The incidence, pathogenesis, and management of non-clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and is divided into two distinct subtypes, clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC). Although many treatments exist for RCC, these are largely based on clinical trials performed in ccRCC and there are limited studies on the management of nccRCC. Non-clear cell RCC consists of multiple histological subtypes: papillary, chromophobe, translocation, medullary, collecting duct, unclassified, and other rare histologies. Due to variations in pathogenesis and therapeutic response, therapy should be tailored to specific variant histologies. For patients with localized nccRCC, surgical resection remains the gold standard. In the metastatic setting, the standard of care has yet to be clearly defined, and most guidelines recommend clinical trial participation. General therapeutic options include immunotherapy, either as monotherapy or in combination, targeted therapies such as vascular endothelial growth factor tyrosine kinase inhibitors and MET inhibitors, and chemotherapy in certain subtypes. Here we present a review of the incidence and pathogenesis of the various subtypes, as well as available clinical data to support therapeutic recommendations for these subtypes. We also highlight currently available clinical trials in nccRCC and future directions in investigating novel treatment modalities tailored to patients with variant histology.

The emerging roles of next-generation metabolomics in critical care nutrition.

Critical illness leads to millions of deaths worldwide each year, with a significant surge due to the COVID-19 pandemic. Patients with critical illness are frequently associated with systemic metabolic disorders and malnutrition. The idea of intervention for critically ill patients through enteral and parenteral nutrition has been paid more and more attention gradually. However, current nutritional therapies focus on evidence-based practice, and there have been lacking holistic approaches for nutritional support assessment. Metabolomics is a well-established omics technique in system biology that enables comprehensive profiling of metabolites in a biological system and thus provides the underlying information expressed and modulated by all other omics layers. In recent years, with the development of high-resolution and accurate mass spectrometry, metabolomics entered a new "generation", promoting its broader applications in critical care nutrition. In this review, we first described the technological development and milestones of next-generation metabolomics in the past 20 years. We then discussed the emerging roles of next-generation metabolomics in advancing our understanding of critical care nutrition, such as nutritional deficiency risk evaluation, metabolic mechanisms of nutritional therapies, and novel nutrition target identification.

Health promotion challenges for young adults living with intellectual disability and type 1 diabetes.

BACKGROUND: Self-management of type 1 diabetes mellitus (T1DM) can be challenging for people with intellectual disability. Often, parents provide health support due to lack of appropriate services outside the home. The study aim was to identify barriers and facilitators to T1DM self-management for young adults with intellectual disability and the implications for health promotion. METHODS: Five male participants with intellectual disability, aged 17-26 years, and seven parents were interviewed between October 2017 and February 2019. Interview data were descriptively analysed. FINDINGS: Two categories for barriers and facilitators were identified: 1) Diabetes self-management is complex (carbohydrate counting, blood glucose level monitoring, insulin therapy); 2) support for diabetes care (reliance on parents and carers, the National Disability Insurance Scheme, mainstream diabetes service support). CONCLUSIONS: Parents are critical for the support of people with intellectual disability and T1DM in the absence of disability staff with appropriate health skills.

Protein energy wasting-based nutritional assessment predicts outcomes of acute ischemic stroke and solves the epidemiologic paradox.

