Comparison of flexible endoscopic needle-knife septotomy and peroral endoscopic myotomy for treatment of Zenker's diverticulum.

BACKGROUND AND AIMS: Treatment of Zenker's diverticulum (ZD) has evolved from flexible endoscopic septotomy (FES) to peroral endoscopic myotomy for ZD (Z-POEM). In this study, we compare the efficacy and safety of flexible endoscopic needle-knife septotomy (FENKS) and Z-POEM for symptomatic ZD. METHODS: Consecutive patients at a single institution who underwent endoscopic ZD treatment by FENKS or Z-POEM were identified. Demographics, clinical characteristics, procedure technique, technical and clinical success, and adverse events (AEs) within 30 days were reviewed and compared between the 2 groups. AEs were classified by the AGREE classification. Baseline and postprocedure Dakkak and Bennett (DB) scores were reported at 6, 12, and 24 months. Clinical success (DB score ≤1) was assessed by per-protocol (PP) and intention-to-treat analyses (ITT). RESULTS: Sixty patients (55% men; mean age, 72 ± 12 years) underwent FENKS (n = 21) or Z-POEM (n = 39) between 2016 and 2023. Baseline clinical characteristics were similar, and overall technical success was 98.3%. Clinical success by PP and ITT analyses at 6, 12, and 24 months after each intervention were similar between both groups. The FENKS group had a higher prevalence (29% vs 5%, P = .018) and severity (P = .032) of AEs and were more likely to be hospitalized after treatment (71% vs 33%, P = .007). During a median follow-up of 18 months, reintervention was required for 5 cases (10%), 2 (9%) in the FENKS and 3 (7.6%) in the Z-POEM group (P = 1.0) a mean 7.6 ± 4.4 months after initial therapy. CONCLUSIONS: Treatment of ZD with Z-POEM appears to be safer than FENKS with similar short and midterm clinical success.

Increased expression of proton pump and allergic inflammation genes predicts PPI failure in pediatric eosinophilic esophagitis.

Proton pump inhibitors (PPIs) are one of the standards of care of eosinophilic esophagitis (EoE) treatment, though PPI response rates are variable ranging from 23 to 63% in pediatric studies. We sought to determine if expression of select genes in esophageal mucosa can predict PPI responsiveness in EoE. Children with a new diagnosis of EoE (15 or more eosinophils/hpf on esophageal biopsy) were prospectively treated with 8 weeks of PPI therapy before follow-up esophagogastroduodenoscopy (EGD). Children with <15 eosinophils/hpf on follow-up were classified as having PPI-Responsive EoE (PPI-R) and ≥ 15 eosinophils/hpf as PPI-Nonresponsive EoE (PPI-NR). Using the Nanostring nCounter Analysis System, mRNA expression of a custom panel of genes was measured in esophageal biopsies. Immunohistochemical staining of biopsies was performed. Among children with EoE, 32% (8/25) had PPI-R EoE. ATP12A, ATP4A, tryptase-beta 2 (TPSB2), CLC and IL13 had higher expression in PPI-NR EoE compared to PPI-R EoE or controls. Immunohistochemical staining of ATP12A was higher among PPI-R EoE and PPI-NR EoE, compared to non-EoE controls. In this study, PPI-NR EoE had significantly higher baseline gene expression of mast cell, cytokine, proton pump, and eosinophil genes compared to PPI-R EoE. PPIs may be involved in an inflammatory cascade of mast cell activation that stimulates IL-13 release, which upregulates ATP12A and ATP4A that leads to eosinophil recruitment. Histologic PPI failure may occur when increased gene expression of these components is high and cannot be overcome pharmacologically, especially in the case of proton pump genes.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction - A prospective study.

INTRODUCTION: The aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. METHODS: This was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. RESULTS: There were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). CONCLUSION: MVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Health Care Discrimination Affects Patient Activation, Communication Self-Efficacy, and Pain for Black Americans.

