Penetrance of Gastric Adenocarcinoma Susceptibility Genes: A Systematic Review.

BACKGROUND: Gastric adenocarcinoma (GAC) is the fifth most common cancer in the world, and the presence of germline pathogenic variants has been linked with approximately 5% of gastric cancer diagnoses. Multiple GAC susceptibility genes have been identified, but information regarding the risk associated with pathogenic variants in these genes remains obscure. We conducted a systematic review of existing studies reporting the penetrance of GAC susceptibility genes. METHODS: A structured search query was devised to identify GAC-related papers indexed in MEDLINE/PubMed. A semi-automated natural language processing algorithm was applied to identify penetrance papers for inclusion. Original studies reporting the penetrance of GAC were included and the full-text articles were independently reviewed. Summary statistics, effect estimates, and precision parameters from these studies were compiled into a table using a predetermined format to ensure consistency. RESULTS: Forty-five studies were identified reporting the penetrance of GAC among patients harboring mutations in 13 different genes: APC, ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, MUTYH-Monoallelic, NBN, and STK11. CONCLUSION: Our systematic review highlights the importance of testing for germline pathogenic variants in patients before the development of GAC. Management of patients who harbor a pathogenic mutation is multifactorial, and clinicians should consider cancer risk for each applicable gene-cancer association throughout the screening and management process. The scarcity of studies we found investigating the risk of GAC among patients with pathogenic variants in GAC susceptibility genes highlights the need for more investigations that focus on producing robust risk estimates for gene-cancer associations.

Anemia is associated with higher mortality and morbidity after thoracic endovascular aortic repair.

BACKGROUND: It is uncertain whether preoperative anemia is independently associated with thoracic endovascular aortic repair (TEVAR) outcomes. Using a national vascular surgery database, we evaluated the associations between preoperative anemia and 30-day mortality, postoperative complications, and 1-year survival for patients undergoing TEVAR. METHODS: We retrospectively analyzed all patients in the Vascular Quality Initiative who had undergone TEVAR for aortic dissection, aortic aneurysm, penetrating aortic ulcer, hematoma, or thrombus between January 2011 and December 2019. We excluded patients with a ruptured aneurysm, traumatic dissection, emergent repair, treated aorta distal to zone 5, polycythemia, transfusion of >4 U of packed red blood cells intraoperatively or postoperatively, and missing data on hemoglobin level or surgical indications. The final study cohort was dichotomized into two groups: normal/mild anemia (women, ≥10 g/dL; men, ≥12 g/dL) and moderate/severe anemia (women, <10 g/dL; male, <12 g/dL). Propensity scores by stratification were used to control for confounding in the analysis of the association between the outcomes of 30-day mortality, postoperative complications, and 1-year survival and a binary indicator variable of moderate/severe anemia vs normal/mild anemia. Kaplan-Meier analysis and log-rank tests were used to compare the 1-year survival between the two groups. A Cox regression model was fitted to assess the associations between anemia and survival outcomes. RESULTS: A total of 3391 patients were analyzed, 958 (28.3%) of whom had had moderate/severe anemia. After adjustment for multiple clinical factors using propensity score stratification, moderate/severe anemia was associated with a 141% increased odds of 30-day mortality (adjusted odds ratio [aOR], 2.41; 95% confidence interval [CI], 1.15-5.05; P = .019), 58% increased odds of any in-hospital complication (aOR, 1.58; 95% CI, 1.17-2.13; P = .003), 281% increased odds of intraoperative transfusion (aOR, 3.81; 95% CI, 2.68-5.53; P < .001). In addition, moderate/severe anemia was associated with significantly worse survival within the first year after TEVAR (log-rank P < .001; 1-year survival rate using Kaplan-Meier estimates, 86.4% ± 1.3% standard error vs 92.5% ± 0.6% standard error) and with an increased risk of mortality in the first postoperative year (adjusted hazard ratio, 1.81; 95% CI, 1.16-2.82; P = .009). CONCLUSIONS: We found that moderate or severe anemia is associated with significantly increased odds of mortality, postoperative complications, and worse 1-year survival after TEVAR. Future studies are needed to evaluate the effect of anemia correction on the outcomes of TEVAR.

