Homogeneous Oligomers of Pro-apoptotic BAX Reveal Structural Determinants of Mitochondrial Membrane Permeabilization.

BAX is a pro-apoptotic protein that transforms from a cytosolic monomer into a toxic oligomer that permeabilizes the mitochondrial outer membrane. How BAX monomers assemble into a higher-order conformation, and the structural determinants essential to membrane permeabilization, remain a mechanistic mystery. A key hurdle has been the inability to generate a homogeneous BAX oligomer (BAXO) for analysis. Here, we report the production and characterization of a full-length BAXO that recapitulates physiologic BAX activation. Multidisciplinary studies revealed striking conformational consequences of oligomerization and insight into the macromolecular structure of oligomeric BAX. Importantly, BAXO enabled the assignment of specific roles to particular residues and α helices that mediate individual steps of the BAX activation pathway, including unexpected functionalities of BAX α6 and α9 in driving membrane disruption. Our results provide the first glimpse of a full-length and functional BAXO, revealing structural requirements for the elusive execution phase of mitochondrial apoptosis.

Surpoint algorithm for improved guidance of ablation for ventricular tachycardia (SURFIRE-VT): A pilot study.

INTRODUCTION: The utility of ablation index (AI) to guide ventricular tachycardia (VT) ablation in patients with structural heart disease is unknown. The aim of this study was to assess procedural characteristics and clinical outcomes achieved using AI-guided strategy (target value 550) or conventional non-AI-guided parameters in patients undergoing scar-related VT ablation. METHODS: Consecutive patients (n = 103) undergoing initial VT ablation at a single center from 2017 to 2022 were evaluated. Patient groups were 1:1 propensity-matched for baseline characteristics. Single lesion characteristics for all 4707 lesions in the matched cohort (n = 74) were analyzed. The impact of ablation characteristics was assessed by linear regression and clinical outcomes were evaluated by Cox proportional hazard model. RESULTS: After propensity-matching, baseline characteristics were well-balanced between AI (n = 37) and non-AI (n = 37) groups. Lesion sets were similar (scar homogenization [41% vs. 27%; p = .34], scar dechanneling [19% vs. 8%; p = .18], core isolation [5% vs. 11%; p = .4], linear and elimination late potentials/local abnormal ventricular activities [35% vs. 44%; p = .48], epicardial mapping/ablation [11% vs. 14%; p = .73]). AI-guided strategy had 21% lower procedure duration (-47.27 min, 95% confidence interval [CI] [-81.613, -12.928]; p = .008), 49% lower radiofrequency time per lesion (-13.707 s, 95% CI [-17.86, -9.555]; p < .001), 21% lower volume of fluid administered (1664 cc [1127, 2209] vs. 2126 cc [1750, 2593]; p = .005). Total radiofrequency duration (-339 s [-24%], 95%CI [-776, 62]; p = .09) and steam pops (-155.6%, 95% CI [19.8%, -330.9%]; p = .08) were nonsignificantly lower in the AI group. Acute procedural success (95% vs. 89%; p = .7) and VT recurrence (0.97, 95% CI [0.42-2.2]; p = .93) were similar for both groups. Lesion analysis (n = 4707) demonstrated a plateau in the magnitude of impedance drops once reaching an AI of 550-600. CONCLUSION: In this pilot study, an AI-guided ablation strategy for scar-related VT resulted in shorter procedure time and average radiofrequency time per lesion with similar acute procedural and intermediate-term clinical outcomes to a non-AI-guided approach utilizing traditional ablation parameters.

Breaking Radial Dipole Symmetry in Planar Macrocycles Modulates Edge-to-Edge Packing and Disrupts Cofacial Stacking.

