Community-acquired pneumonia in people with Human Immunodeficiency Virus (HIV) during the current era of effective antiretroviral therapy: A multi-center retrospective cohort study.

BACKGROUND: It is unclear if Human Immunodeficiency Virus (HIV) infection affects the prognosis for community acquired pneumonia (CAP) in the current era of effective anti-retroviral therapy. In this multi-center retrospective cohort study of patients admitted for CAP, we compared the in-hospital mortality rate between people with HIV (PWH) and people without HIV. METHODS: The study included consecutive patients admitted with a diagnosis of CAP across 31 hospitals in Ontario, Canada from 2015 to 2022. HIV infection was based on discharge diagnoses and anti-retroviral prescription. The primary outcome was in-hospital mortality. Competing risk models were used to describe time to death in hospital or discharge. Potential confounders were balanced using overlap weighting of propensity scores. RESULTS: Of 82,822 patients admitted with CAP, 1,518 (1.8%) patients had a diagnosis of HIV. PWH were more likely to be younger, be male and have less comorbidities. In hospital, 67 (4.4%) PWH and 6,873 (8.5%) people without HIV died. HIV status had an adjusted sub-distribution hazard ratio (sHR) of 1.02 (95% CI 0.80-1.31 P=0.8440) for dying in hospital. Of 1,518 PWH, 440 (29.0%) patients had a diagnosis of acquired immunodeficiency syndrome (AIDS). AIDS diagnosis had an adjusted sHR of 3.04 (95% CI 1.69-5.45 P=0.0002) for dying in hospital compared to HIV without AIDS. CONCLUSION: People with and without HIV admitted for CAP had a similar in-hospital mortality rate. For PWH, AIDS significantly increased the mortality risk. HIV infection by itself without AIDS should not be considered a poor prognostic factor for CAP.

Human Factors Validation of a Wearable, On-Body Infusor for Subcutaneous Administration of Furosemide.

Purpose: Furoscix® (subcutaneous furosemide) is administered using a wearable On-Body Infusor (OBI) and is approved for the treatment of congestion associated with heart failure (HF). The purpose of this study was to assess the safe and effective use of the OBI and Instructions for Use (IFU) by patients with HF, caregivers, and healthcare practitioners (HCPs). Methods: Sixty participants (patients, n=30; caregivers, n=15; HCPs, n=15) were evaluated on completion of OBI use tasks and IFU knowledge tasks in a simulated use environment. Fifteen of the patients received OBI/IFU training before evaluation. Results: Overall, 893/900 (99.2%) use tasks and 2211/2220 (99.6%) knowledge tasks were completed successfully, without differences due to training. The most common (n=6) use error was failure to wipe skin or cartridge tip with an alcohol wipe. Errors were due to forgetfulness/misinterpretation rather than IFU clarity. Conclusion: The subcutaneous furosemide OBI can be safely and effectively used by patients, caregivers, and HCPs, regardless of training.

Impact of interrupting antiretroviral therapy started during primary HIV-1 infection on plasma neurofilament light chain protein, a marker of neuronal injury: The SPARTAC trial.

Objective: Antiretroviral therapy (ART)-conferred suppression of HIV replication limits neuronal injury and inflammation. ART interruption tests efficacy in HIV cure trials and viral rebound after ART interruption may induce neuronal injury. We investigated the impact of protocol-defined ART interruption, commenced during primary HIV-1 infection (PHI) on a biomarker of neuro-axonal injury (neurofilament light protein (NfL)), and its associations with inflammation (D-dimer and interleukin-6 (IL-6)) and HIV-1 reservoir size (total HIV-1 DNA). Design: Retrospective study measuring plasma NfL in 83 participants enrolled in SPARTAC randomised to receive 48-weeks ART initiated during PHI, followed by ART interruption. Methods: NfL (Simoa immunoassay, Quanterix™) was measured before ART, after 48 weeks on ART, and 12 weeks after stopping ART. Plasma D-dimer and IL-6, and total HIV-1 DNA in peripheral CD4+ T-cells results were available in a subset of participants. Longitudinal NfL changes were assessed using mixed models, and associations with clinical and laboratory parameters using linear regression. Results: NfL decreased following 48-weeks ART (geometric mean 6.9 to 5.8 pg/mL, p = 0.006) with no further significant change up to 12-weeks post-stopping ART despite viral rebound in the majority of participants (median 1.7 to 3.9 plasma HIV-1 RNA log10 copies/mL). Higher baseline NfL was independently associated with higher plasma HIV-1 RNA (p = 0.020) and older age (p = 0.002). While NfL was positively associated with D-dimer (n = 48; p = 0.002), there was no significant association with IL-6 (n = 48) or total HIV-1 DNA (n = 51). Conclusions: Using plasma NfL as a surrogate marker, a decrease in neuro-axonal injury was observed in a cohort of participants following ART initiation during PHI, with no evidence of neuro-axonal injury rebound following ART interruption for up to 12 weeks, despite viral rebound in the majority of participants.

