Comparison of failure to rescue in younger versus elderly patients following lung cancer resection.

Objective: Failure to rescue (FTR), defined as in-hospital death following a major complication, has been increasingly studied in patients who undergo cardiothoracic surgery. This study tested the hypothesis that elderly patients undergoing lung cancer resection have greater rates of FTR compared with younger patients. Methods: Patients who underwent surgery for primary lung cancer between 2011 and 2020 and had at least 1 major postoperative complication were identified using the National Surgical Quality Improvement Program database. Patients who died following complications (FTR) were compared with those who survived in an elderly (80+ years) and younger (<80 years) cohort. Results: Of the 2823 study patients, the younger cohort comprised 2497 patients (FTR: n = 139 [5.6%]), whereas the elderly cohort comprised 326 patients (FTR: n = 39 [12.0%]). Pneumonia was the most common complication in younger (877/2497, 35.1%) and elderly patients (118/326, 36.2%) but was not associated with FTR on adjusted analysis. Increasing age was associated with FTR (adjusted odds ratio [AOR], 1.55 per decade, P < .001), whereas unplanned reoperation was associated with reduced risk (AOR, 0.55, P = .01). Within the elderly cohort, surgery conducted by a thoracic surgeon was associated with lower FTR risk (AOR, 0.29, P = .028). Conclusions: FTR following lung cancer resection was more frequent with increasing age. Pneumonia was the most common complication but not a predictor of FTR. Unplanned reoperation was associated with reduced FTR, as was treatment by a thoracic surgeon for elderly patients. Surgical therapy for complications after lung cancer resection and elderly patients managed by a thoracic specialist may mitigate the risk of death following an adverse postoperative event.

Surgical outcomes of patients at prohibitive risk who are reconsidered for surgery.

Objectives: Transcatheter treatment of advanced mitral and tricuspid valve disease is largely limited to patients at prohibitive surgical risk, although many are not candidates for transcatheter treatment. Here, we describe surgical outcomes of patients at prohibitive risk who were ineligible for transcatheter therapies to guide surgeons in management of this unique population. Methods: Patients at prohibitive risk, defined per surgeon or cardiologist discretion, who were initially referred for a transcatheter mitral or tricuspid intervention in a multidisciplinary atrioventricular valve clinic, were identified from 2019 to 2022. Preoperative risk, operative outcomes, and long-term mortality were evaluated. Results: A total of 337 patients at prohibitive risk were referred for evaluation in a multidisciplinary atrioventricular valve clinic. Of those, 161 underwent transcatheter therapy, 130 patients underwent continued medical management, and 45 were reevaluated and had high-risk surgery. Among surgical patients, 51% were women with a median age of 76 years (quartile 1-quartile 3, 65-81 years). Most patients presented in heart failure (83%; n = 37 out of 45), and 73% were in New York Heart Association functional class III or IV. Most patients (94%; n = 43) had a mitral valve intervention, of whom 56% (24 out of 43) had a mitral valve replacement. The 30-day mortality rate was 4% (2 out of 45) and major morbidity occurred in 33% (15 out of 45). By Kaplan-Meier analysis, 1-year survival was 86% ± 9%. Conclusions: Select patients at prohibitive risk who were ineligible for transcatheter mitral or tricuspid valve intervention underwent surgery with overall low operative mortality and excellent 1-year survival. Patients a prohibitive risk whose anatomy is not amenable to transcatheter devices should be reconsidered for surgery.

Impact of guideline therapy on survival of patients with stage I-III epithelioid mesothelioma.

Background: Modern treatment guidelines recommend multimodal therapy with at least chemotherapy and surgery for patients with potentially resectable epithelioid mesothelioma. This study evaluated guideline compliance for patients with stage I-III epithelioid mesothelioma and tested the hypothesis that guideline-concordant therapy improved survival. Methods: The National Cancer Database was queried for patients with stage I-III epithelioid malignant pleural mesothelioma between 2004 and 2016. The impact of therapy was evaluated using logistic regression, Kaplan-Meier analysis, Cox-proportional hazards analysis, and propensity-scoring methods. Results: During the study period, guideline-concordant therapy was used in 677 patients (19.1%), and 2,857 patients (80.8%) did not have guideline-concordant therapy. Younger age, being insured, living in a census tract with a higher income, clinical stage, and being treated at an academic or research program were all predictors of receiving guideline-concordant therapy in multivariable analysis. Guideline-concordant therapy yielded improved median survival [24.7 (22.4-26.1) vs. 13.7 (13.2-14.4) months] and 5-year survival [17.7% (14.7-21.3%) vs. 8.0% (7.0-9.3%)] (P<0.001), and continued to be associated with better survival in both multivariable analysis and propensity-matched analysis. In the patients who received guideline therapy, median survival [24.9 (21.9-27.2) vs. 24.5 (21.7-28.1) months] and 5-year survival [14.9% (10.9-20.2%) vs. 20.1% (16.0-25.4%)] was not significantly different between patients who underwent induction (n=304) versus adjuvant (n=373) chemotherapy (P=0.444). Conclusions: Guideline-concordant therapy for potentially resectable epithelioid mesothelioma is associated with significantly improved survival but used in a minority of patients. The timing of chemotherapy with surgery in this study did not have a significant impact on overall survival.