Association of Intravenous Drug Use and Length of Stay Following Infective Endocarditis.

INTRODUCTION: Intravenous drug use (IVDU) and associated infective endocarditis (IE) has been on the rise in the US since the beginning of the opioid epidemic. IVDU-IE has high morbidity and mortality, and treatment can be lengthy. We aim to quantify the association between IVDU and length of stay (LOS) in IE patients. METHODS: The National Inpatient Sample database was used to identify IE patients, which was then stratified into IVDU-IE and non-IVDU-IE groups. Weighted values of hospitalizations were used to generate national estimates. Multivariable linear and logistic regression analyses were applied to estimate the effects of IVDU on LOS. RESULTS: We identified 1,114,257 adult IE patients, among which 123,409 (11.1%) were IVDU-IE. Compared to non-IVDU-IE patients, IVDU-IE patients were younger, had fewer comorbidities, and had an overall longer LOS (median [interquartile range]: 10 [5-20] versus 7 [4-13] d, P < 0.001), with a greater percentage of patients with a LOS longer than 30 d (13.7% versus 5.7%, P < 0.001). After adjusting for multiple demographic and clinical factors, IVDU was independently associated with a 1.25-d increase in LOS (beta-coefficient = 1.25, 95% confidence interval [CI]: 0.95-1.54, P < 0.001) and 35% higher odds of being hospitalized for more than 30 d (odds ratio = 1.35, 95% CI: 1.27-1.44, P < 0.001). CONCLUSIONS: Among IE patients, being IVDU has associated with a longer LOS and a higher risk of prolonged hospital stay. Steps toward the prevention of IE in the IVDU population should be taken to avoid an undue burden on the healthcare system.

Air Pollutants and Asthma Hospitalization in the Medicaid Population.

Rationale: Risk of asthma hospitalization and its disparities associated with air pollutant exposures are less clear within socioeconomically disadvantaged populations, particularly at low degrees of exposure. Objectives: To assess effects of short-term exposures to fine particulate matter (particulate matter with an aerodynamic diameter of ⩽2.5 µm [PM2.5]), warm-season ozone (O3), and nitrogen dioxide (NO2) on risk of asthma hospitalization among national Medicaid beneficiaries, the most disadvantaged population in the United States, and to test whether any subpopulations were at higher risk. Methods: We constructed a time-stratified case-crossover dataset among 1,627,002 hospitalizations during 2000-2012 and estimated risk of asthma hospitalization associated with short-term PM2.5, O3, and NO2 exposures. We then restricted the analysis to hospitalizations with degrees of exposure below increasingly stringent thresholds. Furthermore, we tested effect modifications by individual- and community-level characteristics. Measurements and Main Results: Each 1-µg/m3 increase in PM2.5, 1-ppb increase in O3, and 1-ppb increase in NO2 was associated with 0.31% (95% confidence interval [CI], 0.24-0.37%), 0.10% (95% CI, 0.05 - 0.15%), and 0.28% (95% CI, 0.24 - 0.32%) increase in risk of asthma hospitalization, respectively. Low-level PM2.5 and NO2 exposures were associated with higher risk. Furthermore, beneficiaries with only one asthma hospitalization during the study period or in communities with lower population density, higher average body mass index, longer distance to the nearest hospital, or greater neighborhood deprivation experienced higher risk. Conclusions: Short-term air pollutant exposures increased risk of asthma hospitalization among Medicaid beneficiaries, even at concentrations well below national standards. The subgroup differences suggested individual and contextual factors contributed to asthma disparities under effects of air pollutant exposures.

Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study.

