Síntomas reveladores de la presencia de reacciones de estrés en personal de primera respuesta a emergencias en Cali, Colombia / Revealing symptoms of the presence of stress reactions in first responders to emergencies in Cali, Colombia

Resumen Introducción: Los trabajadores de primera respuesta a emergencias se encuentra expuestos a factores psicosociales que pueden incrementar el riesgo de estrés, debido, entre otras variables, a las condiciones propias de las funciones ejercidas lo cual puede menoscabar el estado de salud de esta población. Objetivo: Determinar los síntomas reveladores de la presencia de reacciones de estrés en personal de primera respuesta a emergencias y su asociación con la edad y la antigüedad en la institución. Método: Se realizó un estudio transversal que incluyó el personal de primera respuesta a emergencias de una institución de bomberos en Colombia, 215 participantes. Se realizó asociación entre el nivel de estrés y las variables edad y antigüedad. Resultados: Se encontró un nivel de estrés alto y muy alto del 50.3%. Los síntomas fisiológicos y de comportamiento social presentaron los niveles más altos. Los trabajadores con mayor edad presentaron mayor estrés. No se presentó asociación con la antigüedad en el cargo. Conclusión: Más de la mitad de la población tiene niveles de estrés alto y muy alto. Los trabajadores de primera respuesta a emergencias con mayor edad fueron los que presentaron niveles de riesgo más alto de estrés.

Abstract Introduction: First responders in emergencies are exposed to psychosocial factors that can increase the risk of stress, due, among other variables, to the conditions of the functions performed, which can undermine the health status of this population. Objective: Determine the symptoms that reveal the presence of stress reactions in first responders to emergencies and their association with age and seniority in the institution. Method: A cross-sectional study was carried out that included first responders to emergencies from a fire department in Colombia, 215 participants. An association was made between the level of stress and the variables age and seniority. Results: A high and very high stress level of 50.3% was found. Physiological and social behavior symptoms presented the highest levels. Older workers had greater stress. There was no association with length of service. Conclusion: More than half of the population has high and very high stress levels. The oldest emergency first responders were those with the highest risk levels of stress.

Strengthening the military stoic tradition: enhancing resilience in military service members and public safety personnel through functional disconnection and reconnection.

This paper addresses operational stress injuries (OSIs) among military service members (SM) and public safety personnel (PSP) resulting from prolonged exposure to potentially psychologically traumatic events (PPTEs). While psychotherapeutic interventions for post-traumatic stress injuries (PTSIs) are well established, there is a significant gap in evidence-based mental health training programs addressing proactive mitigation of negative outcomes from PPTEs. Building on the Functional Disconnection/Functional Reconnection (FD/FR) model, we introduce FD/FR 2, emphasizing early identification and management of psychological risks. FD/FR 2 discusses the practice of emotional suppression, or "pseudo-stoicism," and its potential negative impact on mental health. By integrating authentic Stoic principles, FD/FR 2 offers practical exercises to enhance resilience and well-being, addressing a critical need in current training approaches for military SM and PSP.

Influence of Emulsion Lipid Droplet Crystallinity on Postprandial Endotoxin Transporters and Atherogenic And Inflammatory Profiles in Healthy Men - A Randomized Double-Blind Crossover Acute Meal Study.

SCOPE: Consumption of high-fat meals is associated with increased endotoxemia, inflammation, and atherogenic profiles, with repeated postprandial responses suggested as contributors to chronically elevated risk factors. However, effects of lipid solid versus liquid state specifically have not been investigated. METHODS AND RESULTS: This exploratory randomized crossover study tests the impact of lipid crystallinity on plasma levels of endotoxin transporters (lipopolysaccharide [LPS] binding protein [LBP] and soluble cluster of differentiation 14 [sCD14]) and select proinflammatory and atherogenic markers (tumor necrosis factor-alpha [TNF-α], C-reactive protein [CRP], interleukin-1-beta [IL-1ß], interferon-gamma [IFN-γ], interleukin-6 [IL-6], soluble intercellular adhesion molecule [sICAM], soluble vascular cell adhesion molecule [sVCAM], monocyte chemoattractant protein-1 [MCP-1/CCL2], plasminogen activator inhibitor-1 [PAI-1], and fibrinogen). Fasted healthy men (n = 14, 28 ± 5.5 years, 24.1 ± 2.6 kg m-2) consumed two 50 g palm stearin oil-in-water emulsions tempered to contain either liquid or crystalline lipid droplets at 37 °C on separate occasions with blood sampling at 0, 2-, 4-, and 6-h post-meal. Timepoint data, area under the curve, and peak concentration values are compared. Overall, no treatment effects are seen (p > 0.05). There are significant effects of time, with values decreasing from baseline, for TNF-α, MCP-1/CCL2, PAI-1, and fibrinogen (p < 0.05). CONCLUSION: Responder analysis pointed to differential treatment effects associated with some participant baseline characteristics but, overall, palm-stearin emulsion droplet crystallinity does not acutely affect plasma endotoxin transporters nor select inflammatory and atherogenic markers.