Dipolar interactions are ever-present in supramolecular architectures, though their impact is typically revealed by making dipoles stronger. While it is also possible to assess the role of dipoles by altering their orientations by using synthetic design, doing so without altering the molecular shape is not straightforward. We have now done this by flipping one triazole unit in a rigid macrocycle, tricarb. The macrocycle is composed of three carbazoles (2 Debye) and three triazoles (5 Debye) defining an array of dipoles aligned radially but organized alternately in and out. These dipoles are believed to dictate edge-to-edge tiling and face-to-face stacking. We modified our synthesis to prepare isosteric macrocycles with the orientation of one triazole dipole rotated 40°. The new dipole orientation guides edge-to-edge contacts to reorder the stability of two surface-bound 2D polymorphs. The impact on dipole-enhanced π stacking, however, was unexpected. Our stacking model identified an unchanged set of short-range (3.4 Å) anti-parallel dipole contacts. Despite this situation, the reduction in self-association was attributed to long-range (~6.4 Å) dipolar repulsions between π-stacked macrocycles. This work highlights our ability to control the build-up and symmetry of macrocyclic skeletons by synthetic design, and the work needed to further our understanding of how dipoles control self-assembly.

Procedural and Intermediate-term Results of the Electroanatomical-guided Cardioneuroablation for the Treatment of Supra-Hisian Second- or Advanced-degree Atrioventricular Block: the PIRECNA multicentre registry.

AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

Diagnostic Approach to Interstitial Lung Diseases Associated with Connective Tissue Diseases.

Interstitial lung disorders are a group of respiratory diseases characterized by interstitial compartment infiltration, varying degrees of infiltration, and fibrosis, with or without small airway involvement. Although some are idiopathic (e.g., idiopathic pulmonary fibrosis, idiopathic interstitial pneumonias, and sarcoidosis), the great majority have an underlying etiology, such as systemic autoimmune rheumatic disease (SARD, also called Connective Tissue Diseases or CTD), inhalational exposure to organic matter, medications, and rarely, genetic disorders. This review focuses on diagnostic approaches in interstitial lung diseases associated with SARDs. To make an accurate diagnosis, a multidisciplinary, personalized approach is required, with input from various specialties, including pulmonary, rheumatology, radiology, and pathology, to reach a consensus. In a minority of patients, a definitive diagnosis cannot be established. Their clinical presentations and prognosis can be variable even within subsets of SARDs.

Does Preoperative Pharmacogenomic Testing of Patients Undergoing TKA Improve Postoperative Pain? A Randomized Trial.

