Ventricular Arrhythmias After Primary Percutaneous Coronary Intervention for STEMI.

Importance: Currently, mortality risk for patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) with an uncomplicated postprocedure course is low. Less is known regarding the risk of in-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF). Objective: To evaluate the risk of late VT and VF after primary PCI for STEMI. Design, Setting, and Participants: This cohort study included adults aged 18 years or older with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, identified in the US National Cardiovascular Data Registry Chest Pain-MI Registry. Data were analyzed from April to December 2020. Main Outcomes and Measures: Multivariable logistic regression was used to evaluate the risk of late VT (≥7 beat run of VT during STEMI hospitalization ≥1 day after PCI) or VF (any episode of VF≥1 day after PCI) associated with cardiac arrest and associations between late VT or VF and in-hospital mortality in the overall cohort and a cohort with uncomplicated STEMI without prior myocardial infarction or heart failure, systolic blood pressure less than 90 mm Hg, cardiogenic shock, cardiac arrest, reinfarction, or left ventricular ejection fraction (LVEF) less than 40%. Results: A total of 174 126 eligible patients with STEMI were treated with primary PCI at 814 sites in the study; 15 460 (8.9%) had VT or VF after primary PCI, and 4156 (2.4%) had late VT or VF. Among the eligible patients, 99 905 (57.4%) at 807 sites had uncomplicated STEMI. The median age for patients with late VT or VF overall was 63 years (IQR, 55-73 years), and 75.5% were men; the median age for patients with late VT or VF with uncomplicated STEMI was 60 years (IQR, 53-69 years), and 77.7% were men. The median length of stay was 3 days (IQR, 2-7 days) for the overall cohort with late VT or VF and 3 days (IQR, 2-4 days) for the cohort with uncomplicated STEMI with late VT or VF. The risk of late VT or VF was 2.4% (overall) and 1.7% (uncomplicated STEMI). Late VT or VF with cardiac arrest occurred in 674 patients overall (0.4%) and in 117 with uncomplicated STEMI (0.1%). LVEF was the most significant factor associated with late VT or VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54-1.85). Late VT or VF events were associated with increased odds of in-hospital mortality in the overall cohort (AOR, 6.40; 95% CI, 5.63-7.29) and the cohort with uncomplicated STEMI (AOR, 8.74; 95% CI, 6.53-11.70). Conclusions and Relevance: In this study, a small proportion of patients with STEMI treated with primary PCI had late VT or VF. However, late VT or VF with cardiac arrest was rare, particularly in the cohort with uncomplicated STEMI. This information may be useful when determining the optimal timing for hospital discharge after STEMI.

First-line Palliative Chemotherapy for Colorectal Cancer: a Population-based Analysis of Delivery and Outcomes in a Single-payer Health System.

AIMS: Clinical practice guidelines recommend palliative chemotherapy for most patients with metastatic colorectal cancer. However, outcomes observed in the real world compared with patients enrolled in clinical trials have not been sufficiently described. The objective of this study was to evaluate the delivery and outcomes of first-line palliative chemotherapy administered to patients with colorectal cancer in routine clinical practice compared with clinical trials. MATERIALS AND METHODS: Using linked health administrative data, we carried out a retrospective population-level cohort study on patients diagnosed with colorectal cancer in Ontario, Canada from 2010 to 2019. Patient, disease and treatment characteristics were summarised. The primary outcome was median overall survival, stratified by treatment prescribed and age. Demographics and outcomes in this real-world population were compared with those from pivotal clinical trials. A multivariable Cox regression model reporting hazard ratios and 95% confidence intervals was used to determine factors associated with survival in patients receiving systemic treatment. RESULTS: We identified 70 987 patients with a new diagnosis of colorectal cancer, of which 4613 received first-line chemotherapy for unresectable locally advanced or metastatic disease and formed the study cohort. Fifty-eight per cent were male and the mean age was 63 years. Most had colon cancer (69%), at least one comorbidity (73%) and lived in an urban location (79%). Less than half (47%) had surgery after diagnosis. The most common regimen prescribed was folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) with bevacizumab or epidermal growth factor receptor inhibitors (EGFRi; n = 2784, 60%). Among all treated patients, the median overall survival was 17.1 months, with survival difference by regimen [median overall survival 18.3 for FOLFIRI with bevacizumab or EGFRi, 19.6 for folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (XELOX) with bevacizumab or EGFRi, 13.6 for FOLFIRI alone and 7.8 for 5-fluorouracil or capecitabine]. Patients aged >80 years were most likely to have received single-agent 5-fluorouracil or capecitabine, and had inferior overall survival compared with their younger counterparts. Compared with pivotal clinical trials, patients in the real world had inferior overall survival outcomes despite similar demographic characteristics (including age and sex). CONCLUSIONS: In this real-world population-based analysis of patients receiving first-line chemotherapy for unresectable locally advanced or metastatic colorectal cancer, survival outcomes were inferior to those reported in randomised trials despite similarities in age and sex. This information can be used when counselling patients in routine practice about expected outcomes.

