centeredness; (2) emotional support and partnership; and (3) correcting misperceptions about HIV. Each theme encompassed both conceptual approaches to offering Rapid ART and concrete examples of messaging to the patient that providers used in the Rapid interaction. We describe and show examples of these themes, offer key take-aways for implementation, and provide expanded narratives of providers' personal approaches to the Rapid interaction., Conclusions: Exploration of provider-level approaches to Rapid ART implementation, as carried out in the patient-provider Rapid interaction, contributes a critical layer of evidence for wider implementation. It is our hope that, together with existing research showing positive outcomes and core components of systems-level implementation, these findings add to an instructive body of findings that facilitates the implementation of Rapid ART as an enhanced model of HIV care., (© 2023. The Author(s).)

The aftermath of severe COVID-19 frequently involves considerable cardiopulmonary damage, necessitating rehabilitation. This study aimed to evaluate the impact of COVID-19 on cardiopulmonary health and assess the effectiveness of various rehabilitative interventions. Conducted between September 2021 and September 2022, this prospective study included patients who had been diagnosed with severe COVID-19 and admitted at the "Victor Babes" Infectious Diseases and Pulmonology Hospital, Timisoara, Romania. The patients were stratified into low- and high-intensity rehabilitation groups. The rehabilitation protocols were individually tailored, and the patient recovery was closely monitored over a 3-month period. Our cohort comprised 84 patients, with a mean age of 56.3 years for the low-intensity group ( n = 42) and 53.1 years for the high-intensity group ( n = 42). Both groups showed significant improvements in the lung injury area, need for oxygen supplementation, ejection fraction, systolic pulmonary artery pressure, and forced vital capacity. Additionally, considerable enhancements were observed in maximal voluntary ventilation, FEV1, FEV1/FVC ratio, peak expiratory flow, and forced expiratory flow at 25-75%. The work intensity also demonstrated substantial improvements from the initial testing to the 3-month mark in both groups. This study provides evidence that personalized, targeted rehabilitation strategies can improve long-term cardiopulmonary health in patients recovering from severe COVID-19, proving both low-intensity and high-intensity training as sufficient to improve heart and lung function if performed correctly and over a relatively short duration of 3 months. The study findings underscore the importance of implementing comprehensive cardiopulmonary rehabilitation protocols in the care of post-COVID-19 patients and highlight the value of stratified rehabilitation intensity based on individual patient dynamics and recovery features.

Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals who died. Active autopsy results may be crucial for understanding how COVID-19 infection operates and preventing severe effects. In contrast to younger persons, however, the patient's age, lifestyle, and concomitant comorbidities might alter the morpho-pathological aspects of the damaged lungs. Through a systematic analysis of the available literature until December 2022, we aimed to provide a thorough picture of the histopathological characteristics of the lungs in patients older than 70 years who died of COVID-19. A thorough search was conducted on three electronic databases (PubMed, Scopus, and Web of Science), including 18 studies and a total of 478 autopsies performed. It was observed that the average age of patients was 75.6 years, of which 65.4% were men. COPD was identified in an average of 16.7% of all patients. Autopsy findings indicated significantly heavier lungs, with an average weight of the right lung of 1103 g, while the left lung mass had an average weight of 848 g. Diffuse alveolar damage was a main finding in 67.2% of all autopsies, while pulmonary edema had a prevalence of between 50% and 70%. Thrombosis was also a significant finding, while some studies described focal and extensive pulmonary infarctions in 72.7% of elderly patients. Pneumonia and bronchopneumonia were observed, with a prevalence ranging from 47.6% to 89.5%. Other important findings described in less detail comprise hyaline membranes, the proliferation of pneumocytes and fibroblasts, extensive suppurative bronchopneumonic infiltrates, intra-alveolar edema, thickened alveolar septa, desquamation of pneumocytes, alveolar infiltrates, multinucleated giant cells, and intranuclear inclusion bodies. These findings should be corroborated with children's and adults' autopsies. Postmortem examination as a technique for studying the microscopic and macroscopic features of the lungs might lead to a better knowledge of COVID-19 pathogenesis, diagnosis, and treatment, hence enhancing elderly patient care.