Prophylactic Antibiotic Choice and Deep Infection in Lower Extremity Endoprosthetic Reconstruction: Comparison of Cefazolin, Cefazolin-Vancomycin, and Alternative Regimens.

INTRODUCTION: Infection is a common mode of failure in lower extremity endoprostheses. The Prophylactic Antibiotic Regimens in Tumor Surgery trial reported that 5 days of cefazolin had no difference in surgical site infection compared with 24 hours of cefazolin. Our purpose was to evaluate infection rates of patients receiving perioperative cefazolin monotherapy, cefazolin-vancomycin dual therapy, or alternative antibiotic regimens. METHODS: A single-center retrospective review was conducted on patients who received lower extremity endoprostheses from 2008 to 2021 with minimum 1-year follow-up. Three prophylactic antibiotic regimen groups were compared: cefazolin monotherapy, cefazolin-vancomycin dual therapy, and alternative regimens. The primary outcome was deep infection, defined by a sinus tract, positive culture, or clinical diagnosis. Secondary outcomes were revision surgery, microorganisms isolated, and superficial wound issues. RESULTS: The overall deep infection rate was 10% (30/294) at the median final follow-up of 3.0 years (IQR 1.7 to 5.4). The deep infection rates in the cefazolin, cefazolin-vancomycin, and alternative regimen groups were 8% (6/72), 10% (18/179), and 14% (6/43), respectively (P = 0.625). Patients not receiving cefazolin had an 18% deep infection rate (6/34) and 21% revision surgery rate (7/34) compared with a 9% deep infection rate (24/260) (P = 0.13) and 12% revision surgery rate (31/260) (P = 0.17) in patients receiving cefazolin. In those not receiving cefazolin, 88% (30/34) were due to a documented penicillin allergy, only two being anaphylaxis. All six patients in the alternative regimen group who developed deep infections did not receive cefazolin secondary to nonanaphylactic penicillin allergy. CONCLUSION: The addition of perioperative vancomycin to cefazolin in lower extremity endoprosthetic reconstructions was not associated with a lower deep infection rate. Patients who did not receive cefazolin trended toward higher rates of deep infection and revision surgery, although not statistically significant. The most common reason for not receiving cefazolin was a nonanaphylactic penicillin allergy, highlighting the continued practice of foregoing cefazolin unnecessarily.

Comparison of pain after prophylactic anticoagulant injections to prevent venous thromboembolism.

Subcutaneous injection of unfractionated heparin (UH) or low molecular weight heparin (LMWH) is frequently utilized for venous thromboembolism chemoprophylaxis. We previously discovered that nurses believe patients experience more pain with UH compared to the LMWH enoxaparin; however, no published studies that are appropriately powered exist comparing pain associated with subcutaneous chemoprophylaxis. Our objective was to assess if differences exist in pain associated with subcutaneous administration of UH and enoxaparin. We conducted an observational study of patients who underwent major abdominal surgery between 11/2017-4/2019. All patients received one of three prophylactic regimens: (1) UH only, (2) Initial dose of UH followed by enoxaparin, or (3) enoxaparin only. Of the 74 patients observed, 40 patients received UH followed by enoxaparin, 17 received UH only, and 17 received enoxaparin only. There was a significant difference in patients' mean perceived pain between subcutaneous UH and enoxaparin injections (mean post-injection pain after UH 3.3 vs. enoxaparin 1.5; p < 0.001). There was no significant difference in perceived pain for patients who received consecutive UH or enoxaparin injections. Differences in pain associated with different chemoprophylaxis agents may be an unrecognized driver of patient refusals of VTE chemoprophylaxis and may lead to worse VTE outcomes.

Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.

Fe-rich X-ray amorphous material records past climate and persistence of water on Mars.

X-ray amorphous material comprises 15-73 wt.% of sedimentary rocks and eolian sediments in Gale crater. This material is variably siliceous and iron rich but aluminum poor. The presence of volatiles is consistent with the existence of incipient weathering products. To better understand the implications of this material for past aqueous conditions on Mars, here we investigate X-ray amorphous material formation and longevity within terrestrial iron rich soils with varying ages and environmental conditions using bulk and selective dissolution methods, X-ray diffraction, and transmission electron microscopy. Results indicate that in situ aqueous alteration is required to concentrate iron into clay-size fraction material. Cooler climates promote the formation and persistence of X-ray amorphous material whereas warmer climates promote the formation of crystalline secondary phases. Iron rich X-ray amorphous material formation and persistence on Mars are therefore consistent with past cool and relatively wet environments followed by long-term cold and dry conditions.