First responders' occupational injury and disease associated with periods of extreme bushfires.

There has been limited research on the health impacts of extreme bushfire exposure among emergency responders (ER) involved in suppressing extreme bushfires. This study aimed to evaluate the associations between extreme bushfires and ER's compensated injury and illness in Victoria, Australia. State-wide ER compensation claims from January 2005 to April 2023 were analysed. Logistic regression modelling was used to identify factors associated with compensation claims during the extreme bushfire periods in 2009 and 2019/20, compared to all other claims, adjusting for seasonality (summer). Of the 44,164 included claims, 1105 (2.5%) had recorded injury/disease onset dates within extreme bushfire periods, and 11,642 (26.4%) occurred in summer months. Over half of claims were made by police (52.4%), followed by ambulance officers/paramedics (27.2%) and firefighters (20.5%). Extreme bushfire period claims were associated with older workers (odds ratio/OR = 1.58,95%CI = 1.30-1.92, ages ≥ 55 vs. 35-44 years). Mental disorders (OR = 1.61,95%CI = 1.25-2.07), intracranial injuries (OR = 3.04,95%CI = 1.69-5.48) and infections/parasites (OR = 3.11,95%CI = 1.61-5.98) vs. wounds were associated with extreme bushfire period claims. Given the expected increase in extreme bushfire events and the ageing workforce, study findings underscore the importance of primary and secondary prevention in ER. This can include periodic health surveillance for older workers, access to early treatment, and ongoing support for mental health conditions.

Twenty Years of International Research on First Aid: A Bibliometric Visualization of Scientific Outputs.

Although first aid research is a wide-ranging and diverse field within medical science, so far no attempts have been made to provide a holistic view of international scientific outputs in the first aid domain. To determine strategic directions for conducting future studies, it is important to understand the status of the research, including its frontiers and blind spots. This study explored the global landscape of first aid research using bibliometric visualization analysis of relevant literature published within the last 20 years. The search yielded a total of 2,057 relevant papers. There was a trend of increasing annual numbers of publications throughout the 20 year period. The following topics were identified as the mainstream directions of first aid research: cross-sectional studies on attitudes and knowledge of first aid; cardiac arrest and cardiopulmonary resuscitation; bleeding and hemorrhage control; burns, scalds, and their management; envenomations and their management; and systematic evaluation of the scientific evidence. Evidence evaluation is one of the main frontiers of first aid research. Studies concerning first aid for the most common and deadliest diseases, including myocardial infarction and stroke, are not in the scope of contemporary international first aid research. Considering that effective implementation of first aid can reduce morbidity and mortality, it is advisable to advance research on first aid management of major emergencies that are the most common potentially avoidable causes of death.

Self-care strategies used by disaster responders after the 2023 earthquake in Turkey and Syria: a mixed methods study.

BACKGROUND: Disaster responders are exposed to several physical and mental health risks. This study aimed to describe self-care strategies used by disaster responders after the earthquake in Syria and eastern Turkey in February 2023. METHODS: A study specific web-based questionnaire survey was used to collect quantitative and qualitative data according to a convergent mixed methods approach. Data from 252 disaster responders responding to the earthquakes in Turkey and Syria were analyzed using both descriptive and analytical statistics and summative content analysis of free-text answers. Data were collected in March to July, 2023. RESULTS: The most used self-care strategies included resting, social support from colleagues in the field, extra intake of food or drink, and intake of medicines. The recovery strategies varied due to previous disaster response experience, indicating that supportive self-care strategies can be developed or learned. CONCLUSION: Given the extreme conditions and limited possibilities of external support, sufficient self-care is an essential competence among disaster responders. Self-care strategies can be both external processed such as intake of medicines, social support from others, and internal processes such as personal reflection. Providing oneself with self-care activities seems to be a skill developed with increasing experience supported by pre-deployment training. Therefore, to enhance resilience, self-care strategies should be encompassed in pre-disaster response training.

