Tumor microenvironment governs the prognostic landscape of immunotherapy for head and neck squamous cell carcinoma: A computational model-guided analysis.

Immune checkpoint inhibition (ICI) has emerged as a critical treatment strategy for squamous cell carcinoma of the head and neck (HNSCC) that halts the immune escape of the tumor cells. Increasing evidence suggests that the onset, progression, and lack of/no response of HNSCC to ICI are emergent properties arising from the interactions within the tumor microenvironment (TME). Deciphering how the diversity of cellular and molecular interactions leads to distinct HNSCC TME subtypes subsequently governing the ICI response remains largely unexplored. We developed a cellular-molecular model of the HNSCC TME that incorporates multiple cell types, cellular states, and transitions, and molecularly mediated paracrine interactions. An exhaustive simulation of the HNSCC TME network shows that distinct mechanistic balances within the TME give rise to the five clinically observed TME subtypes such as immune/non-fibrotic, immune/fibrotic, fibrotic only and immune/fibrotic desert. We predict that the cancer-associated fibroblast, beyond a critical proliferation rate, drastically worsens the ICI response by hampering the accessibility of the CD8+ killer T cells to the tumor cells. Our analysis reveals that while an Interleukin-2 (IL-2) + ICI combination therapy may improve response in the immune desert scenario, Osteopontin (OPN) and Leukemia Inhibition Factor (LIF) knockout with ICI yields the best response in a fibro-dominated scenario. Further, we predict Interleukin-8 (IL-8), and lactate can serve as crucial biomarkers for ICI-resistant HNSCC phenotypes. Overall, we provide an integrated quantitative framework that explains a wide range of TME-mediated resistance mechanisms for HNSCC and predicts TME subtype-specific targets that can lead to an improved ICI outcome.

Pilot Randomized Controlled Trial of a Yoga-Based Intervention Targeting Anger Management for People Who Are Incarcerated.

Introduction: Incarceration represents an opportune moment to improve self-management of anger and aggression. A hatha yoga-based intervention (YBI) could serve as a useful adjunctive intervention for anger within prisons. Methods: We enrolled 40 people with elevated levels of anger who were incarcerated (20 in a women's facility, and 20 in a men's facility) in a 10-week pilot randomized controlled trial of a YBI versus. a health education (HE) control group. Participants attended their respective groups once per week. We examined indices of feasibility and acceptability, including intervention credibility, expectancy the intervention would be helpful, intervention satisfaction, class attendance, engagement in personal practice, instructor fidelity, intervention safety, and study recruitment and retention rates. We also examined changes in clinical outcomes including anger, depression, anxiety, and behavioral infractions over time. Results: We met targets for several outcomes: credibility of the YBI and HE interventions, expectancy that they would be helpful, and satisfaction with the programs. Instructors demonstrated fidelity to both manuals. There were no serious adverse events related to study participation. Class attendance did not meet our target outcome in either facility and rates of personal practice met our target outcome in the men's but not the women's facility. For people enrolled in the YBI, anger, depression, and anxiety tended to decrease over time. Qualitative interviews with participants pointed to overall high satisfaction with the YBI and provided information on facility-related barriers to class attendance. Conclusion: Although we did not meet all our feasibility targets in this study, we note high participant enthusiasm. Thus, we believe this line of research is worth pursuing, with further attention to ways to decrease facility-related barriers to class attendance and personal practice. Clinical trials registration: NCT05336123.

Stress responses in an Arctic microalga (Pelagophyceae) following sudden salinity change revealed by gene expression analysis.

Marine microbes that have for eons been adapted to stable salinity regimes are confronted with sudden decreases in salinity in the Arctic Ocean. The episodic freshening is increasing due to climate change with melting multi-year sea-ice and glaciers, greater inflows from rivers, and increased precipitation. To investigate algal responses to lowered salinity, we analyzed the responses and acclimatation over 24 h in a non-model Arctic marine alga (pelagophyte CCMP2097) following transfer to realistic lower salinities. Using RNA-seq transcriptomics, here we show rapid differentially expressed genes related to stress oxidative responses, proteins involved in the photosystem and circadian clock, and those affecting lipids and inorganic ions. After 24 h the pelagophyte adjusted to the lower salinity seen in the overexpression of genes associated with freezing resistance, cold adaptation, and salt tolerance. Overall, a suite of ancient widespread pathways is recruited enabling the species to adjust to the stress of rapid salinity change.