OBJECTIVE: Overweight and hyperlipidemia, the two established risk factors for acute ischemic stroke, are paradoxically associated with favorable outcomes. The paradox may be resolved by the concept of protein energy wasting (PEW), in which total cholesterol level and body mass index are used as nutritional indexes for predicting outcomes of chronic kidney disease. METHODS: Among 12 271 people with acute ischemic stroke and chronic kidney disease, 2086 were defined as being at risk of PEW-with a body mass index <22 kg/m2 plus either a serum albumin level <38 g/L or a total cholesterol level <4.14 mmol/L (160 mg/dL) without the use of lipid-lowering drugs-and all the others were a control group. The hazards of PEW for mortality and functional outcomes were evaluated using propensity score matching and multivariate Cox regression analysis. RESULTS: Based on the propensity score, 2081 PEW participants were matched to the same number of non-PEW control participants. PEW was associated with a higher mortality risk at 3 mo (adjusted hazard ratio, 1.19; 95% confidence interval [CI], 1.02-1.42) and 1 y (adjusted hazard ratio, 1.33; 95% CI1.13-1.52). PEW was also associated with poor functional outcomes (modified Rankin Scale score >2) at 1 mo (adjusted odds ratio, 1.32; 95% CI, 1.08-1.61) and 3 mo (adjusted odds ratio, 1.27; 95% CI, 1.03-1.56). CONCLUSIONS: According to the PEW-based assessment system, a modest decrease in body mass index and total cholesterol levels suggests malnutrition and is associated with adverse outcomes of acute ischemic stroke.

The geochemical behavior of trace metals and nutrients in submerged sediments of the Three Gorges Reservoir and a critical review on risk assessment methods.

Permanently submerged sediment samples (SS) were collected in the center stream of eleven tributaries of Changjiang (Yangtze River) and at eight confluence zones in the Three Gorges Reservoir (TGR) in May and December of 2017. The work showed that aqua regia digestion is a simpler, more reliable and robust method compared to total digestion with hydrofluoric acid (HF) for the determination of trace metals (TMs) in sediment for risk assessment purpose. Our study revealed a remarkable accumulation of TMs at the confluence zones and a trend of their gradual increase toward this zone. The presence of iron and manganese (oxy)hydroxides combined with hydrodynamic conditions created by the Three Gorges Dam (TGD) and its operation are believed to play a crucial role. This work also found that concentrations of [Formula: see text] in May sediment were significantly higher than those in December, which could have been caused by both the cyclic hydrodynamic conditions and the warmer water. TOC and TP were both very low in the sediment. Although TN was 2 times higher than the Lowest Effect Level suggested by the Ontario Ministry of Environment, it is uncertain if it reflects a natural background level or due to anthropogenic activities. A critical discussion is made by comparing the conclusions obtained when using different TMs risk assessment models. Necessary precautions are highly recommended when performing this exercise. In this study, no significant risk from either TMs or nutrients was identified.

Water quality assessment based on the water quality index method in Lake Poyang: The largest freshwater lake in China.

Twenty-four samplings were conducted every 3 months at 15 sites from January 2009 to October 2014 in Lake Poyang, and 20 parameters were analyzed and classified into three groups (toxic metals, easily treated parameters, and others). The assessment results based on water quality index (WQI) showed that the water quality in Lake Poyang was generally "moderate", according to the classification of the surface water quality standard (GB3838-2002) in China, but a deteriorating trend was observed at the interannual scale. Seasonally, the water quality was best in summer and worst in winter. Easily treated parameters generally determined the WQI value in the assessment, especially total nitrogen (TN) and total phosphorus (TP), while toxic metals and other parameters in Lake Poyang were generally at low and safe levels for drinking water. Water level (WL) has a net positive effect on water quality in Lake Poyang through dilution of environmental parameters, which in practice means TN. Consequently, local management agencies should pay more attention to nutrient concentrations during the monitoring schedule, as well as during the low-water periods which manifest a relatively bad water quality state, especially with the prevailing low WL observed recently in Lake Poyang.

Safety and Effectiveness of Intravenous Thrombolysis for Acute Ischemic Stroke Outside the Coverage of National Health Insurance in Taiwan.

