A double-blinded randomized control trial to compare the duration of analgesia using morphine, clonidine, or dexmedetomidine as adjuvants to ropivacaine in caudal anesthesia in children undergoing infraumbilical surgeries.

Background and Aims: Adjuvants added to the caudal block prolong the duration of analgesia. In a developing country with economic constraints, the choice of an adjuvant will be the medication with a longer duration of analgesia, a favorable side-effect profile, and the least expensive option. We wished to study the duration of postoperative analgesia afforded by three adjuvants: morphine, clonidine, and dexmedetomidine, at doses wherein minimal or nil adverse effects would be attributed to the adjuvant. The primary objective of the current study is to compare the duration of postoperative analgesia with morphine, clonidine, or dexmedetomidine as adjuvants to 0.2% ropivacaine in a for caudal block, in children undergoing elective abdominal, urogenital, and lower limb surgeries. The secondary objectives are (a) to study the total analgesic requirement during the first 24 hours after surgery and (b) to compare the incidence of complications among the three groups. Material and Methods: Sixty-three children aged 1-6 years, belonging to American Society of Anesthesia (ASA) physical status I, II, and scheduled to undergo elective infraumbilical surgeries, were enrolled in the study. The children were randomly assigned to one of three groups: Group D received a caudal block with dexmedetomidine 1 µg/kg, Group M received morphine 30 µg/kg, and Group C received clonidine 1.5 µg/kg. All groups also received 0.2% ropivacaine (1-1.25 ml/kg) as part of the caudal block. The duration of analgesia, total analgesic requirements during the first 24 hours after the surgery, and the incidence of complications in the three groups were monitored by a pain nurse who was blinded to the study allocation. Results: The three groups were comparable with respect to age, sex, weight, and duration of surgery. The median time taken for the first rescue analgesic in the dexmedetomidine group was 380 minutes, in the clonidine group was 360 minutes, and in the morphine group was 405 minutes. Though the morphine group had a longer duration of analgesia, it was not statistically significant (P = 0.843). The total perioperative opioids used and side effects were similar among the three groups. There were no episodes of intraoperative bradycardia noted in Groups D, M, and C. However, one patient in Group D required treatment for bradycardia in the postanesthesia care unit. In terms of intraoperative hypotension, 10 patients (43.5%) in Group D, 5 patients (27.8%) in Group C, and 5 patients (22.7%) in Group M required treatment, but this difference was not statistically significant (P = 0.299). There was no significant difference observed in the time to awakening after the anesthesia among the three groups. Postoperative nausea and vomiting were noted in five patients (21.7%) in Group D, one patient (5.6%) in Group C, and four patients (18.2%) in Group M (P = 0.382). One patient in Group M had a sedation score of 5 and required 4 hours of supplemental oxygen via face mask in the ward. Additionally, one patient in Group D reported numbness in both feet lasting 12 hours with spontaneous resolution. While a significant number of patients in all three study groups experienced urinary retention, no patient reported pruritus in the ward. Conclusion: Caudal administration of morphine, dexmedetomidine, and clonidine in children undergoing infraumbilical surgery resulted in an equivalent duration of analgesia.

Third-Trimester Cardiovascular Function and Risk of Hypertensive Disorders of Pregnancy.

BACKGROUND: Whether cardiovascular dysfunction is associated with preeclampsia in women without fetal growth restriction (FGR) is unclear. Our objective was to investigate associations between third-trimester cardiac output (CO) and systemic vascular resistance and risk of hypertensive disorders of pregnancy in women with and without FGR. METHODS AND RESULTS: A case-cohort study in 906 pregnant women in Denmark with repeated third-trimester cardiac function assessments was performed using the Ultrasound Cardiac Output Monitor 1A. Using Cox regression, we compared rates of hypertensive disorders of pregnancy in women with low, normal, and high CO and normal and high systemic vascular resistance, by FGR status and gestational age, and evaluated associations between a third-trimester drop in CO or increase in systemic vascular resistance and preeclampsia risk in women without FGR. The analysis included 249 women with preeclampsia (42 with FGR) and 119 women with gestational hypertension. Low CO was strongly associated with preeclampsia at <37 weeks (women with FGR: hazard ratio [HR], 5.25 [95% CI, 1.26-21.9]; women without FGR: HR, 2.19 [95% CI, 1.07-4.48]). Our results also suggested an association between low CO and preeclampsia at ≥37 weeks among women without FGR (HR, 1.31 [95% CI, 0.84-2.03]), and between a third-trimester drop in CO >75th percentile and preeclampsia in women without FGR (odds ratio, 1.91 [95% CI, 0.84-4.36]). High systemic vascular resistance was strongly associated with increased rates of all forms of hypertensive disorders of pregnancy. CONCLUSIONS: Low CO is associated with preeclampsia risk in women with and without FGR, particularly before 37 weeks. Repeated measurements of third-trimester cardiovascular function might identify women without FGR for monitoring for preeclampsia, but this result needs to be confirmed in other studies.

