AFP score and metroticket 2.0 perform similarly and could be used in a "within-ALL" clinical decision tool.

Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs. 0.68; p = 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models ("within-ALL") at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6). Conclusions: In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach. Impact and implications: Composite models were recently proposed for the selection of liver transplant (LT) candidates among individuals with hepatocellular carcinoma (HCC). We found that both the AFP score and Metroticket 2.0 predicted post-LT HCC recurrence and survival better than Milan criteria; the Metroticket 2.0 did not result in better reclassification for transplant selection compared to the AFP score, with predictive gaps and overlaps between the two models; patients who met low-risk thresholds for both models had the lowest 5-year recurrence rate. We propose prospectively testing the combination of both models, to further optimize the LT selection process for candidates with HCC.

Acute kidney injury following cardiopulmonary bypass in Jamaica.

Objectives: The study objectives were to describe the incidence, risk factors, and outcomes of acute kidney injury after cardiopulmonary bypass in Jamaica. Method: We performed a review of the medical records of adult patients (aged ≥ 18 years) with no prior dialysis requirement undergoing cardiopulmonary bypass at the University Hospital of the West Indies, Mona, between January 1, 2016, and June 30, 2019. Demographic, preoperative, intraoperative, and postoperative data were abstracted. Acute kidney injury was defined using Kidney Disease Improving Global Outcomes criteria. The primary outcomes were acute kidney injury incidence and all-cause 30-day mortality. Multivariable logistic regression and Cox proportional analyses were used to examine the association between the acute kidney injury risk factors and the primary outcome. Results: Data for 210 patients (58% men, mean age 58.1 ± 12.9 years) were analyzed. Acute kidney injury occurred in 80 patients (38.1%), 44% with Kidney Disease Improving Global Outcomes I, 33% with Kidney Disease Improving Global Outcomes II, and 24% with Kidney Disease Improving Global Outcomes III. From multivariable logistic regression models, European System for Cardiac Operative Risk Evaluation II (odds ratio, 1.19; 95% confidence interval, 1.01-1.39 per unit), bypass time (odds ratio, 1.94; 95% confidence interval, 1.40-2.67 per hour), perioperative red cell transfusion (odds ratio, 3.03; 95% confidence interval, 1.36-6.76), and postoperative neutrophil lymphocyte ratio (odds ratio, 1.65; 95% confidence interval, 1.01-2.68 per 10-unit difference) were positively associated with acute kidney injury. Acute kidney injury resulted in greater median hospital stay (18 vs 11 days, P < .001) and intensive care unit stay (5 vs 3 days, P < .001), and an 8-fold increase in 30-day mortality (hazard ratio, 8.15; 95% confidence interval, 2.76-24.06, P < .001). Conclusions: Acute kidney injury after cardiopulmonary bypass surgery occurs frequently in Jamaica and results in poor short-term outcomes. Further studies coupled with quality interventions to reduce the mortality of those with acute kidney injury are needed in the Caribbean.

Current Medical Treatment for Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

Early systolic lengthening by speckle tracking echocardiography predicts outcome after coronary artery bypass surgery.

BACKGROUND: Early systolic lengthening (ESL), a paradoxical stretch of myocardial fibers, has been linked to loss of myocardial viability and contractile dysfunction. We assessed the long-term prognostic potential of ESL in coronary artery bypass graft (CABG) patients. METHODS: We retrospectively included patients (n = 709; mean age 68 years; 85% men) who underwent speckle tracking echocardiography (median 15 days) prior to CABG. Endpoints were cardiovascular death (CVD) and all-cause mortality. We assessed amplitude of ESL (%), defined as peak positive strain, and duration of ESL (ms), determined as time from Q-wave on the ECG to peak positive strain. We applied Cox models adjusted for clinical risk assessed as EuroSCORE II. RESULTS: During median follow-up of 3.8 years [IQR 2.7-4.9 years], 45 (6%) experienced CVD and 80 (11%) died. In survival analyses adjusted for EuroSCORE II, each 1% increase in amplitude of ESL was associated with CVD (HR 1.35 [95%CI 1.09-1.68], P = 0.006) and all-cause mortality (HR 1.29 [95%CI 1.08-1.54], P = 0.004). Similar findings applied to duration of ESL (per 10ms increase) and CVD (HR 1.12 [95%CI 1.02-1.23], P = 0.016) and all-cause mortality (HR 1.09 [95%CI 1.01--1.17], P = 0.031). The prognostic value of ESL amplitude was modified by sex (P interaction < 0.05), such that the prognostic value was greater in women for both endpoints. When adding ESL duration to EuroSCORE II, the net reclassification index improved significantly for both CVD and all-cause mortality. CONCLUSIONS: Assessment of ESL provides independent and incremental prognostic information in addition to the EuroSCORE II for CVD and all-cause mortality in CABG patients.