PURPOSE: Only a small percentage of ischemic stroke patients were treated with intravenous thrombolysis in Taiwan, partly because of the narrow reimbursement criteria of the National Health Insurance (NHI). We aimed to assess the safety and effectiveness of intravenous thrombolysis not covered by the NHI. METHODS: This is a retrospective analysis of register data from four hospitals. All patients who received intravenous tissue plasminogen activator and fulfilled the American Heart Association/American Stroke Association (AHA/ASA) thrombolysis guidelines between January 2007 and June 2012 were distinguished into two groups: those in accordance (reimbursement group) and those not in accordance (non-reimbursement group) with the NHI reimbursement criteria. Primary outcome was symptomatic intracerebral hemorrhage (SICH). Secondary outcomes were dramatic improvement in the National Institutes of Health Stroke Scale (NIHSS) score at discharge, good functional outcome (modified Rankin Scale ≤2) at discharge, and all-cause in-hospital mortality. RESULTS: In 569 guideline-eligible patients, 177 (31%) were treated without reimbursement. The reasons for exclusion from reimbursement included age >80 (n=42), baseline NIHSS less than 6 (n=29), baseline NIHSS >25 (n=15), thrombolysis beyond 3 hours (n=49), prior stroke with diabetes (n=28), use of oral anticoagulant (n=2), and more than one contraindication (n=12). Overall, we observed no differences between the reimbursement and non-reimbursement groups in the rate of SICH (7% versus 6%), dramatic improvement (36% versus 36%), good functional outcome (39% versus 37%), and in-hospital mortality (8% versus 6%) Conclusion: In stroke patients treated with intravenous thrombolysis according to the AHA/ASA guidelines, the outcomes were comparable between the reimbursement and non-reimbursement groups.

National Trends in Admission for Aspiration Pneumonia in the United States, 2002-2012.

RATIONALE: Aspiration pneumonia is a subset of pneumonias prevalent in elderly patients and patients with neurologic disorders. Researchers in previous studies mostly reported incidence and/or mortality rates based on regional data or in specific subgroups of patients. There is a paucity of nationwide data in the contemporary U.S. OBJECTIVES: To describe U.S. national trends in acute care hospital admission for aspiration pneumonia from 2002 to 2012. METHODS: We used the U.S. National (Nationwide) Inpatient Sample database to identify patients admitted with a primary diagnosis of aspiration pneumonia between 2002 and 2012. We estimated trends in the incidence, in-hospital mortality, length of stay, and total hospitalization cost for patients admitted for aspiration pneumonia and stratified on the basis of patient age (≥65 yr vs. <65 yr). Multivariable logistic regression analysis was used to identify independent predictors for in-hospital mortality. RESULTS: A total of 406,798 patients (weighted total, 1,741,517) admitted for aspiration pneumonia were included in this study. There were 84,200 (20.7%) patients younger than 65 years of age and 322,598 patients (79.3%) aged 65 years or older. From 2002 to 2012, the overall incidence of aspiration pneumonia decreased from 8.2 to 7.1 cases per 10,000 people, and in-hospital mortality decreased from 18.6 to 9.8%. For patients aged 65 years or older, the incidence decreased from 40.7 to 30.9 cases per 10,000 people, and the in-hospital mortality decreased from 20.7 to 11.3%. The median total hospitalization charges increased in both groups (age ≥65 yr, from $16,173 to $30,280; age <65 yr, from $17,517 to $30,526). In multivariable logistic analysis, patients aged 65 years or older or treatment in a nonteaching hospital were independent predictors of in-hospital mortality. CONCLUSIONS: The incidence and mortality of patients admitted to acute care hospitals for aspiration pneumonia decreased between 2002 and 2012 in the United States. This difference was more evident for elderly patients. However, the cost of hospitalization almost doubled. Being older than 65 years of age is an independent predictor of in-hospital mortality among patients admitted for aspiration pneumonia. Strategies to prevent aspiration pneumonia in the community should be implemented in the aging U.S.

Validation of a novel claims-based stroke severity index in patients with intracerebral hemorrhage.