AIMS: Galectin-3, a ß-galactoside-binding lectin, is abnormally increased in cardiovascular disease. Plasma Galectin-3 receives a Class II recommendation for heart failure management and has been extensively studied for multiple cellular functions. The direct effects of Galectin-3 on platelet activation remain unclear. This study explores the direct effects of Galectin-3 on platelet activation and thrombosis. METHODS AND RESULTS: A strong positive correlation between plasma Galectin-3 concentration and platelet aggregation or whole blood thrombus formation was observed in patients with coronary artery disease (CAD). Multiple platelet function studies demonstrated that Galectin-3 directly potentiated platelet activation and in vivo thrombosis. Mechanistic studies using the Dectin-1 inhibitor, laminarin, and Dectin-1-/- mice revealed that Galectin-3 bound to and activated Dectin-1, a receptor not previously reported in platelets, to phosphorylate spleen tyrosine kinase and thus increased Ca2+ influx, protein kinase C activation, and reactive oxygen species production to regulate platelet hyperreactivity. TD139, a Galectin-3 inhibitor in a Phase II clinical trial, concentration dependently suppressed Galectin-3-potentiated platelet activation and inhibited occlusive thrombosis without exacerbating haemorrhage in ApoE-/- mice, which spontaneously developed increased plasma Galectin-3 levels. TD139 also suppressed microvascular thrombosis to protect the heart from myocardial ischaemia-reperfusion injury in ApoE-/- mice. CONCLUSION: Galectin-3 is a novel positive regulator of platelet hyperreactivity and thrombus formation in CAD. As TD139 has potent antithrombotic effects without bleeding risk, Galectin-3 inhibitors may have therapeutic advantages as potential antiplatelet drugs for patients with high plasma Galectin-3 levels.

Penetrance of male breast cancer susceptibility genes: a systematic review.

PURPOSE: Several male breast cancer (MBC) susceptibility genes have been identified, but the MBC risk for individuals with a pathogenic variant in each of these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes to better summarize current estimates of penetrance. METHODS: A search query was developed to identify MBC-related papers indexed in PubMed/MEDLINE. A validated natural language processing method was applied to identify papers reporting penetrance estimates. These penetrance studies' bibliographies were reviewed to ensure comprehensiveness. We accessed the potential ascertainment bias for each enrolled study. RESULTS: Fifteen penetrance studies were identified from 12,182 abstracts, covering five purported MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2. Cohort (n = 6, 40%) and case-control (n = 5, 33%) studies were the two most common study designs, followed by family-based (n = 3, 20%), and a kin-cohort study (n = 1, 7%). Seven of the 15 studies (47%) adjusted for ascertainment adequately and therefore the MBC risks reported by these seven studies can be considered applicable to the general population. Based on these seven studies, we found pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 show an increased risk for MBC. The association between BRCA1 and MBC was not statistically significant. CONCLUSION: This work supports the conclusion that pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 increase the risk of MBC, whereas pathogenic variants in BRCA1 may not be associated with increased MBC risk.

Low-volume hospitals are not associated with inferior outcomes after thoracic endovascular aortic repair.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has been increasingly used to treat complex thoracic aortic pathology. In the present study, we assessed the hospital volume's effects on the outcomes of patients who had undergone TEVAR. METHODS: Patients who had undergone TEVAR from January 2015 to December 2019 were identified from the Vascular Quality Initiative database. The participating centers were stratified by volume as low-volume hospitals (LVHs) and high-volume hospitals (HVHs). We assessed the effects of hospital volume on 30-day mortality and major postoperative complications using multivariable logistic regression analysis. RESULTS: A total of 3584 TEVAR patients (1720 asymptomatic and 1864 symptomatic or ruptured) were identified at 147 centers. The median average annual number of TEVAR cases at the LVHs and HVHs was 6 and 17 cases, respectively. No significant differences were found in 30-day mortality between the LVHs and HVHs (asymptomatic, 3.7% vs 3.7% [P = .98]; symptomatic or ruptured, 9.3% vs 7.3% [P = .13]). After adjusting for multiple clinical and anatomic factors, treatment at a LVH was not associated with increased 30-day mortality (asymptomatic: odds ratio, 0.98; 95% confidence interval, 0.52-1.87; P = .96; symptomatic or ruptured: odds ratio, 1.15; 95% confidence interval, 0.75-1.77; P = .53) nor an increased risk of major complications, including renal, neurologic, cardiac, pulmonary, and femoral artery access complications (P > .05 for all). CONCLUSIONS: Using a large national database, we have demonstrated that treatment at LVHs is not associated with inferior TEVAR outcomes compared with HVHs. The technical aspect of the procedure might play a role in the similarity of outcomes across the different institutional experiences.