Self-rated health (SRH) is a predictive factor for health-related prognoses such as mortality. This study aimed to comprehensively investigate the risk factors for poor SRH in the general population of Japan, focusing on the combination of the number of teeth and self-rated mastication. Individuals aged at least 40 years in Yamagata Prefecture, Japan, were surveyed from 2017 to 2021. The participants answered a self-administered postal survey on lifestyle factors, medical history, physical and mental conditions, oral health, and dietary intake, and 6739 participants were included. Multivariate logistic regression analysis showed that individuals with less than 20 teeth and who bite tightly on one side or neither side were at a 1.422- and 1.952-fold significantly higher risk, respectively, of poor SRH than individuals with at least 20 teeth and who bite tightly on both sides. Moreover, individuals who had less than 20 teeth but could bite tightly on both sides did not have a significant risk compared to those who had at least 20 teeth and could bite tightly on both sides. Regarding individuals with more than 20 teeth, there was no difference between those who could and could not bite tightly on both sides, although the odds ratios for poor SRH tended to increase for those who could bite on one side or neither side. Our results emphasize the importance of having at least 20 teeth without periodontal disease and oral rehabilitation using a type of prosthesis for SRH, even with less than 20 teeth., (© 2022. The Author(s).)

Background: This study aimed to compare the usefulness of arterial stiffness parameters, cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV), for evaluating arterial damage and risk of cardiovascular disease (CVD) in subjects with diabetes., Methods: The study subjects were 277 patients with type 1 or type 2 diabetes. All subjects were evaluated for vascular stiffness using CAVI (n = 154) or baPWV (n = 123). Carotid intima-media thickness (IMT) and the Suita score were also measured because these are established risk factors for future CVD. Associations of both CAVI and baPWV with these established parameters were evaluated in all subjects, and then in 174 subjects with adjustment for covariates by using propensity score matching., Results: In all subjects, CAVI and baPWV correlated significantly with both IMT (r = 0.462, P < 0.001, and r = 0.212, P = 0.019, respectively) and the Suita score (r = 0.573, P < 0.001, and r = 0.373, P < 0.001, respectively). The correlation between CAVI and IMT was more significant than that between baPWV and IMT (Z = 2.33, P = 0.020). Similarly, the correlation between CAVI and the Suita score was more significant than that between baPWV and the Suita score (Z = 2.13, P = 0.033). After adjustment by propensity score matching, significant correlations between CAVI and IMT (r = 0.432 P < 0.001) and between CAVI and the Suita score (r = 0.544, P < 0.001) were preserved, though only the association between baPWV and the Suita score was significant (r = 0.289, P = 0.007) while that between baPWV and IMT showed no significance. Again, CAVI showed a significant association with the Suita score than baPWV (Z = 2.02, P = 0.043)., Conclusions: CAVI is more closely associated than baPWV with arterial damage and risk of CVD in patients with diabetes., (© 2022. The Author(s).)

This study evaluated the association between fibrosis-4 (FIB 4) index and arterial damage or future risk of coronary heart disease (CHD) in type 2 diabetes. The study subjects were 253 patients with type 2 diabetes. The FIB4 index, as a marker of hepatic fibrosis based on age, aspartate aminotransferase and alanine aminotransferase levels, and platelet count, was calculated for all subjects. Carotid intima-media thickness (IMT), carotid artery calcification (CAC), and aortic arch calcification (AAC) grade (0-2) were assessed as atherosclerotic variables. The Suita score was calculated as the future risk of coronary heart disease (CHD). We assessed whether the FIB4 index was associated with both atherosclerotic variables and the Suita score. FIB4 index was significantly associated with IMT ( r  = 0.241, P < 0.001) and Suita score ( r  = 0.291, P < 0.001). Subjects with CAC showed a significantly higher FIB4 index score compared to subjects without (1.70 ± 0.74 and 1.24 ± 0.69, respectively, P < 0.001), whereas the FIB4 index was significantly elevated with a higher grade of AAC (1.24 ± 0.74, 1.56 ± 0.66, and 1.79 ± 0.71, respectively, P < 0.001). Linear regression analysis adjusted for clinical characteristics indicated that the FIB4 index was positively associated with IMT, Suita score, CAC, and AAC grade ( β  = 0.241, P =0.004; β  = 2.994, P < 0.001; β  = 0.139, P =0.001; and β  = 0.265, P < 0.001, respectively). FIB4 index is closely associated with arterial damage and future risk of CHD in type 2 diabetes., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Kentaro Watanabe et al.)

