Interhospital variability in cardiac rehabilitation use after cardiac surgery among Medicare beneficiaries.

OBJECTIVE: Despite guideline recommendation, cardiac rehabilitation (CR) after cardiac surgery remains underused, and the extent of interhospital variability is not well understood. This study evaluated determinants of interhospital variability in CR use and outcomes. METHODS: This retrospective cohort study included 166,809 Medicare beneficiaries undergoing cardiac surgery who were discharged alive between July 1, 2016, and December 31, 2018. CR participation was identified in outpatient facility claims within a year of discharge. Hospital-level CR rates were tabulated, and multilevel models evaluated the extent to which patient, organizational, and regional factors accounted for interhospital variability. Adjusted 1-year mortality and readmission rates were also calculated for each hospital quartile of CR use. RESULTS: Overall, 90,171 (54.1%) participated in at least 1 CR session within a year of discharge. Interhospital CR rates ranged from 0.0% to 96.8%. Hospital factors that predicted CR use included nonteaching status and lower-hospital volume. Before adjustment for patient, organizational, and regional factors, 19.3% of interhospital variability was attributable to the admitting hospital. After accounting for covariates, 12.3% of variation was attributable to the admitting hospital. Patient (0.5%), structural (2.8%), and regional (3.7%) factors accounted for the remaining explained variation. Hospitals in the lowest quartile of CR use had greater adjusted 1-year mortality rates (Q1 = 6.7%, Q4 = 5.2%, P < .001) and readmission rates (Q1 = 37.6%, Q4 = 33.9%, P < .001). CONCLUSIONS: Identifying best practices among high CR use facilities and barriers to access in low CR use hospitals may reduce interhospital variability in CR use and advance national improvement efforts.

The relationship between discharge location and cardiac rehabilitation use after cardiac surgery.

BACKGROUND: Cardiac rehabilitation (CR) is a guideline-recommended risk-reduction program offered to cardiac surgical patients. Despite CR's association with better outcomes, attendance remains poor. The relationship between discharge location and CR use is poorly understood. METHODS: This study was a nationwide, retrospective cohort analysis of Medicare fee-for-service claims for beneficiaries undergoing coronary artery bypass grafting and/or surgical aortic valve repair between July 1, 2016, and December 31, 2018. The primary outcome was attendance of any CR session. Discharge location was categorized as home discharge or discharge to extended care facility (ECF) (including skilled nursing facility, inpatient rehabilitation, and long-term acute care). Multivariable logistic regression models evaluated the association between discharge location, CR attendance, and 1-year mortality. RESULTS: Of the 167,966 patients who met inclusion criteria, 34.1% discharged to an ECF. Overall CR usage rate was 53.9%. Unadjusted and adjusted CR use was lower among patients discharged ECFs versus those discharged home (42.1% vs 60.0%; adjusted odds ratio, 0.66; P < .001). Patients discharged to long-term acute care were less likely to use CR than those discharged to skilled nursing facility or inpatient rehabilitation (reference category: home; adjusted odds ratio for long-term acute care, 0.36, adjusted odds ratio for skilled nursing facility, 0.69, and adjusted odds ratio for inpatient rehabilitation, 0.71; P < .001). CR attendance was associated with a greater reduction in adjusted 1-year mortality in patients discharged to ECFs (9.7% reduction) versus those discharged home (4.3% reduction). CONCLUSIONS: In this national analysis of Medicare beneficiaries, discharge to ECF was associated with lower CR use, despite a greater association with improved 1-year mortality. Interventions aimed at increasing CR enrollment at ECFs may improve CR use and advance surgical quality.

Cardiac Rehabilitation Reduces 2-Year Mortality After Coronary Artery Bypass Grafting.

