Profound Coronary Vasospasm Associated with Intraoperative Ketamine Administration: A Case Report.

We report a case of a 62-year-old woman with a decade-long history of atypical chest pain resulting in a largely negative cardiac workup, who developed significant angiographically demonstrated coronary vasospasm thought to be due to a small dose of intravenous ketamine. In patients with a history of atypical chest pain despite a reassuring cardiac evaluation, providers should carefully consider medications that may precipitate coronary vasospasm and be prepared to treat it accordingly.

Evaluating the Association between the Implementation of the PoET (Prevention of Error-Based Transfers) Southwest Spread Project and Palliative Care Provision: A Quasi-Experimental Matched Cohort Study Using Population-Level Health Administrative Data.

OBJECTIVES: The PoET (Prevention of Error-based Transfers) project seeks to align long-term care (LTC) home informed consent practices to existing legislation, thereby reducing consent-related error-based transfers to acute care. We sought to measure changes in resident-level palliative care provision after participating in the PoET Southwest Spread Project (PSSP), and to identify patient and LTC home characteristics associated with palliative care provision. DESIGN: Quasi-experimental matched (1:1 ratio) cohort study design using linked population-based health administrative data. SETTING: Sixty LTC homes (PSSP = 30; Control = 30) in Ontario, Canada, from November 2019 to December 2021. METHODS: We matched 30 PSSP to 30 control homes and described incidence rates for resident-level palliative care provision (ie, physician palliative care encounters and palliative medication prescriptions) during the 7-month postimplementation period. We used generalized linear mixed models to evaluate the association between PSSP implementation and palliative care provision during the postimplementation period. We adjusted for resident-level characteristics (ie, age, sex, comorbidity status) and home-level characteristics (ie, rurality status, profit model, COVID-19 impact). We identified a decedent subcohort to measure palliative care provision patterns during the last 2 months of life. RESULTS: We captured a matched cohort of 8894 residents (PSSP = 4103; Control = 4791). Incidence rates of palliative care encounters increased during the postimplementation period for PSSP (82.6 to 85.4 per 100 person-months) but not for control residents (68.8 to 65.3 per 100 person-months). After adjusting for key covariates, PSSP exposure was associated increased palliative care provision (incidence rate ratio 2.47, 95% CI 2.31-2.64) and palliative care medication prescription (1.16, 95% CI 1.12-1.20). Larger home size, certain health regions, and higher number of comorbidities were associated with increased physician palliative care encounters. CONCLUSIONS AND IMPLICATIONS: By promoting correct informed consent practices in LTC, PSSP participation increased palliative care provision for PSSP LTC residents across all settings.

Neuronal and behavioral responses to naturalistic texture images in macaque monkeys.

The visual world is richly adorned with texture, which can serve to delineate important elements of natural scenes. In anesthetized macaque monkeys, selectivity for the statistical features of natural texture is weak in V1, but substantial in V2, suggesting that neuronal activity in V2 might directly support texture perception. To test this, we investigated the relation between single cell activity in macaque V1 and V2 and simultaneously measured behavioral judgments of texture. We generated stimuli along a continuum between naturalistic texture and phase-randomized noise and trained two macaque monkeys to judge whether a sample texture more closely resembled one or the other extreme. Analysis of responses revealed that individual V1 and V2 neurons carried much less information about texture naturalness than behavioral reports. However, the sensitivity of V2 neurons, especially those preferring naturalistic textures, was significantly closer to that of behavior compared with V1. The firing of both V1 and V2 neurons predicted perceptual choices in response to repeated presentations of the same ambiguous stimulus in one monkey, despite low individual neural sensitivity. However, neither population predicted choice in the second monkey. We conclude that neural responses supporting texture perception likely continue to develop downstream of V2. Further, combined with neural data recorded while the same two monkeys performed an orientation discrimination task, our results demonstrate that choice-correlated neural activity in early sensory cortex is unstable across observers and tasks, untethered from neuronal sensitivity, and thus unlikely to reflect a critical aspect of the formation of perceptual decisions. Significance statement: As visual signals propagate along the cortical hierarchy, they encode increasingly complex aspects of the sensory environment and likely have a more direct relationship with perceptual experience. We replicate and extend previous results from anesthetized monkeys differentiating the selectivity of neurons along the first step in cortical vision from area V1 to V2. However, our results further complicate efforts to establish neural signatures that reveal the relationship between perception and the neuronal activity of sensory populations. We find that choice-correlated activity in V1 and V2 is unstable across different observers and tasks, and also untethered from neuronal sensitivity and other features of nonsensory response modulation.