Permanent pacemaker placement following valve surgery is not independently associated with worse outcomes.

Background: Permanent pacemaker placement (PPM) is associated with morbidity following cardiac surgery. This study identified associations between PPM placement and 5-year outcomes for patients that require PPM following valvular surgery. Methods: All patients who underwent valvular surgery at our medical center from 2011 to 2018 were considered for analysis. Multivariable analysis identified associations between PPM placement, mortality, and readmissions. Primary outcomes were operative complications and mortality. Secondary outcomes included 5-year survival and readmission. Results: A total of 175 (4.86%) of 3602 valvular surgery patients required postoperative PPM. The PPM cohort had significantly worse baseline comorbidities, including greater Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) scores (3.8 vs 2.4 P < .0001). The PPM cohort had greater rates of blood product transfusion, prolonged ventilation, and new-onset atrial fibrillation. PPM placement was significantly associated with third-degree heart block (5.26; 95% confidence interval [95% CI], 1.00-27.53; P = .0496), ventricular fibrillation/tachycardia (3.90; 95% CI, 1.59-9.59; P = .01), and atrial fibrillation/flutter (1.53; 95% CI, 1.05-2.24; P = .03). On Kaplan-Meier estimates, 5-year survival (68.8% vs 83.1%; P = 01) was significantly reduced in the PPM cohort. Five-year all-cause readmission (60.4% vs 50.04%; P = .01) and heart failure readmission (35.5% vs 20.1%; P < .000) occurred more frequently in the PPM cohort. On multivariable Cox regression analysis, PPM placement (hazard ratio, 1.12; 95% CI, 0.84-1.50; P = .444) was not an independent predictor of mortality. On competing risk analysis, PPM (hazard ratio, 1.33; 95% CI, 0.99-1.80; P = .062) was not a predictor of hospital readmission. Conclusions: Valvular surgery patients who required postoperative PPM had elevated baseline operative risk. However, PPM implantation was not associated with mortality or readmission.

COVID-19 in liver transplant recipients.

Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients; (2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.

Provider delay in treatment initiation and its influence on survival outcomes in women with operable breast cancer.

AIM: The goal of this study was to determine whether a delay in starting treatment via surgery or neoadjuvant chemotherapy is related to a decrease in cancer-specific survival (CSS) in women with operable breast cancer (BrCr). BACKGROUND: Limited medical infrastructure and a lack of cancer prevention awareness in low- and middle-income countries have caused high BrCr incidence and mortality rates. METHODS: We analyzed a retrospective cohort of 720 women treated at a single center from 2005 to 2012. CSS estimates were obtained by the Kaplan-Meier method. A Cox model of proportional risks was performed to obtain the risk of dying from BrCr. We also obtained the risk according to the category of treatment initiation. RESULTS: Women with locally advanced stages and without hormone receptor expression were more likely to initiate treatment after 45 days. Patients in Stage IIIA had a 78.1% survival if treatment was initiated before 45 days (95% CI, 0.70-0.84) and 63.6% survival if treatment was started after 45 days (95% CI, 0.44-0.78; p < 0.001). Patients in Stage IIIB had a 62.9% survival if treatment was initiated before 45 days (95% CI, 0.53-0.72) and 57.4% survival if treatment started after 45 days (95% CI, 0.31-0.89; p < 0.001). Prognostic factors in which lower survival was recognized were Stage IIIA, Stage IIIB, treatment initiation after 45 days, and triple-negative tumors. CONCLUSIONS: The initiation of treatment within the first 45 days of diagnosis of BrCr in women portends better survival compared with those who began treatment longer than 45 days from diagnosis.

Efficacy of Dexrazoxane in Preventing Anthracycline Cardiotoxicity in Breast Cancer.