This study examines whether a key psychosocial factor-perceiving racial discrimination in health care-is associated with worse patient activation, communication self-efficacy, and physical health outcomes for Black veterans with chronic pain. Moreover, we explore the role of physician-patient working alliance as a moderator that may alleviate the potential consequences of perceiving racial discrimination. This work is a secondary analysis of baseline data from a clinical trial with 250 U.S. Black veterans with chronic musculoskeletal pain. Participants were recruited from primary care clinics at a Midwestern VA hospital between 2018 and 2021. Perceiving racial discrimination in health care was associated with lower patient activation, lower self-efficacy in communicating with one's physician, higher pain intensity, and lower pain management self-efficacy (ps < .049) but was unrelated to reports of pain interference or use of pain coping strategies (ps > .157). Although the relationship between perceived discrimination and patient activation was moderated by working alliance (P = .014), having a stronger working alliance improved patient activation to varying degrees across levels of perceived discrimination (rather than buffering against negative outcomes when perceiving higher levels of discrimination). Moderation was not significant on any other measures. This study deepens our understanding of the broad range of health outcomes that are (not) associated with perceiving racial discrimination in health care. Contrary to prior theorizing, this work also indicates that having a strong working alliance does not attenuate the consequences of perceiving discrimination among Black individuals living with pain. These results highlight the need for system-level interventions to address perceptions of racial mistreatment in health care. PERSPECTIVE: This work has important public health implications by identifying the broad range of outcomes associated with perceived discrimination in health care among Black Americans. Importantly, a strong physician-patient relationship did not buffer Black individuals from the consequences of perceiving discrimination. These findings inform intervention targets to mitigate racial health disparities.

Sex-Specific Changes to Brain Fatty Acids, Plasmalogen, and Plasma Endocannabinoids in Offspring Exposed to Maternal and Postnatal High-Linoleic-Acid Diets.

Linoleic acid (LA) is required for neuronal development. We have previously demonstrated sex-specific changes in cardiovascular and hepatic function in rat offspring from mothers consuming a high-LA diet, with some effects associated with reduced LA concentration in the postnatal diet. At this time, the impact of a high-maternal-LA diet on offspring brain development and the potential for the postnatal diet to alter any adverse changes are unknown. Rat offspring from mothers fed low- (LLA) or high-LA (HLA) diets during pregnancy and lactation were weaned at postnatal day 25 (PN25) and fed LLA or HLA diets until sacrifice in adulthood (PN180). In the offspring's brains, the postnatal HLA diet increased docosapentaenoate in males. The maternal HLA diet increased LA, arachidonate, docosapentaenoate, C18:0 dimethylacetal (DMA), C16:0 DMA, C16:0 DMA/C16:0, and C18:0 DMA/C18:0, but decreased eoicosenoate, nervoniate, lignocerate, and oleate in males. Maternal and postnatal HLA diets reduced oleate and vaccenate and had an interaction effect on myristate, palmitoleate, and eicosapentaenoate in males. In females, maternal HLA diet increased eicosadienoate. Postnatal HLA diet increased stearate and docosapentaenoate. Maternal and postnatal HLA diets had an interaction effect on oleate, arachidate, and docosahexaenoic acid (DHA)/omega (n)-6 docosapentaenoic acid (DPA) in females. Postnatal HLA diet decreased DHA/n-6 DPA in males and females. Postnatal HLA diet increased plasma endocannabinoids (arachidonoyl ethanolamide and 2-arachidonoyl glycerol), as well as other N-acyl ethanolamides and testosterone. HLA diet alters brain fatty acids, plasma endocannabinoids, and plasmalogen concentrations in a development-specific and sex-specific manner.

Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction.