The Effect of Interlayer Delay on the Heat Accumulation, Microstructures, and Properties in Laser Hot Wire Directed Energy Deposition of Ti-6Al-4V Single-Wall.

Laser hot wire directed energy deposition (LHW-DED) is a layer-by-layer additive manufacturing technique that permits the fabrication of large-scale Ti-6Al-4V (Ti64) components with a high deposition rate and has gained traction in the aerospace sector in recent years. However, one of the major challenges in LHW-DED Ti64 is heat accumulation, which affects the part quality, microstructure, and properties of as-built specimens. These issues require a comprehensive understanding of the layerwise heat-accumulation-driven process-structure-property relationship in as-deposited samples. In this study, a systematic investigation was performed by fabricating three Ti-6Al-4V single-wall specimens with distinct interlayer delays, i.e., 0, 120, and 300 s. The real-time acquisition of high-fidelity thermal data and high-resolution melt pool images were utilized to demonstrate a direct correlation between layerwise heat accumulation and melt pool dimensions. The results revealed that the maximum heat buildup temperature of the topmost layer decreased from 660 °C to 263 °C with an increase to a 300 s interlayer delay, allowing for better control of the melt pool dimensions, which then resulted in improved part accuracy. Furthermore, the investigation of the location-specific composition, microstructure, and mechanical properties demonstrated that heat buildup resulted in the coarsening of microstructures and, consequently, the reduction of micro-hardness with increasing height. Extending the delay by 120 s resulted in a 5% improvement in the mechanical properties, including an increase in the yield strength from 817 MPa to 859 MPa and the ultimate tensile strength from 914 MPa to 959 MPa. Cooling rates estimated at 900 °C using a one-dimensional thermal model based on a numerical method allowed us to establish the process-structure-property relationship for the wall specimens. The study provides deeper insight into the effect of heat buildup in LHW-DED and serves as a guide for tailoring the properties of as-deposited specimens by regulating interlayer delay.

Variety in Pleasant Activities is Associated with Improved Mental Health: Evidence from Two National Samples of U.S. Adults.

Engaging in a wide range of pleasant activities may provide mental health benefits, particularly for those genetically predisposed to depression. This study examined associations between pleasant activity variety, mental health, and genetic vulnerability in two U.S. cohort studies (N = 2,088). Participants reported depressive symptoms, mental healthcare visits, and engagement in pleasant activities over the past month. Greater variety of pleasant activities was associated with fewer depressive symptoms in both study samples. Individuals engaging in more diverse pleasant activities also had fewer mental health visits. Individuals with a higher genetic risk for depression experienced a stronger negative association between variety of pleasant activities and depressive symptoms compared to those with a lower genetic risk. These results highlight the potential of diverse pleasant activities as a means to enhance well-being, particularly among individuals genetically susceptible to depression. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00225-x.

Mean Affect Moderates the Association between Affect Variability and Mental Health.

Increasing evidence suggests that within-person variation in affect is a dimension distinct from mean levels along which individuals can be characterized. This study investigated affect variability's association with concurrent and longitudinal mental health and how mean affect levels moderate these associations. The mental health outcomes of depression, panic disorder, self-rated mental health, and mental health professional visits from the second and third waves of the Midlife in the United States Study were used for cross-sectional (n = 1,676) and longitudinal outcomes (n = 1,271), respectively. These participants took part in the National Study of Daily Experiences (NSDE II), where they self-reported their affect once a day for 8 days, and this was used to compute affect mean and variability. Greater positive affect variability cross-sectionally predicted a higher likelihood of depression, panic disorder, mental health professional use, and poorer self-rated mental health. Greater negative affect variability predicted higher panic disorder probability. Longitudinally, elevated positive and negative affect variability predicted higher depression likelihood and worse self-rated mental health over time, while greater positive affect variability also predicted increased panic disorder probability. Additionally, mean affect moderated associations between variability and health such that variability-mental health associations primarily took place when mean positive affect was high (for concurrent mental health professional use and longitudinal depression) and when mean negative affect was low (for concurrent depression, panic disorder, self-rated mental health, and longitudinal self-rated mental health). Taken together, affect variability may have implications for both short- and long-term health and mean levels should be considered. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-024-00238-0.

