Speech markers of depression dimensions across cognitive status.

Introduction: Depression and its components significantly impact dementia prediction and severity, necessitating reliable objective measures for quantification. Methods: We investigated associations between emotion-based speech measures (valence, arousal, and dominance) during picture descriptions and depression dimensions derived from the geriatric depression scale (GDS, dysphoria, withdrawal-apathy-vigor (WAV), anxiety, hopelessness, and subjective memory complaint). Results: Higher WAV was associated with more negative valence (estimate = -0.133, p = 0.030). While interactions of apolipoprotein E (APOE) 4 status with depression dimensions on emotional valence did not reach significance, there was a trend for more negative valence with higher dysphoria in those with at least one APOE4 allele (estimate = -0.404, p = 0.0846). Associations were similar irrespective of dementia severity. Discussion: Our study underscores the potential utility of speech biomarkers in characterizing depression dimensions. In future research, using emotionally charged stimuli may enhance emotional measure elicitation. The role of APOE on the interaction of speech markers and depression dimensions warrants further exploration with greater sample sizes. Highlights: Participants reporting higher apathy used more negative words to describe a neutral picture.Those with higher dysphoria and at least one APOE4 allele also tended to use more negative words.Our results suggest the potential use of speech biomarkers in characterizing depression dimensions.

The Impact of Race/Ethnicity on Disparities in Utilization and Outcomes of Neuraxial Anesthesia for Hip and Femoral Shaft Fractures.

Background/Objectives: The use of neuraxial anesthesia versus general anesthesia for hip fracture surgery remains an active area of research, with recent studies demonstrating mixed findings supporting neuraxial over general anesthesia. The benefits of neuraxial anesthesia have been documented in associated surgeries, including total joint arthroplasty. However, racial disparities in the administration of neuraxial anesthesia have been identified in numerous procedures. We aimed to examine the association of race/ethnicity with neuraxial anesthesia use and the effect of neuraxial anesthesia on length of stay, non-home discharge, 30-day severe adverse events, and rates of readmission among patients undergoing isolated hip and femoral shaft fracture operations. Methods: The American College of Surgeons National Quality Improvement Program database was queried for isolated hip or femoral shaft fractures from 2015 to 2019. Stepwise logistic regression was performed to assess the relationship between race/ethnicity and neuraxial anesthesia use. Within each sex-race stratum, neuraxial anesthesia recipients were propensity-matched to general anesthesia recipients in a 1:2 ratio. Logistic regression and negative binomial regression were performed on the propensity-matched cohort. Results: A total of 12,004 neuraxial and 64,250 general anesthesia hip and femoral shaft fracture patients were identified. Compared to White patients, Black and Hispanic patients were between 0.64 and 0.61 times less likely to receive neuraxial anesthesia over general anesthesia, respectively (p < 0.05). 11,993 patients who received neuraxial anesthesia were propensity matched to 23,946 patients who received general anesthesia. Propensity-matched logistic regressions found that neuraxial anesthesia was associated with decreased length of stay, 30-day severe adverse events, and acute rehab/skilled nursing facility discharge for White patients (p < 0.05 for all), but only decreased length of stay in Black and Hispanic patients (p = 0.01 and p = 0.02, respectively). Conclusions: Notable disparities exist in the administration of neuraxial anesthesia for isolated hip and femoral shaft fracture patients. Hispanic and Black race/ethnicity in particular influences provision of neuraxial anesthesia. Further research is required to understand the degree of effect modification and root causes of regional anesthesia access and benefits for this high-volume patient population.

Postoperative Acute Kidney Injury is Associated with Persistent Renal Dysfunction: A Multicenter Propensity Matched Cohort Study.