BACKGROUND: Stroke severity is an important outcome predictor for intracerebral hemorrhage (ICH) but is typically unavailable in administrative claims data. We validated a claims-based stroke severity index (SSI) in patients with ICH in Taiwan. METHODS: Consecutive ICH patients from hospital-based stroke registries were linked with a nationwide claims database. Stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes, assessed using the modified Rankin Scale (mRS), were obtained from the registries. The SSI was calculated based on billing codes in each patient's claims. We assessed two types of criterion-related validity (concurrent validity and predictive validity) by correlating the SSI with the NIHSS and the mRS. Logistic regression models with or without stroke severity as a continuous covariate were fitted to predict mortality at 3, 6, and 12 months. RESULTS: The concurrent validity of the SSI was established by its significant correlation with the admission NIHSS (r = 0.731; 95% confidence interval [CI], 0.705-0.755), and the predictive validity was verified by its significant correlations with the 3-month (r = 0.696; 95% CI, 0.665-0.724), 6-month (r = 0.685; 95% CI, 0.653-0.715) and 1-year (r = 0.664; 95% CI, 0.622-0.702) mRS. Mortality models with NIHSS had the highest area under the receiver operating characteristic curve, followed by models with SSI and models without any marker of stroke severity. CONCLUSIONS: The SSI appears to be a valid proxy for the NIHSS and an effective adjustment for stroke severity in studies of ICH outcome with administrative claims data.

Physicochemical properties and intestinal protective effect of ultra-micro ground insoluble dietary fibre from carrot pomace.

Carrot pomace is an abundant, but underutilized, byproduct from the juice industry. In this study, the insoluble dietary fiber from carrot pomace was treated using an ultra-microgrinding process, and the resulting changes in its physicochemical properties and intestinal protective effect against heavy metal damage were examined. The SEM and fluorescence microscopy results showed that the grinding process could significantly decrease the particle size of carrot insoluble dietary fibre and increase its Brunauer-Emmett-Teller surface area from 0.374 to 1.835 m(2) g(-1). Correspondingly, the water-holding capacity, swelling capacity, and oil-holding capacity increased by 62.09%, 49.25% and 45.45%, respectively. The glucose-, nitrite-, and lead ion-adsorbing abilities also improved significantly compared with the raw samples. In addition, apoptosis assessment by AO/EB revealed that the ground fibre could effectively protect Caco-2 cells from lead ion damage. The MTT assay showed that carrot insoluble dietary fibre has no toxicity for Caco-2 cells at a concentration of 10.0 mg L(-1). The findings of this study highlighted the potential of the ultra-microgrinding process to produce a high added-value fibre ingredient from carrot residues.

Cost-effectiveness of Management Options for Small Renal Mass: A Systematic Review.

Costs of surgery for small renal masses (SRMs) are high. This study aimed to systematically review and evaluate the cost-effectiveness analyses of management options for SRMs. Six databases were searched from inception to August 2015. Inclusion criteria were full original research, full economic evaluation of management options for SRM, and written in English. Among 776 studies screened, 6 met the inclusion criteria. Ablation was cost-effective versus nephron-sparing surgery. Laparoscopic partial nephrectomy was cost-effective versus the open approach. Renal mass biopsy dominated immediate treatment in the United States, but not in Canada. According to the Consolidated Health Economic Evaluation Reporting Standards, all the studies had relatively good quality. Despite the observed evidence, future research is needed to fill in the knowledge gap. A few suggestions should be kept in mind such as conducting the cost-effectiveness analysis in a variety of countries.

Shifting brachytherapy monotherapy case mix toward intermediate-risk prostate cancer.

PURPOSE: The relative use of brachytherapy (BT) for prostate cancer has declined in recent years. In this setting, we sought to determine whether the case mix of BT monotherapy-treated men has changed over time in terms of risk group composition. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was used to identify 30,939 patients diagnosed with prostate adenocarcinoma between 2004 and 2011 who received BT monotherapy. The case mix of BT monotherapy patients was calculated by patient risk group and year of diagnosis. RESULTS: Between 2004 and 2011, the use of BT monotherapy declined overall. The relative percentage of men undergoing BT with low-risk disease declined by 4.5%, whereas the relative percentage of patients with intermediate-risk disease increased by 4.7%. Non-white patients and those from poorer counties did not show shifts in the risk group makeup of BT monotherapy patients, whereas white patients and those from wealthier counties did. CONCLUSIONS: Although fewer patients with prostate cancer are undergoing BT monotherapy, men with intermediate-risk disease comprised a significantly larger portion of the BT case mix in 2011 compared with 2004. Future research efforts by brachytherapists should be directed toward improving BT technique, optimizing radiation doses, and obtaining long-term followup data for patients with intermediate-risk prostate cancer.