Perceptions of mental health, suicide and working conditions in the construction industry-A qualitative study.

OBJECTIVE: The aim of the study was to explore perceptions of mental ill health, suicidal behaviour and working conditions among male construction workers, in order to gain an in-depth understanding of these phenomenon and to identify relevant avenues for workplace interventions. METHOD: Data were collected in individual and group interviews, and 43 individuals from the Swedish construction industry, workers, union representative and managers, participated in the study. Inductive thematic analysis was used to analyse the data. RESULTS: Five main themes were found: Difficult to talk about mental health, Demanding working environment affects mental health, Substance abuse among construction workers, Importance of management, and Need for routines and social support in the workplace. Many participants reported that there was a stigma related to mental health. Suicides that had occurred among colleagues were perceived to come out of the blue. The working environment in the construction industry was perceived to have a negative effect on mental health, and it was reported that the management played an important role in both the cause and prevention of mental health problems. CONCLUSIONS: The results from this Swedish study are in accordance with previous international research regarding a macho culture, stigma of mental health and a demanding working environment in the construction industry. The study adds to existing knowledge by highlighting that suicides were perceived to be very unexpected, that poor physical health affected mental health and that many participants did not know how to deal with mental health issues in the workplace.

Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Assessing the impact of health-care access on the severity of low back pain by country: a case study within the GBD framework.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is key for policy making. Low back pain is the leading cause of disability in terms of years lived with disability (YLDs). Due to sparse data, a current limitation of GDB is that a uniform severity distribution is presumed based on 12-Item Short Form Health Survey scores derived from US Medical Expenditure Panel Surveys (MEPS). We present a novel approach to estimate the effect of exposure to health interventions on the severity of low back pain by country and over time. METHODS: We extracted treatment effects for ten low back pain interventions from the Cochrane Database, combining these with coverage data from the MEPS to estimate the hypothetical severity in the absence of treatment in the USA. Severity across countries was then graded using the Health Access and Quality Index, allowing estimates of averted and avoidable burden under various treatment scenarios. FINDINGS: We included 210 trials from 36 Cochrane systematic reviews in the network analysis. The pooled effect sizes (measured as a standardised mean difference) for the most effective intervention classes were -0·460 (95% uncertainty interval -0·606 to -0·309) for a combination of psychological and physical interventions and -0·366 (-0·525 to -0·207) for surgery. Globally, access to treatment averted an estimated 17·6% (14·8 to 23·8) of the low back pain burden in 2020. If all countries had provided access to treatment at a level estimated for Iceland with the highest Health Access and Quality Index score, an extra 9·1% (6·4 to 11·2) of the burden of low back pain could be avoided. Even with full coverage of optimal treatment, a large proportion (65·9% [56·9 to 70·4]) of the low back pain burden is unavoidable. INTERPRETATION: This methodology fills an important shortcoming in the GBD by accounting for low back pain severity variations over time and between countries. Assumptions of unequal treatment access increased YLD estimates in resource-poor settings, with a modest decrease in countries with higher Health Access and Quality Index scores. Nonetheless, the large proportion of unavoidable burden indicates poor intervention efficacy. This method, applicable to other GBD conditions, provides policy makers with insights into health gains from improved treatment and underscores the importance of investing in research for new interventions. FUNDING: Bill and Melinda Gates Foundation and Queensland Health.

The arsenic eaters of Styria, the toxicophagi.

INTRODUCTION: From at least the fifteenth to late nineteenth centuries, peasants in the Austrian province of Styria ate up to several hundred milligrams of arsenic trioxide or sulfide daily or weekly for periods up to a number of years. Taking these doses of arsenic was believed to increase muscular power and enhance the beauty and sexual attractiveness of peasant girls. There do not appear to be contemporaneous records of the known consequences of chronic arsenic exposure. The historical records of arsenic eating there are reviewed and appear to be valid. The benefits are subjective judgements by arsenic eaters. The lack of objective reports of the anticipated external and internal clinical and pathological effects of arsenic poisoning depends on a smaller number of clinical accounts and autopsy reports and the general medical literature of those times, so it is weaker, but it is consistent. CAN THE CLAIMED BENEFITS OF ARSENIC EATING AND THE APPARENT ABSENCE OF HARMFUL TOXIC EFFECTS BE TRUE?: Why the arsenic eaters did not show the well-known consequences of prolonged exposure to high doses of arsenic is not known. Possible explanations include increases in detoxifying metabolism in the consumers due to induced genomic changes and selection in people and in the gut microbiome, as shown in other populations. Whether these effects would suffice to protect people against their high doses of arsenic has not been explored. CONCLUSION: Although the nature and mechanisms of arsenic toxicity have been extensively described, much still remains to be discovered.

