Effectiveness and safety of early treatment with spironolactone for new-onset acute heart failure.

BACKGROUND: The effectiveness and safety of mineralocorticoid receptor antagonists (MRA) in acute heart failure (HF) is uncertain. We sought to describe the prescription of spironolactone during acute HF and whether early treatment is effective and safe in a real-world setting. METHODS: We performed a retrospective cohort study of adult (≥18 years) nonpregnant patients hospitalized with new-onset HF with reduced ejection fraction (HFrEF, defined by ejection fraction ≤40%) within 15 Kaiser Permanente Southern California medical centers between 2016 and 2021. Early treatment was defined by spironolactone prescription at discharge. The primary effectiveness outcome was a composite of HF readmission or all-cause mortality at 180 days. Safety outcomes were hypotension and hyperkalemia at 90 days. RESULTS: Among 2318 HFrEF patients, 368 (15.9%) were treated with spironolactone at discharge. After 1:2 propensity score matching, 354 early treatment and 708 delayed/no treatment patients were included in the analysis. The median age was 63 (IQR: 52-74) years; 61.6% were male, and 38.6% were White. By 90 days, ~20% had crossed over in the two groups. Early treatment was not associated with the composite outcome at 180 days (HR [95% CI]: 0.81 [0.56-1.17]), but a trend towards benefit by 365 days that did not reach statistical significance (0.78 [0.58-1.06]). Early treatment was also associated with hyperkalemia (subdistribution HR [95% CI]: 2.33 [1.30-4.18]) but not hypotension (0.93 [0.51-1.72]). CONCLUSIONS: Early treatment with spironolactone at discharge for new-onset HFrEF in a real-world setting did not reduce the risk of HF readmission or mortality in the first year after discharge. The risk of hyperkalemia was increased.

Association Between Coronary Artery Disease Testing in Patients with New-Onset Heart Failure and Heart Failure Readmission and Mortality.

BACKGROUND: In patients with new-onset heart failure (HF), coronary artery disease (CAD) testing remains underutilized. Whether widespread CAD testing in patients with new-onset HF leads to improved outcomes remains to be determined. OBJECTIVE: We sought to examine whether CAD testing, and its timing, among patients hospitalized with new-onset HF with reduced ejection fraction (HFrEF), is associated with improved outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: Adult (≥ 18 years) non-pregnant patients with new-onset HFrEF hospitalized within one of 15 Kaiser Permanente Southern California medical centers between 2016 and 2021. Key exclusion criteria included history of heart transplant, hospice, and a do-not-resuscitate order. MAIN MEASURES: Primary outcome was a composite of HF readmission or all-cause mortality through end of follow-up on 12/31/2022. KEY RESULTS: Among 2729 patients hospitalized with new-onset HFrEF, 1487 (54.5%) received CAD testing. The median age was 66 (56-76) years old, 1722 (63.1%) were male, and 1074 (39.4%) were White. After a median of 1.8 (0.6-3.4) years, the testing group had a reduced risk of HF readmission or all-cause mortality (aHR [95%CI], 0.71 [0.63-0.79]). These results were consistent across subgroups by history of atrial fibrillation, diabetes, renal disease, myocardial infarction, and elevated troponin during hospitalization. In a secondary analysis where CAD testing was further divided to early (received testing before discharge) and late testing (up to 90 days after discharge), there was no difference in late vs early testing (0.97 [0.81-1.16]). CONCLUSIONS: In a contemporary and diverse cohort of patients hospitalized with new-onset HFrEF, CAD testing within 90 days of hospitalization was associated with a lower risk of HF readmission or all-cause mortality. Testing within 90 days after discharge was not associated with worse outcomes.

Mechanical and thermal properties of mud dauber nests under atmospheric drying.