BACKGROUND: Pharmacogenomics is an emerging and affordable tool that may improve postoperative pain control. One challenge to successful pain control is the large interindividual variability among analgesics in their efficacy and adverse drug events. Whether preoperative pharmacogenomic testing is worthwhile for patients undergoing TKA is unclear. QUESTIONS/PURPOSES: (1) Are the results of preoperative pharmacogenetic testing associated with lower postoperative pain scores as measured by the Overall Benefit of Analgesic Score (OBAS)? (2) Do the results of preoperative pharmacogenomic testing lead to less total opioids given? (3) Do the results of preoperative pharmacogenomic testing lead to changes in opioid prescribing patterns? METHODS: Participants of this randomized trial were enrolled from September 2018 through December 2021 if they were aged 18 to 80 years and were undergoing primary TKA under general anesthesia. Patients were excluded if they had chronic kidney disease, a history of chronic pain or narcotic use before surgery, or if they were undergoing robotic surgery. Preoperatively, patients completed pharmacogenomic testing (RightMed, OneOME) and a questionnaire and were randomly assigned to the experimental group or control group. Of 99 patients screened, 23 were excluded, one before randomization; 11 allocated patients in each group did not receive their allocated interventions for reasons such as surgery canceled, patients ultimately undergoing spinal anesthesia, and change in surgery plan. Another four patients in each group were excluded from the analysis because they were missing an OBAS report. This left 30 patients for analysis in the control group and 38 patients in the experimental group. The control and experimental groups were similar in age, gender, and race. Pharmacogenomic test results for patients in the experimental group were reviewed before surgery by a pharmacist, who recommended perioperative medications to the clinical team. A pharmacist also assessed for clinically relevant drug-gene interactions and recommended drug and dose selection according to guidelines from the Clinical Pharmacogenomics Implementation Consortium for each patient enrolled in the study. Patients were unaware of their pharmacogenomic results. Pharmacogenomic test results for patients in the control group were not reviewed before surgery; instead, standard perioperative medications were administered in adherence to our institutional care pathways. The OBAS (maximum 28 points) was the primary outcome measure, recorded 24 hours postoperatively. A two-sample t-test was used to compare the mean OBAS between groups. Secondary measures were the mean 24-hour pain score, total morphine milligram equivalent, and frequency of opioid use. Postoperatively, patients were assessed for pain with a VAS (range 0 to 10). Opioid use was recorded preoperatively, intraoperatively, in the postanesthesia care unit, and 24 hours after discharge from the postanesthesia care unit. Changes in perioperative opioid use based on pharmacogenomic testing were recorded, as were changes in prescription patterns for postoperative pain control. Preoperative characteristics were also compared between patients with and without various phenotypes ascertained from pharmacogenomic test results. RESULTS: The mean OBAS did not differ between groups (mean ± SD 4.7 ± 3.7 in the control group versus 4.2 ± 2.8 in the experimental group, mean difference 0.5 [95% CI -1.1 to 2.1]; p = 0.55). Total opioids given did not differ between groups or at any single perioperative timepoint (preoperative, intraoperative, or postoperative). We found no difference in opioid prescribing pattern. After adjusting for multiple comparisons, no difference was observed between the treatment and control groups in tramadol use (41% versus 71%, proportion difference 0.29 [95% CI 0.05 to 0.53]; nominal p = 0.02; adjusted p > 0.99). CONCLUSION: Routine use of pharmacogenomic testing for patients undergoing TKA did not lead to better pain control or decreased opioid consumption. Future studies might focus on at-risk populations, such as patients with chronic pain or those undergoing complex, painful surgical procedures, to test whether pharmacogenomic results might be beneficial in certain circumstances. LEVEL OF EVIDENCE: Level I, therapeutic study.

Detection of carbapenemase producing Acinetobacter baumannii ST19 from Georgia and Ukraine carrying bla OXA-23, bla OXA-72, and/or bla NDM-5, December 2019 to June 2023.

In 2003-2023, amid 5,436 Acinetobacter baumannii isolates collected globally through the Multidrug-Resistant Organism Repository and Surveillance Network, 97 were ST19PAS, 34 of which carbapenem-resistant. Strains (n = 32) sampled after 2019 harboured either bla OXA-23, bla OXA-72, and/or bla NDM-5. Phylogenetic analysis of the 97 isolates and 11 publicly available ST19 genomes revealed three sub-lineages of carbapenemase-producing isolates from mainly Ukraine and Georgia, including an epidemic clone carrying all three carbapenemase genes. Infection control and global surveillance of carbapenem-resistant A. baumannii remain important.

Clostridium difficile Infection Prior to Total Hip Arthroplasty Independently Increases the Risk of Periprosthetic Joint Infection.

BACKGROUND: Periprosthetic joint infection (PJI) following total hip arthroplasty (THA) is associated with major morbidity. There may be a link between the gut microbiome and an individual's overall immune system. A Clostridium difficile (C. difficile) infection portends poor gut microbiome health and has been previously associated with increased 90-day complication rates in total joint arthroplasty (TJA). The purpose of this study was to determine the effect of a previous history of C. difficile infection within 2 years of undergoing THA on PJI within 2 years postoperatively. METHODS: Patients undergoing THA from 2010 to 2021 were identified in a patient claims database (n = 770,075). Patients who had active records 2 years before and after THA as well as a history of C. difficile infection within 2 years prior to THA (n = 1,836) were included and propensity matched to a control group using age, sex, and Elixhauser comorbidity index. The primary outcome was the 2-year incidence of postoperative PJI. The exposed C. difficile infection cohort was stratified into 4 groups based on the time proximity of the C. difficile infection. Chi-square tests and logistic regressions were used to compare the groups. RESULTS: A C. difficile infection anytime within 2 years prior to total hip arthroplasty was independently associated with higher odds of PJI (OR [odds ratio]: 1.49 [95% CI (confidence interval) 1.09 to 2.02, P = .014]). Proximity of C. difficile infection to arthroplasty was associated with increased risk of PJI (infection 0 to 3 months before THA: OR 2.01 [95% CI 1.23 to 3.20], infection 3 to 6 months before THA: OR 1.84 [95% CI 1.06 to 3.04], infection 6 to 12 months before THA: OR 1.10 [95% CI 0.65 to 1.77], infection 1 to 2 years before THA: OR 1.40 [95% CI 0.94 to 2.06]). CONCLUSIONS: A C. difficile infection prior to THA is an independent risk factor for PJI. Proximity of C. difficile infection is associated with increased risk of PJI. Future investigations should evaluate how to adequately optimize patients prior to THA and pursue strategies to determine appropriate timing for proceeding with THA.