Effectiveness of Postoperative Single-shot and Continuous Transverse Abdominis Plane Block Compared to Conventional Analgesia in Hand-assisted Laparoscopic Live-donor Nephrectomy.

Background: Few studies have evaluated the efficacy of transverse abdominis plane (TAP) block in patients undergoing hand-assisted laparoscopic live-donor nephrectomy (HALN). We aimed to evaluate the analgesic effectiveness of TAP block as part of a multimodal pain management regimen in patients undergoing HALN. Methods: We retrospectively reviewed the medical records of living kidney donors at our center between June 2016 and February 2020. HALNs were performed via a transperitoneal approach through a suprapubic incision. Additional laparoscopic ports were used in the upper midabdomen. In consenting donors, TAP block was performed postoperatively under ultrasound guidance with either a single-shot or continuous infusion of long-acting local anesthetic (0.2%-0.5% ropivacaine). All the patients received postoperative around-the-clock ketorolac and acetaminophen. Results: Overall, 72 donors received the block (block group, 38 single-shot, 34 continuous), whereas 86 donors did not receive the block (control group). Baseline characteristics were comparable between the groups except for body weight (control: 71.8 ±â€…13.3 versus block: 77.8 ±â€…17.3 kg; P = 0.01) and intraoperative opioid dose (32.1 ±â€…9.6 versus 26.6 ±â€…10.7 morphine milligram equivalents; P < 0.001). After adjusting for baseline differences, postoperative opioid requirements were similar between the groups. When the baseline pain scale was adjusted for, there was no difference in the overall pain scale scores between the groups (P = 0.242). Subgroup analyses comparing single-shot or continuous TAP versus control did not show any differences. Conclusions: With the caveat of the retrospective nature of the study, the adjunctive effect of TAP block after transabdominal HALN was limited when other multimodal analgesia was used.

SURGE: uncovering context-specific genetic-regulation of gene expression from single-cell RNA sequencing using latent-factor models.

Genetic regulation of gene expression is a complex process, with genetic effects known to vary across cellular contexts such as cell types and environmental conditions. We developed SURGE, a method for unsupervised discovery of context-specific expression quantitative trait loci (eQTLs) from single-cell transcriptomic data. This allows discovery of the contexts or cell types modulating genetic regulation without prior knowledge. Applied to peripheral blood single-cell eQTL data, SURGE contexts capture continuous representations of distinct cell types and groupings of biologically related cell types. We demonstrate the disease-relevance of SURGE context-specific eQTLs using colocalization analysis and stratified LD-score regression.

Prediction of High-Risk Donors for Kidney Discard and Nonrecovery Using Structured Donor Characteristics and Unstructured Donor Narratives.