Metabolomics is the study of small molecules (metabolites), within cells, tissues and biofluids. Maternal metabolites can provide important insight into the health and development of both mother and fetus throughout pregnancy. This study assessed metabolic profiles in the maternal circulation prior to and at the time of diagnosis of preeclampsia and fetal growth restriction. Maternal plasma samples were collected from two independent cohorts: (1) Established disease cohort: 50 participants diagnosed with early-onset preeclampsia (< 34 weeks' gestation), 14 with early-onset fetal growth restriction, and 25 gestation-matched controls. (2) Prospective cohort, collected at 36 weeks' gestation before diagnosis: 17 participants later developed preeclampsia, 49 delivered infants with fetal growth restriction (birthweight < 5th centile), and 72 randomly selected controls. Metabolic evaluation was performed by Metabolomics Australia on the Agilent 6545 QTOF Mass Spectrometer. In the established disease cohort, 77 metabolites were altered in circulation from participants with preeclampsia - increased L-cysteine (3.73-fold), L-cystine (3.28-fold), L-acetylcarnitine (2.57-fold), and carnitine (1.53-fold) (p < 0.05). There were 53 metabolites dysregulated in participants who delivered a fetal growth restriction infant-including increased levulinic acid, citric acid (1.93-fold), and creatine (1.14-fold) (p < 0.05). In the prospective cohort, 30 metabolites were altered in participants who later developed preeclampsia at term - reduced glutaric acid (0.85-fold), porphobilinogen (0.77-fold) and amininohippuric acid (0.82-fold) (p < 0.05) was observed. There were 5 metabolites altered in participants who later delivered a fetal growth restriction infant - including reduced 3-methoxybenzenepropanoic acid (p < 0.05). Downstream pathway analysis revealed aminoacyl-tRNA biosynthesis to be most significantly altered in the established cohort in preeclampsia (13/48 hits, p < 0.001) and fetal growth restriction (7/48 hits, p < 0.001). The predictive cohort showed no significant pathway alterations. This study observed altered metabolites in maternal plasma collected before and after diagnosis of a preeclampsia or fetal growth restriction. While a significant number of metabolites were altered with established disease, few changes were observed in the predictive cohort. Thus, metabolites measured in this study may not be useful as predictors of preeclampsia or fetal growth restriction.

Collaborative Care for Injured Older Adults: The Trauma Medical Home Randomized Clinical Trial.

Importance: Older adults with recent injuries can have impaired long-term biopsychosocial function and may benefit from interventions adapted to their needs. Objective: To determine if a collaborative care intervention, Trauma Medical Home (TMH), improved the biopsychosocial function of older patients in the year after injury. Design, Setting, and Participants: This was a single-blinded, randomized clinical trial conducted at 4 level I trauma centers in Indianapolis, Indiana, and Madison, Wisconsin. Between October 2017 and October 2021, patients aged 50 years and older with an Injury Severity Score (ISS) of 9 or greater and without traumatic brain or spinal cord injury were enrolled. Exclusions were significant brain injury or a spinal cord injury with a persistent neurologic deficit at the time of enrollment, extensive burns, pregnancy, incarceration, neurodegenerative disease, visual or auditory impairment that would preclude study participation, a life expectancy of less than 1 year, significant alcohol or drug use history, and acute stroke during admission. Of 10 276 patients screened, 430 were randomized and 299 completed 12-month follow-up. Data were analyzed from March to July 2023. Intervention: Intervention patients received 6 months of TMH delivered by a nurse care coordinator guided by an interdisciplinary team (trauma surgeon, pulmonary critical care and geriatrician physicians, nurses, and psychologist) in partnership with primary care. The care coordinator used standard protocols to monitor and treat biopsychosocial symptoms. Main Outcomes and Measures: Primary outcomes were Medical Outcome Study Short Form-36 (SF-36) score and Short Physical Performance Battery (SPPB) score at 12 months. Secondary outcomes were Patient Health Questionnaire-9 (PHQ-9) score, the Generalized Anxiety Disorder scale-7 (GAD-7) score, and health care utilization. Results: A total of 429 participants (228 [53.1%] female; mean [SD] age, 69.3 [10.8] years; mean [SD] ISS, 12.3 [4.6]) completed baseline assessments and were randomized. Follow-up was 76% (n = 324) at 6 months and 70% (n = 299) at 12 months. There were no differences between the TMH and usual care groups at 12 months in SF-36 Physical Component Summary score (mean [SD], 40.42 [12.82] vs 39.18 [12.43]), SF-36 Mental Component Summary score (mean [SD], 53.92 [10.02] vs 53.21 [10.82]), or SPPB score (mean [SD], 8.00 [3.60] vs 8.28 [3.88]). Secondary outcomes were also no different. Planned subgroup analysis revealed patients with baseline symptoms of anxiety or depression (high GAD-7 and PHQ-9 scores) experienced improvement in the Mental Component Summary score when randomized to the TMH intervention. Conclusions and Relevance: The TMH intervention did not significantly influence quality of life, depressive and anxiety symptoms, or physical function of older adults with injury at 12 months. Subgroup analysis showed positive impact in patients with a high burden of anxiety and depression symptoms at enrollment. Collaborative care interventions may improve long-term outcomes of select patients, but further research is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03108820.