OBJECTIVES: The authors performed a systematic review and meta-analysis of randomized and nonrandomized trials on the efficacy of dexrazoxane in patients with breast cancer who were treated with anthracyclines with or without trastuzumab. BACKGROUND: Breast cancer treatment with anthracyclines and trastuzumab is associated with an increased risk of cardiotoxicity. Among the various strategies to reduce the risk of cardiotoxicity, dexrazoxane is an option for primary prevention, but it is seldom used in clinical practice. METHODS: Online databases were searched from January 1990 up to March 1, 2019, for clinical trials on the use of dexrazoxane for the prevention of cardiotoxicity in patients with breast cancer receiving anthracyclines with or without trastuzumab. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model meta-analysis. RESULTS: Seven randomized trials and 2 retrospective trials with a total of 2,177 patients were included. Dexrazoxane reduced the risk of clinical heart failure (RR: 0.19; 95% CI: 0.09 to 0.40; p < 0.001) and cardiac events (RR: 0.36; 95% CI: 0.27 to 0.49; p < 0.001) irrespective of previous exposure to anthracyclines. The rate of a partial or complete oncological response, overall survival, and progression-free survival were not affected by dexrazoxane. CONCLUSIONS: Dexrazoxane reduced the risk of clinical heart failure and cardiac events in patients with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and did not significantly impact cancer outcomes. However, the quality of available evidence is low, and further randomized trials are warranted before the systematic implementation of this therapy in clinical practice.

Micronutrient status in middle childhood and age at menarche: results from the Bogotá School Children Cohort.

Childhood intake of animal foods is associated with age at first menstrual period (menarche). It is unknown whether the micronutrients present in these foods could explain this association. Our objective was to investigate the associations of micronutrient status biomarkers in middle childhood with age at menarche. We quantified circulating Hb, ferritin, mean corpuscular volume, Zn, vitamin B12, erythrocyte folate and retinol in 1464 pre-menarcheal girls aged 5-12 years in Bogotá, Colombia, and followed them for a median 5·7 years for the occurrence and date of menarche. We estimated median age at menarche and hazard ratios (HR) with 95 % CI by levels of each biomarker with use of Kaplan-Meier survival probabilities and Cox regression, respectively. Median age at menarche was 12·4 years. Middle childhood Hb was inversely related to age at menarche whereas plasma ferritin was positively associated with this outcome in a linear manner. HR of menarche for every 1 sd of Hb (11 g/l) and ferritin (23·2 µg/l) were 1·11 (95 % CI 1·04, 1·18; P=0·001) and 0·94 (95 % CI 0·88, 0·99; P=0·02), respectively, after adjustment for baseline age, C-reactive protein concentration, maternal age at menarche and parity and socioeconomic status. The association with ferritin was stronger in girls aged 9-10 years at baseline. Additional adjustment for baseline height- and BMI-for-age did not change the results. We conclude that higher Fe status in middle childhood is related to later age at menarche whereas Hb concentrations are inversely associated with age at onset of menses.

Egg and cholesterol intake and incident type 2 diabetes among French women.

Egg consumption is a major source of dietary cholesterol, a nutrient that may disrupt glucose metabolism. We prospectively evaluated the relation between egg consumption and cholesterol-intake and diabetes in 65 364 French disease-free women who responded to a validated diet history questionnaire in 1993. Egg consumption included hardboiled eggs and eggs consumed in an omelette or a mixed dish, and dietary cholesterol was estimated using a French nutrient database. Over 14 years of follow-up, 1803 incident diabetes cases were identified through self-reports, supplementary questionnaires and drug reimbursement information. Multivariable Cox regression models were adjusted for age, education, menopause, menopausal hormone therapy, hypertension and hypercholesterolaemia, BMI, physical activity, smoking, alcohol, fruit, vegetables, processed red meat, coffee and sugar and artificially sweetened beverages. No association was observed between egg consumption and risk of type 2 diabetes. When comparing women who consumed at least five eggs per week with non-consumers, the multivariable hazard ratio (HR) was found to be 1·00 (95 % CI 0·78, 1·29; across categories, P trend=0·11). Women in the highest quintile of dietary cholesterol had a 40 % higher rate of diabetes compared with those in the lowest quintile (HR 1·40; 95 % CI 1·19, 1·63; across quintiles, P trend<0·0001). A 100 mg increase of dietary cholesterol per 4184 kJ (or 1000 kcal) was associated with a 14 % increase in the risk of diabetes (HR 1·14; 95 % CI 1·02, 1·26). In this large prospective cohort, we observed an association between dietary cholesterol and type 2 diabetes, but no association with egg consumption. In the absence of a clear underlying mechanism and potential residual confounding, these results should be interpreted with caution.