Interleukin 38 reduces antigen-presentation capacity and antibody production after vaccination.

The mechanisms that underpin low vaccine responses, which can lead to inadequate protection against infection, are still partially unclear. Interleukin (IL)-38 is a member of the IL-1 family, expressed by B cells among others, that regulates inflammatory responses. A recent study shows that IL-38 suppresses plasma cell generation and antibody production upon immune activation. We hypothesis that IL-38 affects antigen-presentation capacity of innate immune cells, effecting antibody production. Here, we investigated the effect of recombinant human IL-38 on human peripheral blood mononuclear cells and myeloid-derived DCs regarding cytokine production, phagocytosis, and expression of MCH II and co-stimulatory proteins in vitro, and further relate circulating plasma IL-38 concentrations to antibody responses in a cohort of 75 females aged 18-48 vaccinated with BCG and Tdap-IPV. To this end, we found that IL-38 decreased the expression of HLA-DR, HLA-DM, and CD83 on PBMCs, and CD40 and CD86 on MDDCs. IL-38 further impaired phagocytosis capacity of monocytes. Lastly, antibody production against diphtheria toxoids up to eight months post-vaccination was negatively associated with IL-38 plasma concentrations. These data suggest that IL-38 could dampen the effectiveness of antigen-presentation and phagocytosis, and could therefore modulate the immunogenicity of some vaccine types.

Current Pharmacotherapy and Nutrition Therapy of Alcohol-Associated Liver Disease.

Patients with alcohol-associated liver disease (ALD) consume large amounts of empty calories and are at risk for malnutrition. Malnutrition can present with micro- or macro-nutrient deficiencies. The standard-of-care drug treatment for severe alcohol-associated hepatitis (AH) is corticosteroids. While still in the standard treatment there are limitations in efficacy and certain patients do not respond to treatment (Lille score ≥.45). This article will focus on important concepts related to nutrition and ALD and on recent findings on predicting corticosteroid response and prognosis for AH patients.

Client Perspectives of Case Stories in Internet-Delivered Cognitive Behavioral Therapy for Public Safety Personnel: Mixed Methods Study.

BACKGROUND: Internet-delivered cognitive behavioral therapy (ICBT) is an effective and convenient means of offering cognitive behavioral therapy to the general population. To increase access to ICBT among Canadian public safety personnel (PSP)-a group that experiences elevated rates of mental health concerns and barriers to mental health care-a clinical research unit called PSPNET has tailored ICBT to PSP, primarily through offering case stories and PSP-specific examples within an ICBT program. PSPNET's first and most frequently used ICBT program, called the PSP Wellbeing Course, has been found to reduce symptoms of mental disorders (eg, anxiety, depression, and posttraumatic stress) among PSP. Little research, however, has investigated clients' perceptions of the case stories in this course. OBJECTIVE: This study was designed to expand the literature on the use and evaluation of case stories in ICBT among PSP. Specifically, this study investigated (1) PSP's perceptions of the case stories using the theoretical model provided by Shaffer and Zikmund-Fisher and (2) PSP feedback on the case stories in the PSP Wellbeing Course. METHODS: This study included 41 clients who completed the PSP Wellbeing Course. Of these, 27 clients completed a bespoke questionnaire called the Stories Questionnaire, 10 of whom also participated in a semistructured interview. RESULTS: Findings show that perceptions of the case stories in the PSP Wellbeing Course were largely positive and that the case stories were generally successful in achieving the 5 purposes of case stories (ie, informing, comforting, modeling, engaging, and persuading) proposed by Shaffer and Zikmund-Fisher. Client feedback also identified 3 tangible areas for story improvement: characters, content, and delivery. Each area highlights the need for and potential benefits of story development. Not all PSP engaged with the case stories, though, so results must be interpreted with caution. CONCLUSIONS: Overall, this study adds to the growing body of research supporting the use of case stories in internet-delivered interventions among PSP. TRIAL REGISTRATION: ClinicalTrials.gov NCT04127032; https://www.clinicaltrials.gov/ct2/show/NCT04127032.