In their own words: Perspectives of IPV survivors on obtaining support within the healthcare system.

BACKGROUND: Almost half of all women in the US experience intimate partner violence (IPV) in their lifetime. The US Preventive Services Task Force recommends IPV screening paired with intervention for women of reproductive age. We aim to understand clinical practices and policies that are beneficial, detrimental, or insufficient to support survivors of IPV in a safety-net healthcare system. METHODS: We sampled 45 women who were 18-64 years old, had experienced IPV within the prior year and were patients in the San Francisco Health Network. We conducted in-depth, semi-structured interviews to elicit their perspectives on disclosing IPV and obtaining support within the healthcare system. We analyzed our data using thematic analysis and grounded theory practices informed by ecological systems theory. FINDINGS: We identified four themes regarding factors that impeded or facilitated discussing and addressing IPV across interpersonal and systemic levels relating to relationship-building, respect, autonomy and resources. (1) Interpersonal barriers included insufficient attention to relationship-building, lack of respect or concern for survivor circumstances, and feeling pressured to disclose IPV or to comply with clinicians' recommended interventions. (2) Interpersonal facilitators consisted of patient-centered IPV inquiry, attentive listening, strength-based counseling and transparency regarding confidentiality. (3) Systemic barriers such as visit time limitations, clinician turn-over and feared loss of autonomy from involvement of governmental systems leading to separation from children or harm to partners, negatively affected interpersonal dynamics. (4) Systemic facilitators involved provision of resources through IPV universal education, on-site access to IPV services, and community partnerships. CONCLUSIONS: Women experiencing IPV in our study reported that relationship-building, respect, autonomy, and IPV-related resources were essential components to providing support, promoting safety, and enabling healing in the healthcare setting. Successful trauma-informed transformation of healthcare systems must optimize interpersonal and systemic factors that improve survivor wellbeing while eliminating barriers.

Benzodiazepine use for anxiety disorders is associated with increased long-term risk of mood and substance use disorders: A large-scale retrospective cohort study.

Background: Benzodiazepines (BZDs) are widely prescribed for anxiety disorders. However, the long-term implications on mental health remain uncertain, especially the potential association between chronic BZD use and subsequent diagnosis of mood and substance use disorders (SUDs). Method: We conducted a 5-year retrospective cohort study by analyzing the TriNetX database, a real-time electronic medical record network. The study population was defined as patients aged 18-65 with anxiety disorders (ICD-10-CM: F40-F48). We employed propensity score matching to pair a BZD-exposed cohort (≥12 BZD prescriptions) with a BZD-unexposed control cohort. The outcomes were defined as depressive disorders, bipolar disorders, and SUDs. We employed Kaplan-Meier analyses to assess the survival probability over five years following diagnosis and BZD exposure; log-rank test to obtain the hazard ratio (HR) with 95 % confidence interval (CI). Results: We identified and matched 76,137 patients in the study and control cohorts. Compared to the control cohort, the BZD-exposed group exhibited significantly higher risks of being diagnosed with depressive disorders (HR, 2.64; 95 % CI, 2.59-2.68), bipolar disorders (HR, 4.39; 95 % CI, 4.15-4.64), overall substance use disorders (HR, 3.00; 95 % CI, 2.92-3.08), alcohol use disorder (HR, 3.38; 95 % CI, 3.20-3.57), stimulant use disorder (HR, 3.24; 95 % CI, 2.95, 3.55), cannabis use disorder (HR, 2.93; 95 % CI, 2.75-3.11), inhalant use disorder (HR, 4.14; 95 % CI, 3.38-5.06), and nicotine use disorder (HR, 2.72; 95 % CI, 2.63-2.81). Conclusion: Our findings demonstrate a concerning association between BZD use and an increased risk of being diagnosed with various mood disorders and SUDs.