Incidence and risk factors of heat-related illness in dogs from New South Wales, Australia (1997-2017).

Heat Related Illness (HRI) in dogs is expected to increase as heatwaves surge due to global warming. The most severe form of HRI, heat stroke, is potentially fatal in dogs. The current study investigated the incidence and risk factors for HRI in dogs in NSW, Australia, from 1997 to 2017. We identified 119 HRI cases during this period, with a fatality rate of 23%. Dog breeds at elevated risk of HRI were Australian Stumpy Tail Cattle Dog, British Bulldog, French Bulldog, Maremma Sheepdog, Italian Greyhound, Chow Chow, Airedale Terrier, Pug, Samoyed, English Springer Spaniel, Labrador Retriever, Golden Retriever, Cavalier King Charles Spaniel, Border Collie, Staffordshire Bull Terrier, and pooled non-Australian National Kennel Council breeds (which included the American and Australian Bulldog) when compared with cross breeds (i.e., the reference variable). As expected, HRI cases were more likely in December and January, during the Australian summer and during hotter years (e.g., 2016). There were no differences in the risk of HRI between males and females nor between desexed or un-desexed dogs; but older dogs were at increased risk of HRI. These findings underscore the need for data collection that will enable the incidence of HRI in dogs to be monitored and to better understand canine risk factors particularly as temperatures will continue to rise due to global warming. The risk of mortality from HRI underpins the need for education programs focussed on prevention and early identification of HRI so that owners present affected dogs to their veterinarian as promptly as possible.

A Prospective Single-Center Brazilian Study Investigating the Efficacy and Safety of Prophylactic Phenylephrine Infusion for the Management of Hypotension During Cesarean Section Under Spinal Anesthesia.

Background Maternal hypotension occurs in up to 80% of parturients during cesarean section (CS) under spinal anesthesia. Phenylephrine, a direct-acting α-1 agonist, has been widely recommended for the prevention of hypotension. We evaluated the efficacy and safety of phenylephrine infusion to prevent hypotension in obese and non-obese patients during cesarean section. Methods One hundred forty-one patients were included in this single-arm study. Patients received prophylactic phenylephrine infusion at a rate of 50 µg/min-1 immediately after spinal local anesthetic injection until delivery. Hypotension was defined as a systolic blood pressure <100 mmHg or <20% of baseline. The primary outcome was the incidence of hypotension. Results The incidence of hypotension was 17%. The median and interquartile range (IQR) of the number of hypotensive episodes was 0 (0-0). It was observed that 79.1% of the patients had hypotension in the first six minutes. Reactive hypertension and bradycardia occurred in 20.5 and 12.7% of the patients, respectively. In addition, there was a higher incidence of bradycardia in pregnant women with a body index mass of < 30 kg/m-2. Patients with baseline systolic blood pressure <120 mmHg had a threefold increased risk of hypotension. The incidence of nausea and vomiting was 13.4 and 2.8%, respectively. The incidence of an Apgar score <7 at the first minute was 2.8%, and no neonates presented an Apgar score <7 at the fifth minute. A pH of <7.2 occurred in 6.3% of the neonates. All neonates had no sequelae and were discharged together with their mothers. Conclusion The prophylactic infusion of phenylephrine 50 µg/min-1 is safe and demonstrates efficacy in reducing maternal hypotension providing adequate maternal hemodynamic stability during CS under spinal anesthesia.

Immuno-PET Imaging of CD69 Visualizes T-Cell Activation and Predicts Survival Following Immunotherapy in Murine Glioblastoma.