Increased risk of first-ever stroke in younger patients with atrial fibrillation not recommended for antithrombotic therapy by current guidelines: a population-based study in an East Asian cohort of 22 million people.

OBJECTIVE: To assess the risk of first-ever ischemic stroke in younger patients with atrial fibrillation (AF) who have none of the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category [female sex]) risk factors (excluding female sex) by using the National Health Insurance research database in Taiwan. PATIENTS AND METHODS: From 22,842,778 insured people, we identified 24,612 hospitalized patients with newly diagnosed AF between January 1, 2002, and December 31, 2004, as the AF group and randomly selected 98,448 age- and sex-matched persons without AF as the non-AF group. Both groups were followed up until December 31, 2010, to estimate ischemic stroke incidences in relation to other stroke risk factors. RESULTS: During a follow-up period of 89,468 person-years, the stroke rate was higher in patients with AF than in those without AF (5.79 per 100 person-years vs 2.25 per 100 person-years). The higher prevalence of CHA2DS2-VASc comorbidities (heart failure, hypertension, diabetes, coronary artery disease, and peripheral artery disease) in patients with AF further increased the stroke risk. In 790 patients with AF aged 30 to 55 years who had none of the CHA2DS2-VASc comorbidities at baseline and retained a "low risk," that is, those with a CHA2DS2-VASc score of 0 in men and 1 in women during follow-up, the stroke rate remained considerably higher than that in their non-AF counterparts (1.00 per 100 person-years vs 0.25 per 100 person-years), with a sex-adjusted hazard ratio of 4.09 (95% CI, 2.97-5.62). CONCLUSION: This study finds an increased risk of stroke in younger patients with AF who are not recommended for prevention of thromboembolism by current guidelines. Better stroke risk stratification tools are needed to prioritize younger patients with AF for thromboprophylactic therapy in this population.

Distribution of polycyclic aromatic hydrocarbon (PAH) residues in several tissues of edible fishes from the largest freshwater lake in China, Poyang Lake, and associated human health risk assessment.

The residual levels, tissue distribution and human health risk assessment of polycyclic aromatic hydrocarbons (PAHs) in edible fishes, bighead carp (Aristichthys nobilis) and silver carp (Hypophthalmichthys molitrix), from the largest freshwater lake in China, Poyang Lake, were studied. PAH concentrations ranged from 105 to 513ng g(-1)ww and from 53.9 to 401ng g(-1)ww in different tissues of bighead carp and silver carp, respectively. Low molecular weight (LMW) PAHs were the predominant compounds, suggesting the gill-water transfer might be the major exposure route for PAHs in the studied fish species. Tissue distribution indicated that the hepatobiliary system accumulated higher concentrations of PAHs than the extrahepatic tissues with bile being the most predominant tissue for both species. Composition analysis demonstrated that PAHs were from the combined petrogenic and pyrogenic origin, and the gasoline combustion might be the main source. A preliminary evaluation of human health risk using benzo[a]pyrene (BaP) potency equivalent concentration (PEC) as well as the incremental lifetime cancer risk (ILCR) indicated that PAHs in fish would induce potential carcinogenic effects.

Bicarbonate can improve the prognostic value of the MELD score for critically ill patients with cirrhosis.