The effects of work-family conflict, work engagement, and job burnout on self-rated health of public health emergency responders in Jilin Province, China, in the context of the COVID-19.

Introduction: Amid sudden public health crises, preserving the well-being and optimal working states of frontline healthcare professionals is imperative for efficaciously managing the emergences. However, there is a paucity of research investigating the health status of frontline healthcare professionals through the perspective of work-family conflict. This study sought to elucidate the complex interrelations between work-family conflict, work engagement, job burnout, and self-rated health among public health emergency responders within the context of the COVID-19 pandemic. Methods: A convenience sampling method was employed to survey 1,309 public health emergency responders at the Jilin Provincial Center for Disease Control and Prevention. An online survey was administered utilizing a self-constructed questionnaire. The hypothesized relationships between the variables were tested using structural equation modeling. Results: The direct impact of work-family conflict on self-rated health is not significant. The association between work-family conflicts and self-rated health was significantly mediated by work engagement and job burnout, respectively. Meanwhile, work engagement and job burnout had a chain mediating effect on work-family conflict and self-rated health. Conclusion: Work-family conflict plays a critical role in shaping the health and work status of public health emergency responders during public health crises. Organizations and managers should, in their workplace management practices, focus not only on work-related factors but also give due consideration to family-related factors. Supportive policies, including family-friendly initiatives, should be developed to safeguard the health and work engagement of public health emergency responders.

Psychometric evaluation of the Turkish version of the Work-Related Stress Scale: A study among search and rescue workers responding to the 2023 Kahramanmaras earthquakes.

This study evaluates the reliability and validity of the Turkish version of the Work-Related Stress Scale (WRSS) among search and rescue workers who responded to the 2023 Kahramanmaras earthquakes. Data were collected from 275 workers between January and April 2024 using the Personal Information Form and the Turkish version of the WRSS. Language, content, and construct validity were assessed, and reliability was determined using item-total correlation, Cronbach's alpha, split-half, and test-retest methods. The scale demonstrated strong content validity with a CVI range of 0.9-1.0 and a mean CVI of 0.98. Exploratory factor analysis yielded factor loadings from 0.469 to 0.932, resulting in four factors that explained 75.3% of the variance. The reliability coefficients for the sub-dimensions ranged from 0.833 to 0.900, with an overall Cronbach's alpha of 0.913. These results indicate that the Turkish WRSS is a valid and reliable tool for assessing stress among search and rescue workers.

Developing Training in Response to High-Consequence Infectious Diseases and Preparedness Measures for the Future.

In recent history, outbreaks of high-consequence infectious diseases (HCIDs) have raised health security concerns among the global community. As HCIDs continue to emerge, public health systems around the world experience the burden of implementing adequate preparedness and response measures to ensure the safety and security of their populations. HCID outbreak response efforts have highlighted the need for specialized training in safety and infection prevention and control for frontline workers who may encounter ill patients. The COVID-19 Mission Prep program for National Disaster Medical System personnel and the Deployment Safety Academy for Field Experiences (D-SAFE) program for US Public Health Service officers are 2 examples of virtual training programs that successfully provided foundational education on infection prevention and control and safety as well as deployable just-in-time training during HCID outbreak response efforts. The methods used to develop these training programs can be adopted by other countries to enhance the global outbreak response infrastructure for the next HCID event. The global outbreak response infrastructure demands investments in training as a preparedness measure, which will ultimately lead to safer, more coordinated outbreak response efforts with competent responders.

Learner evaluation of an immersive virtual reality mass casualty incident simulator for triage training.