Skilled Nursing Facility Quality Rating and Surgical Outcomes Following Coronary Artery Bypass Grafting.

Centers for Medicare and Medicaid Services created a 5-star quality rating system to evaluate skilled nursing facilities (SNFs). Patient discharge to lower-star quality SNFs has been shown to adversely impact surgical outcomes. Recent data has shown that over 20% of patients are discharged to an SNF after CABG, but the link between SNF quality and CABG outcomes has not been established. The purpose of this study is to evaluate the impact of SNF quality ratings on postoperative outcomes after CABG. Retrospective cohort review of Medicare patients undergoing CABG and discharged to an SNF between the years 2016-2017. Patients were categorized into 3 groups according to the star rating of the SNF with receipt of care after discharge (ie, below average, average, above average). Risk-adjusted 30-day to 1-year outcomes of mortality, readmission, and SNF length of stay were calculated and compared using multivariable logistic regression and Poisson models across SNF quality categories. Of the 73,164 Medicare patients in our sample, 15,522 (21.2%) were discharged to an SNF. Patients in below average SNFs were more likely to be younger, Black, Medicare/Medicaid dual eligible, and have more comorbidities. Compared to above average SNFs, patients discharged to below average SNFs experienced higher risk-adjusted 30-day mortality (2.1% vs 1.6%, P<0.02), readmission (21.6% vs 19.3%, P<0.01) and SNF length of stay (17.3d vs 16.5d, P<0.0001). Within 90-days, below average SNFs experienced higher risk-adjusted readmission rates (31.7% vs 30.0%, P<0.004). Outcomes at 1-year were not statistically significant. Medicare beneficiaries discharged to lower quality SNFs experienced worse postoperative outcomes after CABG. Identifying best practices at high performing SNFs, to potentially implement at low performing facilities, may improve equitable care for patients.

Early Discharge After Lobectomy for Lung Cancer Does Not Equate to Early Readmission.

BACKGROUND: Enhanced recovery after surgery pathways in several specialties reduce length of stay, but accelerated discharge after thoracic surgery is not well characterized. This study tested the hypothesis that patients discharged on postoperative day 1 (POD1) after lobectomy for lung cancer have an increased risk of readmission. METHODS: Patients who underwent a lobectomy for lung cancer between 2011 and 2019 in the American College of Surgeons National Surgical Quality Improvement Program database were identified. Readmission rates were compared between patients discharged on postoperative day 1 (POD 1) and patients discharged on POD 2 to 6. Early discharge and readmission predictors were evaluated using multivariable logistic regression analysis. RESULTS: Only 854 (3.8%) of 22,585 patients who met inclusion criteria were discharged on POD 1, although POD 1 discharge rates increased from 2.3% to 8.1% (P < .001) from 2011 to 2019, respectively. Median hospitalization for patients discharged on POD 2 to 6 was 4 days (interquartile range, 3 to 5 days). Patients' characteristics associated with a lower likelihood of POD 1 discharge were increasing age, smoking, or a history of dyspnea, whereas a minimally invasive approach was the strongest predictor of early discharge (adjusted odds ratio, 5.42; P < .001). Readmission rates were not significantly different for the POD 1 and POD 2 to 6 groups in univariate analysis (6.0% vs 7.0%; P = .269). Further, POD 1 discharge was not a risk factor for readmission in multivariable analysis (adjusted odds ratio, 1.10; P = .537). CONCLUSIONS: Select patients can be discharged on POD 1 after lobectomy for lung cancer without an increased readmission risk, a finding supporting this accelerated discharge target inclusion in lobectomy enhanced recovery after surgery protocols.

Rationale and design of a mechanistic clinical trial of JAK inhibition to prevent ventilator-induced diaphragm dysfunction.