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Immunotherapy may be promising for the treatment of some patients with GBM; however, there is a need for noninvasive neuroimaging techniques to predict immunotherapeutic responses. The effectiveness of most immunotherapeutic strategies requires T-cell activation. Therefore, we aimed to evaluate an early marker of T-cell activation, CD69, for its use as an imaging biomarker of response to immunotherapy for GBM. Herein, we performed CD69 immunostaining on human and mouse T cells following in vitro activation and post immune checkpoint inhibitors (ICI) in an orthotopic syngeneic mouse glioma model. CD69 expression on tumor-infiltrating leukocytes was assessed using single-cell RNA sequencing (scRNA-seq) data from patients with recurrent GBM receiving ICI. Radiolabeled CD69 Ab PET/CT imaging (CD69 immuno-PET) was performed on GBM-bearing mice longitudinally to quantify CD69 and its association with survival following immunotherapy. We show CD69 expression is upregulated upon T-cell activation and on tumor-infiltrating lymphocytes (TIL) in response to immunotherapy. Similarly, scRNA-seq data demonstrated elevated CD69 on TILs from patients with ICI-treated recurrent GBM as compared with TILs from control cohorts. CD69 immuno-PET studies showed a significantly higher tracer uptake in the tumors of ICI-treated mice compared with controls. Importantly, we observed a positive correlation between survival and CD69 immuno-PET signals in immunotherapy-treated animals and established a trajectory of T-cell activation by virtue of CD69-immuno-PET measurements. Our study supports the potential use of CD69 immuno-PET as an immunotherapy response assessment imaging tool for patients with GBM. Significance: Immunotherapy may hold promise for the treatment of some patients with GBM. There is a need to assess therapy responsiveness to allow the continuation of effective treatment in responders and to avoid ineffective treatment with potential adverse effects in the nonresponders. We demonstrate that noninvasive PET/CT imaging of CD69 may allow early detection of immunotherapy responsiveness in patients with GBM.

Outcomes of umbilical hernia repair in cirrhotic veterans: a VASQIP study.

PURPOSE: Umbilical hernia repair (UHR) in cirrhotics with ascites is a challenging problem associated with increased morbidity and mortality. This study examines the outcomes of UHR in veterans, comparing those undergoing elective versus emergent repair. METHODS: VASQIP was queried for all UHRs during the period 2008-2015. Data collection included demographics, operative details, Model for End-stage Liver Disease (MELD) score, and postoperative outcomes. Univariate and multivariate regression analyses were performed, and a p value of ≤ 0.05 was considered significant. RESULTS: A total of 383 patients were included in the analysis. Overall, mean age was 58.9, 99.0% were males, mean body mass index (BMI) was 26.7 kg/m2, 98.2% had American Society of Anesthesiologists (ASA) classification ≥ III, and 87.7% had independent functional status. More than 1/3 the patients underwent emergent UHR (37.6%). Compared with the elective UHR group, who underwent emergent repair were older, more likely to be functionally dependent, higher MELD score. Hypoalbuminemia, emergency repair and MELD score were found to be independent predictors of poor outcomes. CONCLUSION: UHR in cirrhotic veterans has worse outcomes when performed emergently. Diagnosis should be followed by medical optimization and elective repair, rather than waiting for an emergent indication in > 1/3 of patients.

Effects of heat stress on markers of skeletal muscle proteolysis in dairy cattle.

Heat stress (HS) markedly affects postabsorptive energetics and protein metabolism. Circulating urea nitrogen increases in multiple species during HS and it has been traditionally presumed to stem from increased skeletal muscle proteolysis; however, this has not been empirically established. We hypothesized HS would increase activation of the calpain and proteasome systems as well as increase degradation of autophagosomes in skeletal muscle. To test this hypothesis, lactating dairy cows (~139 d in milk; parity ~2.4) were exposed to thermal neutral (TN) or HS conditions for 7 d (8 cows/environment). To induce HS, cattle were fitted with electric blankets for the duration of the heating period and the semitendinosus was biopsied on d 7. Heat stress increased rectal temperature (1.3°C) and respiratory rate (38 breaths per minute) while it decreased dry matter intake (34%) and milk yield (32%). Plasma urea nitrogen (PUN) peaked following 3 d (46%) and milk urea nitrogen (MUN) peaked following 4 d of environmental treatment and while both decreased thereafter, PUN and MUN remained elevated compared with TN (PUN: 20%; MUN: 27%) on d 7 of HS. Contrary to expectations, calpain I and II abundance and activation and calpain activity were similar between groups. Likewise, relative protein abundance of E3 ligases, muscle atrophy F-box protein/atrogin-1 and muscle ring-finger protein-1, total ubiquitinated proteins, and proteasome activity were similar between environmental treatments. Finally, autophagosome degradation was also unaltered by HS. Counter to our hypothesis, these results suggest skeletal muscle proteolysis is not increased following 7 d of HS and call into question the presumed dogma that elevated skeletal muscle proteolysis, per se, drives increased AA mobilization.