Maternal Diet High in Linoleic Acid Alters Renal Branching Morphogenesis and mTOR/AKT Signalling Genes in Rat Fetal Kidneys.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at embryonic (E) day 20 (E20). We investigated the effects of an HLA diet on embryonic offspring renal branching morphogenesis, leptin signalling, megalin signalling and angiogenesis gene expression. Female Wistar Kyoto rats were fed low-LA (LLA; 1.44% energy from LA) or high-LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring were sacrificed and mRNA from kidneys was analysed by real-time PCR. Maternal HLA decreased the targets involved in branching morphogenesis Ret and Gdnf in offspring, independent of sex. Furthermore, downstream targets of megalin, namely mTOR, Akt3 and Prkab2, were reduced in offspring from mothers consuming an HLA diet, independent of sex. There was a trend of an increase in the branching morphogenesis target Gfra1 in females (p = 0.0517). These findings suggest that an HLA diet during pregnancy may lead to altered renal function in offspring. Future research should investigate the effects an HLA diet has on offspring kidney function in adolescence and adulthood.

Placentae of small appropriately-grown-for-gestational-age neonates exhibit sexually dimorphic transcriptomic changes representative of placental insufficiency.

INTRODUCTION: Previous studies have reported that neonates less than the 25th BWC especially if they were male, were more likely to be associated with birth complications suggesting small neonates often identified as appropriately grown are at risk of adverse outcomes. We have questioned whether smaller neonates not typically categorized as "small for gestational age" may not reach their genetically determined growth due to placental insufficiency. METHODS: RNA-Seq was performed on the Illumina NovaSeq 600 using term placentae from neonates that were less than the 10th birthweight centile (BWC) (n = 39), between the 10th and the 30th BWC (n = 15) or greater than the 30th BWC (n = 23). Bioinformatic analyses were conducted and statistical significance was assessed at a level of P < 0.05 for single comparisons or FDR <0.05 unless otherwise noted. RESULTS: Gene set enrichment analysis revealed differences between BWC groups and in relation to the sex of the placenta. Genes associated with hypoxia, inflammatory responses, estrogen responsive genes, and androgen responsive genes were enriched (FDR <0.1) for in placentae of neonates <10th BWC regardless of sex and also in male placentae of neonates between the 10th-30th BWC. Female placenta of neonates between the 10th-30th BWC were comparable to placentae of neonates >30th BWC. DISCUSSION: These findings provide evidence that small male neonates may be at a greater risk of an adverse outcome than females due to changes in gene expression that are associated with placental dysfunction. The current data raises questions of whether placental pathology for smaller appropriately grown neonates should be scientifically and clinically examined in more depth.

Placenta-Specific Transcripts Containing Androgen Response Elements Are Altered In Silico by Male Growth Outcomes.

A birthweight centile (BWC) below the 25th is associated with an elevated risk of adverse perinatal outcomes, particularly among males. This male vulnerability may stem from alterations in placenta-specific androgen signalling, a signalling axis that involves the androgen receptor (AR)-mediated regulation of target genes containing androgen response elements (AREs). In this study, we examined global and ARE-specific transcriptomic signatures in term male placentae (≥37 weeks of gestation) across BWC subcategories (<10th, 10th-30th, >30th) using RNA-seq and gene set enrichment analysis. ARE-containing transcripts in placentae with BWCs below the 10th percentile were upregulated compared to those in the 10th-30th and >30th percentiles, which coincided with the enrichment of gene sets related to hypoxia and the suppression of gene sets associated with mitochondrial function. In the absence of ARE-containing transcripts in silico, <10th and 10th-30th BWC subcategory placentae upregulated gene sets involved in vasculature development, immune function, and cell adhesion when compared to those in the >30th BWC subcategory. Collectively, our in silico findings suggest that changes in the expression of ARE-containing transcripts in male placentae may contribute to impaired placental vasculature and therefore result in reduced fetal growth outcomes.

Expanding Access to Comprehensive Geriatric Evaluation via Telehealth: Development of Hybrid-Virtual Home Visits.