Objectives: Ischemic stroke and concurrent cancer is increasingly recognized. However, optimal management is uncertain. As mechanical thrombectomy has become the standard of care for large vessel occlusion, more patients with cancer are presenting for embolectomy. However, it is unknown whether this subgroup has the same benefit profile described in multiple randomized trials for thrombectomy for large vessel occlusion. Our objective was to retrospectively evaluate a North American embolectomy database for safety and outcomes in patients with active cancer., Materials and Methods: A case series of 284 embolectomies over 30 months at a single North American stroke center were divided into thrombectomy patients with active cancer(n=25) and those without active cancer (n=259). We compared patient characteristics, procedural characteristics, and procedural outcomes between patients with and without active cancer. Univariate and multivariate analysis of angiographic outcomes, postoperative hemorrhage, and functional outcome was performed., Results: Of the 284 thrombectomy cases, 9% were performed on patients with active cancer. Active cancer patients had a similar recanalization grade and post-operative hemorrhage rate, compared to patients without cancer. Active cancer patients had a significantly higher 90 day mortality (40% vs 20%, p=0.018). On multivariate analysis, good functional outcome (mRS 0-2) was not impacted by active cancer. However, when mRS was evaluated as an ordinal shift analysis, worse functional outcome was associated with active cancer (OR 2.98; 95% CI, 1.29 to 6.59), greater age, NIHSS> 10, and ASPECTS<9., Conclusions: This single center retrospective series of active cancer patients undergoing thrombectomy for large vessel occlusion demonstrates similar rates of recanalization, post-operative hemorrhage, and good outcomes. While the active cancer group has a high short-term mortality, the potential to maintain quality of life in the survivors makes thrombectomy reasonable in this patient population. Awareness of ischemic stroke as a complication of cancer and the safety of thrombectomy in this population are important as this population subtype is expected to grow with improved oncology and stroke care., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study evaluated the associations between aortic arch calcification (AAC) with pericardial fat (PF) mass detected on a single chest X-ray image and predictive variables of future cardiovascular disease (CVD). The subjects were 353 patients treated with at least one of the hypertension, dyslipidemia or diabetes. All subjects were evaluated for AAC; divided into 3 groups with AAC grades of 0, 1, or 2; and examined for the presence of PF. Carotid intima-media thickness (IMT, n = 353), cardio-ankle vascular index (CAVI, n = 218), the Suita score (n = 353), and cardiovascular risk points defined in the Hisayama study (n = 353), an assessment of the risk of future cardiovascular disease, were measured. The relationship of AAC grades, with or without PF, and CVD risks was evaluated. The IMT (1.62 ± 0.74 mm, 2.33 ± 1.26, and 2.43 ± 0.89 in patients with AAC grade 0, 1 and 2, respectively, p < 0.001), CAVI (8.09 ± 1.32, 8.71 ± 1.32, and 9.37 ± 1.17, respectively, p < 0.001), the Suita score (46.6 ± 10.7, 51.8 ± 8.3, and 54.2 ± 8.2, respectively, p < 0.001), and cardiovascular risk points (8.5 ± 2.6, 10.6 ± 2.3, and 11.5 ± 2.3, respectively, p < 0.001) were significantly elevated with AAC progression. Multinomial logistic regression analysis adjusted for clinical characteristics showed that the relative risk ratios of the Suita score or cardiovascular risk points were elevated according to the progress of AAC grade with PF. Therefore, aortic arch calcification with pericardial mass detected on a single chest X-ray image is closely associated with the predictive variables of future CVD., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: Antiretroviral therapy (ART) initiation on the day of an HIV diagnosis or as soon as possible after diagnosis, known as rapid ART (henceforth "RAPID"), is considered to be a safe and effective intervention to quickly reduce viral load and potentially improve engagement in care over time. However, implementation of RAPID programming is not yet widespread. To facilitate broader dissemination of RAPID, we sought to understand health care worker experiences with RAPID implementation and to identify essential programmatic elements., Methods: We conducted 27 key informant interviews with medical providers and staff involved in RAPID service delivery in three distinct clinical settings: an HIV clinic, a Federally Qualified Health Center and a sexual health and wellness clinic. Interviews were structured around domains associated with the Consolidated Framework for Implementation Research and were audio-recorded, transcribed, and thematically analyzed., Findings: We identified seven (7) essential elements across settings associated with successful RAPID program implementation. These high-impact elements represent essential components without which a RAPID program could not function. There was no one requisite formation. Instead, we observed a constellation of essential elements that could be operationalized in various formations and by various people in various roles. The essential elements included: (1) presence of an implementation champion; (2) comfort and competence prescribing RAPID ART; (3) expedited access to ART medications; (4) expertise in benefits, linkage, and care navigation; (5) RAPID team member flexibility and organizations' adaptive capacity; (6) patient-centered approach; and (7) strong communication methods and culture., Conclusions: The RAPID model can be applied to a diverse range of clinical contexts. The operational structure of RAPID programs is shaped by the clinical setting in which they function, and therefore the essential elements identified may not apply equally to all programs. Based on the seven essential elements described above we recommend future implementers identify where these elements currently exist within a practice; leverage them when possible; strengthen them when necessary or develop them if they do not yet exist; and look to these elements when challenges arise for potential solutions., (© 2022. The Author(s).)