BACKGROUND: Cardiac rehabilitation (CR) is a supervised outpatient exercise and risk reduction program offered to patients who have undergone coronary revascularization procedures. Multiple professional societal guidelines support the use of CR after coronary artery bypass grafting (CABG) based on studies in combined percutaneous coronary intervention and CABG populations with surrogate outcomes. This statewide analysis of patients undergoing CABG evaluated the relationship between CR use and long-term mortality. METHODS: Medicare fee-for-service claims were linked to surgical data for patients discharged alive after isolated CABG from January 1, 2015, through September 30, 2019. Outpatient facility claims were used to identify any CR use within 1 year of discharge. Death within 2 years of discharge was the primary outcome. Mixed-effects logistic regression was used to predict CR use, adjusting for a variety of comorbidities. Unadjusted and inverse probability treatment weighting (IPTW) were used to compare 2-year mortality among CR users vs nonusers. RESULTS: A total of 3848 of 6412 patients (60.0%) were enrolled in CR for an average of 23.2 (SD, 12.0) sessions, with 770 of 6412 (12.0%) completing all recommended 36 sessions. Logistic regression identified increasing age, discharge to home (vs extended care facility), and shorter length of stay as predictors of postdischarge CR use (P < .05). Unadjusted and IPTW analyses showed significant reduction in 2-year mortality in CR users compared with CR nonusers (unadjusted: 9.4% reduction; 95% CI, 10.8%-7.9%; P < .001; IPTW: -4.8% reduction; 95% CI, 6.0%-3.5%; P < .001). CONCLUSIONS: These data suggest that CR use is associated with lower 2-year mortality. Future quality initiatives should consider identifying and addressing root causes of poor CR enrollment and completion.

Role of IL4 and GMCSF in Predicting Survival in Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study's objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients. STUDY DESIGN: A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma). RESULTS: Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p < 0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040). CONCLUSIONS: These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.

Interhospital variability in failure to rescue rates following aortic valve surgery.

Objective: This study evaluated interhospital variability and determinants of failure-to-rescue for patients undergoing surgical aortic valve replacement. Methods: An observational study was conducted among 28,842 patients undergoing aortic valve replacement with or without coronary artery bypass grafting between July 2011 and June 2017 across 90 hospitals participating in the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Postoperative complications were defined as major (stroke, renal failure, reoperation, prolonged ventilation, sternal infection) and overall (major plus 14 other morbidities). Hospital terciles of observed to expected (O/E) mortality were compared on crude rates of major and overall complications, operative mortality, and failure to rescue (among major and overall complications). The correlation between hospital observed and expected failure-to-rescue rates was assessed. Results: Median Society of Thoracic Surgeons Adult Cardiac Surgery Database predicted mortality risk was similar across hospital O:E mortality terciles (P = .10). As expected, mortality rates significantly increased across terciles (low O/E tercile: 1.6%, high O/E tercile: 4.7%; P < .001). Failure-to-rescue rates increased substantially across hospital mortality terciles among patients with major (low tercile, 8.8% and high tercile, 20.8%) and overall (low tercile, 3.0% and high tercile, 8.9%) complications. Hospital-level expected failure to rescue had a higher correlation with observed complications for overall complications (R2 = 0.71) compared with Society of Thoracic Surgeons major complications (R2 = 0.24). Conclusions: Considerable interhospital variation exists in failure-to-rescue rates following aortic valve replacement. Hospitals in the low O/E mortality tercile experience failure to rescue nearly one-third less than those in the high O/E mortality tercile. Efforts to advance quality will benefit from identifying and disseminating optimal rescue strategies in this patient population.

Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair.

Macrophage plasticity is critical for normal tissue repair following injury. In pathologic states such as diabetes, macrophage plasticity is impaired, and macrophages remain in a persistent proinflammatory state; however, the reasons for this are unknown. Here, using single-cell RNA sequencing of human diabetic wounds, we identified increased JMJD3 in diabetic wound macrophages, resulting in increased inflammatory gene expression. Mechanistically, we report that in wound healing, JMJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 signaling. However, in the diabetic state, we found that IL-6, a cytokine increased in diabetic wound tissue at later time points post-injury, regulates JMJD3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JMJD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 mechanism. Interestingly, RNA sequencing of wound macrophages isolated from mice with JMJD3-deficient myeloid cells (Jmjd3f/fLyz2Cre+) identified that the STING gene (Tmem173) is regulated by JMJD3 in wound macrophages. STING limits inflammatory cytokine production by wound macrophages during healing. However, in diabetic mice, its role changes to limit wound repair and enhance inflammation. This finding is important since STING is associated with chronic inflammation, and we found STING to be elevated in human and murine diabetic wound macrophages at late time points. Finally, we demonstrate that macrophage-specific, nanoparticle inhibition of JMJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and STING. Taken together, this work highlights the central role of JMJD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.