Dodecafluoropentane emulsion as an oxygen therapeutic.

Dodecafluoropentane emulsion (DDFPe) is a fluorocarbon (FC) under clinical development as an oxygen therapeutic and is regulated as a blood substitute. Compared to all the prior FCs studied, DDFP is the most advantageous for oxygen delivery and it is active at a lower concentration (1/200th to 1/1000th the weight of other FCs). DDFP has a boiling point of 29 °C, is more water soluble than prior FCs, and following IV administration clears via exhalation. Prior FCs had boiling points ≥ 140 °C and were retained long-term in the body causing adverse events. DDFP is a gas at biological temperature while prior FCs were liquids. Gases deliver roughly 1000 times more oxygen than liquids. DDFPe has two mechanisms of action: (1) The size of the molecule is the smallest that is a liquid at room temperature; on a molar volume basis this equates to more dissolution of oxygen. (2) Because of its boiling point close to physiologic temperature, DDFP delivers oxygen more effectively than liquid FCs.Highlight PointsFluorocarbons (FCs) dissolve oxygen and other respirable gases.FC emulsions generally do not have biological effects of and by themselves, but rather they increase the oxygen carrying capacity of the blood.There are a variety of FCs that were developed in the past as blood substitutes but they all caused accumulation in humans leading to toxic responses.Dodecafluoropentane emulsion (DDFPe) is being developed as an oxygen therapeutic to increase the oxygen carrying capacity of the blood and oxygen delivery to tissues.

Missing voices: building women living with HIV's meaningful engagement in HIV clinical and cure research.

Women living with HIV are consistently under-represented in HIV clinical trials, including cure trials. Little is known about how cisgender women living with HIV in Australia perceive HIV cure research, their level of trust in research institutions/staff, and factors salient to participation in HIV cure trials. Semi-structured interviews were conducted with women living with HIV and clinicians working with women living with HIV to investigate motivations and barriers to gender-equitable representation in HIV clinical research. Participant motivations for participation included altruistic desires to benefit younger women, and to optimise resulting interventions. Women living with HIV expressed optimism that a cure would dispel HIV-related stigma and brings about substantial material improvement to their lives. Reluctance to participate related to concerns regarding potential side-effects, antiretroviral treatment interruption, and impacts on fertility. Unfamiliarity with trials, confidentiality concerns and logistical difficulties were also cited. Lastly, onerous eligibility criteria, clinicians' assumptions about women's willingness and ability to meaningfully provide consent to participation were cited as barriers which could be addressed. Bolstering women's participation in HIV cure research requires consideration of factors relating to reproductive health, analytical treatment interruption, and recruitment. Engaging women living with HIV in trial design and promotion may help overcome these issues.

National needs assessment of emergency medicine faculty regarding scholarly activity practices and support.

Objectives: We aimed to assess the attitudes and perceptions of scholarly activity (SA) practices among emergency medicine (EM) physicians who are engaged in training residents. This study examined the belief and need for modern-day SA, potential barriers, and department resources provided. Methods: We conducted a descriptive cross-sectional survey study of EM physicians across the United States identified from the American College of Emergency Physicians and American College of Osteopathic Physicians directories. The survey consisted of 18 items regarding demographics, attitude toward SA, department support, and questions regarding residency programs. Results: A total of 660 survey recipients completed the survey out of a possible pool of 4296 individuals (15% response rate), of which 530 (80%) indicated they were core faculty. Of core faculty, 428 (80.8%) were part of an allopathic program, whereas 102 (19.2%) were part of an osteopathic program. Department support was provided for protected time (385; 58.3%), research staff (346; 52.4%), Institutional Review Board preparation (240; 36.4%), and biostatistics (314; 47.6%). Of all the institutional roles, the largest percentage (82/125, 65.6%) of chair/vice chair/associate chairs strongly agreed or agreed (score of 5 or 4 of 5) with the statement, "Overall, I am satisfied with the scholarly support provided by my department." There was no difference in agreement with this statement between respondents in an allopathic versus osteopathic program (210/428, 49.1% allopathic; 45/102, 44.1% osteopathic). Conclusion: There is a need for increased departmental support for SA. To optimally implement the Accreditation Council for Graduate Medical Education (ACGME) SA requirements into strategy and action, the ACGME should consider providing EM residency programs with an outline of best SA practices to foster a uniform consensus across academic institutions.