Remifentanil versus Dexmedetomidine in Cardiac Surgery Patients with Noninvasive Ventilation Intolerance: Protocol for the REDNIVI Trial.

BACKGROUND: Respiratory failure is one of the most common complications following cardiac surgery. Although noninvasive ventilation (NIV) has been an effective treatment, it has a high rate of intolerance. Both remifentanil and dexmedetomidine are used as sedatives in cardiac surgery (CS) patients with NIV intolerance. However, no randomized controlled trials have compared the effects of these drugs in relieving the intolerance. METHODS: REDNIVI will be a multicenter, prospective, single-blind, randomized controlled trial carried out in six clinical sites in China. Subjects with NIV intolerance will be randomized to receive remifentanil or dexmedetomidine in a ratio of 1:1. Primary outcomes of intolerance remission rate at different timings (15 minutes, 1, 3, 6, 12, 24, 36, 48, 60, 72 hours after initiation of treatment) and 72 h average remission rate will be determined. In addition, secondary outcomes such as mortality, duration of intensive care unit (ICU) stay, duration of mechanical ventilation (MV), the need for endotracheal intubation, hemodynamic changes, and delirium incidence will also be determined. CONCLUSIONS: This trial will provide evidence to determine the effects of remifentanil and dexmedetomidine in patients with NIV intolerance after cardiac surgery. CLINICAL TRIAL REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT04734418).

Effects of Angiotensin II Receptor Blockers on Ventricular Hypertrophy in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Animal studies have suggested that angiotensin II receptor blockers (ARBs) can attenuate or reverse the progression of hypertrophic cardiomyopathy, while clinical studies yielded conflicting results. We sought to conduct a meta-analysis to investigate the effect of ARBs in patients with hypertrophic cardiomyopathy. METHODS: PubMed and EMBASE databases were searched through June 2020. Only randomized controlled trials (RCTs) were included, and each study's quality was assessed using the Jadad scale. The primary outcome was left ventricular mass reduction, and the secondary outcome was the change in left ventricular ejection fraction (LVEF). Data were pooled using the random effects model. RESULTS: A total of 1294 articles were screened. Five RCTs were included in the final analysis, enrolling 209 patients with hypertrophic cardiomyopathy (101 patients were in the ARB arm). ARB treatment was not associated with either significant left ventricular mass reduction (standardized mean difference: - 0.25; 95% CI: - 0.73, 0.22; p = 0.29) or change in LVEF (weighted mean difference: 0.73%; 95% CI: - 1.10%, 2.56%; p = 0.43). Subgroup analysis showed that losartan, one of the most investigated and commonly used ARBs, was also not associated with significant decreases of left ventricular mass (standardized mean difference: - 0.13; 95% CI: - 0.61, 0.36; p = 0.61). CONCLUSION: This meta-analysis showed that ARB treatment is not associated with reduced left ventricular mass nor remarkable LVEF change among patients with hypertrophic cardiomyopathy. Further studies with a larger number of patients will be required to confirm these findings.

Dietary fat and fatty acids in relation to risk of colorectal cancer.

PURPOSE: Epidemiologic evidence for specific types and sources of dietary fat and individual fatty acid with colorectal cancer (CRC) risk remains inconclusive. We aimed to comprehensively examine the associations of intakes of specific types (saturated, monounsaturated, polyunsaturated, and trans) and sources (animal, dairy, and vegetable) of dietary fat and individual fatty acid with CRC risk. DESIGN: We prospectively followed 65,550 women from the Nurses' Health Study (1986-2014) and 45,684 men from the Health Professionals Follow-up Study (1986-2014). Dietary intake was assessed every 4 years using food frequency questionnaires. Self-reported CRC cases were confirmed through medical record review. Time-dependent Cox proportional hazards regression was used to estimate the hazard ratios (HRs) for intakes of dietary fats and fatty acids and CRC risk. RESULTS: During 2,705,560 person-years of follow-up, 2726 incident CRC cases were confirmed. Intake of monounsaturated fat tended to be positively associated with the risk of CRC (HR comparing extreme quintiles 1.22; 95% CI 1.01, 1.47; p = 0.06 for trend). This positive association was mainly driven by monounsaturated fatty acids from animal sources (MUFA-As) (HR comparing extreme quintiles 1.23; 95% CI 1.02, 1.49; p = 0.02 for trend). The positive association between MUFA-As and CRC was attenuated after adjusting for red and processed meat consumption (HR comparing extreme quintiles 1.17; 95% CI 0.95, 1.44; p = 0.13 for trend). We did not find clear associations between other types and sources of dietary fat or individual fatty acid and CRC risk. CONCLUSIONS: Higher intake of MUFA-As was associated with higher CRC risk. This could be partly explained by confounding due to other components of red and processed meat.