Rheumatoid Arthritis Is Not a Contraindication to Unicompartmental Knee Arthroplasty.

BACKGROUND: Rheumatoid arthritis (RA) has historically been considered a contraindication for unicompartmental knee arthroplasty (UKA). However, the widespread use of disease-modifying antirheumatic drugs has substantially improved the management of RA and prevented disease progression. The objective of this study was to ascertain whether RA impacts UKA revision-free survivorship. METHODS: Patients undergoing UKA from 2010 to 2021 were identified in an administrative claims database (n = 105,937) using Current Procedural Terminology code 27446. All patients who underwent UKA who had a diagnosis of RA with a minimum of 2-year follow-up (n = 1,422) were propensity score matched based on age, sex, and Elixhauser Comorbidity Index to those who did not have RA (n = 1,422). Laterality was identified using the 10th Revision of International Classification of Diseases codes. The primary outcome was ipsilateral revision to total knee arthroplasty (TKA) within 2 years, and the secondary outcome was ipsilateral revision at any time. RESULTS: Among the 1,422 patients who had a UKA and a diagnosis of RA, 37 patients (2.6%) underwent conversion to TKA within 2 years, and 48 patients (3.4%) underwent conversion to TKA at any point. In comparison, 28 patients (2.0%) in the propensity-matched control group underwent conversion to TKA within 2 years, and 40 patients (2.8%) underwent conversion to TKA at any point. Statistical analysis revealed no significant difference in conversion to TKA between patients who had and did not have RA, either within 2 years (P = .31) or anytime (P = .45). CONCLUSIONS: Patients who had RA and underwent UKA did not have an increased risk of revision to TKA compared to those who did not have RA. This may indicate that modern management of RA could allow for expanded UKA indications for RA patients.

Low Risk of Periprosthetic Joint Infection After Aseptic Revision Total Knee Arthroplasty With Intraosseous Vancomycin.

BACKGROUND: Aseptic revisions are the most common reason for revision total knee arthroplasty (rTKA). Previous literature reports early periprosthetic joint infection (PJI) rates after aseptic rTKA to range from 3 to 9.4%. Intraosseous (IO) regional administration of vancomycin has previously been shown to produce high local tissue concentrations in primary and rTKA. However, no data exist on the effect of prophylactic IO vancomycin on early PJI rates in the setting of aseptic rTKA. The aim of this study was to determine the following: (1) what is the rate of early PJI during the first year after surgery in aseptic rTKA performed with IO vancomycin; and (2) how does this compare to previously published PJI rates after rTKA. METHODS: A consecutive series of 117 cases were included in this study who underwent rTKA between January 2016 and March 2022 by 1 of 2 fellowship-trained adult reconstruction surgeons and received IO vancomycin at the time of surgery in addition to standard intravenous antibiotic prophylaxis. Rates of PJI at 3 months, 1 year, and the final follow-up were evaluated and compared to prior literature. RESULTS: Follow-up at 3 months was available for 116 of the 117 rTKAs, with 1 lost to follow-up. The rate of PJI was 0% at 3 months postoperatively. Follow-up at 1 year was obtained for 113 of the 117 rTKAs, and the PJI rate remained 0%. The rate of PJI at the final follow-up of ≥ 1 year was 0.88% (95% confidence interval: -0.84 to 2.61). Previous literature reports PJI rates in aseptic rTKA to range from 3 to 9.4%. CONCLUSIONS: Dual prophylactic antibiotics with IO vancomycin in conjunction with intravenous cephalosporins or clindamycin were associated with a substantial reduction in early PJI compared to prior published literature. These data supplement the early evidence about the potential clinical benefits of IO vancomycin for infection prevention in high-risk cases. LEVEL OF EVIDENCE: Level III, therapeutic study.