Low HIV drug resistance prevalence among recently diagnosed HIV-positive men who have sex with men in a setting of high PrEP use.

INTRODUCTION: New South Wales (NSW) has one of the world's highest uptake rates of HIV pre-exposure prophylaxis (PrEP). This uptake has been credited with sharp declines in HIV transmission, particularly among Australian-born gay and bisexual men. Concerns have been raised around the potential for the emergence of tenofovir (TFV) and XTC (lamivudine/emtricitabine) resistance in settings of high PrEP use. Such an emergence could also increase treatment failure and associated clinical outcomes among people living with HIV (PLHIV). Despite low levels of nucleoside reverse-transcriptase inhibitor (NRTI) resistance relating to PrEP use in clinical settings, there are few published studies describing the prevalence of NRTI resistance among people newly diagnosed with HIV in a setting of high PrEP use. METHODS: Using HIV antiretroviral drug resistance data linked to NSW HIV notifications records of people diagnosed from 1 January 2015 to 31 December 2021 and with HIV attributed to male-to-male sex, we described trends in TFV and XTC resistance. Resistance was identified using the Stanford HIV Drug Resistance genotypic resistance interpretation system. To focus on transmitted drug resistance, resistance prevalence estimates were generated using sequences taken less than 3 months post-HIV diagnosis. These estimates were stratified by timing of sequencing relative to the date of diagnosis, year of sequencing, birthplace, likely place of HIV acquisition, and stage of HIV at diagnosis. RESULTS: Among 1119 diagnoses linked to HIV genomes sequenced less than 3 months following diagnosis, overall XTC resistance prevalence was 1.3%. Between 2015 and 2021, XTC resistance fluctuated between 0.5% to 2.9% and was 1.0% in 2021. No TFV resistance was found over the study period in any of the sequences analysed. Higher XTC resistance prevalence was observed among people with newly acquired HIV (evidence of HIV acquisition in the 12 months prior to diagnosis; 2.9%, p = 0.008). CONCLUSIONS: In this Australian setting, TFV and XTC resistance prevalence in new HIV diagnoses remained low. Our findings offer further evidence for the safe scale-up of PrEP in high-income settings, without jeopardizing the treatment of those living with HIV.

Identification and Evaluation of Reversible Covalent Binders to Cys55 of Bfl-1 from a DNA-Encoded Chemical Library Screen.

Bfl-1 is overexpressed in both hematological and solid tumors; therefore, inhibitors of Bfl-1 are highly desirable. A DNA-encoded chemical library (DEL) screen against Bfl-1 identified the first known reversible covalent small-molecule ligand for Bfl-1. The binding was validated through biophysical and biochemical techniques, which confirmed the reversible covalent mechanism of action and pointed to binding through Cys55. This represented the first identification of a cyano-acrylamide reversible covalent compound from a DEL screen and highlights further opportunities for covalent drug discovery through DEL screening. A 10-fold improvement in potency was achieved through a systematic SAR exploration of the hit. The more potent analogue compound 13 was successfully cocrystallized in Bfl-1, revealing the binding mode and providing further evidence of a covalent interaction with Cys55.

Multi-bounce self-mixing in terahertz metasurface external-cavity lasers.

The effects of optical feedback on a terahertz (THz) quantum-cascade metasurface vertical-external-cavity surface-emitting laser (QC-VECSEL) are investigated via self-mixing. A single-mode 2.80 THz QC-VECSEL operating in continuous-wave is subjected to various optical feedback conditions (i.e., feedback strength, round-trip time, and angular misalignment) while variations in its terminal voltage associated with self-mixing are monitored. Due to its large radiating aperture and near-Gaussian beam shape, we find that the QC-VECSEL is strongly susceptible to optical feedback, which is robust against misalignment of external optics. This, in addition to the use of a high-reflectance flat output coupler, results in high feedback levels associated with multiple round-trips within the external cavity-a phenomenon not typically observed for ridge-waveguide QC-lasers. Thus, a new theoretical model is established to describe self-mixing in the QC-VECSEL. The stability of the device under variable optical feedback conditions is also studied. Any mechanical instabilities of the external cavity (such as vibrations of the output coupler), are enhanced due to feedback and result in low-frequency oscillations of the terminal voltage. The work reveals how the self-mixing response differs for the QC-VECSEL architecture, informs other systems in which optical feedback is unavoidable, and paves the way for QC-VECSEL self-mixing applications.

Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis.

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.