Respiratory infection with influenza A virus delays remyelination and alters oligodendrocyte metabolism.

Peripheral viral infection disrupts oligodendrocyte (OL) homeostasis such that endogenous remyelination may be affected. Here, we demonstrate that influenza A virus infection perpetuated a demyelination- and disease-associated OL phenotype following cuprizone-induced demyelination that resulted in delayed OL maturation and remyelination in the prefrontal cortex. Furthermore, we assessed cellular metabolism ex vivo, and found that infection altered brain OL and microglia metabolism in a manner that opposed the metabolic profile induced by remyelination. Specifically, infection increased glycolytic capacity of OLs and microglia, an effect that was recapitulated by lipopolysaccharide (LPS) stimulation of mixed glia cultures. In contrast, mitochondrial dependence was increased in OLs during remyelination, which was similarly observed in OLs of myelinating P14 mice compared to adult and aged mice. Collectively, our data indicate that respiratory viral infection is capable of suppressing remyelination, and suggest that metabolic dysfunction of OLs is implicated in remyelination impairment.

Defective endomembrane dynamics in Rab27a deficiency impairs nucleic acid sensing and cytokine secretion in immune cells.

Endosomal Toll-like receptors (eTLRs) are essential for the sensing of non-self through RNA and DNA detection. Here, using spatiotemporal analysis of vesicular dynamics, super-resolution microscopy studies, and functional assays, we show that endomembrane defects associated with the deficiency of the small GTPase Rab27a cause delayed eTLR ligand recognition, defective early signaling, and impaired cytokine secretion. Rab27a-deficient neutrophils show retention of eTLRs in amphisomes and impaired ligand internalization. Extracellular signal-regulated kinase (ERK) signaling and ß2-integrin upregulation, early responses to TLR7 and TLR9 ligands, are defective in Rab27a deficiency. CpG-stimulated Rab27a-deficient neutrophils present increased tumor necrosis factor alpha (TNF-α) secretion and decreased secretion of a selected group of mediators, including interleukin (IL)-10. In vivo, CpG-challenged Rab27a-null mice show decreased production of type I interferons (IFNs) and IFN-γ, and the IFN-α secretion defect is confirmed in Rab27a-null plasmacytoid dendritic cells. Our findings have significant implications for immunodeficiency, inflammation, and CpG adjuvant vaccination.

Cascade of care for substance use and mental health disorders for justice-involved populations.

INTRODUCTION: Justice-involved populations have dramatically higher rates of substance use disorders (SUD) and mental health disorders (MHD) compared to the general population. Despite high rates of SUD and MHD, treatment for this population is often limited and not evidence-based. The cascade of care model estimates drop-offs in the continuum of care from screening to identification of need, referral, care initiation, care engagement, and care completion. Recently, healthcare providers have utilized the cascade of care to improve the continuity of care for people with SUD and MHD in justice settings. The purpose of the current study is to 1) identify typologies that explain the proportion of new intakes that pass through each level of the cascade of care for SUD and MHD, and 2) describe agency-level factors that predict typology assignments and agency ability to assess client flow through the levels of the care cascade. METHOD: Using Latent Class Analysis, we classify 791 agencies serving justice-involved individuals into typologies according to utilization of each stage in the mental health and substance cascades of care. Then, we examined county and agency characteristics that affect three stages of the cascade process: identification of need for behavioral health services, referrals to appropriate services, and treatment initiation. We build on previous work by exploring these patterns for both SUD and MHD treatment. RESULTS: The study identified four SUD/MHD treatment patterns: Low Access, SUD-Focused, High Need-High Access, and Lower Need-High Access classes. Factors influencing typology alignment include location, specialized staff availability, warm hand-off coordination, Medicaid reimbursement, and performance measure tracking. Thirty-nine percent (39 %) of agencies could not be classified because they were unable to report their rate of care along the cascade measures. CONCLUSION: Focusing on factors influencing typology assignment can help counties in assessing service delivery, identifying barriers, and targeting areas for improvements in policies and practices, potentially facilitating long-term changes and overall improvement in the care of individuals with mental health and substance use disorders. Identification of these factors and typologies can improve mental health treatment and access in counties and agencies with large resource barriers or limited attention to mental health treatment.