Background: The risk of developing a persistent reduction in renal function after postoperative acute kidney injury (pAKI) is not well-established. Objective: Perform a multi-center retrospective propensity matched study evaluating whether patients that develop pAKI have a greater decline in long-term renal function than patients that did not develop postoperative AKI. Design: Multi-center retrospective propensity matched study. Setting: Anesthesia data warehouses at three tertiary care hospitals were queried. Patients: Adult patients undergoing surgery with available preoperative and postoperative creatinine results and without baseline hemodialysis requirements. Measurements: The primary outcome was a decline in follow-up glomerular filtration rate (GFR) of 40% relative to baseline, based on follow-up outpatient visits from 0-36 months after hospital discharge. A propensity score matched sample was used in Kaplan-Meier analysis and in a piecewise Cox model to compare time to first 40% decline in GFR for patients with and without pAKI. Results: A total of 95,208 patients were included. The rate of pAKI ranged from 9.9% to 13.7%. In the piecewise Cox model, pAKI significantly increased the hazard of a 40% decline in GFR. The common effect hazard ratio was 13.35 (95% CI: 10.79 to 16.51, p<0.001) for 0-6 months, 7.07 (5.52 to 9.05, p<0.001) for 6-12 months, 6.02 (4.69 to 7.74, p<0.001) for 12-24 months, and 4.32 (2.65 to 7.05, p<0.001) for 24-36 months. Limitations: Retrospective; Patients undergoing ambulatory surgery without postoperative lab tests drawn before discharge were not captured; certain variables like postoperative urine output were not reliably available. Conclusion: Postoperative AKI significantly increases the risk of a 40% decline in GFR up to 36 months after the index surgery across three institutions.

Erector Spinae Plane Block Decreases Narcotic Requirements in Patients Undergoing Subcutaneous Implantable Cardioverter-defibrillator Placement Under Sedation.

Providing adequate analgesia perioperatively during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation can be a challenge. The objective of our study was to assess the efficacy and safety of the erector spinae plane (ESP) block technique in providing analgesia and minimizing the risk of opioid use in high-risk patient populations. We enrolled consecutive patients >18 years of age undergoing S-ICD implantation from February 2020 to February 2022 at our center prospectively. Patients were randomly assigned to receive the ESP block or traditional wound infiltration. A total of 24 patients were enrolled, including 13 patients randomized to ESP block and 11 patients as controls who received only wound infiltration. The primary outcome assessed was the overall use of perioperative analgesic medications in the ESP block group versus the surgical wound infiltration group. A significant reduction in intraoperative fentanyl use was observed [median ([interquartile range]) in the ESP block group (0 [0-50] µg) compared to the wound infiltration block group (75 [50-100] µg) (P = .001). The overall postoperative day (POD) 0 fentanyl use was also significantly decreased (75 [50-100] µg) in the ESP block group compared to the surgical wound infiltration group (100 [87.5-150] µg) (P = .049). There was also a trend of decreased POD 0 oxycodone-acetaminophen use. Finally, the number of days to discharge was less in the ESP block group. These results indicate that ESP block is an innovative, safe, and effective technique that decreases intraoperative and postoperative opioid consumption and may be a useful adjunct pain-management technique in these high-risk patients. Larger studies are needed to further validate its use.

Relationship of pain relief with catastrophizing following interventional pain procedures for low back pain.