Correlation of serum level of squamous cell carcinoma antigen with severity of cutaneous psoriasis, assessed using the simplified psoriasis index.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) is a biomarker of disease progression in squamous cell carcinoma but also contributes to the pathogenesis of psoriasis. Eight previous studies have shown a correlation between psoriasis severity, assessed using the Psoriasis Assessment Severity Index or body surface area, and serum level of SCCA, mainly SCCA2, assessed by means of non-commercial tests. We examined the correlation between serum SCCA level, measured with a commercial kit, and psoriasis severity assessed using the Simplified Psoriasis Index (SPI). METHODS: We conducted a prospective, non-interventional, single-centre study at the University Hospital of Tours over 18 months. The primary endpoint was same-day measurement of serum SCCA level and the psoriasis severity score on the professional version of the SPI (proSPI-s) at both baseline and follow-up. Secondary endpoints were same-day measurement of serum SCCA level and the proSPI psychosocial score (proSPI-p), proSPI treatment score, Dermatology Life Quality Index (DLQI), and inflammation parameters (C-reactive protein level, neutrophil-to-lymphocyte ratio). RESULTS: We included 50 psoriasis patients. Serum SCCA level was correlated with the proSPI-s at baseline and follow-up (Spearman r = 0.686 and r = 0.674, p < 0.0001) for both. It was correlated with the proSPI-p and DLQI. Serum SCCA level was not correlated with either neutrophil-to-lymphocyte ratio (r = 0.083) or C-reactive protein level (r = 0.192). CONCLUSION: This study is the first to correlate serum SCCA level with proSPI-s. Moreover, SCCA was measured using a widely available kit. SCCA may be used to assess the severity of psoriasis.

Risk Factors for Ebola Virus Persistence in Semen of Survivors in Liberia.

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola virus disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within 1 year after discharge from the Ebola treatment unit or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR >1 year after discharge from the Ebola treatment unit or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical examinations and blood work. RESULTS: Compared with early clearers, late clearers were older (median, 42.5 years; P < .001) and experienced fewer severe clinical symptoms (median 2, P = .006). Late clearers had more lens opacifications (odds ratio, 3.9 [95% confidence interval, 1.1-13.3]; P = .03), after accounting for age, higher total serum immunoglobulin G3 (IgG3) titers (P = .005), and increased expression of the HLA-C*03:04 allele (0.14 [.02-.70]; P = .007). CONCLUSIONS: Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.

Six Extensively Drug-Resistant Bacteria in an Injured Soldier, Ukraine.

Blood and surveillance cultures from an injured service member from Ukraine grew Acinetobacter baumannii, Klebsiella pneumoniae, Enterococcus faecium, and 3 distinct Pseudomonas aeruginosa strains. Isolates were nonsusceptible to most antibiotics and carried an array of antibiotic resistant genes, including carbapenemases (blaIMP-1, blaNDM-1, blaOXA-23, blaOXA-48, blaOXA-72) and 16S methyltransferases (armA and rmtB4).

Death from hunger or thirst? Phloem death, rather than xylem hydraulic failure, as a driver of fire-induced conifer mortality.