Understanding social risk factors in patients presenting to the emergency Department for Acute Heart Failure: A pilot study.

BACKGROUND: The standard of care for congestive heart failure (CHF) aims to slow disease progression and maximize patient function, however there is an increase in emergency department (ED) revisits and readmissions. Social risk factors play a role in the disease management and prognosis of CHF. There is a gap in the identification of low-risk CHF patient who would be safely discharged using an initial social risk factor stratification. OBJECTIVES: To generate a social risk profile for patients presenting to the ED with acute CHF exacerbation and identify variables that may increase the risk of 7-day and overall mortality, 30-day ED revisit, and readmission. METHODS: We conducted a pilot prospective survey-based study among adult patients presenting to the ED with acute CHF exacerbation. The combination of a self-report questionnaire and retrospective chart review was used to generate a CHF risk profile. RESULTS: A total of 62 patients were recruited in the pilot study with a mean age of 69.5 years. The preliminary data indicated that prior to this ED visit, 21% of patients were not aware of a previous CHF diagnosis; 64.5% of patients rated their sleep quality as poor or very poor; 72.6% reported orthopnea; and 43.5% reported recent weight gain. 37.1% of patients did not adhere to dietary recommendations and some patients did not adhere to their medication regime 100%. CONCLUSION: This study suggests establishing a social risk profile for patients presenting to the ED with CHF can help formulate a CHF-specific care plan and optimize multidisciplinary management to reduce ED revisits and readmissions.

Altered extracellular matrix correlates with an immunosuppressive tumor microenvironment and disease progression in younger adults with oral cavity squamous cell carcinoma.

Introduction: Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (<45 years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options. Methods: Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) processes in younger (≤45 years) vs. older adults (≥60 years). NanoString nCounter analysis was performed using isolated total RNA from formalin-fixed paraffin-embedded (FFPE) tumor samples. Stained tumor slides from young and old OSCC patients were evaluated for CD8+ T-cell counts using immunohistochemistry. Results: Younger OSCC patients demonstrated significantly increased expression of ECM remodeling and EMT process genes, as well as TME immunosuppression. Gene set enrichment analyses demonstrated increased ECM pathways and concurrent decreased immune pathways in young relative to old patients. Transcripts per million of genetic markers involved in ECM remodeling including LAMB3, VCAN, S100A9, COL5A1, and ITGB2 were significantly increased in tumors of younger vs. older patients (adjusted p-value < 0.10). Young patient TMEs demonstrated a 2.5-fold reduction in CD8+ T-cells as compared to older patients (p < 0.05). Conclusion: Differential gene expression impacting ECM remodeling and TME immunosuppression may contribute to disease progression in younger adult OSCC and has implications on response to evolving treatment modalities, such as immune checkpoint inhibitor therapy.

SMARCB1-Retained and SMARCB1-Deficient SNUC are Genetically Distinct: A Pilot Study Using RNA Sequencing.