Right ventricular wall dissection complicating myocardial infarction.

Right ventricular wall dissection is extremely rare and can result in dismal clinical outcomes. We report a 68-year-old patient who presented with acute myocardial infarction and was found to have right ventricular wall dissection by ventriculography. At surgery, the infarcted myocardium was excised, and a two-patch technique was used to repair the ventricular septal defect.

Non-medullary Thyroid Cancer Susceptibility Genes: Evidence and Disease Spectrum.

BACKGROUND: The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention. OBJECTIVE: The aim of this study was to provide the current panorama of susceptibility genes associated with NMTC and the spectrum of diseases associated with these genes. METHODS: Twenty-five candidate genes were identified by searching for relevant studies in PubMed. Each candidate gene was carefully checked using six authoritative genetic resources: ClinGen, National Comprehensive Cancer Network guidelines, Online Mendelian Inheritance in Man, Genetics Home Reference, GeneCards, and Gene-NCBI, and a validated natural language processing (NLP)-based literature review protocol was used to further assess gene-disease associations where there was ambiguity. RESULTS: Among 25 candidate genes, 10 (APC, DICER1, FOXE1, HABP2, NKX2-1, PRKAR1A, PTEN, SDHB, SDHD, and SRGAP1) were verified among the six genetic resources. Two additional genes, CHEK2 and SEC23B, were verified using the NLP protocol. Seventy-nine diseases were found to be associated with these 12 NMTC susceptibility genes. The following diseases were associated with more than one NMTC susceptibility gene: colorectal cancer, breast cancer, gastric cancer, kidney cancer, gastrointestinal stromal tumor, paraganglioma, pheochromocytoma, and benign skin conditions. CONCLUSION: Twelve genes predisposing to NMTC and their associated disease spectra were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk.

Outcomes of intact thoracic endovascular aortic repair in octogenarians.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) is a suitable alternative to open aortic surgery especially for older patients with poor general health and functional status. However, data on the benefit of TEVAR in elderly patients are limited. The aim of this study was to use a large national database to compare the outcomes of TEVAR in octogenarians vs nonoctogenarians in the treatment of thoracic aortic aneurysms and dissection. METHODS: All patients who underwent TEVAR for nonruptured thoracic aneurysms or dissection (zones 1-5) between January 2014 and February 2019 were identified in the Vascular Quality Initiative database. The primary outcome was in-hospital mortality. Secondary outcomes included cardiac adverse events; neurologic events; respiratory complications; new-onset dialysis; leg compartment syndrome; postoperative hematoma in addition to spinal, bowel, arm, and leg emboli/ischemia; and return to the operating room. Outcomes were compared between octogenarians (age ≥80 years) and nonoctogenarians (age <80 years) using univariable and multivariable logistic regression models. RESULTS: A total of 2042 patients were identified, including 390 octogenarians (19.1%). Compared with nonoctogenarians, octogenarians had higher percentages of females (49.5% vs 40.4%; P < .01) and White patients (75.9% vs 68.6%; P < .01) and were more likely to present with thoracic aneurysms (86.2% vs 64.3%; P < .001). They also had larger aortic diameters (maximum diameter, 60.3 ± 15.8 mm vs 53.4 ± 17.4 mm), less proximal disease zones (zone 1, 3.3% vs 5.5%; zone 2, 13.9% vs 24.1%; P < .001) and were more likely to undergo the procedure under local/regional anesthesia (5.4% vs 2.4%; P < .01) compared with patients less than 80 years of age. No association was observed between octogenarians and in-hospital mortality after TEVAR for aneurysms (5.1% vs 3.3%; odds ratio [OR], 1.38; 95% confidence interval [CI], 0.72-2.61; P = .33) or dissection (5.6% vs 4.9%; OR, 0.68; 95% CI, 0.14-3.32; P = .63). However, for thoracic aneurysm repair, octogenarians had a 44% higher adjusted odds of in-hospital complications (27.4% vs 20.7%; OR, 1.44; 95% CI, 1.04-1.98; P = .03) compared with their younger counterparts. In-hospital complications (27.8% vs 26.2%; P = .79; OR, 1.02; 95% CI, 0.50-2.11; P = .95) were similar in octogenarians undergoing endovascular repair for dissections of the thoracic aorta. Octogenarians were also associated with 1.74 times the mortality hazard compared with nonoctogenarians (adjusted hazard ratio, 1.74; 95% CI, 1.18-2.58; P = .01). CONCLUSIONS: TEVAR is an acceptable treatment option for octogenarians who have aortic arch and descending aortic aneurysms or dissections (zones 1-5). However, in case of aneurysms, they might be at a higher risk of in-hospital complications. Octogenarians also had increased hazard of 1-year mortality; however, the exact cause of this mortality could not be deciphered. Our findings suggest that elderly patients should not be denied TEVAR based on age if they are medically and anatomically fit for this procedure.