BACKGROUND: In response to the aging population, the Department of Veterans Affairs (VA) seeks to expand access to evidence-based practices which support community-dwelling older persons such as the Geriatric Resources for Assessment and Care of Elders (GRACE) program. GRACE is a multidisciplinary care model which provides home-based geriatric evaluation and management for older Veterans residing within a 20-mile drive radius from the hospital. We sought to expand the geographic reach of VA-GRACE by developing a hybrid-virtual home visit (TeleGRACE). OBJECTIVES: The objectives were to: (1) describe challenges encountered and solutions implemented during the iterative, pre-implementation program development process; and (2) illustrate potential successes of the program with two case examples. DESIGN: Quality improvement project with longitudinal qualitative data collection. PROGRAM DESCRIPTION: The hybrid-virtual home visit involved a telehealth technician travelling to patients' homes and connecting virtually to VA-GRACE team members who participated remotely. APPROACH & PARTICIPANTS: We collected multiple data streams throughout program development: TeleGRACE staff periodic reflections, fieldnotes, and team meeting notes; and VA-GRACE team member interviews. KEY RESULTS: The five program domains that required attention and problem-solving were: telehealth connectivity and equipment, virtual physical examination, protocols and procedures, staff training, and team integration. For each domain, we describe several challenges and solutions. An example from the virtual physical examination domain: several iterations were required to identify the combination of telehealth stethoscope with dedicated headphones that allowed remote nurse practitioners to hear heart and lung sounds. The two cases illustrate how this hybrid-virtual home visit model provided care for patients who would not otherwise have received timely healthcare services. CONCLUSIONS: These results provide a blueprint to translate an in-person home-based geriatrics program into a hybrid-virtual model and support the feasibility of using hybrid-virtual home visits to expand access to comprehensive geriatric evaluation and ongoing care for high-risk, community-dwelling older persons who reside geographically distant from the primary VA facility.

Maternal Diet High in Linoleic Acid Alters Offspring Lipids and Hepatic Regulators of Lipid Metabolism in an Adolescent Rat Model.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. A maternal high LA (HLA) diet alters cardiovascular development in adolescent rats and hepatic function in adult rats in a sex-specific manner. We investigated the effects of an HLA diet on adolescent offspring hepatic lipids and hepatic lipid metabolism gene expression, and the ability of the postnatal diet to alter these effects. Female Wistar Kyoto rats were fed low LA (LLA; 1.44% energy from LA) or high LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring, weaned at postnatal day (PN) 25, were fed LLA or HLA and euthanised at PN40 (n = 6-8). Maternal HLA increased circulating uric acid, decreased hepatic cholesterol and increased hepatic Pparg in males, whereas only hepatic Srebf1 and Hmgcr increased in females. Postnatal (post-weaning) HLA decreased liver weight (% body weight) and increased hepatic Hmgcr in males, and decreased hepatic triglycerides in females. Maternal and postnatal HLA had an interaction effect on Lpl, Cpt1a and Pparg in females. These findings suggest that an HLA diet both during and after pregnancy should be avoided to improve offspring disease risk.

Mobile Critical Care Recovery Program for Survivors of Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Over 50% of Acute Respiratory Failure (ARF) survivors experience cognitive, physical, and psychological impairments that negatively impact their quality of life (QOL). Objective: To evaluate the efficacy of a post-intensive care unit (ICU) program, the Mobile Critical Care Recovery Program (m-CCRP) consisting of a nurse care coordinator supported by an interdisciplinary team, in improving the QOL of ARF survivors. Design, Setting, and Participants: This randomized clinical trial with concealed outcome assessments among ARF survivors was conducted from March 1, 2017, to April 30, 2022, with a 12-month follow-up. Patients were admitted to the ICU services of 4 Indiana hospitals (1 community, 1 county, 2 academic), affiliated with the Indiana University School of Medicine. Intervention: A 12-month nurse-led collaborative care intervention (m-CCRP) supported by an interdisciplinary group of clinicians (2 intensivists, 1 geriatrician, 1 ICU nurse, and 1 neuropsychologist) was compared with a telephone-based control. The intervention comprised longitudinal symptom monitoring coupled with nurse-delivered care protocols targeting cognition, physical function, personal care, mobility, sleep disturbances, pain, depression, anxiety, agitation or aggression, delusions or hallucinations, stress and physical health, legal and financial needs, and medication adherence. Main Outcomes and Measures: The primary outcome was QOL as measured by the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), with scores on each component ranging from 0-100, and higher scores indicating better health status. Results: In an intention-to-treat analysis among 466 ARF survivors (mean [SD] age, 56.1 [14.4] years; 250 [53.6%] female; 233 assigned to each group), the m-CCRP intervention for 12 months did not significantly improve the QOL compared with the control group (estimated difference in change from baseline between m-CCRP and control group: 1.61 [95% CI, -1.06 to 4.29] for SF-36 PCS; -2.50 [95% CI, -5.29 to 0.30] for SF-36 MCS. Compared with the control group, the rates of hospitalization were higher in the m-CCRP group (117 [50.2%] vs 95 [40.8%]; P = .04), whereas the 12-month mortality rates were not statistically significantly lower (24 [10.3%] vs 38 [16.3%]; P = .05). Conclusions and Relevance: Findings from this randomized clinical trial indicated that a nurse-led 12-month comprehensive interdisciplinary care intervention did not significantly improve the QOL of ARF survivors after ICU hospitalization. These results suggest that further research is needed to identify specific patient groups who could benefit from tailored post-ICU interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03053245.