Background Understanding the genetic basis for the molecular classification of sinonasal undifferentiated carcinoma (SNUC) based on SMARCB1 may improve our understating regarding the nature of the disease. The objective of the study was to compare the genetic profile of SMARCB1-retained (SR-SNUC) and SMARCB1-deficient SNUC (SD-SNUC). Methods Formalin-fixed, paraffin-embedded tissue from treatment-naive patients with SNUC were selected. Three cases of SR-SNUC, four cases of SD-SNUC, and four samples of nontumor tissue (control samples) were selected. Ribonucleic acid (RNA) sequencing was performed. Results SR-SNUC had a higher number of variants (1 variant for every 15,000 bases) compared with SD-SNUC (1 variant every 29,000 bases). The ratio of missense to silent mutation ratio was higher for SR-SNUC (0.8) as compared with SD-SNUC (0.7). Approximately 1,500 genes were differentially expressed between SR-SNUC and SD-SNUC. The genes that had a higher expression in SR-SNUC included TPD52L1, B3GNT3, GFY, TJP3, ELL3, CYP4F3, ALDH3B2, CKMT1B, VIPR1, SLC7A5, PPP2R2C, UPK3B, MUC1, ELF5, STY7, and H2AC14. The gene that had a higher expression in SD-SNUC was ZFHX4. Most of these genes were related to either protein translation or immune regulation. The most common ( n = 3, 75%) mechanisms of loss of SMARCB1 gene in SD-SNUC was loss of heterozygosity. Conclusion RNA sequencing is a viable and informative approach for genomic profiling of archival SNUC samples. Both SR-SNUC and SD-SNUC were noted to have distinct genetic profiles underlying the molecular classification of these diseases.

Temperature Control Parameters Are Important: Earlier Preinduction Is Associated With Improved Outcomes Following Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: Temperature control trials in cardiac arrest patients have not reliably conferred neuroprotective benefit but have been limited by inconsistent treatment parameters. To evaluate the presence of a time dependent treatment effect, we assessed the association between preinduction time and clinical outcomes. METHODS: In this retrospective, single academic center study between 2014 and 2022, consecutive out-of-hospital cardiac arrest (OHCA) patients treated with temperature control were identified. Preinduction was defined as the time from hospital arrival to initiation of a closed-loop temperature feedback device [door to temperature control initiation time], and early door to temperature control device time was defined a priori as <3 hours. We assessed the association between good neurologic outcome (cerebral performance category 1 to 2) and door to temperature control device time using logistic regression. The proportion of patients who survived to hospital discharge was evaluated as a secondary outcome. A sensitivity analysis using inverse probability treatment weighting, created using a propensity score, was performed to minimize measurable confounding. RESULTS: Three hundred and forty-seven OHCA patients were included; the early door to temperature control device cohort included 75 (21.6%) patients with a median (interquartile range) door to temperature control device time of 2.50 (2.03 to 2.75) hours, whereas the late door to temperature control device cohort included 272 (78.4%) patients with a median (interquartile range) door to temperature control device time of 5.18 (4.19 to 6.41) hours. In the multivariable logistic regression model, early door to temperature control device time was associated with improved good neurologic outcome and survival before [adjusted odds ratio (OR) (95% confidence interval) 2.36 (1.16 to 4.81) and 3.02 (1.54 to 6.02)] and after [adjusted OR (95% confidence interval) 1.95 (1.19 to 3.79) and 2.14 (1.33 to 3.36)] inverse probability of treatment weighting, respectively. CONCLUSION: In our study of OHCA patients, a shorter preinduction time for temperature control was associated with improved good neurologic outcome and survival. This finding may indicate that early initiation in the emergency department will confer benefit. Our findings are hypothesis generating and need to be validated in future prospective trials.

Feasibility and acceptability of a mobile intervention for patients with psychosis following psychiatric hospitalization: A pilot randomized controlled trial.

This pilot randomized control trial examines the feasibility and acceptability of a novel mHealth intervention for patients with schizophrenia spectrum disorders following discharge from inpatient hospitalization. Using cognitive behavior therapy for psychosis strategies, the app provides just-in-time assessment and intervention for individuals to promote healthy coping skills and treatment adherence. We assessed the mHealth intervention relative to a comparison app that included mobile assessment plus psychoeducation alone. Patients were assessed at hospital discharge, as well as 1-, 2-, and 4-months postdischarge. Forty-two adults with schizophrenia spectrum disorders discharging from inpatient care participated in the study. Our a priori-defined feasibility and acceptability goals were mostly achieved during the study, in terms of the proposed recruitment and retention rates, mHealth app engagement, app satisfaction ratings, clinical improvement observed over time, and absence of adverse events related to the study. The participants were significantly more engaged in the mHealth intervention (74%) versus the comparison app (43%). Over the course of the study, dysfunctional coping and psychiatric symptoms significantly declined in both groups. Future larger trials are needed to confirm the efficacy of the mHealth intervention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predictive capacity of immune-related adverse events and cytokine profiling in neoadjuvant immune checkpoint inhibitor trials for head and neck squamous cell carcinoma.

