Postoperative subphenotypes modified the hepatoma arterial-embolization prognostic score: A novel smHAP-II nomogram.

Background: Three subphenotypes were identified for unresectable hepatocellular carcinoma (uHCC) after frontline transarterial chemoembolization (TACE). This study aimed to develop an individual smHAP-Ⅱ nomogram for uHCC patients after TACE. Methods: Between January 2007 to December 2016, 1517 uHCC patients undergoing TACE were included from four hospitals in China (derivation cohort: 597 cases; validation cohort: 920 cases). Multivariable Cox proportion regression analysis was used to develop a nomogram, incorporating postoperative subphenotypes (Phenotype 1, 2, 3) and HAP score (Score 0 to 4). The model was validated by a 1000-time bootstrap resampling procedure. The performance of the model was compared with existing ones by Harrell's C-index and Area Under Curve (AUC). Results: Postoperative subphenotypes modified the HAP score (smHAP-Ⅱ nomogram) was developed and validated, with the Harrell's C-index of the nomogram was 0.679 (SD: 0.029) for the derivation cohort and 0.727(SD:0.029) for the external cohort. The area under curves of the nomogram for 1-, 3-, and 5-year OS were 0.750, 0.710, and 0.732 for the derivation cohort, respectively (0.789, 0.762, and 0.715 for the external cohort). In the calibration curves stratified by treatment after TACE, the lines for re-TACE and stop-TACE cross at 0.23, indicating that patients with a 3-year predicted survival >23% would not benefit from TACE. Conclusions: The addition of postoperative subphenotypes significantly improved the prognostic performance. The smHAP-Ⅱ nomogram can be used for accurate prognostication and selection of optimal candidates for TACE, with the value to guide sequential treatment strategy.

Reliability and Time Course of Postexercise Hypotension during Exercise Training among Adults with Hypertension.

Postexercise hypotension (PEH), or the immediate decrease in blood pressure (BP) lasting for 24 h following an exercise bout, is well-established; however, the influence of exercise training on PEH dynamics is unknown. This study investigated the reliability and time course of change of PEH during exercise training among adults with hypertension. PEH responders (n = 10) underwent 12 weeks of aerobic exercise training, 40 min/session at moderate-to-vigorous intensity for 3 d/weeks. Self-measured BP was used to calculate PEH before and for 10 min after each session. The intraclass correlation coefficient (ICC) and Akaike Information Criterion (AIC) determined PEH reliability and goodness-of-fit for each week, respectively. Participants were obese (30.6 ± 4.3 kg∙m-2), middle-aged (57.2 ± 10.5 years), and mostly men (60%) with stage I hypertension (136.5 ± 12.1/83.4 ± 6.7 mmHg). Exercise training adherence was 90.6 ± 11.8% with 32.6 ± 4.2 sessions completed. PEH occurred in 89.7 ± 8.3% of these sessions with BP reductions of 9.3 ± 13.1/3.2 ± 6.8 mmHg. PEH reliability was moderate (ICC ~0.6). AIC analysis revealed a stabilization of maximal systolic and diastolic BP reductions at 3 weeks and 10 weeks, respectively. PEH persisted throughout exercise training at clinically meaningful levels, suggesting that the antihypertensive effects of exercise training may be largely due to PEH. Further studies in larger samples and under ambulatory conditions are needed to confirm these novel findings.

Prognosis of Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization(MC-hccAI 001): Development and Validation of the ALFP Score.

Background: Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage Hepatocellular carcinoma (HCC) patients. However, predicting the survival of HCC patients receiving TACE remains challenging. Methods: In this retrospective study, we analyzed a total of 1805 HCC patients who received TACE. The patients were randomly divided into a training set (n = 1264) and a validation set (n = 541). We examined various prognostic factors within the training set and developed a simple ALFP (ALBI grade, AFP, and Prothrombin time) score, which was subsequently validated using the independent validation set. Results: Our multivariate analysis revealed that baseline ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s were independent unfavorable prognostic factors for HCC patients receiving TACE (p < 0.05). Based on these findings, we constructed the ALFP score, which assigns 1 point each for ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s. The score has a range of 0 to 3, and higher scores are associated with poorer outcomes. The median overall survival (OS) varied significantly among different ALFP score groups, both in the training set and the validation set (p < 0.001). We further examined the ALFP score in subgroups based on tumor diameter and the number of intrahepatic lesions. In each subgroup, higher ALFP scores were consistently associated with lower OS (p < 0.05). Conclusion: Our study confirms the prognostic value of the ALFP score in predicting the survival of HCC patients undergoing TACE. The score incorporates easily obtainable baseline parameters and provides a simple and practical tool for risk stratification and treatment decision-making in HCC patients.

Mechanical mechanism to induce inspiratory flow limitation in obstructive sleep apnea patients revealed from in-vitro studies.

Inspiratory flow limitation means that when the flowrate reaches a certain value, it no longer increases, or even decreases, which is called negative effort dependence flow limitation, even if the inspiration effort is increased. This occurs often in obstructive sleep apnea patients, but its mechanism remains unclear. To reveal the mechanism of inspiratory flow limitation, we constructed a unique partially collapsible in-vitro upper airway model of obstructive sleep apnea patients to observe the change of airway resistance with inspiratory driving pressure. The important findings demonstrate that with the increase of inspiratory effort, the driving pressure increases faster than the airway resistance in the early stages, and then the reverse occurs as the airway becomes narrower. The airway collapse caused by the transmural pressure can lead to a rapid increase in downstream resistance with the increase of inspiratory effort, which is the key reason causing the flow reduction and the formation of typical negative effort dependence flow limitation. The mechanical mechanism revealed in this study will lead to fully new insights into the study and treatment of obstructive sleep apnea.