INTRODUCTION: Catastrophizing is associated with worse pain outcomes after various procedures suggesting its utility in predicting response. However, the stability of pain catastrophizing as a static predictor has been challenged. We assess, among patients undergoing steroid injections for chronic low back pain (cLBP), whether catastrophizing changes with the clinical response to pain interventions. METHODS: This prospective study enrolled patients undergoing fluoroscopic-guided injections for cLBP. Patients filled out Brief Pain Inventory (BPI) and Pain Catastrophizing Scale (PCS) at baseline and 1-month follow-up. We assessed the change in PCS scores from pre-injection to post-injection and examined its predictors. We also examined the correlation of various domains of BPI, such as pain severity and effect on Relationships, Enjoyment, and Mood (REM), with PCS scores at baseline and follow-up. RESULTS: 128 patients were enrolled. Mean (SD) PCS and pain severity scores at baseline were 22.38 (±13.58) and 5.56 (±1.82), respectively. Follow-up PCS and pain severity scores were 19.76 (±15.25) and 4.42 (±2.38), respectively. The change in PCS pre-injection to post-injection was not significant (p=0.12). Multiple regression models revealed baseline PCS and REM domain of BPI as the most important predictors of change in PCS after injection. Pain severity, activity-related pain, age, sex, insurance status, depression, prior surgery, opioid use, or prior interventions did not predict change in PCS score. In correlation analysis, change in PCS was moderately correlated with change in pain (r=0.38), but weakly correlated with baseline pain in all pain domains. CONCLUSIONS: PCS showed non-significant improvement following steroid injections; the study was not powered for this outcome. Follow-up PCS scores were predicted by the REM domain of BPI, rather than pain severity. Larger studies are needed to evaluate a statistically significant and clinically meaningful change in catastrophizing scores following pain interventions.

Pulmonary Hypertension and the Risk of 30-Day Postoperative Pulmonary Complications after Gastrointestinal Surgical or Endoscopic Procedures: A Retrospective Propensity Score-Weighted Cohort Analysis.

Background: Pulmonary hypertension (PH) patients are at higher risk of postoperative complications. We analyzed the association of PH with 30-day postoperative pulmonary complications (PPCs). Methods: A single-center propensity score overlap weighting (OW) retrospective cohort study was conducted on 164 patients with a mean pulmonary artery pressure (mPAP) of >20 mmHg within 24 months of undergoing elective inpatient abdominal surgery or endoscopic procedures under general anesthesia and a control cohort (N = 1981). The primary outcome was PPCs, and the secondary outcomes were PPC sub-composites, namely respiratory failure (RF), pneumonia (PNA), aspiration pneumonia/pneumonitis (ASP), pulmonary embolism (PE), length of stay (LOS), and 30-day mortality. Results: PPCs were higher in the PH cohort (29.9% vs. 11.2%, p < 0.001). When sub-composites were analyzed, higher rates of RF (19.3% vs. 6.6%, p < 0.001) and PNA (11.2% vs. 5.7%, p = 0.01) were observed. After OW, PH was still associated with greater PPCs (RR 1.66, 95% CI (1.05-2.71), p = 0.036) and increased LOS (median 8.0 days vs. 4.9 days) but not 30-day mortality. Sub-cohort analysis showed no difference in PPCs between pre- and post-capillary PH patients. Conclusions: After covariate balancing, PH was associated with a higher risk for PPCs and prolonged LOS. This elevated PPC risk should be considered during preoperative risk assessment.

Impact of cell salvage on hematocrit and post-partum anemia in low hemorrhage risk elective cesarean delivery.

BACKGROUND: Postpartum anemia is a significant contributor to peripartum morbidity. The utilization of cell salvage in low risk cases and its impact on postpartum anemia has not been investigated. We therefore aimed to examine the impact of autologous blood transfusion/cell salvage in routine cesarean delivery on postoperative hematocrit and anemia. STUDY DESIGN AND METHODS: Retrospective cohort study from a perfusion database from a large academic center where cell salvage is performed at the discretion of the obstetrical team. Data from 99 patients was obtained. All patients were scheduled elective cesarean deliveries that took place on the labor and delivery floor. Thirty patients in the cohort had access to cell salvage where autologous blood was transfused after surgery. Pre-procedural hemoglobin/hematocrit measurements were obtained along will postpartum samples that were collected on post-partum day one. RESULTS: The median amount of blood returned to cell salvage patients was 250 mL [206-250]. Hematocrit changes in cell salvage patients was significantly smaller than controls (-1.85 [-3.87, -0.925] vs -6.4 [-8.3, -4.75]; p < 0.001). The odds of developing new anemia following surgery were cut by 74% for the cell salvage treatment group, compared to the odds for the control group (OR = 0.26 (0.07-0.78); p = 0.028) DISCUSSION: Despite losing more blood on average, patients with access to cell salvage had higher postoperative HCT, less postpartum anemia, and no difference in complications related to transfusion. The utilization of cell salvage for routine cesarean delivery warrants further research.

Amyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes.

Diabetes is associated with cognitive decline, but the underlying mechanisms are complex and their relationship with Alzheimer's Disease biomarkers is not fully understood. We assessed the association of small vessel disease (SVD) and amyloid burden with cognitive functioning in 47 non-demented older adults with type-2 diabetes from the Israel Diabetes and Cognitive Decline Study (mean age 78Y, 64% females). FLAIR-MRI, Vizamyl amyloid-PET, and T1W-MRI quantified white matter hyperintensities as a measure of SVD, amyloid burden, and gray matter (GM) volume, respectively. Mean hemoglobin A1c levels and duration of type-2 diabetes were used as measures of diabetic control. Cholesterol level and blood pressure were used as measures of cardiovascular risk. A broad neuropsychological battery assessed cognition. Linear regression models revealed that both higher SVD and amyloid burden were associated with lower cognitive functioning. Additional adjustments for type-2 diabetes-related characteristics, GM volume, and cardiovascular risk did not alter the results. The association of amyloid with cognition remained unchanged after further adjustment for SVD, and the association of SVD with cognition remained unchanged after further adjustment for amyloid burden. Our findings suggest that SVD and amyloid pathology may independently contribute to lower cognitive functioning in non-demented older adults with type-2 diabetes, supporting a multimodal approach for diagnosing, preventing, and treating cognitive decline in this population.

Real-Time Machine Learning Alerts to Prevent Escalation of Care: A Nonrandomized Clustered Pragmatic Clinical Trial.

OBJECTIVES: Machine learning algorithms can outperform older methods in predicting clinical deterioration, but rigorous prospective data on their real-world efficacy are limited. We hypothesized that real-time machine learning generated alerts sent directly to front-line providers would reduce escalations. DESIGN: Single-center prospective pragmatic nonrandomized clustered clinical trial. SETTING: Academic tertiary care medical center. PATIENTS: Adult patients admitted to four medical-surgical units. Assignment to intervention or control arms was determined by initial unit admission. INTERVENTIONS: Real-time alerts stratified according to predicted likelihood of deterioration sent either to the primary team or directly to the rapid response team (RRT). Clinical care and interventions were at the providers' discretion. For the control units, alerts were generated but not sent, and standard RRT activation criteria were used. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the rate of escalation per 1000 patient bed days. Secondary outcomes included the frequency of orders for fluids, medications, and diagnostic tests, and combined in-hospital and 30-day mortality. Propensity score modeling with stabilized inverse probability of treatment weight (IPTW) was used to account for differences between groups. Data from 2740 patients enrolled between July 2019 and March 2020 were analyzed (1488 intervention, 1252 control). Average age was 66.3 years and 1428 participants (52%) were female. The rate of escalation was 12.3 vs. 11.3 per 1000 patient bed days (difference, 1.0; 95% CI, -2.8 to 4.7) and IPTW adjusted incidence rate ratio 1.43 (95% CI, 1.16-1.78; p < 0.001). Patients in the intervention group were more likely to receive cardiovascular medication orders (16.1% vs. 11.3%; 4.7%; 95% CI, 2.1-7.4%) and IPTW adjusted relative risk (RR) (1.74; 95% CI, 1.39-2.18; p < 0.001). Combined in-hospital and 30-day-mortality was lower in the intervention group (7% vs. 9.3%; -2.4%; 95% CI, -4.5% to -0.2%) and IPTW adjusted RR (0.76; 95% CI, 0.58-0.99; p = 0.045). CONCLUSIONS: Real-time machine learning alerts do not reduce the rate of escalation but may reduce mortality.

