Emergent Esophagectomy in Patients with Esophageal Malignancy Is Associated with Higher Rates of Perioperative Complications but No Independent Impact on Short-Term Mortality.

Background: Data on perioperative outcomes of emergent versus elective resection in esophageal cancer patients requiring esophagectomy are lacking. We investigated whether emergent resection was associated with increased risks of morbidity and mortality. Methods: Data on patients with esophageal malignancy who underwent esophagectomy from 2005 to 2020 were retrospectively analyzed from the American College of Surgeons National Surgical Quality Improvement Program database. Thirty-day complication and mortality rates were compared between emergent esophagectomy (EE) and non-emergent esophagectomy. Logistic regression assessed factors associated with complications and mortality. Results: Of 10,067 patients with malignancy who underwent esophagectomy, 181 (1.8%) had EE, 64% had preoperative systemic inflammatory response syndrome, sepsis, or septic shock, and 44% had bleeding requiring transfusion. The EE group had higher American Society of Anesthesiologists (ASA) class and functional dependency. More transhiatal esophagectomies and diversions were performed in the EE group. After EE, the rates of 30-day mortality (6.1% vs. 2.8%), overall complications (65.2% vs. 44.2%), bleeding, pneumonia, prolonged intubation, and positive margin (17.7% vs. 7.4%) were higher, while that of anastomotic leak was similar. On adjusted logistic regression, older age, lower albumin, higher ASA class, and fragility were associated with increased complications and mortality. McKeown esophagectomy and esophageal diversion were associated with a higher risk of postoperative complications. EE was associated with 30-day postoperative complications (odds ratio, 2.39; 95% confidence interval, 1.66-3.43; p<0.0001). Conclusion: EE was associated with a more than 2-fold increase in complications compared to elective procedures, but no independent increase in short-term mortality. These findings may help guide data-driven critical decision-making for surgery in select cases of complicated esophageal malignancy.

Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men.

Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities.

Challenges of AI driven diagnosis of chest X-rays transmitted through smart phones: a case study in COVID-19.

Healthcare delivery during the initial days of outbreak of COVID-19 pandemic was badly impacted due to large number of severely infected patients posing an unprecedented global challenge. Although the importance of Chest X-rays (CXRs) in meeting this challenge has now been widely recognized, speedy diagnosis of CXRs remains an outstanding challenge because of fewer Radiologists. The exponential increase in Smart Phone ownership globally, including LMICs, provides an opportunity for exploring AI-driven diagnostic tools when provided with large volumes of CXRs transmitted through Smart Phones. However, the challenges associated with such systems have not been studied to the best of our knowledge. In this paper, we show that the predictions of AI-driven models on CXR images transmitted through Smart Phones via applications, such as WhatsApp, suffer both in terms of Predictability and Explainability, two key aspects of any automated Medical Diagnosis system. We find that several existing Deep learning based models exhibit prediction instability-disagreement between the prediction outcome of the original image and the transmitted image. Concomitantly we find that the explainability of the models deteriorate substantially, prediction on the transmitted CXR is often driven by features present outside the lung region, clearly a manifestation of Spurious Correlations. Our study reveals that there is significant compression of high-resolution CXR images, sometimes as high as 95%, and this could be the reason behind these two problems. Apart from demonstrating these problems, our main contribution is to show that Multi-Task learning (MTL) can serve as an effective bulwark against the aforementioned problems. We show that MTL models exhibit substantially more robustness, 40% over existing baselines. Explainability of such models, when measured by a saliency score dependent on out-of-lung features, also show a 35% improvement. The study is conducted on WaCXR dataset, a curated dataset of 6562 image pairs corresponding to original uncompressed and WhatsApp compressed CXR images. Keeping in mind that there are no previous datasets to study such problems, we open-source this data along with all implementations.

Percutaneous Dilatational Tracheostomy in a Cardiac Surgical Intensive Care Unit: A Single-Center Experience.