Development of malignancies and their outcomes in patients supported on continuous-flow left ventricular assist devices-a systematic review.

BACKGROUND: With increased use of continuous-flow left ventricular assist devices (CF-LVAD), development of malignant tumors in this population is not uncommon. We sought to evaluate malignancies in CF-LVAD patients and evaluate the outcomes of treatment strategies. METHODS: Overall, 18 articles consisting of 28 patients were identified who developed malignancies after CF-LVAD placement. Patient-level data were extracted for systematic review. RESULTS: Median patient age was 60 years [59-67] and 85.7% (24/28) were male. CF-LVAD was placed as bridge-to-transplant (BTT) in 60.9% (14/23) of patients. The three most common malignancy types were GI in 35.7% (10/28) of patients, lung in 21.4% (6/28) and skin in 10.7% (3/28). Median time from CF-LVAD implant to malignancy diagnosis was 6.9 [2.5-12.8] months. Metastatic disease occurred in 17.9% (5/28) over a median time of 5.0 [1.0-82.0] months from the diagnosis. Surgical resection of the malignancy was performed in 57.1% (16/28) of patients. Our results showed that while there was a significantly higher probability of survival among patients who underwent surgery versus those who did not, when only stage I and II patients were included in the analysis, this difference was no longer statistically significant. Three patients were relisted for heart transplant after surgical treatment, and two received the transplant. CONCLUSIONS: Surgical management of malignancies in patients on CF-LVADs may improve survival and transplant eligibility status, therefore, a CF-LVAD should not always preclude surgical treatment.

Bernard J. Miller: MD, ScD. (Hon), FACS: Lifelong Surgeon-Scientist and Critical Contributor to the Gibbon Heart-Lung Machine.

Bernard J. Miller, MD, ScD. (Hon), FACS, is known as a critical contributor for his work in the John H. Gibbon, MD, laboratory for his work on the heart-lung machine (HLM). In this setting, Dr. Miller developed the fluid control servo system, which was necessary to prevent malfunctioning of the HLM and prevent air emboli. Additionally, Dr. Miller assisted in conceiving and testing the left ventricular vent, the positive-negative pressure ventilator, and the HLM oxygenator; these inventions were all the product of extensive collaboration between the International Business Machines Corporation and the members of Dr. Gibbon's laboratory. Furthermore, Dr. Miller was a surgical assistant and perfusionist in the first successful open-heart surgery. Herein, we seek to describe Dr. Miller's story and his contributions to the HLM, as well as the contributions that were developed by the laboratory at that time. Additionally, we describe critical events leading up to the first successful use of the HLM on May 6, 1953, including a previously unreported use of the HLM for partial bypass of the right heart at Pennsylvania Hospital in 1952. Finally, we present the rest of Dr. Miller's professional and personal successes after his work on the HLM ended.

The Pathway to Low Outlier Status in Venous Thromboembolism Events: An Analysis of Pancreatic Surgery in the National Surgical Quality Improvement Program.