A 26-year-old male presented to the emergency department feeling unwell in February of 2021 with symptoms including diaphoresis, loose stools, and loss of taste sensation. Workup not only confirmed a diagnosis of COVID-19 but also revealed discordant HIV test results, with a reactive fourth-generation antigen/antibody test but a negative HIV-1/2 differentiation immunoassay. Subsequent HIV viral load testing obtained two days later ultimately established a diagnosis of acute HIV (AHI). Screening for HIV and other sexually transmitted infections decreased during the COVID-19 pandemic. It is critical that providers (1) continue recommended screening for HIV as an essential service; (2) consider acute HIV in the differential when evaluating patients with acute viral syndromes; (3) recognize that AHI can occur concurrently with other infections, including COVID-19; and (4) understand the differential diagnosis for discordant HIV test results and know when HIV viral load testing is needed to resolve such discordant results., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Kelly A. Johnson et al.)

Background: Guidelines recommend immediate antiretroviral therapy (ART) at or shortly after human immunodeficiency virus (HIV) diagnosis, yet little is known about how people living with HIV (PLWH) experience this treatment strategy, including racial/ethnic minorities, cisgender/transgender women, and those with housing instability., Methods: To assess the acceptability of immediate ART offer among urban PLWH, understand how this approach affects the lived experience of HIV diagnosis, and explore reasons for declining immediate ART, we conducted a cross-sectional qualitative study using semi-structured interviews with individuals who had been offered immediate ART after HIV diagnosis at a safety-net HIV clinic in San Francisco and a federally qualified health center in Chicago. Interviews were analyzed using thematic analysis., Results: Among 40 participants with age range 19-52 years, 27% of whom were cisgender/transgender women or gender-queer, 85% racial/ethnic minority, and 45% homeless/unstably housed, we identified 3 major themes: (1) Individuals experienced immediate ART encounters as supportive; (2) individuals viewed immediate ART as sensible; and (3) immediate ART offered emotional relief by offsetting fears of death and providing agency over one's health. Reasons for declining immediate ART ranged from simply needing a few more days to complex interactions of logistical and psychosocial barriers., Conclusions: Immediate ART was highly acceptable to urban persons with newly diagnosed HIV infection. Immediate ART was viewed as a natural next step after HIV diagnosis and provided a sense of control over one's health, mitigating anxiety over a decline in physical health. As such, immediate ART somewhat eased but in no way obviated the psychosocial challenges of HIV diagnosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Credentialing and certification are essential processes during hiring to ensure that the physician is competent and possesses the qualifications and skill sets claimed. Peer review ensures the continuing evolution of these skills to meet a standard of care. We have provided an overview and discussion of these processes in the United States. Credentialing is the process by which a physician is determined to be competent and able to practice, used to ensure that medical staff meets specific standards, and to grant operative privileges at an institution. Certification is a standardized affirmation of a physician's competence on a nationwide basis. Although not legally required to practice in the United States, many institutions emphasize certification for full privileges on an ongoing basis at a hospital. In the United States, peer review of adverse events is a mandatory prerequisite for accreditation. The initial lack of standardization led to the development of the Health Care Quality Improvement Act, which protects those involved in the peer review process from litigation, and the National Provider Databank, which was established as a national database to track misconduct. A focus on quality improvement in the peer review process can lead to improved performance and patient outcomes. A thorough understanding of the processes of credentialing, certification, and peer review in the United States will benefit neurosurgeons by allowing them to know what institutions are looking for as well and their rights and responsibilities in any given situation. It could also be useful to compare these policies and practices in the United States to those in other countries., (Copyright © 2021. Published by Elsevier Inc.)