Background: A significant proportion of cardiac surgery intensive care unit (CSICU) patients require long-term ventilation, necessitating tracheostomy placement. The goal of this study was to evaluate the long-term postoperative outcomes and complications associated with percutaneous dilatational tracheostomy (PDT) in CSICU patients. Methods: All patients undergoing PDT after cardiac, thoracic, or vascular operations in the CSICU between January 1, 2013 and January 1, 2021 were identified. They were evaluated for mortality, decannulation time, and complications including bleeding, infection, and need for surgical intervention. Multivariable regression models were used to identify predictors of early decannulation and the complication rate. Results: Ninety-three patients were identified for this study (70 [75.3%] male and 23 [24.7%] female). Furthermore, 18.3% of patients had chronic obstructive pulmonary disease (COPD), 21.5% had history of stroke, 7.5% had end-stage renal disease, 33.3% had diabetes, and 59.1% were current smokers. The mean time from PDT to decannulation was 39 days. Roughly one-fifth (20.4%) of patients were on dual antiplatelet therapy and 81.7% had anticoagulation restarted 8 hours post-tracheostomy. Eight complications were noted, including 5 instances of bleeding requiring packing and 1 case of mediastinitis. There were no significant predictors of decannulation prior to discharge. Only COPD was identified as a negative predictor of decannulation at any point in time (hazard ratio, 0.28; 95% confidence interval, 0.08-0.95; p=0.04). Conclusion: Percutaneous tracheostomy is a safe and viable alternative to surgical tracheostomy in cardiac surgery ICU patients. Patients who undergo PDT have a relatively short duration of tracheostomy and do not have major post-procedural complications.

Chest vs. neck anastomotic leak post esophagectomy for malignancy: rate, predictors, and outcomes.

Background: Anastomotic leak is a major contributor to comorbidity and mortality following esophagectomy. We sought to assess rate and predictors of leak after esophagectomy and compare outcomes of chest versus neck anastomotic leaks. Methods: A retrospective review was performed utilizing National-Surgical-Quality-Improvement-Program data from 2016-2019 for patients undergoing esophagectomy for malignancy. Preoperative characteristics and postoperative outcomes were compared. Patients were classified into two groups: Ivor Lewis esophagectomy [ILE, chest leak (CL)] and transhiatal esophagectomy (THE)/McKeown esophagectomy [ME, neck leak (NL)]. Multivariable regression models were constructed to determine predictors of each type of leak and postoperative complications. Results: A total of 1,665 patients underwent esophagectomy with 14.1% reported post-operative leak, 61% of patients underwent ILE while 39% underwent THE or ME. Of patients who underwent ILE, 13.8% had CL with complications including significantly higher length of stay and mortality compared to patients without leak. Independent predictors of CL included: diabetes, hypertension, advanced disease stage, chronic steroid use, and operative time. Ninety-five patients (14.6%) who underwent either THE or ME had NL with similar complications. Diabetes, pre-operative white blood cell (WBC), and operative time were independent predictors for NL. On multivariable regression, CL was associated with greater odds of requiring intervention compared with NL. Conclusions: Post-esophagectomy CL and NL are associated with higher morbidity and mortality. Diabetes and operative time were independent predictors for both leaks while steroid use, hypertension, and advanced disease stage predicted CL. CL was associated with greater odds of needing an intervention, but contrary to conventional wisdom, was not associated with higher morbidity or mortality.

Dynamic Long-Range Interactions Influence Substrate Binding and Catalysis by Human Histidine Triad Nucleotide-Binding Proteins (HINTs), Key Regulators of Multiple Cellular Processes and Activators of Antiviral ProTides.

