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High-frequency driven resonant spin rotators are routinely used as standard instruments in polarization experiments in particle and nuclear physics. Maintaining the continuous exact parametric spin resonance condition of the equality of the spin rotator and the spin precession frequency during operation is one of the challenges. We present a detailed analytical description of the effects of detuning the exact spin resonance on the precessing vertical and in-plane components of the polarization. An important part of the formalism presented here is the consideration of experimentally relevant spin decoherence effects. Within the developed formalism, we address the impact of feedback via pilot-bunch-based comagnetometry on continuous spin flips and on the related interpretation of charged-particle electric dipole moment searches using storage rings. We propose a spin-flip-based tomography of the longitudinal profile of polarization in a bunch, which is important for the evaluation of the polarization-dependent luminosity in collider experiments. We emphasize the potential importance of the previously unexplored phase of the horizontal polarization of the envelope as an indicator of the stability of radio-frequency-driven spin rotations in storage rings and as a testing ground for spin decoherence mechanisms.

Background: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors., Methods: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from Analysis of Pre-treatment Tumor biopsies (PREDAPT), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in patients with recurrent or metastatic HNSCC treated with anti-PD-1 immune checkpoint inhibitors as a single agent (monotherapy) and in combination with chemotherapy (chemo-immunotherapy). The test used RNA-sequencing data and machine learning models to score each patient and place them into groups of low, medium, or high., Results: The OncoPrism-HNSCC prediction significantly correlated with disease control in both the monotherapy cohort (n=62, p=0.004) and the chemo-immunotherapy cohort (n=50, p=0.01). OncoPrism-HNSCC also significantly predicted progression-free survival in both cohorts (p=0.015 and p=0.037, respectively). OncoPrism-HNSCC had more than threefold higher specificity than programmed death-ligand 1 combined positive score and nearly fourfold higher sensitivity than tumor mutational burden for predicting disease control., Conclusions: Here, we demonstrate the clinical validity of the OncoPrism-HNSCC assay in identifying patients with disease control in response to anti-PD-1 immune checkpoint inhibitors., Trial Registration Number: NCT04510129., Competing Interests: Competing interests: KCF, JE, JH, RLW, MMP, DNM, JIG, and EJD are employed, have stock interests, and/or a financial relationship with Cofactor Genomics, maker of the OncoPrism-HNSCC test., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Treatment for people with HIV-1 and end-stage kidney disease (ESKD) on haemodialysis (HD) has previously required complex dose-adjusted regimens, with limited data on the use of a single-tablet regimen in this population. Our aim was to assess the efficacy and safety of once-daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and to evaluate the pharmacokinetics of bictegravir (BIC) in adults with HIV-1 and ESKD on HD., Methods: We performed an open-label extension (OLE) of an open-label, multicentre, single-group phase 3b study (NCT02600819) of adults with ESKD on HD and HIV-1 with virological suppression. Participants switched to elvitegravir/cobicistat/F/TAF (E/C/F/TAF) 150/150/200/10 mg for 96 weeks, following which a subgroup of US participants entered an OLE phase in which they switched to B/F/TAF 50/200/25 mg for 48 weeks, returning for study visits at weeks 4 and 12, and every 12 weeks thereafter. Study assessments included virological response, safety and pharmacokinetic analysis of BIC., Results: Ten participants entered the OLE (median age, 55 years). Virological suppression (HIV-1 RNA <50 copies/mL) was maintained in all participants over 48 weeks of B/F/TAF treatment. B/F/TAF was well tolerated, with no treatment discontinuations. Mean BIC trough concentrations were lower than those previously reported for people with HIV-1 with normal kidney function, but remained four- to seven-fold higher than the established protein-adjusted 95% effective concentration against wild-type HIV-1., Conclusion: These findings support the use of the once-daily B/F/TAF single-tablet regimen