INTRODUCTION: Ventilator-induced diaphragm dysfunction (VIDD) is an important phenomenon that has been repeatedly demonstrated in experimental and clinical models of mechanical ventilation. Even a few hours of MV initiates signaling cascades that result in, first, reduced specific force, and later, atrophy of diaphragm muscle fibers. This severe, progressive weakness of the critical ventilatory muscle results in increased duration of MV and thus increased MV-associated complications/deaths. A drug that could prevent VIDD would likely have a major positive impact on intensive care unit outcomes. We identified the JAK/STAT pathway as important in VIDD and then demonstrated that JAK inhibition prevents VIDD in rats. We subsequently developed a clinical model of VIDD demonstrating reduced contractile force of isolated diaphragm fibers harvested after ∼7 vs ∼1 h of MV during a thoracic surgical procedure. MATERIALS AND METHODS: The NIH-funded clinical trial that has been initiated is a prospective, placebo controlled trial: subjects undergoing esophagectomy are randomized to receive 6 preoperative doses of the FDA-approved JAK inhibitor Tofacitinib (commonly used for rheumatoid arthritis) vs. placebo. The primary outcome variable will be the difference in the reduction that occurs in force generation of diaphragm single muscle fibers (normalized to their cross-sectional area), in the Tofacitinib vs. placebo subjects, over 6 h of MV. DISCUSSION: This trial represents a first-in-human, mechanistic clinical trial of a drug to prevent VIDD. It will provide proof-of-concept in human subjects whether JAK inhibition prevents clinical VIDD, and if successful, will support an ICU-based clinical trial that would determine whether JAK inhibition impacts clinical outcome variables such as duration of MV and mortality.

Short-term and intermediate-term readmission after esophagectomy.

BACKGROUND: The objective of this study was to characterize short- and intermediate-term readmissions following esophagectomy and to identify predictors of readmission in these two groups. METHODS: Patients who underwent esophagectomy in the National Readmissions Database (2013-2014) were grouped according to whether first readmission was "short-term" (readmitted <30 days) or "intermediate-term" (readmitted 31-90 days) following index admission for esophagectomy. Predictors of readmission were evaluated using multivariable logistic regression modeling. RESULTS: Of the 3,005 patients who underwent esophagectomy, 544 (18.1%) had a short-term readmission and 305 (10.1%) had an intermediate-term readmission. The most frequent reasons for short-term readmission were post-operative infection (7.5%), dysphagia (6.3%) and pneumonia (5.1%). The most common intermediate-term complications were pneumonia (7.2%), gastrointestinal stricture/stenosis (6.9%) and dysphagia (5.9%). In multivariable analysis, being located in a micropolitan area, increasing number of comorbidities and higher severity of illness score were associated with an increased likelihood of having a short-term readmission while being discharged to a facility (as opposed to directly home) was associated with increased likelihood of both short- and intermediate-term readmission (all P<0.05). CONCLUSIONS: In this analysis, postoperative infection was the most common reason for short-term readmission. Dysphagia and pneumonia were common reasons for both short- and intermediate-term readmission of patients following esophagectomy. Interventions focused on reducing the risk of postoperative infection and pneumonia may reduce hospital readmissions. Gastrointestinal stricture and dysphagia were associated with increased risk of intermediate readmission and should be examined in the context of morbidity associated with pyloric procedures (e.g., pyloromyotomy) at the time of esophagectomy.

Cancer diagnoses and survival rise as 65-year-olds become Medicare-eligible.

BACKGROUND: A Medicare effect has been described to account for increased health care utilization occurring at the age of 65 years. The existence of such an effect in cancer care, where it would be most likely to reduce mortality, has been unclear. METHODS: Patients aged 61 to 69 years who were diagnosed with lung, breast, colon, or prostate cancer from 2004 to 2016 were identified with the Surveillance, Epidemiology, and End Results database and were dichotomized on the basis of eligibility for Medicare (61-64 vs 65-69 years). With age-over-age (AoA) percent change calculations, trends in cancer diagnoses and staging were characterized. After matching, uninsured patients who were 61 to 64 years old (pre-Medicare group) were compared with insured patients who were 65 to 69 years old (post-Medicare group) with respect to cancer-specific mortality. RESULTS: In all, 134,991 patients were identified with lung cancer, 175,558 were identified with breast cancer, 62,721 were identified with colon cancer, and 238,823 were identified with prostate cancer. The AoA growth in the number of cancer diagnoses was highest at the age of 65 years in comparison with all other ages within the decade for all 4 cancers (P < .01, P < .001, P < .01, and P < .001, respectively). In a comparison of diagnoses at the age of 65 years with those in the 61- to 64-year-old cohort, the greatest difference for all 4 cancers was seen in stage I. In matched analyses, the 5-year cancer-specific mortality was worse for lung (86.3% vs 78.5%; P < .001), breast (32.7% vs 11.0%; P < .001), colon (57.1% vs 35.6%; P < .001), and prostate cancer (16.9% vs 4.8%; P < .001) in the uninsured pre-Medicare group than the insured post-Medicare group. CONCLUSIONS: The age threshold of 65 years for Medicare eligibility is associated with more cancer diagnoses (particularly stage I), and this results in lower long-term cancer-specific mortality for all cancers studied. LAY SUMMARY: Contributing to the current debate regarding Medicare for all, this study shows that the expansion of Medicare would improve cancer outcomes for the near elderly.