Black patients have a higher burden of comorbidities but a lower risk of 30-day and 1-year mortality after thoracic endovascular aortic repair.

BACKGROUND: Racial disparities in open thoracic aortic aneurysm repair have been well-documented, with Black patients reported to suffer from poor outcomes compared with their White counterparts. It is unclear whether these disparities extend to the less invasive thoracic endovascular aortic repair (TEVAR). This study aims to examine the clinical characteristics, perioperative outcomes, and 1-year survival of Black vs White patients undergoing TEVAR in a national vascular surgery database. METHODS: The Vascular Quality Initiative database was retrospectively queried to identify all patients who underwent TEVAR between January 2011 and December 2019. The primary outcomes were 30-day mortality and 1-year survival after TEVAR. Secondary outcomes included various types of major postoperative complications. Multivariable logistic regression analyses were performed to identify predictors of 30-day mortality and perioperative complications. Multivariable Cox regression analysis was used to determine the predictors of 1-year survival. RESULTS: A total of 2669 patients with TEVAR were identified in the Vascular Quality Initiative, of whom 648 were Black patients (24.3%). Compared with White patients, Black patients were younger and had a higher burden of comorbidities, including hypertension, diabetes, congestive heart failure, dialysis dependence, and anemia. Black patients were more likely to be symptomatic, present with aortic dissection, and undergo urgent or emergent repair. There was no statistically significant difference in 30-day mortality between Black and White patients (3.4% vs 4.9%; P = .1). After adjustment for demographics, comorbidities, and operative factors, Black patients were independently associated with a 56% decrease in 30-day mortality risk compared with their White counterparts (odds ratio, 0.44; 95% confidence interval [CI], 0.22-0.85; P = .01) and not associated with an increased risk of perioperative complications (odds ratio, 0.90; 95% CI, 0.68-1.17; P = .42). Black patients also had a significantly better 1-year overall survival (log-rank, P = .024) and were associated with a significantly decreased 1-year mortality (hazard ratio, 0.65; 95% CI, 0.47-0.91; P = .01) after adjusting for multiple clinical factors. CONCLUSIONS: Although Black patients carried a higher burden of comorbidities, the racial disparities in perioperative outcomes and 1-year survival do not persist in TEVAR.

The transition and outcomes of perioperative low ejection fraction status in cardiac surgical patients.