for people with HIV-1 and ESKD on HD. This regimen offers a convenient treatment option for this population as it reduces the need for dose adjustment, eases pill burden and avoids potential drug-drug interactions associated with alternatives that may impact individuals on multiple medications or awaiting transplantation., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Upregulation of IL-6 has been associated with worse prognosis in COVID-19 patients. Impact on IL-6 signalling has mostly been limited to clinical outcomes in IL-6 receptor antagonist trials., Methods: We performed a phase 2, randomised, double-blind, placebo-controlled trial (NCT04380961) of US-based hospitalised adults (<85 years) with laboratory-confirmed SARS-CoV-2 infection and severe (low levels of supplemental oxygen) or critical disease (high levels of oxygen supplementation). Patients received sirukumab 5 mg/kg or placebo single dose IV on Day 1 plus standard of care. The primary endpoint was time to sustained clinical improvement up to Day 28 based on an ordinal scale. Secondary endpoints included clinical improvement, all-cause mortality, and safety. Following an interim analysis, the protocol was amended to only recruit patients with critical COVID-19., Findings: From May 2020 to March 2021, 209 patients were randomised; 112 had critical disease (72 sirukumab, 40 placebo) at baseline. Median time to sustained clinical improvement in critical patients was 17 and 23 days in the sirukumab and placebo groups (HR, 1∙1; 95% CI, 0∙66-1∙88; p > 0∙05). At Day 28, 59∙4% versus 55∙0% of patients achieved clinical improvement with sirukumab versus placebo and rates of all-cause mortality were 24∙6% versus 30∙0%, respectively. Rates of grade ≥3 adverse events were comparable between the sirukumab and placebo groups (25∙9% vs 32∙9%; all patients)., Interpretation: In critical COVID-19 patients who received sirukumab, there was no statistically significant difference in time to sustained clinical improvement versus placebo despite objective sequestration of circulating IL-6, questioning IL-6 as a key therapeutic target in COVID-19., Competing Interests: Declaration of Competing Interest Robert L. Gottlieb served as coordinating national principal investigator and as a consultant for this trial. He reports service on scientific advisory boards for AbbVie, AstraZeneca, Eli Lilly, Gilead Sciences, GSK, and Roche, and consulting via his institution for Kinevant Sciences, also related to COVID-19. Service on speakers bureau with Alnylam Pharmaceuticals and Pfizer, consultancy to Alnylam, research support from CareDx, and a gift-in-kind to his institution from Gilead Sciences to support NCT03383419 are also reported, all outside the submitted work. Meredith Clement has received research support (grants to institution) from Gilead Sciences and ViiV Healthcare, has served on advisory boards for Roche Diagnostics Corporation and ViiV Healthcare. Paul Cook is a PI for the following: NIH, Janssen, Gilead, ViiV, Seres, and Finch. Audra Deveikis, Kap Sum Foong, Philip Robinson, and Cedric W. Spak have nothing to declare. Jihad Slim serves on speakers bureaus for Gilead, ViiV, Merck, Janssen, AbbVie, and Thera. Katleen Callewaert is an employee of Janssen Pharmaceutica NV. Annemie Buelens, Sandra De Meyer, Liesbeth Van Wesenbeeck, and Erika Van Landuyt are employees of Janssen Pharmaceutica NV and own stock in Johnson & Johnson. Wai Ling Mo is an employee of Janssen-Cilag Limited. Inge Verbrugge and Magda Opsomer were employees of Janssen Pharmaceutica NV at the time of the study. Yanli Zhuang and Jacon Chien were employees of Janssen Research & Development, LLC at the time of the study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fever in tuberculosis has always been a challenge to clinicians treating the disease throughout history. There is a constant interplay between the host immune response and the bacillary load that results in high-grade fevers in patients with tuberculosis. In the setting of pulmonary tuberculosis, there is scant data regarding how long fevers last and the exact pathophysiology of its prolonged duration, especially once appropriate antituberculosis medication is initiated.  This case report elucidates our experience in treating a patient presenting with smear-positive pulmonary tuberculosis with significant bacillary load; despite responding microbiologically to antituberculosis therapy, he clinically continued to have persistent fever., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tewoldemedhin et al.)