Importance: Despite the unmet need, many deceased-donor kidneys are discarded or not recovered. Inefficient allocation and prolonged ischemia time are contributing factors, and early detection of high-risk donors may reduce organ loss. Objective: To evaluate the feasibility of machine learning (ML) and natural language processing (NLP) classification of donors with kidneys that are used vs not used for organ transplant. Design, Setting, and Participants: This retrospective cohort study used donor information (structured donor characteristics and unstructured donor narratives) from the United Network for Organ Sharing (UNOS). All donor offers to a single transplant center between January 2015 and December 2020 were used to train and validate ML models to predict donors who had at least 1 kidney transplanted (at our center or another center). The donor data from 2021 were used to test each model. Exposures: Donor information was provided by UNOS to the transplant centers with potential transplant candidates. Each center evaluated the donor and decided within an allotted time whether to accept the kidney for organ transplant. Main Outcomes and Measures: Outcome metrics of the test cohort included area under the receiver operating characteristic curve (AUROC), F1 score, accuracy, precision, and recall of each ML classifier. Feature importance and Shapley additive explanation (SHAP) summaries were assessed for model explainability. Results: The training/validation cohort included 9555 donors (median [IQR] age, 50 [36-58] years; 5571 male [58.3%]), and the test cohort included 2481 donors (median [IQR] age, 52 [40-59] years; 1496 male [60.3%]). Only 20% to 30% of potential donors had at least 1 kidney transplanted. The ML model with a single variable (Kidney Donor Profile Index) showed an AUROC of 0.69, F1 score of 0.42, and accuracy of 0.64. Multivariable ML models based on basic a priori structured donor data showed similar metrics (logistic regression: AUROC = 0.70; F1 score = 0.42; accuracy = 0.62; random forest classifier: AUROC = 0.69; F1 score = 0.42; accuracy = 0.64). The classic NLP model (bag-of-words model) showed its best metrics (AUROC = 0.60; F1 score = 0.35; accuracy = 0.59) by the logistic regression classifier. The advanced Bidirectional Encoder Representations From Transformers model showed comparable metrics (AUROC = 0.62; F1 score = 0.39; accuracy = 0.69) only after appending basic donor information. Feature importance and SHAP detected the variables (and words) that affected the models most. Conclusions and Relevance: Results of this cohort study suggest that models using ML can be applied to predict donors with high-risk kidneys not used for organ transplant, but the models still need further elaboration. The use of unstructured data is likely to expand the possibilities; further exploration of new approaches will be necessary to develop models with better predictive metrics.

Association of a Heart Failure Management Incentive in Primary Care With Clinical Outcomes: A Retrospective Cohort Study.

BACKGROUND: We aim to examine the association between primary care physicians' billing of Q050A, a pay-for-performance heart failure (HF) management incentive fee code, and the composite outcome of mortality, hospitalization, and emergency department visits. METHODS AND RESULTS: This population-based cohort study linked administrative health databases in Ontario, Canada, for patients with HF aged >66 years between January 1, 2008, and March 31, 2020. Cases were patients with HF who had a Q050A fee code billed. Cases and controls were matched 1:1 on age, sex, patient status on being rostered to a primary care physician, cardiologist, or internist visit in the 6 months before study enrollment, Johns Hopkins Adjusted Clinical Group resource use bands, days between HF diagnosis and study enrollment (±2 years), and the logit of the propensity score. A Cox proportional hazards model assessed the association of Q050A with the outcome. A total of 59 664 cases had a Q050A billed, whereas 244 883 patients did not. Before matching, patients who had a Q050A billed were more likely to be men (52% versus 49%), were rostered to a primary care physician (100% versus 96%), had a higher Charlson Comorbidity Index, and had higher health care costs. The mean follow-up was 481 days for cases and 530 days for controls. The composite outcome (hazard ratio, 1.11 [95% CI, 1.09-1.12]) was significantly higher for cases than controls. CONCLUSIONS: The Q050A incentive improved financial compensation for primary care physicians managing patients with HF but was not associated with improvements in the outcome. Research on promoting evidence-based HF management is warranted.

A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling.

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Evaluating the Association between the Implementation of the PoET Southwest Spread Project and Reductions in Acute Care Transfers from Long-Term Care: A Quasi-Experimental Matched Cohort Study Using Population-Level Health Administrative Data.