Connectivity Changes Following Episodic Future Thinking in Alcohol Use Disorder.

[Please note that in order to respond to reviewers request we had exceed the 300 word limit. The following is NOT revised from the first submission, please see the actual revised manuscript file for the reviewer-driven changes]. INTRODUCTION: Recent addiction and obesity-related research suggest that episodic future thinking (EFT) can serve as a promising intervention to promote healthy decision making. This study investigated the neural effects of EFT in alcohol use disorder (AUD). METHODS: Participants received either a brief EFT or control intervention to examine differences in resting-state connectivity. We then used these findings to characterize psychophysiological interaction (PPI) differences during a delay discounting (DD) fMRI task. In addition, we used a second control group of AUD participants without any intervention to reproduce and aid in interpreting our key findings. RESULTS: EFT participants, but not controls, showed statistically improved discounting rates - a behavioral marker for addiction. Resting state analyses of the left hippocampus revealed connectivity differences in the frontal poles. The directionality of this difference suggested that EFT reduced a hypoconnectivity relationship between these regions in AUD. We also found resting state connectivity differences between the salience network and the right dorsolateral prefrontal cortex (R DLPFC), which then led us to discover R-to-L DLPFC PPI differences during DD. Moreover, the resting state salience-to-DLPFC functional connectivity showed an inverse relationship to discounting rate while hyperconnectivity between left and right DLPFC reflected slower reaction times during difficult DD trials. DISCUSSION: These findings suggest that EFT produces beneficial changes in neural connectivity patterns in AUD. The alterations in connectivity highlight potential mechanisms underlying the effectiveness of EFT in improving decision-making in AUD. Understanding these neural effects may contribute to the further development of targeted interventions for AUD and related disorders.

Chromothripsis-mediated small cell lung carcinoma.

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here we performed detailed clinicopathologic, genomic and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis - massive, localized chromosome shattering - recurrently involving chromosomes 11 or 12, and resulting in extrachromosomal (ecDNA) amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers.

Efficient and Selective, In Vitro and In Vivo, Antimicrobial Photodynamic Therapy with a Dicationic Chlorin in Combination with KI.

Various cationic photosensitizers employed in antimicrobial photodynamic therapy (aPDT) have the ability to photoinactivate planktonic bacteria under conditions of low phototoxicity to mammalian cells and without generating antimicrobial resistance (AMR). However, the photoinactivation of biofilms requires orders-of-magnitude higher photosensitizer concentrations, which become toxic to host cells. Remarkably, the bactericidal effect of a dicationic di-imidazolyl chlorin toward planktonic S. aureus and E. coli was observed in this work for concentrations below 400 nM under illumination at 660 nm and below 50 µM for the corresponding biofilms. At the latter concentrations, the chlorin is phototoxic toward human keratinocyte cells. However, in the presence of 50 mM KI, bactericidal concentrations are reduced to less than 50 nM for planktonic bacteria and to less than 1 µM for biofilms. It is shown that the potentiation with KI involves the triiodide anion. This potentiation elicits a bactericidal effect without appreciable cytotoxicity to keratinocytes. It becomes possible to selectively inactivate biofilms with aPDT. An exploratory study treating mice with wounds infected with E. coli expressing GFP with 20 µM chlorin and 120 J cm-2 at 652 nm confirmed the potential of this chlorin to control localized infections.

Re-visiting the association between antidepressant use and the risk of lung cancer.

Observational studies suggest a potential correlation between antidepressants and increased lung cancer risks. However, existing studies are limited to small sample sizes, unadjusted covariates especially smoking status, and unclear exposure duration. We performed a large-scale retrospective cohort study to re-examine the association. We analyzed non-smokers and smokers separately to eliminate the confounding effect of smoking status. We found patients with long-term antidepressant use were at a lower risk of lung cancer in both smokers and non-smokers (odds ratio (OR), 0.61; 95% CI: 0.46-0.80, OR: 0.75; 95% CI: 0.65-0.86). None of the antidepressants was associated with an increased lung cancer risk.