Low left ventricular ejection fraction (LVEF) was always considered a high-risk factor for surgery. A growing number of patients with preoperative low LVEF have undergone cardiac surgery in recent years. The transition of postoperative LVEF and its correlation with short-term outcomes is not yet clear. We retrospectively collected the clinical data of cardiac surgery patients with low preoperative LVEF (≤40%). LVEF measurements were collected preoperatively and at least twice postoperatively. The primary endpoint was the composite endpoint of hospital mortality or length of intensive care unit (ICU) stay ≥7 days. Univariate logistic regression was used to evaluate the association of each indicator with the outcomes, including calculation of the area under the receiver operating characteristic (ROC) curve. A two-piecewise linear regression model was applied to examine the threshold effect of the LVEF on the composite endpoint using a smoothing function. From 1 January to 31 December 2018, a total of 123 patients had low LVEF preoperatively, of whom 35 (28.5%) met the composite endpoint. LVEF was 35% [interquartile range (IQR) 30%-42%] at first measurement and increased to 40% (IQR 35%-45%) at final measurement during their hospitalization. There was a linear relationship between composite endpoint and lowest level of postoperative LVEF. The base e logarithm of odds ratio [Ln(OR)] of composite endpoint decreased with increasing LVEF (OR = 0.83, 95% confidence interval 0.76-0.91, p < 0.01). Most patients with low preoperative LVEF will benefit from cardiac surgery. The lowest measurement of postoperative LVEF can be used to evaluate the short-term outcome of patients after cardiac surgery.

Extracorporeal membrane oxygenation in the management of granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA, also known as Wegener's granulomatosis) is a type of systematic vasculitis that primarily involves the lung and kidney. Diffuse alveolar hemorrhage (DAH) and associated acute respiratory failure are uncommon but devastating complications of GPA. Experience in using extracorporeal membrane oxygenation (ECMO) to manage DAH caused by GPA is limited. We report two GPA patients with DAH that were successfully managed using ECMO support. Examining 13 cases identified in the literature and two of our own, we observed that most patients experienced rapid deterioration in respiratory function in conjunction with a precedent respiratory infection. All 15 patients received veno-venous ECMO support. The median duration of ECMO support was 11 days (interquartile range: 7.5-20.75 days). Bleeding was the most common complication, seen in four (26.7%) cases. All patients were successfully weaned off ECMO after a median length of hospital stay of 42 days (interquartile range: 30-78 days). We demonstrated that the use of ECMO is a reasonable and effective support option in the management of GPA patients with DAH. The risk of bleeding is high but maybe reduced using a lower anticoagulation goal.

Breast imaging, breast surgery, and cancer genetics in the age of COVID-19.

BACKGROUND: The objective of the current study was to provide insight into the effect of coronavirus disease 2019 (COVID-19) on breast cancer screening, breast surgery, and genetics consultations. METHODS: User data from a risk assessment company were collected from February 2 to April 11, 2020. The use of risk assessment was used as a proxy for the use of 3 breast cancer services, namely, breast imaging, breast surgery, and genetics consultation. Changes in the use of these services during the study period were analyzed. RESULTS: All 3 services experienced significant declines after the COVID-19 outbreak. The decline in breast surgery began during the week of March 8, followed by breast imaging and genetics consultation (both of which began during the week of March 15). Breast imaging experienced the most significant reduction, with an average weekly decline of 61.7% and a maximum decline of 94.6%. Breast surgery demonstrated an average weekly decline of 20.5%. When surgical consultation was stratified as breast cancer versus no breast cancer, the decrease among in non-breast cancer patients was more significant than that of patients with breast cancer (a decline of 66.8% vs 11.5% from the pre-COVID average weekly volume for non-breast cancer patients and patients with breast cancer, respectively). During the week of April 5, use of genetics consultations dropped to 39.9% of the average weekly volumes before COVID-19. CONCLUSIONS: COVID-19 has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment.

Legacy Genetic Testing Results for Cancer Susceptibility: How Common are Conflicting Classifications in a Large Variant Dataset from Multiple Practices?