Disruption of photosynthesis and carbon transport due to damage to the tree crown and stem cambial cells, respectively, can cause tree mortality. It has recently been proposed that fire-induced dysfunction of xylem plays an important role in tree mortality. Here, we simultaneously tested the impact of a lethal fire dose on nonstructural carbohydrates (NSCs) and xylem hydraulics in Pinus ponderosa saplings. Saplings were burned with a known lethal fire dose. Nonstructural carbohydrates were assessed in needles, main stems, roots and whole plants, and xylem hydraulic conductivity was measured in the main stems up to 29 d postfire. Photosynthesis and whole plant NSCs declined postfire. Additionally, all burned saplings showed 100% phloem/cambium necrosis, and roots of burned saplings had reduced NSCs compared to unburned and defoliated saplings. We further show that, contrary to patterns observed with NSCs, water transport was unchanged by fire and there was no evidence of xylem deformation in saplings that experienced a lethal dose of heat from fire. We conclude that phloem and cambium mortality, and not hydraulic failure, were probably the causes of death in these saplings. These findings advance our understanding of the physiological response to fire-induced injuries in conifer trees.

Carbon starvation following a decade of experimental drought consumes old reserves in Pinus edulis.

Shifts in the age or turnover time of non-structural carbohydrates (NSC) may underlie changes in tree growth under long-term increases in drought stress associated with climate change. But NSC responses to drought are challenging to quantify, due in part to large NSC stores in trees and subsequently long response times of NSC to climate variation. We measured NSC age (Δ14 C) along with a suite of ecophysiological metrics in Pinus edulis trees experiencing either extreme short-term drought (-90% ambient precipitation plot, 2020-2021) or a decade of severe drought (-45% plot, 2010-2021). We tested the hypothesis that carbon starvation - consumption exceeding synthesis and storage - increases the age of sapwood NSC. One year of extreme drought had no impact on NSC pool size or age, despite significant reductions in predawn water potential, photosynthetic rates/capacity, and twig and needle growth. By contrast, long-term drought halved the age of the sapwood NSC pool, coupled with reductions in sapwood starch concentrations (-75%), basal area increment (-39%), and bole respiration rates (-28%). Our results suggest carbon starvation takes time, as tree carbon reserves appear resilient to extreme disturbance in the short term. However, after a decade of drought, trees apparently consumed old stored NSC to support metabolism.

The osmotic balancing act: When sugars matter for more than metabolism in woody plants.

Sugars and other non-structural carbohydrates are known to serve as currency in plants, to either fuel metabolic activities or as storage for later use. They can also serve non-metabolic purposes of osmoregulation and cryoprotection, especially in perennial woody plants.

Depressive Symptoms are Associated With C-Reactive Protein in Older Adults With Obesity.

OBJECTIVES: To test the hypothesis that depressive symptoms vary with high-sensitivity C-reactive protein (hs-CRP), among older adults with obesity. METHODS: This was a cross-sectional, secondary analysis of baseline data from two related lifestyle intervention trials. The study sample comprises 148 consecutively recruited, community-dwelling older adults (age >=65 years) without severe psychiatric illness and with body mass index >=30 kg/m2. Logarithmically transformed GDS was analyzed as the dependent variable. Independent variables included log-transformed hs-CRP and covariates: sex, age, and concurrent use of antidepressant medication at baseline. An additional analysis was performed using binary conversion of the GDS scores, wherein a cutoff score of 5 was considered positive for depressive symptoms. RESULTS: Sample mean GDS score was 2.7 (SD 3.0, range 0 - 14). A significant multivariate model of GDS scores (R2 = .089, F = 3.5, P = .010) revealed log-transformed hs-CRP (P = .017) and male sex (P = .012) as associated with depressive symptoms. Supplemental analysis demonstrated associations between depressive symptoms and log-transformed hs-CRP (OR 2.17, P = .001) and between depressive symptoms and male sex (OR 3.78, P = .013). Univariate logistic regression found hs-CRP to be associated with depressive symptoms. CONCLUSIONS: In older adults with obese BMI, male sex and higher hs-CRP are associated with depression, even in a group with relatively minimal depressive symptoms. Hs-CRP may offer clinical utility as a biomarker for depression among older adults with obese BMI, even among those with non-severe psychiatric symptomatology.