Mud dauber wasps construct soil nests to protect their offspring from predators, extreme temperatures, and rainwater. The mechanical and thermal properties of these nests are important for the reproductive success of mud daubers. The previous study showed that the high densities and strengths of mud dauber nests were due to the repetitive tapping and atmospheric drying used by mud daubers during nest construction. This study investigated the effect of atmospheric drying on the mechanical and thermal properties of mud dauber nests. The soil shrinkage curve, elastic modulus, suction stress characteristic curve, soil water retention curve, shear strength, and thermal conductivity function of mud dauber nest soils were measured by performing drying cake tests, direct shear tests, unconfined compression tests, and thermal conductivity measurements. This study showed atmospheric drying could increase Young's moduli (from hundreds to thousands of kPa), the magnitudes of suction stress (up to 64 kPa), and shear strengths (e.g., unconfined compressive strength increased up to 2100 kPa) of mud dauber nests. The thermal conductivity was reduced by 47% due to atmospheric drying. Investigation of mud dauber nests under atmospheric drying could provide insights and inspiration to improve human manufacturing and manipulation of soils for earthen building construction.

Development and validation of the COVID-19 Hospitalized Patient Deterioration Index.

OBJECTIVES: To develop a COVID-19-specific deterioration index for hospitalized patients: the COVID Hospitalized Patient Deterioration Index (COVID-HDI). This index builds on the proprietary Epic Deterioration Index, which was not developed for predicting respiratory deterioration events among patients with COVID-19. STUDY DESIGN: A retrospective observational cohort was used to develop and validate the COVID-HDI model to predict respiratory deterioration or death among hospitalized patients with COVID-19. Deterioration events were defined as death or requiring high-flow oxygen, bilevel positive airway pressure, mechanical ventilation, or intensive-level care within 72 hours of run time. The sample included hospitalized patients with COVID-19 diagnoses or positive tests at Kaiser Permanente Southern California between May 3, 2020, and October 17, 2020. METHODS: Machine learning models and 118 candidate predictors were used to generate benchmark performance. Logit regression with least absolute shrinkage and selection operator and physician input were used to finalize the model. Split-sample cross-validation was used to train and test the model. RESULTS: The area under the receiver operating curve was 0.83. COVID-HDI identifies patients at low risk (negative predictive value [NPV] > 98.5%) and borderline low risk (NPV > 95%) of an event. Of all patients, 74% were identified as being at low or borderline low risk at some point during their hospitalization and could be considered for discharge with or without home monitoring. A high-risk group with a positive predictive value of 51% included 12% of patients. Model performance remained high in a recent cohort of patients. CONCLUSIONS: COVID-HDI is a parsimonious, well-calibrated, and accurate model that may support clinical decision-making around discharge and escalation of care.

Disease-Specific Factors Associated with Readmissions or Mortality After Hospital Discharge in COVID-19 Patients: a Retrospective Cohort Study.

BACKGROUND: Understanding the implications of disease-specific factors beyond baseline patient characteristics for coronavirus disease 2019 (COVID-19) may allow for identification of indicators for safe hospital discharge. OBJECTIVE: Assess whether disease-specific factors are associated with adverse events post-discharge using a data-driven approach. DESIGN: Retrospective cohort study. SETTING: Fifteen medical centers within Kaiser Permanente Southern California. PARTICIPANTS: Adult patients (n=3508) discharged alive following hospitalization for COVID-19 between 05/01/2020 and 09/30/2020. INTERVENTIONS: None. MAIN MEASURES: Adverse events defined as all-cause readmission or mortality within 14 days of discharge. Least absolute shrinkage and selection operator (LASSO) was used for variable selection and logistic regression was performed to estimate odds ratio (OR) and 95% confidence interval (CI). KEY RESULTS: Four variables including age, Elixhauser index, treatment with remdesivir, and symptom duration at discharge were selected by LASSO. Treatment with remdesivir was inversely associated with adverse events (OR: 0.46 [95%CI: 0.36-0.61]), while symptom duration ≤ 10 days was associated with adverse events (OR: 2.27 [95%CI: 1.79-2.87]) in addition to age (OR: 1.02 [95%CI: 1.01-1.03]) and Elixhauser index (OR: 1.15 [95%CI: 1.11-1.20]). A significant interaction between remdesivir and symptom duration was further observed (p=0.01). The association of remdesivir was stronger among those with symptom duration ≤10 days vs >10 days at discharge (OR: 0.30 [95%CI: 0.19-0.47] vs 0.62 [95%CI: 0.44-0.87]), while the association of symptom duration ≤ 10 days at discharge was weaker among those treated with remdesivir vs those not treated (OR: 1.31 [95%CI: 0.79-2.17] vs 2.71 [95%CI 2.05-3.59]). CONCLUSIONS: Disease-specific factors including treatment with remdesivir, symptom duration, and their interplay may help guide clinical decision making at time of discharge.