OBJECTIVES: To measure changes in resident-level acute care transfer rates after the PoET Southwest Spread Project (PSSP), and to identify patient and long-term care (LTC) home characteristics associated with acute care transfers after program launch. DESIGN: Quasi-experimental matched (1:1 ratio) cohort study design using linked population-based health administrative data. SETTING: Sixty publicly funded LTC homes (PSSP = 30; control = 30) in Ontario, Canada, from November 2019 to December 2021. METHODS: We matched 30 PSSP homes to 30 control homes with similar characteristics and described incidence rates for resident-level acute care transfers during the 7-month post-implementation period. We used generalized linear mixed models to evaluate the association between PSSP implementation and acute care transfers during the post-implementation period. We adjusted resident-level characteristics (ie, age, sex, comorbidity status) and home-level characteristics (ie, rurality status, profit model, COVID-19 impact). We identified a decedent sub-cohort to measure transfer patterns during the last 2 months of life. RESULTS: A matched cohort of 8894 residents (PSSP = 4103; control = 4791) was captured. Incidence rates of transfers increased during the post-implementation period for both PSSP (78.8 to 80.9 transfers per 1000 person-months) and control residents (66.9 to 67.9 transfers per 1000 person-months). After adjusting for covariates of interest, PSSP exposure was associated with a reduction in acute care transfers during the post-implementation period after adjusting for covariates (incidence rate ratio, 0.73; 95% CI, 0.62-0.87; P = .0002). Older age and select health regions were associated with reduced transfers, whereas higher comorbidity status and higher COVID-19 outbreak days were associated with increases. Similar patterns persisted for transfers during the last 2 months of life. CONCLUSIONS AND IMPLICATIONS: This study systematically evaluated the impact of an ethics-based health care intervention in LTC using health care utilization databases. PoET implementation is associated with reduced acute care transfer rates, especially in the last 2 months of life in LTC.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Long-term Survival of Grafts From Small and Very Small Pediatric Donors in Women vs Men With End-stage Kidney Disease.

This cohort study compares graft survival of kidneys from small and very small pediatric donors in women vs men with end-stage kidney disease.

Direct Oral Anticoagulation Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves: a Retrospective, Real-World Cohort Study.

OBJECTIVE: In this retrospective cohort study of consecutive patients with atrial fibrillation and surgical or transcatheter bioprosthetic valve, we compared the efficacy and safety of direct oral anticoagulants with warfarin. METHODS: Using linked health administrative databases housed at the Institute for Clinical Evaluative Sciences, we identified consecutive patients in Ontario (Canada) 65 years of age or older with AF who underwent bioprosthetic valve replacement between 1 April 2012 and 31 March 2017. We created a time-varying Cox model to examine the relationship between the type of anticoagulant and time to thrombotic or bleeding events after adjustment for baseline risk of thrombosis using the CHA2DS2-VASc score and risk of bleeding using the HAS-BLED scores. We conducted prespecified subgroup analyses according to whether valve implantation was surgical or transcatheter. RESULTS: We identified 2245 eligible patients. The mean age was 79 years, 41% were female, and 39% had transcatheter aortic valve replacement. Risk of death or thrombosis was not different between direct oral anticoagulants and warfarin after adjustment for CHA2DS2-VASc score (hazard ratio [HR] 1.02, 95% confidence interval [CI], 0.83-1.25). Risk of death or bleeding was not different between direct oral anticoagulants and warfarin after adjustment for HAS-BLED score (HR 0.89, 95% CI 0.75-1.07). Subgroup analyses of surgical or transcatheter valves were consistent with overall results. CONCLUSIONS: In a real-world population of patients with atrial fibrillation and bioprosthetic valve replacement, we found no difference between direct oral anticoagulants and warfarin with regard to the risk of thrombosis or bleeding.

Septic Arthritis With Superimposed Acute Gouty Arthritis in a Rheumatoid Arthritis Patient.

Septic arthritis is a rare but serious complication of both rheumatoid and gouty arthritis and can lead to significant morbidity and even mortality. Here, we report a case of septic arthritis with bacteremia, monosodium urate crystals, and hyperuricemia in a 75-year-old male with long-standing rheumatoid arthritis. Arthrocentesis revealed gram-positive cocci representing group B streptococcus (Streptococcus agalactiae) infection and monosodium urate crystals. A diagnosis of septic arthritis with superimposed acute gouty arthritis was made and the patient was treated accordingly. Management included surgical irrigation and debridement, antibiotic therapy, and systemic glucocorticoids which resulted in a significant improvement in the patient's clinical status.

Rates of health services use among residents of retirement homes in Ontario: a population-based cohort study.