Purpose: Our institution's hepatopancreaticobiliary surgery service (HPBS) has demonstrated low rates of venous thromboembolism (VTE). We sought to determine whether the HPBS's regimented multimodal VTE prophylaxis pathway, which includes the use of mechanical prophylaxis, pharmacological prophylaxis, and ambulation, plays a role in achieving low VTE rates. Methods: We compared pancreatic surgeries in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) participant user file with our institution's data from 2011 to 2016 using univariate, multivariate, and matching statistics. Results: Among 36,435 NSQIP operations, 850 (2.3%) underwent surgery by the HPBS. The HPBS achieved lower VTE rates than the national cohort (2.0% vs. 3.5%, p = 0.018). Upon multivariate analysis, having an operation performed by the HPBS independently conferred lower odds of VTE incidence in the matched cohort (odds ratio = 0.530, p = 0.041). Conclusions: We identified an independent correlation between the HPBS and decreased VTE incidence, which we believe to be due to strict adherence to and team participation in a high risk VTE prophylaxis pathway, including inpatient pharmacological prophylaxis, thromboembolic deterrent stockings, sequential compression devices, and mandatory ambulation.

Is nonoperative management of partial distal biceps tears really successful?

BACKGROUND: The current treatment of partial distal biceps tears is a period of nonoperative management, followed by surgery, if symptoms persist. Little is known about the success rate and outcomes of nonoperative management of this illness. METHODS: We identified 132 patients with partial distal biceps tears through an International Classification of Diseases, Ninth Revision code query of our institution's database. Patient records were reviewed to abstract demographic information and confirm partial tears of the distal biceps tendon based on clinical examination findings and confirmatory magnetic resonance imaging (MRI). Seventy-four patients completed an outcome survey. RESULTS: In our study, 55.7% of the contacted patients who tried a nonoperative course (34 of 61 patients) ultimately underwent surgery, and 13 patients underwent immediate surgery. High-need patients, as defined by occupation, were more likely to report that they recovered ideally if they underwent surgery, as compared with those who did not undergo surgery (odds ratio, 11.58; P = .0138). For low-need patients, the same analysis was not statistically significant (P = .139). There was no difference in satisfaction scores between patients who tried a nonoperative course before surgery and those who underwent immediate surgery (P = .854). An MRI-diagnosed tear of greater than 50% was a predictor of needing surgery (odds ratio, 3.0; P = .006). CONCLUSIONS: This study has identified clinically relevant information for the treatment of partial distal biceps tears, including the following: the failure rate of nonoperative treatment, the establishment of MRI percent tear as a predictor of failing nonoperative management, the benefit of surgery for the high-need occupational group, and the finding that nonoperative management does not negatively affect outcome if subsequent surgery is necessary.

Genetic Drivers of Pancreatic Cancer Are Identical Between the Primary Tumor and a Secondary Lesion in a Long-Term (>5 Years) Survivor After a Whipple Procedure.

Background: A new mass in the remnant pancreas of a patient with previously resected pancreatic ductal adenocarcinoma (PDA) typically represents either a recurrence of the initial primary tumor or a second primary tumor. Recent advances in next-generation sequencing (NGS) strategies allow us to compare the genetic makeup of primary and secondary lesions. Case presentation: A 50-year-old Caucasian female presented for a surgical evaluation of a new biopsy-proven PDA at the junction of the body and tail of the pancreas. Six years prior, in 2011, the patient was found to have a T3N0M0 PDA of the pancreatic head, which was surgically resected with a classic Whipple procedure and concurrent hemicolectomy. Pathology showed pancreatic intraepithelial neoplasia grade 2 and PDA with negative surgical margins, positive perineural spread, and negative lymphovascular spread, and the patient received adjuvant chemotherapy and local radiation. In 2017, she was diagnosed with a new PDA lesion in the remaining pancreatic body far from the previous anastomosis site and was taken to surgery for a completion pancreatectomy and revision of the gastrojejunostomy. NGS was performed on both specimens. Both lesions shared identical mutations in KRAS, TP53, and CDKN2A genes. Amplifications of MYC and mutant KRAS were identified in the 2017 tumor and an ACVR1B mutation was identified in the 2011 tumor, but was not found in the 2017 tumor. Conclusions: This case demonstrates the ability to evaluate similarities between key genetic drivers from a resected primary tumor and a PDA lesion that presented in the same patient 6 years later. Histological analysis and NGS can be used to understand potential differences and similarities between lesions and may be useful in future studies as predictive markers or to provide insight into resistance mechanisms (e.g., MYC amplification).