Real-world use patterns of angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) among patients with heart failure within a large integrated health system.

BACKGROUND: Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that is now preferred in guidelines over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with heart failure with reduced ejection fraction (HFrEF). However, it has not been broadly adopted in clinical practice. OBJECTIVE: To characterize ARNI use within a large diverse real-world population and assess for any racial disparities. METHODS: We conducted a cross-sectional study within Kaiser Permanente Southern California. Adult patients with HFrEF who received ARNIs, ACEIs, or ARBs between January 1, 2014, and November 30, 2020, were identified. The prevalence of ARNI use among the cohort and patient characteristics by ARNIs vs ACEIs/ARBs use were described. Multivariable regression was performed to estimate odds ratios and 95% CIs of receiving ARNI by race and ethnicity. RESULTS: Among 12,250 patients with HFrEF receiving ACEIs, ARBs, or ARNIs, 556 (4.54%) patients received ARNIs. ARNI use among this cohort increased from 0.02% in 2015 to 7.48% in 2020. Patients receiving ARNIs were younger (aged 62 vs 69 years) and had a lower median ejection fraction (27% vs 32%) compared with patients receiving ACEIs/ARBs. They also had higher use of mineralocorticoid antagonists (24.1% vs 19.8%) and automatic implantable cardioverterdefibrillators (17.4% vs 13.3%). There were no significant differences in rate of ARNI use by race and ethnicity. CONCLUSIONS: Within a large diverse integrated health system in Southern California, the rate of ARNI use has risen over time. Patients given ARNIs were younger with fewer comorbidities, while having worse ejection fraction. Racial minorities were no less likely to receive ARNIs compared with White patients. DISCLOSURES: Dr Huang had stock ownership in Gilead and Pfizer. Dr Liang received support for article processing and medical writing.

Association Between Dexamethasone Treatment After Hospital Discharge for Patients With COVID-19 Infection and Rates of Hospital Readmission and Mortality.

Importance: Current guidelines recommend use of dexamethasone, 6 mg/d, up to 10 days or until discharge for patients hospitalized with COVID-19. Whether patients who received less than 10 days of corticosteroids during hospitalization for COVID-19 benefit from continuing treatment at discharge has not been determined. Objective: To assess whether continuing dexamethasone treatment at discharge is associated with reduced all-cause readmissions or mortality postdischarge. Design, Setting, and Participants: A retrospective cohort study was conducted at 15 medical centers within Kaiser Permanente Southern California. The population included adults who received less than 10 days of dexamethasone, 6 mg/d, until discharge during hospitalization for COVID-19 and were discharged alive between May 1 and September 30, 2020. Exposures: Continued dexamethasone treatment at discharge. Main Outcomes and Measures: All-cause readmissions or mortality within 14 days from discharge. Results: A total of 1164 patients with a median age of 55 (IQR, 44-66) years were identified. Most patients were of Hispanic ethnicity (822 [70.6%]) and male (674 [57.9%]) and required oxygen support during hospitalization (1048 [90.0%]). Of the 1164 patients, 692 (59.5%) continued dexamethasone, 6 mg/d, at discharge. A balanced cohort was created using propensity score and inverse probability of treatment weighting. The adjusted odds ratio (OR) for readmissions or mortality within 14 days was 0.87 (95% CI, 0.58-1.30) for patients who continued dexamethasone therapy at discharge compared with those who did not. Similar results were produced by a sensitivity analysis that restricted the treatment group to those who received exactly 10 days of dexamethasone (OR, 0.89; 95% CI, 0.55-1.43) and by subgroup analyses stratified by the duration of dexamethasone treatment as an inpatient (1-3 days: OR, 0.71; 95% CI, 0.43-1.16; 4-9 days: OR, 1.01; 95% CI, 0.48-2.12), oxygen requirement at discharge (room air: OR, 0.91; 95% CI, 0.53-1.59; supplemental oxygen use: OR, 0.76; 95% CI, 0.42-1.37), and disease duration at discharge (≤10 days: OR, 0.81; 95% CI, 0.49-1.33; >10 days: OR, 0.94; 95% CI, 0.48-1.86). Conclusions and Relevance: In this cohort study of patients with COVID-19, continuing treatment with dexamethasone, 6 mg/d, at discharge was not associated with a reduction in 14-day all-cause readmission or mortality. This finding suggests that dexamethasone should not be routinely prescribed beyond discharge for individuals with COVID-19.