Human histidine triad nucleotide-binding (hHINT) proteins catalyze nucleotide phosphoramidase and acyl-phosphatase reactions that are essential for the activation of antiviral proTides, such as Sofosbuvir and Remdesivir. hHINT1 and hHINT2 are highly homologous but exhibit disparate roles as regulators of opioid tolerance (hHINT1) and mitochondrial activity (hHINT2). NMR studies of hHINT1 reveal a pair of dynamic surface residues (Q62, E100), which gate a conserved water channel leading to the active site 13 Å away. hHINT2 crystal structures identify analogous residues (R99, D137) and water channel. hHINT1 Q62 variants significantly alter the steady-state kcat and Km for turnover of the fluorescent substrate (TpAd), while stopped-flow kinetics indicate that KD also changes. hHINT2, like hHINT1, exhibits a burst phase of adenylation, monitored by fluorescent tryptamine release, prior to rate-limiting hydrolysis and nucleotide release. hHINT2 exhibits a much smaller burst-phase amplitude than hHINT1, which is further diminished in hHINT2 R99Q. Kinetic simulations suggest that amplitude variations can be accounted for by a variable fluorescent yield of the E·S complex from changes in the environment of bound TpAd. Isothermal titration calorimetry measurements of inhibitor binding show that these hHINT variants also alter the thermodynamic binding profile. We propose that these altered surface residues engender long-range dynamic changes that affect the orientation of bound ligands, altering the thermodynamic and kinetic characteristics of hHINT active site function. Thus, studies of the cellular roles and proTide activation potential by hHINTs should consider the importance of long-range interactions and possible protein binding surfaces far from the active site.

Utilization of Supplemental Regional Anesthesia in Lobectomy for Lung Cancer in the United States: A Retrospective Study.

Background: Pulmonary lobectomy is the standard of care for the treatment of early-stage non-small cell lung cancer. This study investigated the rate of utilization of supplemental anesthesia in patients undergoing video-assisted thoracoscopic surgery (VATS) or open lobectomy using a national database and assessed the effect of regional block (RB) on postoperative outcomes. Methods: Patients who underwent lobectomy for lung cancer between 2014-2019 were identified in the American College of Surgeons National Surgical Quality Improvement Program. The patients' primary mode of anesthesia and supplemental anesthesia were recorded. Preoperative characteristics and postoperative outcomes were compared between 2 surgical groups: those who underwent general anesthesia (GA) alone versus GA with RB. Multivariable regression analyses were performed on the outcomes of interest. Results: In total, 13,578 patients met the study criteria, with 87% undergoing GA and the remaining 13% receiving GA and RB. The use of neuraxial anesthesia decreased over the years, while RB use increased up to 20% in 2019. Age, body mass index, and preoperative comorbidities were comparable between groups. Patients who underwent VATS were more likely to receive RB than those who underwent thoracotomy. RB was most often utilized by thoracic surgeons. An adjusted analysis showed that RB use was associated with shorter hospital stays and a reduced likelihood of prolonged length of stay, but a higher rate of surgical site infections (SSIs). Conclusion: In a large surgical database, there was underutilization of supplemental anesthesia in patients undergoing lobectomy for lung cancer. RB utilization was associated with a shorter length of hospital stay and an increase in SSI incidence.

Extrusion, meniscal signal change, loss of shape, synovitis and bone marrow oedema are reliable scoring parameters to assess MRI appearance post meniscal transplant.