HRAS-Mutant Cardiomyocyte Model of Multifocal Atrial Tachycardia.

BACKGROUND: Germline HRAS gain-of-function pathogenic variants cause Costello syndrome (CS). During early childhood, 50% of patients develop multifocal atrial tachycardia, a treatment-resistant tachyarrhythmia of unknown pathogenesis. This study investigated how overactive HRAS activity triggers arrhythmogenesis in atrial-like cardiomyocytes (ACMs) derived from human-induced pluripotent stem cells bearing CS-associated HRAS variants. METHODS: HRAS Gly12 mutations were introduced into a human-induced pluripotent stem cells-ACM reporter line. Human-induced pluripotent stem cells were generated from patients with CS exhibiting tachyarrhythmia. Calcium transients and action potentials were assessed in induced pluripotent stem cell-derived ACMs. Automated patch clamping assessed funny currents. HCN inhibitors targeted pacemaker-like activity in mutant ACMs. Transcriptomic data were analyzed via differential gene expression and gene ontology. Immunoblotting evaluated protein expression associated with calcium handling and pacemaker-nodal expression. RESULTS: ACMs harboring HRAS variants displayed higher beating rates compared with healthy controls. The hyperpolarization activated cyclic nucleotide gated potassium channel inhibitor ivabradine and the Nav1.5 blocker flecainide significantly decreased beating rates in mutant ACMs, whereas voltage-gated calcium channel 1.2 blocker verapamil attenuated their irregularity. Electrophysiological assessment revealed an increased number of pacemaker-like cells with elevated funny current densities among mutant ACMs. Mutant ACMs demonstrated elevated gene expression (ie, ISL1, TBX3, TBX18) related to intracellular calcium homeostasis, heart rate, RAS signaling, and induction of pacemaker-nodal-like transcriptional programming. Immunoblotting confirmed increased protein levels for genes of interest and suppressed MAPK (mitogen-activated protein kinase) activity in mutant ACMs. CONCLUSIONS: CS-associated gain-of-function HRASG12 mutations in induced pluripotent stem cells-derived ACMs trigger transcriptional changes associated with enhanced automaticity and arrhythmic activity consistent with multifocal atrial tachycardia. This is the first human-induced pluripotent stem cell model establishing the mechanistic basis for multifocal atrial tachycardia in CS.

Poor self-rated health is associated with faster cognitive decline and greater small vessel disease in older adults with type 2 diabetes.

OBJECTIVE: Self-rated health (SRH) is a predictor for poor health outcomes and cognition. Older adults with type 2 diabetes mellitus (T2D) have multi-morbidity and greater cognitive impairment. In the present study we investigated the association of SRH with cognitive decline and brain pathology in older adults with T2D. METHODS: Participants (n = 1122) were from the Israel Diabetes and Cognitive Decline study, and SRH was categorised as low (n = 202), moderate (n = 400) or high (n = 520). Cognition was measured by four cognitive domains: episodic memory, executive functions, language, and attention/working memory. Global cognition was the average of the cognitive domains. Statistical models adjusted for sociodemographic, cardiovascular, and clinical variables. In a randomly selected subsample (n = 230) that had magnetic resonance imaging, we examined relationships between baseline SRH and brain characteristics (white matter hyperintensities [WMHs], hippocampal, and total grey matter [GM] volumes). RESULTS: Low SRH was associated with a decline in executive functions, which accelerated over time when compared to high SRH (est = -0.0036; p = <0.001). Compared to high SRH, low SRH was associated with a faster decline in global cognition (est = -0.0024; p = 0.009). Low SRH at baseline was associated with higher volumes of WMHs (est = 9.8420; p < 0.0008). SRH was not associated with other cognitive domains, or with hippocampal and total GM. CONCLUSIONS: Low SRH is associated with cognitive decline in T2D older adults and may serve as a risk assessment. WMHs may represent an underlying mechanism.