Investigating physical and mechanical properties of nest soils used by mud dauber wasps from a geotechnical engineering perspective.

The quality of nest soils has significant effects on reproductive success in mud dauber species. This study investigated the physical and mechanical properties of the nest soils used by mud daubers from a geotechnical engineering perspective. One hundred thirty-one nests of black and yellow mud daubers were collected from five locations in the south of Louisiana. Moisture and organic contents, densities, void ratios, plasticity, grain size distributions, soil classifications, and penetration resistances of the nest soils were measured. Also, the performance of mud daubers' nest-compaction method (i.e., repetitive tapping produced by the front legs and mandibles) was evaluated by comparing the densities and penetration resistances between mud dauber nests and Proctor compacted nest soil samples. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction were used to measure the morphology, elemental composition, and mineralogy of the nest soils. Mud dauber nests were made of hard and very stiff well-graded silty soils. The high strengths and high densities of mud dauber nests were attributed to repetitive tapping (similar to vibratory compaction in geotechnical engineering) used by mud daubers for nest construction, high capillary cohesion in the nest soils, well-graded soil grain size distribution, and clay minerals serving as cementing agents in the nest soils.

Early outcomes of video-assisted thoracic surgery (VATS) Ivor Lewis operation for esophageal squamous cell carcinoma: the extracorporeal anastomosis technique.

PURPOSE: Although the use of a minimally invasive approach in esophageal cancer surgery is gradually increasing, it is generally performed using cervical anastomosis because of the difficulty of intrathoracic anastomosis. Here, we describe our technique for performing intrathoracic esophagogastrostomy using a typical video-assisted thoracic surgery (VATS) approach. METHODS: Between September 2009 and July 2011, VATS esophagectomy and intrathoracic anastomosis was performed in 31 esophageal cancer patients with a utility incision made by a segmental rib resection to enhance the extracorporeal insertion of the end-to-end stapler. We retrospectively reviewed the clinical records of these patients. RESULTS: There were no intraoperative events related to the VATS procedure. The mean VATS time was 180.2 ± 39.2 min. The mean postoperative hospital stay was 15.2 days (range, 11 to 38 d). No significant pulmonary complications were observed. Five patients developed vocal cord palsy due to radical mediastinal lymphadenectomy. No anastomotic complications such as leaking or stricture were observed. Only 1 patient had postoperative pain requiring analgesics. CONCLUSIONS: Our technique can be safely and effectively performed for intrathoracic anastomosis in esophageal surgery with favorable early outcomes and reduced postoperative pulmonary complications.

Alteration of the ß-catenin pathway in spiradenoma.

BACKGROUND: Although skin carcinogenesis has been widely investigated, only limited information is available for epidermal tumors, while even less is known about other skin structures. Alterations in the ß-catenin pathway have been reported in several epidermal tumors, while little is known about in adnexal tumors. This study was performed to assess alterations in the ß-catenin pathway associated with adnexal tumors, and to investigate the mechanisms underlying these alterations. METHODS: ß-Catenin expression in 48 adnexal tumors (trichoepithelioma, trichofolliculoma, pilomatricoma, syringoma, eccrine poroma, spiradenoma, sebaceous hyperplasia and nevus sebaceus) was assessed using immunohistochemistry. The tumors showing intense nuclear reactivity for ß-catenin were further evaluated by immunohistochemistry for ß-catenin degradation complex such as adenomatosis polyposis coli (APC), Axin and glycogen synthase kinase 3ß (GSK-3ß). RESULTS: Intense nuclear immunoreactivity for ß-catenin was observed in pilomatricoma and spiradenoma. Among 12 eccrine spiradenomas, APC was downregulated in 2 (16.7%) cases, and Axin and GSK-3ß were downregulated in 11 (91.7%) and 10 (83.3%) cases, respectively. CONCLUSIONS: This is the first reported analysis of the role of alterations in the ß-catenin pathway in spiradenoma. We suggest that downregulation of Axin and GSK-3ß in the ß-catenin pathway may be an important signaling alteration in the development of spiradenoma.