Transoral incisionless fundoplication with or without hiatal hernia repair for gastroesophageal reflux disease after peroral endoscopic myotomy.

Background and study aims Gastroesophageal reflux disease (GERD) following peroral endoscopic myotomy (POEM) occurs in 40% to 60% of patients. There are limited data evaluating antireflux surgery or transoral incisionless fundoplication (TIF) for refractory post-POEM GERD. Patients and methods In a single-center prospective cohort study, consecutive patients with medically refractory post-POEM regurgitation and/or GERD treated with TIF or combined laparoscopic hernia repair and TIF (cTIF) were evaluated. Baseline evaluation: GERD-Health Related Quality of Life (GERD-HQRL) and Reflux Symptom Questionnaire 7-day recall (RESQ-7) questionnaires, EGD, high-resolution manometry (HRM), 48-hour pH test off proton pump inhibitors (PPIs) and impedance planimetry of the esophagogastric junction (EGJ) to calculate the diameter distensibility index (EGJ-DI). A PPI was taken twice daily for 2 weeks after TIF and restarted later if required. Patients returned 9 to 12 months after treatment when all preoperative studies were repeated. Quality of life, pH studies and EGJ metrics before and after antireflux surgery were compared. Results Seventeen patients underwent TIF (n=2, 12%) or cTIF (n=15, 88%) a mean 25±15 months after POEM. At follow-up a mean of 9±1 months after TIF/cTIF, patients required less frequent daily PPIs (n=0.001), were more satisfied (P=0.008), had improved GERD-HQRL (P=0.001), less intensity and frequency of GERD (P=0.001) and fewer reflux episodes (P=0.04) by pH testing. There was no change in EGJ-DI, EGJ diameter, integrated relaxation pressure, % total time pH <4, or DeMeester score. Conclusions TIF and cTIF for difficult-to-control post-POEM GERD appear safe, decrease PPI use and reflux episodes, and improve QOL without significant change in IRP, EGJ compliance, diameter or esophageal acid exposure time.

Loneliness in older primary care patients and its relationship to physical and mental health-related quality of life.

BACKGROUND: Loneliness is a significant public health challenge in the United States, especially among older adults. The epidemiology of loneliness among older adults in primary care is lacking, and specific research is needed on how loneliness impacts older primary patients' physical, mental, and cognitive health. A large sample of older primary care patients were recruited for a trial during the COVID-19 pandemic to measure the relationship between loneliness and physical and mental quality of life (QOL). METHODS: Baseline data come from the Caregiver Outcomes of Alzheimer's Disease Screening (COADS) study, an ongoing randomized controlled trial evaluating benefits and risks of Alzheimer's disease and related dementias screening among primary care patients ages 65 and older, collected April 2020 to September 2021. Loneliness was measured with the 5-item, Loneliness Fixed Form Ages 18+ from The NIH Toolbox Emotion Battery, physical and mental health-related QOL was measured with the SF-36v2, and depression and anxiety severity were measured with the PHQ-9 and GAD-7, respectively. RESULTS: Spearman correlation analyses revealed that loneliness was moderately correlated with mental health QOL (r[601] = -0.43, p < 0.001), anxiety severity (r[601] = 0.44, p < 0.001), and depression severity (r[601] = 0.42, p < 0.001), while weakly correlated with physical health QOL (r[601] = -0.15, p < 0.001). After conducting unadjusted and adjusted linear regression models, we found that loneliness was significantly associated with both lower mental (p < 0.001) and physical (p < 0.001) QOL. Furthermore, loneliness remained significantly associated with worse mental QOL after adjusting for age, gender, race, ethnicity, educational level, perceived income status, neighborhood disadvantage, severity of comorbidities, and comorbid depression and anxiety. CONCLUSION: Primary care providers should discuss loneliness with their older adult patients and provide resources to help patients develop and maintain meaningful social relationships.