The Impact of Depression in Patients Undergoing Emergency Abdominal Surgery: An Exploratory Study.

BACKGROUND: Depression is associated with poorer outcomes in many disease states. However, its significance in abdominal surgery is unknown. This study investigated rates of depression in emergency abdominal surgery patients and its effects on outcomes. METHODS: A retrospective cohort study was conducted across two UK sites and included all adult patients undergoing emergency abdominal surgery. Primary outcome was the complication rate in depressed patients, including the incidence of post-operative delirium. Secondary outcomes included mortality, time to oral intake and analgesia. RESULTS: Two hundred and ten patients were identified. The commonest indication for surgery was appendicitis (53.3%) followed by small bowel obstruction (9.5%). There was a 17% (n = 36) incidence of depression amongst patients, most of whom (n = 26, 72.2%) were taking antidepressants. Depression was associated with male sex (M:F 27:9 p = 0.003), higher median BMI (28 vs. 25 p = 0.013) and previous surgery (47.2% vs. 28.7% p = 0.032). Despite a higher incidence of post-operative delirium, increased time to oral analgesia and greater 30-day readmission rates in the depression cohort, multivariate analyses showed depression was not a significant independent predictor of these (OR 2.181, 95%CI 0.310-15.344; p = 0.433, OR 0.07, 95%CI 0.499-1.408; p = 0.348 and OR 1.367, 95%CI 0.102-18.34, respectively). Complication and mortality rates between depressed and non-depressed individuals were similar. CONCLUSION: Significant numbers of patients undergoing emergency abdominal surgery have depression, but this did not adversely affect post-operative outcomes. The study included relatively small numbers of participants undergoing procedures with straightforward recovery. Larger population studies are therefore required and should focus on investigating the association between major emergency surgeries with post-operative delirium and uncontrolled pain.

Maternal interventions to decrease stillbirths and neonatal mortality in Tanzania: evidence from the 2017-18 cross-sectional Tanzania verbal and social autopsy study.

BACKGROUND: Reduction of Tanzania's neonatal mortality rate has lagged behind that for all under-fives, and perinatal mortality has remained stagnant over the past two decades. We conducted a national verbal and social autopsy (VASA) study to estimate the causes and social determinants of stillbirths and neonatal deaths with the aim of identifying relevant health care and social interventions. METHODS: A VASA interview was conducted of all stillbirths and neonatal deaths in the prior 5 years identified by the 2015-16 Tanzania Demographic and Health Survey. We evaluated associations of maternal complications with antepartum and intrapartum stillbirth and leading causes of neonatal death; conducted descriptive analyses of antenatal (ANC) and delivery care and mothers' careseeking for complications; and developed logistic regression models to examine factors associated with delivery place and mode. RESULTS: There were 204 stillbirths, with 185 able to be classified as antepartum (88 [47.5%]) or intrapartum (97 [52.5%]), and 228 neonatal deaths. Women with an intrapartum stillbirth were 6.5% (adjusted odds ratio (aOR) = 1.065, 95% confidence interval (CI) 1.002, 1.132) more likely to have a C-section for every additional hour before delivery after reaching the birth attendant. Antepartum hemorrhage (APH), maternal anemia, and premature rupture of membranes (PROM) were significantly positively associated with early neonatal mortality due to preterm delivery, intrapartum-related events and serious infection, respectively. While half to two-thirds of mothers made four or more ANC visits (ANC4+), a third or fewer received quality ANC (Q-ANC). Women with a complication were more likely to deliver at hospital only if they received Q-ANC (neonates: aOR = 4.5, 95% CI 1.6, 12.3) or ANC4+ (stillbirths: aOR = 11.8, 95% CI 3.6, 38.0). Nevertheless, urban residence was the strongest predictor of hospital delivery. CONCLUSIONS: While Q-ANC and ANC4 + boosted hospital delivery among women with a complication, attendance was low and the quality of care is critical. Quality improvement efforts in urban and rural areas should focus on early detection and management of APH, maternal anemia, PROM, and prolonged labor, and on newborn resuscitation.