Background: To minimize loss of life, modern mass casualty response requires swift identification, efficient triage categorization, and rapid hemorrhage control. Current training methods remain suboptimal. Our objective was to train first responders to triage a mass casualty incident using Virtual Reality (VR) simulation and obtain their impressions of the training's quality and effectiveness.We trained subjects in a triage protocol called Sort, Assess, Lifesaving interventions, and Treatment and/or Transport (SALT) Triage then had them respond to a terrorist bombing of a subway station using a fully immersive virtual reality simulation. We gathered learner reactions to their virtual reality experience and post-encounter debriefing with a custom electronic survey. The survey was designed to gather information about participants' demographics and prior experience, including roles, triage training, and virtual reality experience. We then asked them to evaluate the training and encounter and the system's potential for training others. Results: We received 375 completed evaluation surveys from subjects who experienced the virtual reality encounter. Subjects were primarily paramedics, but also included medical learners as well as other emergency medical service (EMS) professionals. Most participants (95%) recommended the experience for other first responders and rated the simulation (95%) and virtual patients (91%) as realistic. Ninety-four percent (94%) of participants rated the virtual reality simulator as "excellent" or "good." We observed some differences between emergency medical service and medical professionals regarding their prior experience with disaster response training and their opinions on how much the experience contributed to their learning. We observed no differences between subjects with extensive virtual reality experience and those without. Conclusions: Our virtual reality simulator is an automated, customizable, fully immersive virtual reality system for training and assessing personnel in the proper response to a mass casualty incident. Participants perceived the simulator as an adequate alternative to traditional triage and treatment training and believed that the simulator was realistic and effective for training. Prior experience with virtual reality was not a prerequisite for the use of this system. Supplementary Information: The online version contains supplementary material available at 10.1186/s44247-024-00117-5.

Do Surrogate Markers of Cardiorespiratory Fitness Predict Individual Changes in VO2peak? A Randomized Controlled Trial.

The purpose of the current study was to test the hypothesis that individual response classification for surrogate markers of cardiorespiratory fitness (CRF) will agree with response classification for VO2peak. Surrogate markers of CRF were time to fatigue on treadmill test (TTF), time trial performance (3kTT), resting heart rate (RHR), submaximal heart rate (SubmaxHR), and submaximal ratings of perceived exertion (SubmaxRPE). Twenty-five participants were randomized into a high-intensity interval training (HIIT: n = 14) group or non-exercise control group (CTL: n = 11). Training consisted of four weeks of high-intensity interval training (HIIT) - 4x4 minute intervals at 90-95% HRmax 3 times per week. We observed poor agreement between response classification for VO2peak and surrogate markers (agreement < 60% for all outcomes). Although surrogate markers and VO2peak correlated at the pre- and post-intervention time points, change scores for VO2peak were not correlated with changes in surrogate markers of CRF. Interestingly, a significant relationship (r 2 = 0.36, p = 0.02) was observed when comparing improvements in estimated training performance (VO2) and change in VO2peak. Contrary to our hypothesis, we observed poor classification agreement and non-significant correlations for changes scores of VO2peak and surrogate markers of CRF. Our results suggest that individuals concerned with their VO2peak response seek direct measurements of VO2.

Therapeutic management in women with a diminished ovarian reserve: a systematic review and meta-analysis of randomized controlled trials.

IMPORTANCE: The clinical management of women with diminished ovarian reserve (DOR) is a challenge in the field of medically assisted reproduction. Several therapeutic strategies have been proposed, but with mixed results, mainly because the definition of DOR used was inconsistent among trials. OBJECTIVE: To investigate adjuvant treatments and protocols involving only women with DOR according to POSEIDON criteria. DATA SOURCES: We conducted a systematic search using the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases to identify relevant studies published up to June 2024. The review protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number CRD42022346117). STUDY SELECTION AND SYNTHESIS: After duplication removal, the titles and abstracts of 4,806 articles were scrutinized, and 124 full-text articles were assessed for eligibility. In total, 38 randomized controlled trials were included in the qualitative/quantitative analysis. The following interventions were evaluated: dehydroepiandrosterone (n = 1,336), testosterone (n = 418), high- versus low-dose gonadotropin (n = 957), delayed-start protocol with GnRH antagonist (n = 398), letrozole (n = 612), clomiphene citrate (1,113), growth hormone (311), luteal phase stimulation (n = 57), dual triggering (n = 139), dual stimulation (168), luteinizing hormone (979), oestradiol pre-treatment (n = 552), and corifollitropin alfa (n = 561). RESULTS: Testosterone supplementation is associated with higher live birth rates compared with non-supplemented women among all interventions evaluated (OR 2.19, 95% CI 1.11-4.32, 4 studies, 368 patients; p = 0.02). Testosterone (WMD 0.88, 95% CI 0.03-1.72; 4 studies, n = 368 patients; p = 0.04), DHEA (WMD 0.60, 95% CI 0.07-1.13; 4 studies, n = 418 patients; p = 0.03), high-dose gonadotropin regimen (WMD -1.57, 95% CI -2.12 to -1.17; 2 studies, n = 905 patients; p < 0.0001) and delayed started protocol (WMD 1.32, 95% CI 0.74 to 1.89; 3 studies, n = 398 patients; p < 0.00001) significantly improved the total number of eggs collected. The other interventions did not produce significant improvements. CONCLUSION AND RELEVANCE: Specific interventions such as testosterone seem to correlate with a better live birth rate in women with diminished ovarian reserve; these findings should be further explored in randomized trials.