Serum proteomic analysis in esophagectomy patients with postoperative delirium: A case-control study.

BACKGROUND: Postoperative delirium occurs in up to 80% of patients undergoing esophagectomy. We performed an exploratory proteomic analysis to identify protein pathways that may be associated with delirium post-esophagectomy. OBJECTIVES: Identify proteins associated with delirium and delirium severity in a younger and higher-risk surgical population. METHODS: We performed a case-control study using blood samples collected from patients enrolled in a negative, randomized, double-blind clinical trial. English speaking adults aged 18 years or older, undergoing esophagectomy, who had blood samples obtained were included. Cases were defined by a positive delirium screen after surgery while controls were patients with negative delirium assessments. Delirium was assessed using Richmond Agitation Sedation Scale and Confusion Assessment Method for the Intensive Care Unit, and delirium severity was assessed by Delirium Rating Scale-Revised-98. Blood samples were collected pre-operatively and on post-operative day 1, and discovery proteomic analysis was performed. Between-group differences in median abundance ratios were reported using Wilcoxon-Mann-Whitney Odds (WMWodds1) test. RESULTS: 52 (26 cases, 26 controls) patients were included in the study with a mean age of 64 (SD 9.6) years, 1.9% were females and 25% were African American. The median duration of delirium was 1 day (IQR: 1-2), and the median delirium/coma duration was 2.5 days (IQR: 2-4). Two proteins with greater relative abundance ratio in patients with delirium were: Coagulation factor IX (WMWodds: 1.89 95%CI: 1.0-4.2) and mannosyl-oligosaccharide 1,2-alpha-mannosidase (WMWodds: 2.4 95%CI: 1.03-9.9). Protein abundance ratios associated with mean delirium severity at postoperative day 1 were Complement C2 (Spearman rs = -0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (rs = 0.61, 95%CI = [0.29, 0.81]). CONCLUSIONS: We identified changes in proteins associated with coagulation, inflammation, and protein handling; larger, follow-up studies are needed to confirm our hypothesis-generating findings.

Risk factors for dementia in older intensive care unit (ICU) survivors.

INTRODUCTION: As the number of older intensive care unit (ICU) survivors grows, there is an urgent need to identify modifiable risk factors for post-ICU dementia. METHODS: We performed a secondary data analysis of 3144 ICU patients ≥ 50 years of age without a history of dementia or severe mental illness who were screened as part of the Pharmacological Management of Delirium (PMD) study. Delirium was assessed using the Confusion Assessment Method for the ICU. Dementia was identified using International Classification of Diseases Ninth and Tenth revision codes for dementia or prescription of anti-dementia medication. RESULTS: Average age (standard deviation) was 65.2 ± 9.5 years; 50.4% were female; and 37.3% were Black. Analyses identified stroke (adjusted hazard ratio [HR] 2.49; 95% confidence interval [CI: 1.52, 4.07], P < 0.001), and depression (adjusted HR 3.03; 95% CI [1.80, 5.10], P < 0.001) as post-ICU risk factors for dementia. DISCUSSION: Future studies will need to examine whether interventions targeting post-ICU stroke and depression can lower dementia incidence in ICU survivors. HIGHLIGHTS: Risk factors for post-intensive care unit (ICU) dementia were distinct from those of Alzheimer's disease. Cardiovascular risk factors were not associated with dementia in older ICU survivors. Post-ICU stroke was associated with a higher risk of dementia in older ICU survivors. Post-ICU depression was associated with a higher risk of dementia in older ICU survivors.