BACKGROUND: Because there are no standardized reporting systems specific to residents of retirement homes in North America, little is known about the health of this distinct population of older adults. We evaluated rates of health services use by residents of retirement homes relative to those of residents of long-term care homes and other populations of older adults. METHODS: We conducted a retrospective cohort study using population health administrative data from 2018 on adults 65 years or older in Ontario. We matched the postal codes of individuals to those of licensed retirement homes to identify residents of retirement homes. Outcomes included rates of hospital-based care and physician visits. RESULTS: We identified 54 733 residents of 757 retirement homes (mean age 86.7 years, 69.0% female) and 2 354 385 residents of other settings. Compared to residents of long-term care homes, residents of retirement homes had significantly higher rates per 1000 person months of emergency department visits (10.62 v. 4.48, adjusted relative rate [RR] 2.61, 95% confidence interval [CI] 2.55 to 2.67), hospital admissions (5.42 v. 2.08, adjusted RR 2.77, 95% CI 2.71 to 2.82), alternate level of care (ALC) days (6.01 v. 2.96, adjusted RR 1.51, 95% CI 1.48 to 1.54), and specialist physician visits (6.27 v. 3.21, adjusted RR 1.64, 95% CI 1.61 to 1.68), but a significantly lower rate of primary care visits (16.71 v. 108.47, adjusted RR 0.13, 95% CI 0.13 to 0.14). INTERPRETATION: Residents of retirement homes are a distinct population with higher rates of hospital-based care. Our findings can help to inform policy debates about the need for more coordinated primary and supportive health care in privately operated congregate care homes.

Single-cell RNA-seq reveals cell type-specific molecular and genetic associations to lupus.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.2 million peripheral blood mononuclear cells (162 cases, 99 controls) with multiplexed single-cell RNA sequencing (mux-seq). Cases exhibited elevated expression of type 1 interferon-stimulated genes (ISGs) in monocytes, reduction of naïve CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell type-specific expression features predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data to map cell type-specific cis-expression quantitative trait loci and to link SLE-associated variants to cell type-specific expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE.

Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial.

Importance: Easy-to-administer anti-SARS-CoV-2 treatments may be used to prevent progression from asymptomatic infection to symptomatic disease and to reduce viral carriage. Objective: To evaluate the effect of combination subcutaneous casirivimab and imdevimab on progression from early asymptomatic SARS-CoV-2 infection to symptomatic COVID-19. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2-infected index case at 112 sites in the US, Romania, and Moldova enrolled July 13, 2020-January 28, 2021; follow-up ended March 11, 2021. Asymptomatic individuals (aged ≥12 years) were eligible if identified within 96 hours of index case positive test collection. Results from 314 individuals positive on SARS-CoV-2 reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) testing are reported. Interventions: Individuals were randomized 1:1 to receive 1 dose of subcutaneous casirivimab and imdevimab, 1200 mg (600 mg of each; n = 158), or placebo (n = 156). Main Outcomes and Measures: The primary end point was the proportion of seronegative participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy end points were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL). Results: Among 314 randomized participants (mean age, 41.0 years; 51.6% women), 310 (99.7%) completed the efficacy assessment period; 204 were asymptomatic and seronegative at baseline and included in the primary efficacy analysis. Subcutaneous casirivimab and imdevimab, 1200 mg, significantly prevented progression to symptomatic disease (29/100 [29.0%] vs 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% CI, 0.30-0.97]; P = .04; absolute risk difference, -13.3% [95% CI, -26.3% to -0.3%]). Casirivimab and imdevimab reduced the number of symptomatic weeks per 1000 participants (895.7 weeks vs 1637.4 weeks with placebo; P = .03), an approximately 5.6-day reduction in symptom duration per symptomatic participant. Treatment with casirivimab and imdevimab also reduced the number of high viral load weeks per 1000 participants (489.8 weeks vs 811.9 weeks with placebo; P = .001). The proportion of participants receiving casirivimab and imdevimab who had 1 or more treatment-emergent adverse event was 33.5% vs 48.1% for placebo, including events related (25.8% vs 39.7%) or not related (11.0% vs 16.0%) to COVID-19. Conclusions and Relevance: Among asymptomatic SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination vs placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04452318.