Challenges and Opportunities in Developing a Comprehensive, Rural, Trauma-Care Program: Experiences from Nepal.

Traumatic injury remains a significant public health problem, with the burden highest in low-middle income countries (LMICs) and rural areas.1,2 The far-western region of Nepal, which has the lowest human development index in the country, has a high burden of traumatic injuries.3-5 One hospital in the far-western district of Achham, Bayalpata Hospital, cares for the majority of patients with traumatic injuries - most of whom arrive without any pre-hospital care. The absence of a professionalized pre-hospital program, such as an established Emergency Medical Services (EMS) system, necessitates creative strategies to address this gap.6,7 In this context, implementing a trauma-training program for community health responders (CHRs) offers a promising solution, leveraging local resources to improve early-stage trauma care.

HIV-1-DNA/RNA and immunometabolism in monocytes: contribution to the chronic immune activation and inflammation in people with HIV-1.

BACKGROUND: Among people living with HIV-1 (PHIV), immunological non-responders (INR) experience incomplete immune recovery despite suppressive antiretroviral treatment (ART), facing more severe non-AIDS events than immunological responders (IR) due to higher chronic immune activation and inflammation (cIA/I). We analyzed the HIV-1 reservoir and immunometabolism in monocytes as a source of cIA/I. METHODS: Cross-sectional study in which 110 participants were enrolled: 25 treatment-naïve; 35 INR; 40 IR; and 10 healthy controls. Cell-associated HIV-1-DNA (HIV-DNA) and -RNA (HIV-RNA) were measured in FACS-isolated monocytes using digital droplet PCR. Intact, 5' deleted, and 3' deleted proviruses were quantified by the intact proviral DNA assay. Systemic inflammation, monocyte immunophenotype, and immunometabolism were characterized by immunoassays, flow cytometry, and real-time cellular bioenergetics measurements, respectively. FINDINGS: Monocytes from INR harbor higher HIV-RNA and HIV-DNA levels than IR. HIV-RNA was found in 14/21 treatment-naïve [2512 copies/106 TBP (331-4666)], 17/33 INR [240 (148-589)], and 15/28 IR [144 (15-309)], correlating directly with sCD163, IP-10, GLUT1high cells and glucose uptake, and inversely with the CD4+/CD8+ ratio. HIV-DNA was identified in all participants with detectable HIV-RNA, with intact provirus in 9/12 treatment-naïve [13 copies/106 monocytes (7-44)], 8/14 INR [46 (18-67)], and 9/13 IR [9 (7-24)]. INR presented glucose metabolism alterations and mitochondrial impairment; decreased coupling efficiency and BHI, and increased mitochondrial dysfunction inversely correlating with the CD4+/CD8+ ratio. INTERPRETATION: HIV-RNA, more than HIV-DNA, in monocytes and their altered metabolism are factors associated with the higher cIA/I that characterize INR. FUNDING: This work was supported by the European Regional Development Fund, ISCIII, grant PI20/01646. Other funding sources: Instituto de Salud Carlos III through the Subprogram Miguel Servet (CP19/00159) to AGV, PFIS contracts (FI19/00304) to EMM, (FI21/00165) to ASA, and (FI19/00083) to CGC, and a mobility grant (MV21/00103) to EMM, from the Ministerio de Ciencia e Innovación, Spain. AJM was granted by a CSL Centenary Award.

Implications of accumulation of clonally expanded and senescent CD4+GNLY+ T cells in immunological non-responders of HIV-1 infection.