Neutrophils Recruited by NKX2-1 Suppression via Activation of CXCLs/CXCR2 Axis Promote Lung Adenocarcinoma Progression.

NK2 Homeobox 1 (NKX2-1) is a well-characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2-1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2-1 is observed in high-grade LUAD. Meanwhile, single-cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell-cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2-1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT-PCR. ATAC-seq revealed the restrictive regulation of NKX2-1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2-1 modulates the infiltration of tumor-promoting neutrophils by inhibiting CXCLs/CXCR2-dependent mechanisms. Hence, targeting CXCR2 in NKX2-1-low tumors is a potential antitumor therapy that may improve LUAD patient outcomes.

"We Remember the Pain": A qualitative study of intergenerational trauma among older adults experiencing homelessness in the HOPE HOME study.

Rates of homelessness among adults aged 50 and over are rising. Common strategies for exiting homelessness rely on social and family support. However, intergenerational trauma may disrupt these social support networks and contribute to homelessness. Understanding the impact of intergenerational trauma on living with family or friends may give insight into addressing homelessness among older adults. We purposefully sampled 46 adults who reported living with family or friends from the HOPE HOME study cohort (350 community-recruited adults, ≥ 50 years and experiencing homelessness in Oakland, California) and 19 family/friends who had hosted the participants in their living spaces. We conducted independent, semi-structured interviews and used grounded theory methodologies to analyze data. We identified four major themes from the interviews: (1) Intergenerational trauma was common and made it difficult to stay with family or friends; (2) Participants and hosts sought to protect future generations from intergenerational trauma; (3) Relationships endured despite intergenerational trauma; and (4) social structures exacerbated the impact of intergenerational trauma and played a significant role in perpetuating homelessness. Trauma-informed policies that confront the structures that propagate or exacerbate intergenerational trauma may mitigate their impact and facilitate housing for older adults.

The Impact of Intimate Partner Violence on Homelessness and Returns to Housing: A Qualitative Analysis From the California Statewide Study of People Experiencing Homelessness.

Homelessness is a public health concern in California and throughout the United States. Intimate partner violence (IPV) is a risk factor for experiencing homelessness. Few studies have examined the interplay between IPV, homelessness, and housing. Qualitative methods can provide a greater understanding of the lived experience of IPV and homelessness to identify potential solutions. We purposefully sampled 104 adults who reported experiencing IPV in the California Statewide Study of People Experiencing Homelessness (CASPEH), a representative, mixed-methods study. We administered semi-structured interviews focusing on IPV and six other topic areas pertaining to homelessness from October 2021 to May 2022. We created and applied a codebook with a multidisciplinary team using a hybrid of deductive and inductive logic. Our analysis included all participants who discussed IPV and homelessness across the seven studies. We conducted a thematic analysis using an interpretivist approach and informed by grounded theory. We found that violence within a partnership was multidimensional (physical, sexual, emotional, and financial) and bidirectional. We identified six themes: (1) IPV precipitated and prolonged homelessness; (2) Need for housing, financial stability, and material resources influenced staying in abusive relationships; (3) Alcohol and illicit substance use exacerbated violence between partners; (4) Participants struggled to find resources in domestic violence (DV) shelters; (5) The healthcare system did not provide substantial support; and (6) discrimination and stigma influenced equitable access to housing and DV resources. Experiencing IPV contributed to homelessness and impeded returns to housing. Limitations in current IPV resources impede care. We propose equitable expansion of survivor-centered services that improve access to long-term subsidized housing, prevent IPV and homelessness with flexible funding options, and facilitate rapid exits from homelessness through trauma-informed, non-congregate shelter that transitions to permanent housing.