PURPOSE: Meniscal allograft transplantation (MAT) has shown good promise in restoring normal knee joint biomechanics in a meniscal deficient patient. However, MRI appearance of the meniscal allograft is often questioned and raises concerns of its viability and function. This paper aims to introduce and validate a new scoring system for MAT MRI appearance at 12 months [MRI appearance in Meniscal Transplant Score (MIMS)], using key changes such as extrusion, meniscal signal change, loss of shape, synovitis and bone marrow oedema. METHODS: A retrospective analysis of 10 patients from a single surgeon series was conducted. All MAT were performed with soft tissue fixation technique. MRI was performed at 12 months post-transplant with two independent consultant musculoskeletal radiologists and one experienced meniscal transplant surgeon scoring the images obtained. Interobserver agreement and intraclass correlation were measured. RESULTS: Interobserver agreement between examiners on individual features of the MIMS was superior for tibial bone oedema, substantial for meniscal extrusion and femoral bone oedema, moderate for meniscal shape and synovitis, and fair for meniscal signal changes. Absolute agreement between raters found good reliability (ICC = 0.774; 95% 0.359, 0.960) for single measures and excellent reliability (ICC = 0.911; 95% 0.627, 0.986) for average measures. CONCLUSION: MIMS is a reliable method of evaluating the meniscal allograft transplant 12 months post-transplant. Further research with larger MAT cohort groups and patient reported outcome measures may be helpful to correlate its clinical significance and guide further management. LEVEL OF EVIDENCE: Level III.

Trends in open lobectomy outcomes for lung cancer over the last 15 years: national cohort.

OBJECTIVE: Adoption of thoracoscopic lobectomy has been increasing in the US; however, open lobectomy (OL) is still performed in half of the cases. Postoperative care and enhanced recovery after surgery (ERAS) pathways have evolved and improved outcomes. The study aims to evaluate postoperative outcomes of OL over the last 15 years. METHODS: Patients who underwent lobectomy for lung cancer between 2005 and 2019 were identified in the National Surgical Quality Improvement Program and divided into three groups; pre-ERAS (2005-2011), transitional period (2012-2015), and wider ERAS implementation (2016-2019). Preoperative characteristics and postoperative outcomes were compared and multivariable regression analysis was constructed to assess independent predictors of outcomes. RESULTS: OL was comprised of 40% of lobectomies for lung cancer. 10,021 patients met inclusion criteria. 49% were males and mean age was 67. Patients who belonged to the (2016-2019) period group had significantly higher comorbidities and ASA classification. General surgeons performed < 10% of OL in 2016-2019 compared to over 30% during 2005-2011. Patients in the 2016-2019 period were less likely to experience unplanned intubation, surgical site infections, and sepsis. Mortality was also significantly lower than the previous groups (1.9% vs 2.0% and 2.8%, p = 0.05). The rate of discharge to facility as well as length of hospital stays improved over the years. The surgeon specialty served as an independent predictor for length of stay, unplanned intubation, and home discharge. CONCLUSION: The outcomes of OL are improving over the years. Increasing number of these surgeries being performed by dedicated thoracic surgeons and ERAS pathways are likely helping improve outcomes.

Bochdalek Hernia With Gastric Necrosis Requiring Roux-en-Y Esophagojejunostomy.

Bochdalek hernias are the most common congenital diaphragmatic hernias and are usually diagnosed during childhood. They can present in adulthood and, in uncommon circumstances, result in gastric herniation with strangulation. We present a case of an adult Bochdalek hernia resulting in total gastric necrosis necessitating Roux-en-Y esophagojejunostomy in an otherwise healthy 39-year-old man. This case highlights the potential morbidity associated with unrepaired congenital diaphragmatic hernias and the need for appropriate referral.

Trends of utilization and perioperative outcomes of robotic and video-assisted thoracoscopic surgery in patients with lung cancer undergoing minimally invasive resection in the United States.