Childhood beverage intake and risk of hypertension and hyperlipidaemia in young adults.

An epidemiological analysis assessing beverage consumption and risk factors for cardiovascular disease was conducted. Participants were 9-16 years old at enrolment, completed food frequency questionnaires in 1996-2001 and self-reported outcomes in 2010-2014. Exclusion criteria included missing data on relevant variables and covariates, prevalent disease before 2005, and implausible/extreme weight or energy intake. Intakes of orange juice, apple/other fruit juice, sugar-sweetened beverages and diet soda were related to the risk of incident hypertension or hyperlipidaemia using Cox proportional hazards regression, adjusting for diet, energy intake, age, smoking, physical activity and body mass index. There were 9,043 participants with 618 cases of hypertension and 850 of hyperlipidaemia in 17 years of mean follow-up. Sugar-sweetened beverage intake but not fruit juice nor diet soda was associated with hypertension (hazard ratio (95% confidence interval): 1.16 (1.03, 1.31)) in males. This study can guide beverage consumption as it relates to early predictors of cardiovascular disease.

Do the combined blood pressure effects of exercise and antihypertensive medications add up to the sum of their parts? A systematic meta-review.

OBJECTIVE: To compare the blood pressure (BP) effects of exercise alone (EXalone), medication alone (MEDSalone) and combined (EX+MEDScombined) among adults with hypertension. DATA SOURCES: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature, SPORTDiscus and the Cochrane Library. ELIGIBILITY CRITERIA: Randomised controlled trails (RCTs) or meta-analyses (MAs) of controlled trials that: (1) involved healthy adults>18 year with hypertension; (2) investigated exercise and BP; (3) reported preintervention and postintervention BP and (4) were published in English. RCTs had an EX+MEDScombined arm; and an EXalone arm and/or an MEDSalone arm; and MAs performed moderator analyses. DESIGN: A systematic network MA and meta-review with the evidence graded using the Physical Activity Guidelines for Americans Advisory Committee system. OUTCOME: The BP response for EXalone, MEDSalone and EX+MEDScombined and compared with each other. RESULTS: Twelve RCTs qualified with 342 subjects (60% women) who were mostly physically inactive, middle-aged to older adults. There were 13 qualifying MAs with 28 468 participants (~50% women) who were mostly Caucasian or Asian. Most RCTs were aerobic (83.3%), while the MAs involved traditional (46%) and alternative (54%) exercise types. Strong evidence demonstrates EXalone, MEDSalone and EX+MEDScombined reduce BP and EX+MEDScombined elicit BP reductions less than the sum of their parts. Strong evidence indicates EX+MEDScombined potentiate the BP effects of MEDSalone. Although the evidence is stronger for alternative than traditional types of exercise, EXaloneelicits greater BP reductions than MEDSalone. CONCLUSIONS: The combined BP effects of exercise and medications are not additive or synergistic, but when combined they bolster the antihypertensive effects of MEDSalone. PROSPERO REGISTRATION NUMBER: The protocol is registered at PROSPERO CRD42020181754.

Associations between fruit juice and milk consumption and change in BMI in a large prospective cohort of U.S. adolescents and preadolescents.

BACKGROUND: There are concerns that fruit juice and milk contribute to childhood obesity. OBJECTIVE: Determine the relationship between fruit juice and milk intakes and body mass index (BMI) change among preadolescents/adolescents. METHODS: Participants aged 9 to 16 years old from the Growing Up Today Study II completed surveys including validated food frequency questionnaires in 2004, 2006 and 2008. The contributions of one serving of juice or milk to total energy intake and 2-year change in BMI were evaluated using multiple linear regression. Additional analyses were conducted with subgroups of juice (orange juice and other fruit juice) and milk (low fat and high fat). Missing values for BMI were imputed using a multiple imputation approach, after which data from 8173 participants and 13 717 2-year interval observations were analysed. RESULTS: Baseline fruit juice consumption was inversely associated with BMI change in girls (ß = -.102 kg/m2 , SE = 0.038, P value = .008) but not boys after controlling for race, age, baseline BMI, and baseline and 2-year changes in total energy intake and physical activity. Orange juice was inversely associated with BMI change among girls (ß = -.137 kg/m2 , SE = 0.053, P value = .010) while other fruit juice, low fat and high fat milk were not associated with BMI change. CONCLUSION: Orange juice was inversely associated with 2-year BMI change among preadolescent/adolescent girls but not boys and there were no significant associations with other juices or milk among either gender.

Synthesis of functionalized 5-substituted thiazolidine-2-thiones via adscititious xanthate-promoted radical cyclization of allyl(alkyl/aryl)dithiocarbamates.

Functionalized 5-substituted thiazolidine-2-thiones were synthesized efficiently from alkyl allyl(alkyl/aryl)-dithiocarbamates via radical cyclization with the corresponding S-alkyl O-ethyl xanthates as the adscititious radical precursors. The application of the adscititious radical precursors improves not only the yields, but also the efficiency in the radical cyclization reaction significantly. The current adscititious radical precursor method provides a new strategy for the achievement and improvement of some radical reactions which are hardly or difficultly realized by the traditional direct methods.