Intratumoral Escherichia Is Associated With Improved Survival to Single-Agent Immune Checkpoint Inhibition in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSEThe impact of the intratumoral microbiome on immune checkpoint inhibitor (ICI) efficacy in patients with non-small-cell lung cancer (NSCLC) is unknown. Preclinically, intratumoral Escherichia is associated with a proinflammatory tumor microenvironment and decreased metastases. We sought to determine whether intratumoral Escherichia is associated with outcome to ICI in patients with NSCLC.PATIENTS AND METHODSWe examined the intratumoral microbiome in 958 patients with advanced NSCLC treated with ICI by querying unmapped next-generation sequencing reads against a bacterial genome database. Putative environmental contaminants were filtered using no-template controls (n = 2,378). The impact of intratumoral Escherichia detection on overall survival (OS) was assessed using univariable and multivariable analyses. The findings were further validated in an external independent cohort of 772 patients. Escherichia fluorescence in situ hybridization (FISH) and transcriptomic profiling were performed.RESULTSIn the discovery cohort, read mapping to intratumoral Escherichia was associated with significantly longer OS (16 v 11 months; hazard ratio, 0.73 [95% CI, 0.59 to 0.92]; P = .0065) in patients treated with single-agent ICI, but not combination chemoimmunotherapy. The association with OS in the single-agent ICI cohort remained statistically significant in multivariable analysis adjusting for prognostic features including PD-L1 expression (P = .023). Analysis of an external validation cohort confirmed the association with improved OS in univariable and multivariable analyses of patients treated with single-agent ICI, and not in patients treated with chemoimmunotherapy. Escherichia localization within tumor cells was supported by coregistration of FISH staining and serial hematoxylin and eosin sections. Transcriptomic analysis correlated Escherichia-positive samples with expression signatures of immune cell infiltration.CONCLUSIONRead mapping to potential intratumoral Escherichia was associated with survival to single-agent ICI in two independent cohorts of patients with NSCLC.

Use of Patient-Reported Outcome Measures to Assess the Effectiveness of Hybrid Psychiatric Visits.

OBJECTIVE: Little empirical evidence exists to support the effectiveness of hybrid psychiatric care, defined as care delivered through a combination of telephone, videoconferencing, and in-person visits. The authors aimed to investigate the effectiveness of hybrid psychiatric care compared with outpatient waitlist groups, assessed with patient-reported outcome measures (PROMs). METHOD: Participants were recruited from an adult psychiatry clinic waitlist on which the most common primary diagnoses were unipolar depression, generalized anxiety disorder, and bipolar disorder. Patients (N=148) were randomly assigned to one of two waitlist groups that completed PROMs once or monthly before treatment initiation. PROMs were used to assess symptoms of depression (Patient Health Questionnaire-9 [PHQ-9]), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), and daily psychological functioning (Brief Adjustment Scale-6 [BASE-6]). Patient measures were summarized descriptively with means, medians, and SDs and then compared by using the Kruskal-Wallis test; associated effect sizes were calculated. PROM scores for patients who received hybrid psychiatric treatment during a different period (N=272) were compared with scores of the waitlist groups. RESULTS: PROM assessments of patients who engaged in hybrid care indicated significant improvements in symptom severity compared with the waitlist groups, regardless of the number of PROMs completed while patients were on the waitlist. Between the hybrid care and waitlist groups, the effect size for the PHQ-9 score was moderate (d=0.66); effect sizes were small for the GAD-7 (d=0.46) and BASE-6 (d=0.45) scores. CONCLUSIONS: The findings indicate the clinical effectiveness of hybrid care and that PROMs can be used to assess this effectiveness.

Clinical and molecular characteristics of hemophilia A affected individuals and carriers: A 24 years experience from three centers.

Hemophilia A is a rare bleeding disorder with variable expressivity and allelic heterogeneity. Despite the advancement of prenatal diagnostics and molecular studies, the number of studies reviewing the reproductive choices of hemophilia A carriers and affected individuals remains limited. Through this retrospective review, we hope to gain a deeper understanding of hemophilia A-affected individuals' clinical and molecular characteristics, as well as the reproductive choices of the at-risk couples. A total of 122 individuals harboring likely causative F8 gene alterations from 64 apparently unrelated families attending three centers between 3/2000 and 3/2023 were included in this study. Their clinical and molecular findings as well as reproductive choices were gathered in a clinical setting and verified through the electronic medical record database of the public health system. Forty-seven affected males and 75 female heterozygous carriers were included in the analysis. Among 64 apparently unrelated families, 36 distinct pathogenic/likely pathogenic variants were identified, of which 30.6% (11/36) of variants were novel. While the majority of clinical findings and genotype-phenotype correlations appear to be in accordance with existing literature, female carriers who had no fertility intention were significantly more likely to have affected sons than those who had fertility intention (5/19 vs. 4/5; p = 0.047). Through this retrospective review, we summarized the clinical and molecular characteristics of 122 individuals harboring pathogenic/likely pathogenic F8 variants, as well as their fertility intentions and reproductive outcomes. Further studies are required to look into the considerations involved in reproductive decision-making.