Objective: The objective of this study was to evaluate utilization and perioperative outcomes of video-assisted thoracoscopic surgery (VATS) or robotic-assisted thoracoscopic surgery (RATS) for lung cancer in the United States using a nationally representative database. Methods: Hospital admissions for lobectomy or sublobar resection (segmentectomy or wedge resection) using VATS or RATS in patients with nonmetastatic lung cancer from October 2015 through December 2018 in the National Inpatient Sample were studied. Patient and hospital characteristics, perioperative complications and mortality, length of stay (LOS), and total hospital cost were compared. Logistic regression was used to assess whether the surgical approach was independently associated with adverse outcomes. Results: There were 83,105 patients who had VATS (n = 65,375) or RATS (n = 17,710) for lobectomy (72.7% VATS) or sublobar resection (84.2% VATS). Utilization of RATS for lobectomy and sublobar resection increased from 19.2% to 34% and 7.3% to 22%, respectively. Mortality, LOS, and conversion rates were comparable. The cost was higher for RATS (P <.01). Multivariate analyses showed comparable RATS and VATS complications with no independent association between the minimally invasive surgery approach used and adverse surgical outcomes, except for a decreased risk of pneumonia with RATS, relative to VATS sublobar resection (P <.01). Thoracic complication rates and LOS decreased after RATS lobectomy in 2018, compared with previous years (P <.005). Conclusions: The utilization of robotic-assisted lung resection for cancer has increased in the United States between 2015 and 2018 for sublobar resection and lobectomy. In adjusted regression analysis, compared with VATS, patients who underwent RATS had similar complication rates and LOS. The robotic approach was associated with increased total hospital cost. LOS and thoracic complication rates trended down after RATS lobectomy.

A narrative review of the health disparities associated with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a cancer of the mesothelial lining of the pleura that has traditionally been associated with asbestos exposure in an industrial setting. Asbestos usage has fortunately been banned or phased out in most industrialized countries resulting in its decline in countries such as the United States. Despite this, MPM continues to place significant burden on its affected patients resulting in overall poor prognosis and survival. Questions arise as to what factors, especially what health disparities, contribute to the disease's dismal prognosis. This article will present a narrative review of recent literature that identifies the impact age, sex, race, access to medical centers, and economics have on the diagnosis, treatment, and prognosis of MPM. As will be discussed, research has shown that factors including younger age, female sex, non-white race, private insurance, Medicare, and higher income have been associated with better survival in MPM. Whereas older age, male sex, white race, lack of insurance, and lower income are associated with worse survival. The identification of these and other health disparities related to MPM may allow for future research, clinical guidelines, and policies to be implemented to decrease the burden health disparities create in the diagnosis, treatment, and prognosis of patients with MPM.

Does Race or Ethnicity Impact Complications After Pulmonary Lobectomy for Patients With Lung Cancer?

BACKGROUND: Racial disparity in surgical access and postoperative outcomes after pulmonary lobectomy continues to be a concern and target for improvement; however, evidence of independent impact of race on complications is lacking. The objective of this study was to investigate the impact of race/ethnicity on surgical outcomes after lobectomy for lung cancer and estimate the distribution of racial/ethnic groups among expected resectable lung cancer cases using a large national database. METHODS: Patients who underwent lobectomy for lung cancer between 2005 and 2016 were identified in the American College of Surgeon National Surgical Quality Improvement Program. Preoperative characteristics and postoperative outcomes were compared between race/ethnicity groups in all patients and in propensity-matched cohorts, controlling for pertinent risk factors. Distribution of each race/ethnicity in the database was calculated relative to estimated numbers of patients with resectable lung cancer in the United States. RESULTS: A total of 10,202 patients (age 67.6 ± 9.7, 46.7% male, 86.4% white) underwent nonemergent lobectomy (46.8% thoracoscopic). Blacks had higher rates of baseline risk factors. In propensity score-matched cohorts of whites, blacks, and Hispanics/Asians (n = 498 each), postoperatively, blacks had higher rates of prolonged intubation and longer hospital stay while whites had a higher rate of pneumonia. Race was independently associated with these adverse outcomes on multivariate analysis. Proportion of blacks and Hispanics in the American College of Surgeon National Surgical Quality Improvement Program was lower than their respective proportion of resectable lung cancer in the United States. CONCLUSIONS: In a large national-level surgical database, there was lower than expected representation of black and Hispanic patients. Black race was independently associated with extended length of stay and prolonged intubation, whereas white was independently associated with postoperative pneumonia.