PURPOSE: The classification of germline variants may differ between labs and change over time. We apply a variant harmonization tool, Ask2Me VarHarmonizer, to map variants to ClinVar and identify discordant variant classifications in a large multipractice variant dataset. METHODS: A total of 7496 variants sequenced between 1996 and 2019 were collected from 11 clinical practices. Variants were mapped to ClinVar, and lab-reported and ClinVar variant classifications were analyzed and compared. RESULTS: Of the 4798 unique variants identified, 3699 (77%) were mappable to ClinVar. Among mappable variants, variants of unknown significance (VUS) accounted for 74% of lab-reported classifications and 60% of ClinVar classifications. Lab-reported and ClinVar discordances were present in 783 unique variants (21.2% of all mappable variants); 121 variants (2.5% of all unique variants) had within-practice lab-reported discordances; and 56 variants (1.2% of all unique variants) had lab-reported discordances across practices. The unmappable variants were associated with a higher proportion of lab-reported pathogenic classifications (50% vs. 21%, p < 0.0001) and a lower proportion of lab-reported VUS classifications (46% vs. 74%, p < 0.0001). CONCLUSIONS: Our study shows that discordant variant classification occurs frequently, which may lead to inappropriate recommendations for prophylactic treatments or clinical management.

Natural language processing to facilitate breast cancer research and management.

The medical literature has been growing exponentially, and its size has become a barrier for physicians to locate and extract clinically useful information. As a promising solution, natural language processing (NLP), especially machine learning (ML)-based NLP is a technology that potentially provides a promising solution. ML-based NLP is based on training a computational algorithm with a large number of annotated examples to allow the computer to "learn" and "predict" the meaning of human language. Although NLP has been widely applied in industry and business, most physicians still are not aware of the huge potential of this technology in medicine, and the implementation of NLP in breast cancer research and management is fairly limited. With a real-world successful project of identifying penetrance papers for breast and other cancer susceptibility genes, this review illustrates how to train and evaluate an NLP-based medical abstract classifier, incorporate it into a semiautomatic meta-analysis procedure, and validate the effectiveness of this procedure. Other implementations of NLP technology in breast cancer research, such as parsing pathology reports and mining electronic healthcare records, are also discussed. We hope this review will help breast cancer physicians and researchers to recognize, understand, and apply this technology to meet their own clinical or research needs.

Trends of 30-day mortality and morbidities in endovascular repair of intact abdominal aortic aneurysm during the last decade.

OBJECTIVE: Significant research efforts have been made to improve the safety and efficacy of endovascular aneurysm repair (EVAR) in treating abdominal aortic aneurysm. This study aimed to examine the trends of perioperative outcomes of EVAR in the recent decade using a national validated database. METHODS: Patients who underwent EVAR for intact abdominal aortic aneurysm between 2006 and 2015 were identified from the National Surgical Quality Improvement Program and divided into early (2006-2010) and late (2011-2015) periods. The primary outcome of the study was 30-day mortality. Secondary outcomes included operative time, length of hospital stay, and 30-day major complications (renal, cardiopulmonary, and wound infection). RESULTS: A total of 30,076 patients were identified, with 11,539 in the early period and 18,537 in the late period. The 30-day mortality was kept at a low level in both periods (1.2% vs 1.2%; P = .98), whereas both the mean operation time (155.5 ± 72.6 minutes vs 141.9 ± 73.7 minutes; P < .001) and length of hospital stay (3.24 ± 5.32 days vs 2.81 ± 4.30 days; P < .001) were decreased in the late period. The 30-day major complication rate was reduced by 19.6% (5.1% vs 4.1%; P < .0001), with decreased renal failure (1.4% vs 1.0%; P = .003), cardiopulmonary complications (2.2% vs 1.7%; P = .006), and wound complications (2.5% vs 1.8%; P < .001). All the decreasing trends of mortality, any 30-day complication, and each type of major complication were statistically significant. Being treated in the late period was independently associated with decreased 30-day major complications (odds ratio, 0.75; 95% confidence interval, 0.65-0.87; P < .001), and this effect was confirmed in the propensity score-matched cohort (odds ratio, 0.76; 95% confidence interval, 0.66-0.90; P < .001). CONCLUSIONS: Although the 30-day mortality remains similar, postoperative complications in EVAR have decreased significantly during the recent decade. The continuous improvement in endograft technology and surgical skills has resulted in decreased operative time, marked reduction in surgical complications, and shorter hospital length of stay after endovascular repair.