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.

Pregnancy dedifferentiates memory CD8+ T cells into hypofunctional cells with exhaustion-enriched programs.

Alloreactive memory, unlike naive, CD8+ T cells resist transplantation tolerance protocols and are a critical barrier to long-term graft acceptance in the clinic. We here show that semiallogeneic pregnancy successfully reprogrammed memory fetus/graft-specific CD8+ T cells (TFGS) toward hypofunction. Female C57BL/6 mice harboring memory CD8+ T cells generated by the rejection of BALB/c skin grafts and then mated with BALB/c males achieved rates of pregnancy comparable with naive controls. Postpartum CD8+ TFGS from skin-sensitized dams upregulated expression of T cell exhaustion (TEX) markers (Tox, Eomes, PD-1, TIGIT, and Lag3). Transcriptional analysis corroborated an enrichment of canonical TEX genes in postpartum memory TFGS and revealed a downregulation of a subset of memory-associated transcripts. Strikingly, pregnancy induced extensive epigenetic modifications of exhaustion- and memory-associated genes in memory TFGS, whereas minimal epigenetic modifications were observed in naive TFGS. Finally, postpartum memory TFGS durably expressed the exhaustion-enriched phenotype, and their susceptibility to transplantation tolerance was significantly restored compared with memory TFGS. These findings advance the concept of pregnancy as an epigenetic modulator inducing hypofunction in memory CD8+ T cells that has relevance not only for pregnancy and transplantation tolerance, but also for tumor immunity and chronic infections.

Association Between Sleep Apnea Treatment and Health Care Resource Use in Patients With Atrial Fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation. METHODS AND RESULTS: Insurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90-day definition. Inverse probability of treatment weighting was used to create covariate-balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all-cause emergency department visits (0.61±1.21 versus 0.77±1.55 [P=0.023] versus 0.95±1.90 [P<0.001]), all-cause hospitalizations (0.19±0.69 versus 0.24±0.72 [P=0.002] versus 0.34±1.16 [P<0.001]), and cardiac-related hospitalizations (0.06±0.26 versus 0.09±0.41 [P=0.023] versus 0.10±0.44 [P=0.004]) were significantly lower in adherent versus intermediate and nonadherent patients, as were all-cause inpatient costs ($2200±$8054 versus $3274±$12 065 [P=0.002] versus $4483±$16 499 [P<0.001]). All-cause emergency department costs were significantly lower in adherent and intermediate versus nonadherent patients ($499±$1229 and $563±$1292 versus $691±$1652 [P<0.001 and P=0.002], respectively). CONCLUSIONS: These data suggest clinical and economic benefits of PAP therapy in patients with concomitant OSA and atrial fibrillation. This supports the value of diagnosing and managing OSA and highlights the need for strategies to enhance PAP adherence in this population.

Intussusception With a Pathological Lead Point in a Two-Month-Old Infant.

Intussusception is one of the most common causes of acute intestinal obstruction in infancy and early childhood. Most cases of intussusception tend to occur in infancy, between the ages of four and six months. The causes can be split into two categories: non-pathologic and pathologic. Non-pathological causes include administration of the rotavirus vaccine, dehydration, and recent illness. Pathological causes can be attributed to Meckel's diverticulum (in 75% of cases), polyps (15%), and lymphoma or other tumors (3%). Intussusception rarely occurs in infants less than three months of age. If intussusception does occur in patients under three months of age, the cause is idiopathic in up to 75% of the cases. Additionally, myoglandular-type polyps are exceedingly rare and very rarely occur in patients under the age of 50. This case report discusses the diagnosis and treatment of intussusception in a two-month-old male patient who initially presented to the pediatric inpatient unit for dehydration secondary to a suspected viral illness, later developing colicky abdominal pain and bloody stools. He was found to have colo-colonic intussusception with a myoglandular-type polyp lead point. In discussing this case, the aim is to teach about intussusception and myoglandular-type polyps, as well as reveal a rarity in both etiologies for this age group.