"Switching On" Enzyme Substrate Specificity Analysis with a Fluorescent Competitive Inhibitor.

Enzymatically driven change to the spectroscopic properties of a chemical substrate or product has been a linchpin in the development of continuous enzyme kinetics assays. These assays inherently necessitate substrates or products that naturally comply with the constraints of the spectroscopic technique being used, or they require structural changes to the molecules involved to make them observable. Here we demonstrate a new analytical kinetics approach with enzyme histidine triad nucleotide binding protein 1 (HINT1) that allows us to extract both useful kcat values and a rank-ordered list of substrate specificities without the need to track substrates or products directly. Instead, this is accomplished indirectly using a "switch on" competitive inhibitor that fluoresces maximally only when bound to the HINT1 enzyme active site. Kinetic information is extracted from the duration of the diminished fluorescence when the monitorable inhibitor-bound enzyme is challenged with saturating concentrations of a nonfluorescent substrate. We refer to the loss of fluorescence, while the substrate competes for the fluorescent probe in the active site, as the substrate's residence transit time (RTT). The ability to assess kcat values and substrate specificity by monitoring the RTTs for a set of substrates with a competitive "switch on" inhibitor should be broadly applicable to other enzymatic reactions in which the "switch on" inhibitor has sufficient binding affinity over the enzymatic product.

Five-Year Experience with VATS Versus Thoracotomy Segmentectomy for Lung Tumor Resection.

OBJECTIVE: Segmentectomy for lung tumors has been performed with either video-assisted thoracoscopic surgery (VATS) or thoracotomy; however, there is a lack of contemporary, multicenter study that compares both approaches. The aim of this study was to compare the 30-day surgical outcomes of VATS versus thoracotomy for segmentectomy using a large national database. METHODS: We performed a retrospective analysis of prospectively maintained American College of Surgeons National Surgical Quality Improvement Program database. Patients who underwent segmentectomy for benign or malignant tumors between 2013 and 2017 were included and divided into 2 groups based on whether they received a thoracotomy or VATS approach. All VATS patients were then into 2 subgroups: early (2013 to 2015) and late (2016 to 2017). Propensity-matched analysis was conducted, and the perioperative variables and outcomes were compared. RESULTS: A total of 1,785 patients met the inclusion criteria. VATS segmentectomy was associated with shorter hospital stays (3.9 vs 5.8 days, P < 0.001) and higher rates of home discharge (94% vs 89%, P = 0.002) compared to thoracotomy segmentectomy. VATS was also associated with less postoperative pneumonia (2.8% vs 5.8%, P = 0.007), unplanned intubation (1.5% vs 3.5%, P = 0.016), prolonged intubation (0.6% vs 2.7%, P = 0.001), transfusion requirement (1.7% vs 5.8%, P < 0.001), and deep venous thrombosis (0.1% vs 1.1%, P = 0.03). Compared to the earlier VATS group, the late group was associated with less cardiac arrests (0% vs 0.8%, P = 0.025) and shorter hospital stays (3.3 vs 4.2 days, P < 0.001). CONCLUSIONS: When compared with thoracotomy, VATS segmentectomy is associated with less postoperative complications and shorter hospital length of stay. VATS segmentectomy has been used more frequently and with improved outcomes.

Deglutition Syncope Treated With Peroral Endoscopic Myotomy.

Deglutition syncope is a rare, neurally mediated reflex syncope associated with swallowing. It is typically associated with pharyngoesophageal disorders with secondary abnormal vagal reflex causing atrioventricular cardiac block and cerebral hypoperfusion. Diagnosis can be delayed and challenging. Various treatment options have been reported, including withholding cardiac blocker agents, diet modifications, and pacemaker placement. We present a case of persistent deglutition syncope secondary to esophagogastric junction outflow obstruction that failed medical therapy and was managed successfully with peroral endoscopic myotomy with excellent long-term outcome.