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status. METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival were compared. Canonical linear discriminant analysis (LDA) was performed to identify combinations of circulating cytokines predictive of irAEs using plasma sample multiplex assay. RESULTS: Of 113 participants meeting inclusion criteria, 32 (28.3%) developed irAEs during treatment or follow-up. Positive p16 status was associated with irAEs (odds ratio [OR] 2.489; 95% CI 1.069-6.119; p = 0.043). irAEs were associated with pathologic treatment response (OR 3.73; 95% CI 1.34-10.35; p = 0.011) and with higher OS in the combined cohort (HR 0.319; 95% CI 0.113-0.906; p = 0.032). Patients with irAEs within the nivolumab cohort had significant elevations of select cytokines pre-treatment. Canonical LDA identified key drivers of irAEs among all trials, which were highly predictive of future irAE status. CONCLUSIONS: irAEs are associated with response to neoadjuvant ICI therapy in HNSCC and can serve as clinical indicators for improved clinical outcomes. irAEs can be predicted by concentrations of several circulating cytokines prior to treatment.

Comparing Experiences of Community Reintegration Following Hospitalization Versus Jail Detention During a Mental Health Crisis.

BACKGROUND: This comparative qualitative study explores the experiences of individuals transitioning back to the community after institutionalization following an episode of acute suicidality. METHODS: Semi-structured interviews were conducted with eight individuals who had either been hospitalized (n=4) or incarcerated (n=4) during a mental health crisis that involved acute suicidality. Thematic analysis was conducted first within groups and then between groups. RESULTS: The findings reveal possible disparities in social determinants of mental health, family dynamics, treatment seeking, and coping mechanisms between groups. Social isolation, barriers to socioeconomic stability, and lack of treatment access were all found to be risk factors for poor outcomes during the vulnerable transition period and were experienced by participants in this limited sample. CONCLUSIONS: Individuals transitioning from the hospital after a suicide crisis may benefit from increased family involvement, follow-up, and social support at discharge. After a suicide crisis and incarceration, there is a significant need for housing and employment support to allow for mental health treatment seeking. Future research should build on the proof of concept for comparing the experiences of individuals across institutional settings.

Share of Adult Suicides After Recent Jail Release.

Importance: Although people released from jail have an elevated suicide risk, the potentially large proportion of this population in all adult suicides is unknown. Objective: To estimate what percentage of adults who died by suicide within 1 year or 2 years after jail release could be reached if the jail release triggered community suicide risk screening and prevention efforts. Design, Setting, and Participants: This cohort modeling study used estimates from meta-analyses and jail census counts instead of unit record data. The cohort included all adults who were released from US jails in 2019. Data analysis and calculations were performed between June 2021 and February 2024. Main Outcomes and Measures: The outcomes were percentage of total adult suicides within years 1 and 2 after jail release and associated crude mortality rates (CMRs), standardized mortality ratios (SMRs), and relative risks (RRs) of suicide in incarcerated vs not recently incarcerated adults. Taylor expansion formulas were used to calculate the variances of CMRs, SMRs, and other ratios. Random-effects restricted maximum likelihood meta-analyses were used to estimate suicide SMRs in postrelease years 1 and 2 from 10 jurisdictions. Alternate estimate was computed using the ratio of suicides after release to suicides while incarcerated. Results: Included in the analysis were 2019 estimates for 7 091 897 adults (2.8% of US adult population; 76.7% males and 23.3% females) who were released from incarceration at least once, typically after brief pretrial stays. The RR of suicide was 8.95 (95% CI, 7.21-10.69) within 1 year after jail release and 6.98 (95% CI, 4.21-9.76) across 2 years after release. A total of 27.2% (95% CI, 18.0%-41.7%) of all adult suicide deaths occurred in formerly incarcerated individuals within 2 years of jail release, and 19.9% (95% CI, 16.2%-24.1%) of all adult suicides occurred within 1 year of release (males: 23.3% [95% CI, 20.8%-25.6%]; females: 24.0% [95% CI, 19.7%-36.8%]). The alternate method yielded slightly larger estimates. Another 0.8% of adult suicide deaths occurred during jail stays. Conclusions and Relevance: This cohort modeling study found that adults who were released from incarceration at least once make up a large, concentrated population at greatly elevated risk for death by suicide; therefore, suicide prevention efforts focused on return to the community after jail release could reach many adults within 1 to 2 years of jail release, when suicide is likely to occur. Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.