Communication and activation in pain to enhance relationships and treat pain with equity (COOPERATE): a randomized clinical trial.

ABSTRACT: Racialized disparities in chronic pain care are well-documented and persist despite national priorities focused on health equity. Similar disparities have been observed in patient activation (ie, having the knowledge, confidence, and skills to manage one's health). As such, interventions targeting patient activation represent a novel approach to addressing and reducing disparities in pain care. Communication and Activation in Pain to Enhance Relationships and Treat Pain with Equity is a randomized controlled trial of a 6-session telephone-delivered intervention to increase patient activation for Black patients with chronic pain. Two hundred fifty Black patients from a Midwestern Veterans Affairs medical center were randomized to the intervention or attention control. The primary outcome was patient activation; secondary outcomes included communication self-efficacy, pain, and psychological functioning. Outcomes were assessed at baseline and at 3 (primary endpoint), 6, and 9 months (sustained effects). Analyses used an intent-to-treat approach. Compared with baseline, patient activation increased 4.6 points at 3 months (versus +0.13 in control group, 95% CI: 0.48, 7.34; P = 0.03). These improvements in the intervention group were sustained, with +7 from baseline at 6 months and +5.77 at 9 months, and remained statistically significant from the control group. Communication self-efficacy increased significantly relative to the control group from baseline to 3 months. Pain intensity and interference improved at 3 months, but differences were not significant after adjusting for multiple comparisons. Most other secondary outcomes improved, but group differences were not statistically significant after controlling for multiple comparisons. Results suggest that increasing patient activation is a potentially fruitful path toward improving pain management and achieving health equity.

Dietary supplements, guideline alignment and biochemical nutrient status in pregnancy: Findings from the Queensland Family Cohort pilot study.

In high-income nations, multiple micronutrient (MMN) supplementation during pregnancy is a common practice. We aimed to describe maternal characteristics associated with supplement use and daily dose of supplemental nutrients consumed in pregnancy, and whether guideline alignment and nutrient status are related to supplement use. The Queensland Family Cohort is a prospective, Australian observational longitudinal study. Maternal characteristics, nutrient intake from food and supplements, and biochemical nutrient status were assessed in the second trimester (n = 127). Supplement use was reported by 89% of participants, of whom 91% reported taking an MMN supplement. Participants who received private obstetric care, had private health insurance and had greater alignment to meat/vegetarian alternatives recommendations were more likely to report MMN supplement use. Private obstetric care and general practitioner shared care were associated with higher daily dose of supplemental nutrients consumed compared with midwifery group practice. There was high reliance on supplements to meet nutrient reference values for folate, iodine and iron, but only plasma folate concentrations were higher in MMN supplement versus nonsupplement users. Exceeding the upper level of intake for folic acid and iron was more likely among combined MMN and individual supplement/s users, and associated with higher plasma concentrations of the respective nutrients. Given the low alignment with food group recommendations and potential risks associated with high MMN supplement use, whole food diets should be emphasized. This study confirms the need to define effective strategies for optimizing nutrient intake in pregnancy, especially among those most vulnerable where MMN supplement use may be appropriate.

Physical and psychosocial determinants of quality of life in children with obesity.

Background: Obesity has a negative impact on the physical and psychosocial quality of life of children. As rates of obesity continue to increase, it is important to recognize the widespread effects obesity has on children and their families. Methods: This clinical investigation evaluated the self-reported quality of life of children with obesity in a weight management program and compared this to a parent/guardian's perspective of the child's quality of life using the Pediatric Quality of Life survey 4.0. The quality of life of children with obesity was compared to children with other chronic diseases and healthy children. Results: An association was discovered between the guardians' responses to the Pediatric Quality of Life survey and the child's age. Guardians with children younger than 11 years reported higher quality of life scores than guardians of children 11 years and older. Race, comorbidities of obesity, insurance type, household structure, and parental education attainment were not significantly associated with a child's quality of life. Children with obesity had a lower quality of life compared to children who were organ transplant recipients and children with organic gastrointestinal disease. Conclusions: These results emphasize the need to evaluate and treat the physical and psychosocial components of wellbeing in children with obesity at an early age.