The prognosis of critically ill patients with cirrhosis is poor. Our aim was to identify an objective variable that can improve the prognostic value of the Model of End-Stage Liver Disease (MELD) score in patients who have cirrhosis and are admitted to the intensive care unit (ICU). This retrospective cohort study included 177 patients who had liver cirrhosis and were admitted to the ICU. Data pertaining to arterial blood gas-related parameters and other variables were obtained on the day of ICU admission. The overall ICU mortality rate was 36.2%. The bicarbonate (HCO3) level was found to be an independent predictor of ICU mortality (odds ratio, 2.3; 95% confidence interval [CI], 1.0-4.8; p = 0.038). A new equation was constructed (MELD-Bicarbonate) by replacing total bilirubin by HCO3 in the original MELD score. The area under the receiver operating characteristic curve for predicting ICU mortality was 0.76 (95% CI, 0.69-0.84) for the MELD-Bicarbonate equation, 0.73 (95% CI, 0.65-0.81) for the MELD score, and 0.71 (95% CI, 0.63-0.80) for the Acute Physiology and Chronic Health Evaluation II score. Bicarbonate level assessment, as an objective and reproducible laboratory test, has significant predictive value in critically ill patients with cirrhosis. In contrast, the predictive value of total bilirubin is not as prominent in this setting. The MELD-Bicarbonate equation, which included three variables (international normalized ratio, creatinine level, and HCO3 level), showed better prognostic value than the original MELD score in critically ill patients with cirrhosis.

Complications observed in older new haemodialysis patients in Taiwan.

AIM: We aimed to evaluate the impacts of heomodialysis (HD) in older patients, and potential consequences of adverse events for health insurance costs. METHODS: Two hundred and fifty-five new patients (130 were younger than 65 years and 125 were older than 65 years) who had received conventional HD for at least 1 year were reviewed. RESULTS: Older patients had significantly more arteriovenous (AV) shunt failures (0.7 ± 0.1 vs 0.4 ± 0.07, P = 0.006) and hospitalisations (0.8 ± 0.1 vs 0.4 ± 0.09, P = 0.03) than younger ones. Stepwise multivariate linear regression analysis showed that AV shunt failure was an independent risk factor for hospitalisation. CONCLUSIONS: The relatively high risk of AV shunt failures and hospitalisation in older patients highlights the additional expenditure on HD required in terms of health insurance.

Get With the Guidelines-Stroke performance indicators: surveillance of stroke care in the Taiwan Stroke Registry: Get With the Guidelines-Stroke in Taiwan.

BACKGROUND: Stroke is a leading cause of death around the world. Improving the quality of stroke care is a global priority, despite the diverse healthcare economies across nations. The American Heart Association/American Stroke Association Get With the Guidelines-Stroke program (GWTG-Stroke) has improved the quality of stroke care in 790 US academic and community hospitals, with broad implications for the rest of the country. The generalizability of GWTG-Stroke across national and economic boundaries remains to be tested. The Taiwan Stroke Registry, with 30 599 stroke admissions between 2006 and 2008, was used to assess the applicability of GWTG-Stroke in Taiwan, which spends ≈ 1/10 of what the United States does in medical costs per new or recurrent stroke. METHODS AND RESULTS: Taiwan Stroke Registry, sponsored by the Taiwan Department of Health, engages 39 academic and community hospitals and covers the entire country with 4 steps of quality control to ensure the reliability of entered data. Five GWTG-Stroke performance measures and 1 safety indicator are applicable to assess Taiwan Stroke Registry quality of stroke care. Demographic and outcome figures are comparable between GWTG-Stroke and Taiwan Stroke Registry. Two indicators (early and discharge antithrombotics) are close to GWTG-Stroke standards, while 3 other indicators (intravenous tissue plasminogen activator, anticoagulation for atrial fibrillation, lipid-lowering medication) and 1 safety indicator fall behind. Preliminary analysis shows that compliance with selected GWTG-Stroke guidelines is associated with better outcomes. CONCLUSIONS: Results suggest that GWTG-Stroke performance measures, with modification for ethnic factors, can become global standards across national and economic boundaries for assessing and improving quality of stroke care and outcomes. GWTG-Stroke can be incorporated into ongoing stroke registries across nations.