A National Analysis of Treatment Patterns and Outcomes for Patients 80 Years or Older With Esophageal Cancer.

The purpose of this study was to evaluate practice patterns and outcomes for patients 80 years or older with esophageal cancer using a nationwide cancer data base. Practice patterns for patients 80 years or older with stage I-IV esophageal cancer in the National Cancer Data Base from 2004 to 2014 were analyzed. Overall survival associated with different treatment strategies were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazard models. In the study period, 40.5% and 46.2% of patients with stage I adenocarcinoma and squamous cell carcinoma, respectively, did not receive any treatment at all. Less than 11% (196/1,865) of patients with stage I-II disease underwent esophagectomy, even though surgery was associated with a better 5-year survival compared to no treatment (stage I: 47.3% [95% confidence interval [CI] 36.2-57.6%] vs 14.9% [95% CI: 11.2-19.1%]; stage II: 29.3% [95% CI 20.1-39.1%] vs 1.2% [95% CI: 0.1-5.5%]). Of the 1,596 (37.7%) patients with stage III disease who received curative-intent treatment (surgery or chemoradiation), the 5-year survival was significantly better than that of patients who received no treatment (11.9% [95% CI: 9.7-14.4% vs 4.3% [95% CI: 1.9-8.3%]). In this national analysis of patients 80 years and older with esophageal cancer, over 40% of patients with stage I disease did not receive treatment. Patients with stage I-III disease had better survival and risks and benefits of treatment for elderly patients should be discussed in a multidisciplinary setting.

Transcervical Thymectomy Is the Most Cost-Effective Surgical Approach in Myasthenia Gravis.

BACKGROUND: Extended thymectomy has been proven to improve the course of myasthenia gravis. Retrospective studies demonstrate that several techniques for thymectomy achieve overlapping remission rates. We therefore compared perioperative outcomes and costs among 3 approaches to thymectomy: sternotomy, video and/or robot assisted, and transcervical. METHODS: To ensure similar study groups, we excluded patients with >4 cm or invasive tumors and those who underwent less than an extended thymectomy or concurrent procedures. Hospital costs were collected and analyzed by blinded finance personnel. RESULTS: The final study group consisted of 25 transcervical, 23 video/robot-assisted, and 14 sternotomy subjects. There was a higher incidence of myasthenia gravis in the transcervical and sternotomy groups (P < 0.001) and of thymoma in the video/robot-assisted and sternotomy groups (P = .002). Mean modified Charlson comorbidity score was higher for sternotomy (2.7 ± 2.1, mean ± SD) than transcervical (1.00 ± 0.58; P < .001) and video/robot-assisted (1.13 ± 0.97; P = .001) procedures. There was no difference in complication rates between approaches (P = 0.828). The cost of transcervical thymectomy was 45% of the cost of sternotomy (P < .001), and was 58% of the cost of video/robot-assisted (P = .018) approaches; these differences remained highly significant on multivariate analysis. Transcervical thymectomy had a shorter mean length of stay (1.2 ± 0.5 days) than median sternotomy (4.4 ± 3.5; P < .001), and video/robot-assisted thymectomy (2.4 ± 0.95; P = .045) and "bed cost" were major contributors to the cost difference between the groups. CONCLUSIONS: Transcervical thymectomy, which provides overlapping myasthenia gravis remission rates versus more invasive approaches, is equally safe and far less costly than sternotomy and video/robot-assisted approaches.

Spontaneous Bleeding From Multiple Intercostal Arteries in a Patient With Coarctation of the Aorta.

A 59-year-old man with a history of coarctation repair, mechanical aortic valve, and warfarin therapy presented with right flank pain. Computed tomography showed a large hematoma encircling an intact descending thoracic aorta. Computed tomography angiography demonstrated multiple areas of intercostal artery extravasation. An interventional radiologist performed angiography and embolization. The patient's course was complicated by an effusion and hypoxia, but no further bleeding was noted. We hypothesize that coarctation associated aneurysms and potential vessel wall weakness are the causes of hematoma in our case. We present this case with history of repaired coarctation with multiple spontaneous intercostal artery aneurysmal rupture.