Background: Early virologic suppression (VS) after human immunodeficiency virus (HIV) infection improves individual health outcomes and decreases onward transmission. In San Francisco, immediate antiretroviral therapy (ART) at HIV diagnosis was piloted in 2013-2014 and expanded citywide in 2015 in a rapid start initiative to link all new diagnoses to care within 5 days and start ART at the first care visit., Methods: HIV providers and linkage navigators were trained on a rapid start protocol with sites caring for vulnerable populations prioritized. Dates of HIV diagnosis, first care visit, ART initiation, and VS were abstracted from the San Francisco Department of Public Health HIV surveillance registry., Results: During 2013-2017, among 1354 new HIV diagnoses in San Francisco, median days from diagnosis to first VS decreased from 145 to 76 (48%; P < .0001) and from first care visit to ART initiation decreased from 28 to 1 (96%; P < .0001). By 2017, 28% of new diagnoses had a rapid start, which was independently associated with Latinx ethnicity (AOR, 1.73; 95% CI, 1.15-2.60) and recent year of diagnosis (2017; AOR, 16.84; 95% CI, 8.03-35.33). Persons with a rapid ART start were more likely to be virologically suppressed within 12 months of diagnosis than those with a non-rapid start (RR, 1.17; 95% CI, 1.10-1.24)., Conclusions: During a multisector initiative to optimize ART initiation, median time from diagnosis to VS decreased by nearly half. Immediate ART at care initiation was achieved across many, but not all, populations, and was associated with improved suppression rates., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Global environmental changes have accelerated at an unprecedented rate in recent decades due to human activities. As a consequence, the incidence of novel abiotic conditions and biotic communities, which have been continuously emerging in the Earth system, has rapidly risen. Despite growing attention to the incidence and challenges posed by novelty in terrestrial ecosystems, novelty has not yet been quantified in marine ecosystems. Here, we measured for the rate of novelty (RoN) in abiotic conditions and community structure for three trophic levels, i.e., phytoplankton, zooplankton, and fish, in a large marine system - the Baltic Sea. We measured RoN as the degree of dissimilarity relative to a specific spatial and temporal baseline, and contrasted this with the rate of change as a measure of within-basin change over time. We found that over the past 35 years abiotic and biotic RoN showed complex dynamics varying in time and space, depending on the baseline conditions. RoN in abiotic conditions was smaller in the open Central Baltic Sea than in the Kattegat and the more enclosed Gulf of Bothnia, Gulf of Riga, and Gulf of Finland in the north. We found a similar spatial pattern for biotic assemblages, which resulted from changes in composition and stock size. We identified sea-surface temperature and salinity as key drivers of RoN in biotic communities. Hence, future environmental changes that are expected to affect the biogeochemistry of the Baltic Sea, may favor the rise of biotic novelty. Our results highlighted the need for a deeper understanding of novelty development in marine ecosystems, including interactions between species and trophic levels, ecosystem functioning under novel abiotic conditions, and considering novelty in future management interventions., (© 2021 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)