Background: Listeria monocytogenes brain abscess is a rare phenomenon that is common in immunocompromised patients. Streptococcus equinus brain abscess has never been reported in the literature to our knowledge. In this case report, we describe a case of brain abscess secondary to Listeria monocytogenes and Streptococcus equinus in an immunocompetent patient with transient low CD4 count., Case Presentation: A 27-year-old white, male patient, previously healthy, nonalcoholic, and occasional smoker, presented to the emergency department for confusion and headache. The patient was found to have a left parietal abscess, which was drained and the fluid was sent for culture. Culture grew Listeria monocytogenes and Streptococcus equinus. The patient was treated with intravenous ampicillin followed by oral amoxicillin for a total of 6 weeks. The CD4 count was low initially. However, after the resolution of the infection, the CD4 count came back within normal range. Another brain magnetic resonance imaging was done that showed a significantly decreased hyperintensity within the left parietal subcortical white matter at the site of surgery with significantly decreased enhancement and almost total resolution of the previous abscess., Conclusion: Transient low CD4 count is a rare phenomenon that exposes patients to unusual and atypical infections. Since low CD4 count is transient, patients treated promptly recover from their illness. Our patient developed a Listeria monocytogenes and Streptococcus equinus brain abscess, which is considered rare and has not been previously described in the literature to our knowledge., (© 2024. The Author(s).)

We present a clinical case detailing the presentation of erysipelas in a 52-year-old immunocompetent female, wherein the infection displayed an unusual localization encompassing the skin of the anterior abdominal area and breast. The patient exhibited a favorable response to medical treatment. It is paramount to underscore the significance of recognizing such cases, which demand a heightened level of clinical suspicion to facilitate swift diagnosis and effective management strategies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abouzeid et al.)

Objectives: Mortality from HIV has significantly declined with the introduction of highly active antiretroviral therapy (HAART). This study sought to examine the longitudinal trends in mortality from HIV-related diseases by race, sex, geographical region, and over time as HAART trends changed., Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database and performed serial cross-sectional analyses of national death certificate data for all-cause mortality with comorbid HIV from 1999 to 2020. HIV diseases (International Classification of Diseases, Tenth Revision codes B20-B24, O98.7, R75) were listed as the contributing cause of death. We calculated the age-adjusted mortality ratio (AAMR) per 1,000,000 individuals and determined mortality trends using the Joinpoint Regression Program. Subgroup analyses were performed by sex, race, region, and organ system. The study period was further stratified into three groups when specific drug regimens were more prevalent., Results: In the 22-year study period, 251,759 all-cause mortalities with comorbid HIV were identified. The leading cause of death was infectious disease (84.0%, N = 211,438). Men recorded a higher AAMR than women (4.66 vs 1.65, P < 0.01). African American individuals had the highest AAMR (13.46) compared to White, American Indian, and Asian individuals (1.70 vs 1.65 vs 0.47). The South region had the highest AAMR (4.32) and urban areas had a higher AAMR compared to rural areas (1.77 vs 0.88)., Conclusions: More than 80% of deaths occurred because of infectious disease over the last 2 decades with a decreasing trend over time when stratified by race, sex, and geographical region. Despite advances in HAART, mortality disparities persist which emphasizes the need for targeted interventions in these populations., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Peritonitis, the inflammation of the protective membrane surrounding parts of the abdominal organs, is a common clinical pathology with multifactorial aetiologies. While bacterial infections are well-recognised as a cause of peritonitis, fungal infections remain relatively uncommon especially Saccharomyces cerevisiae , which is commonly used for breadmaking and as a nutritional supplement. This fungus has been reported to induce peritonitis in patients on peritoneal dialysis. However, it has never been reported as secondary to percutaneous endoscopic gastrostomy (PEG) tube insertion in immunocompromised patients. We present a 64-year-old female with a history of human immunodeficiency virus (HIV) who developed S. cerevisiae peritonitis following PEG tube insertion. The case highlights the importance of considering rare organisms when treating immunocompromised patients with peritonitis, especially after gastrointestinal tract penetration or peritoneal membrane disruption., Learning Points: Fungal infection can be a cause of peritonitis especially in an immunocompromised patient. Saccharomyces cerevisiae can be a pathological organism and induce serious infections.Early recognition of the cause of peritonitis and controlling the source is critical to prevent complications., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)