A Minimally Invasive Approach to Lobectomy After Induction Therapy Does Not Compromise Survival.

BACKGROUND: The objective of this study was to evaluate the impact of a video-assisted thoracoscopic (VATS) approach on outcomes in patients who underwent lobectomy after induction therapy. METHODS: Outcomes of patients with T2-T4, N0, M0 and T1-T4, N1-N2, M0 non-small-cell lung cancer who received induction chemotherapy or chemoradiation followed by lobectomy in the National Cancer Data Base (2010-2014) were assessed using Kaplan-Meier, propensity score-matched, multivariable logistic regression and Cox proportional hazards analyses. RESULTS: In the National Cancer Data Base, 2887 lobectomy patients met inclusion criteria (VATS 676 [23%]; thoracotomy 2211 [77%]). Of the VATS cases, patients who underwent induction chemoradiation were more likely to undergo conversion (adjusted odds ratio 1.70, P = .05). Compared with an open approach, VATS was associated with decreased length of stay (median: 5 days vs 6 days, P < .01) and no significant differences in 30-day mortality (VATS [1.5% (n = 10)] vs open [2.6% (n = 58)]; P = .13) and 90-day mortality (VATS [3.7% (n = 25)] vs open [5.6% (n = 124)]; P = .14). There were no significant differences in 5-year survival between the VATS and open groups in both the entire cohort (VATS [50.3%] vs open [52.3%]; P = .83) and in a propensity score-matched analysis of 876 patients; furthermore, a VATS approach was not associated with worse survival in multivariable analysis (hazard ratio 1.02; 95% confidence interval 0.86-1.20; P = .83). CONCLUSIONS: In this national analysis, a VATS approach for lobectomy in patients who received induction therapy for locally advanced non-small-cell lung cancer was not associated with worse short-term or long-term outcomes when compared with an open approach.

Cougar (Puma concolor) Injury in the United States.

INTRODUCTION: Human encounters with the cougar (Puma concolor) are rare in the United States but may be fatal. METHODS: We performed a retrospective analysis of cougar attacks in the United States. We asked Fish and Wildlife Department officials from the 16 states in which cougars are known to live to identify all verified cougar attacks recorded in state history. Variables describing the human victim, cougar, and conditions surrounding the attack were recorded. The Fisher exact test was used for comparison. RESULTS: Ten states reported 74 cougar attacks from 1924 to 2018. Persons less than 18 y of age were heavily represented among victims; 48% were <18 y old, and 35% were less than 10 y old. Attacks were more common in the summer and fall months. Most attacks occurred during daylight hours. The head, neck, and chest were the most common anatomic sites of injury. Sixteen (46%) victims were hospitalized after being attacked, among the 35 victims with these data available. Eleven (15%) attacks were fatal among 71 reports with this information. None of the hospitalized victims died (P=0.02). No victim variables were predictive of death. CONCLUSIONS: Cougar attacks are uncommon but can be fatal. Attacks commonly affect children and young adults, although all age groups are at risk of attack and death. Most attacks occur during the daytime in the summer and fall. As development and recreational activities put humans in closer contact with cougars, establishing validated public health messaging is critical to minimize injurious encounters.

mTORC1 underlies age-related muscle fiber damage and loss by inducing oxidative stress and catabolism.

Aging leads to skeletal muscle atrophy (i.e., sarcopenia), and muscle fiber loss is a critical component of this process. The mechanisms underlying these age-related changes, however, remain unclear. We show here that mTORC1 signaling is activated in a subset of skeletal muscle fibers in aging mouse and human, colocalized with fiber damage. Activation of mTORC1 in TSC1 knockout mouse muscle fibers increases the content of morphologically abnormal mitochondria and causes progressive oxidative stress, fiber damage, and fiber loss over the lifespan. Transcriptomic profiling reveals that mTORC1's activation increases the expression of growth differentiation factors (GDF3, 5, and 15), and of genes involved in mitochondrial oxidative stress and catabolism. We show that increased GDF15 is sufficient to induce oxidative stress and catabolic changes, and that mTORC1 increases the expression of GDF15 via phosphorylation of STAT3. Inhibition of mTORC1 in aging mouse decreases the expression of GDFs and STAT3's phosphorylation in skeletal muscle, reducing oxidative stress and muscle fiber damage and loss. Thus, chronically increased mTORC1 activity contributes to age-related muscle atrophy, and GDF signaling is a proposed mechanism.