Severe Maternal Morbidity Disparities Before and During the COVID Pandemic in a Medicaid Population.

This study assessed racial and ethnic disparities in severe maternal mortality during delivery through 6 weeks postpartum, before and during the COVID pandemic, in a statewide Medicaid population. This retrospective, population-based, cohort study used Medicaid claims data linked to birth certificates from the Michigan Department of Health and Human Services Health Services Data Warehouse that included all individuals giving birth between January 1, 2017, and October 31, 2021, in Michigan who had Medicaid insurance during the month of childbirth. The SMM rate increased more during the COVID pandemic for Black (1.36 [1.26-1.46]) compared to White individuals (1.17 [1.09-1.26], p-value<0.01 Black vs White). The Black-White and Hispanic-White disparities in severe maternal morbidity, already high in the Medicaid population, widened during the COVID pandemic. Multilevel interventions are needed to reduce disparities in maternal morbidity and mortality. Conflict of interest disclosure: No conflicts to disclose.

Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer.

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient's immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based signature scores were developed to correlate systemic immunity with patient responses to different cancer treatments, including immunotherapy, prognostically and predictively. Our approach and findings illustrate the potential utility of a simple blood test as a flexible tool for stratifying cancer patients into therapy response groups based on systemic immunoprofiling.

Analysis of implementation processes in a hybrid effectiveness-implementation trial of interpersonal psychotherapy (IPT) for major depressive disorder in prisons: Training, supervision, and recommendations.

BACKGROUND: There are 10 million admissions to U.S. prisons and jails each year. More than half of those admitted have mental health problems. The goal of this article is to inform: (1) implementation of evidence-based mental health treatments in prisons and jails, an important effort that needs more evidence to guide it; (2) psychotherapy and interpersonal psychotherapy (IPT) training efforts, especially in low-resource settings. METHODS: A randomized hybrid effectiveness-implementation trial of group IPT for major depressive disorder (MDD) in state prisons found that IPT increased rates of MDD remission and lowered posttraumatic stress disorder symptoms relative to prison treatment as usual. The trial used prison counselors, only some of whom had prior psychotherapy training/experience, to deliver IPT. IPT treatment adherence was high (96%), but trial training and supervision were too costly to be scalable outside the trial. The current article reports results from a planned qualitative analysis of 460 structured implementation and supervision documents in that trial to describe training and supervision processes and lessons learned, inform training recommendations, and facilitate future work to optimize training and supervision for under-resourced settings. RESULTS: Themes identified in implementation and supervision process notes reflected: work on psychotherapy basics (reflective listening, focusing on emotions, open-ended questions, specific experiences), IPT case conceptualization (forming a conceptualization, what is and is not therapeutic work, structure and limit setting, structure vs. flexibility), IPT techniques (enhancing social support, role plays, communication analysis), psychotherapy processes (alliance repair, managing group processes), and managing difficult situations (avoidance, specific clients, challenging work settings). Counselors were receptive to feedback; some relied on study supervisors for support in managing stressful prison working conditions. CONCLUSIONS: Findings can be used to make future training and supervision more efficient. Based on our results, we recommend that initial and refresher training focus on IPT case conceptualization, steps for addressing each IPT problem area, and reflective listening. We also recommend supervision through at least counselors' first two rounds of groups. More low-cost, scalable training methods are needed to get mental health treatment to individuals who need it most, who are often served in challenging, low-resource settings such as prisons. This is a mental health access and equity issue. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT01685294).