Increased CD4+GNLY+ T cells have been confirmed to be inversely associated with CD4+ T cell count in immunological non-responders (INRs), however, the underlying mechanisms are unknown. This study aimed to elucidate the characteristics of CD4+GNLY+ T cells and their relationship with immune restoration. Single-cell RNA sequencing, single-cell TCR sequencing, and flow cytometry were used to analyze the frequency, phenotypes, and function of CD4+GNLY+ T cells. Moreover, Enzyme linked immunosorbent assay was performed to detect plasma cytokines production in patients. CD4+GNLY+ T cells were found to be highly clonally expanded, characterized by higher levels of cytotoxicity, senescence, P24, and HIV-1 DNA than CD4+GNLY- T cells. Additionally, the frequency of CD4+GNLY+ T cells increased after ART, and further increased in INRs, and were positively associated with the antiretroviral therapy duration in INR. Furthermore, increased IL-15 levels in INRs positively correlated with the frequency and senescence of CD4+GNLY+ T cells, suggesting that CD4+GNLY+ T cells may provide new insights for understanding the poor immune reconstitution of INRs. In conclusion, increased, highly clonally expanded, and senescent CD4+GNLY+ T cells may contribute to poor immune reconstitution in HIV-1 infection.

Clinical Outcomes of Elective Early Discontinuation of Immunotherapy Based on Objective Response in Microsatellite Instability-High Metastatic Colorectal Cancer.

BACKGROUND: Patients with microsatellite-high (MSI-H) metastatic colorectal cancers (CRC) may experience long-lasting benefit from immune checkpoint inhibitors (ICI) upon stopping therapy. However, optimal timing and patient selection criteria for early treatment withdrawal remain undefined. In this single-center retrospective study, we characterized the clinical response and associated survival outcomes of patients who received elective early versus late treatment discontinuation. METHODS: We retrospectively analyzed patients with MSI-H metastatic CRC treated with ICI therapy from May 2015 to April 2024. Early ICI discontinuation was defined as treatment withdrawal before 2 years, and late ICI discontinuation as after 2 years. Response was assessed using Response Evaluation Criteria in Solid Tumors. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Efficacy outcomes between early and late ICI discontinuation groups were compared using a log-rank test. RESULTS: Of 36 patients with MSI-H metastatic CRC, 12 underwent elective early ICI discontinuation and 9 experienced late ICI discontinuation. After a median follow-up of 32 months post-treatment, 91.7% (11/12) in the early discontinuation group remain off therapy without progression. PFS and OS outcomes between the early and late discontinuation groups were similarly favorable (P = .88 and P = .85, respectively), despite a 12-month difference in median duration of ICI therapy (13.3 and 25.6 months, respectively). The most common reason for elective early treatment discontinuation was clinical remission (n = 10), defined as a complete response, or a partial response with negative PET and/or ctDNA testing. CONCLUSIONS: Early ICI discontinuation guided by response criteria resulted in low rates of recurrence. Survival outcomes between early and late ICI discontinuation groups were comparable, suggesting that treatment duration can be individualized based on clinical response without compromising favorable long-term prognosis.

Perceived posttraumatic growth: positive change occurring because of or despite the trauma?

BACKGROUND: Some researchers have posited that self-reports of PTG are often illusory, designed to help trauma survivors maintain positive views of the self. We examined whether participants might select an alternative, attractive option to reporting PTG that could similarly help maintain positive views of the self - reporting that the respondent experienced positive growth despite exposure to an adverse event, which we call Positive Change-Despite (PC-Despite). METHOD: In two separate studies, after asking respondents about positive change they experienced following exposure to an adverse event, we then asked about the extent to which they experienced positive change because of the adverse event (PC-Because) or despite the adverse event (PC-Despite). RESULTS: We found that participants rated 40% (Study 1 - undergraduate sample) and 31% (Study 2 - first responder sample) of their positive change as PC-Despite. Further, in both studies PC-Despite scores were positively related to measures of distress and both adaptive and maladaptive coping, suggesting a link with an illusory form of PTG. In contrast, PC-Because was only related to adaptive coping. CONCLUSION: Participants chose an attractive alternative response to reporting PTG at substantial rates, supporting the notion that many self-reports of PTG reflect motivated biases and coping processes.