Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial.

AIMS/HYPOTHESIS: In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin reduced the risks of progressive kidney disease, hospitalised heart failure or cardiovascular death, and death from all causes in patients with chronic kidney disease (CKD) with or without type 2 diabetes. Patients with more severe CKD are at higher risk of kidney failure, cardiovascular events and all-cause mortality. In this post hoc analysis, we assessed the efficacy and safety of dapagliflozin according to baseline Kidney Disease Improving Global Outcomes (KDIGO) risk categories. METHODS: DAPA-CKD was a double-blind, placebo-controlled trial that randomised patients with an eGFR of 25-75 ml min-1 [1.73 m]-2 and urinary albumin/creatinine ratio (UACR) of ≥22.6 and <565.0 mg/mmol (200-5000 mg/g) to dapagliflozin 10 mg/day or placebo. The primary endpoint was a composite of ≥50% reduction in eGFR, end-stage kidney disease (ESKD), and death from a kidney or cardiovascular cause. Secondary endpoints included a kidney composite (≥50% reduction in eGFR, ESKD and death from a kidney cause), a cardiovascular composite (heart failure hospitalisation or cardiovascular death), and death from all causes. We used Cox proportional hazards regression analyses to assess relative and absolute effects of dapagliflozin across KDIGO risk categories. RESULTS: Of the 4304 participants in the DAPA-CKD study, 619 (14.4%) were moderately high risk, 1349 (31.3%) were high risk and 2336 (54.3%) were very high risk when categorised by KDIGO risk categories at baseline. Dapagliflozin reduced the hazard of the primary composite (HR 0.61; 95% CI 0.51, 0.72) and secondary endpoints consistently across KDIGO risk categories (all p for interaction >0.09). Absolute risk reductions for the primary outcome were also consistent irrespective of KDIGO risk category (p for interaction 0.26). Analysing patients with and without type 2 diabetes separately, the relative risk reduction with dapagliflozin in terms of the primary outcome was consistent across subgroups of KDIGO risk categories. The relative frequencies of adverse events and serious adverse events were also similar across KDIGO risk categories. CONCLUSION/INTERPRETATIONS: The consistent benefits of dapagliflozin on kidney and cardiovascular outcomes across KDIGO risk categories indicate that dapagliflozin is efficacious and safe across a wide spectrum of kidney disease severity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03036150. FUNDING: The study was funded by AstraZeneca.

Integrating clinical, morphological, and molecular data to assess prognosis in patients with primary myelofibrosis at diagnosis: A practical approach.

Currently available prognostic scoring systems in primary myelofibrosis (PMF) do not integrate clinical, histological, and molecular data, or they also required information on "other" mutations that are available in the clinical practice only in a very limited number of laboratories. In the present multicenter study, including 401 PMF patients, an integrated International Prognostic Scoring System (I-IPSS) was developed by combining IPSS, grade of bone marrow fibrosis (GBMF), and driver mutations molecular status (MS) to define PMF prognosis at diagnosis. Four prognostic categories were identified: I-IPSS-low risk (113 patients), I-IPSS-intermediate-1 risk (56 patients), I-IPSS-intermediate-2 risk (154 patients), and I-IPSS-high risk (78 patients). Median overall survival was 26.7 years in I-IPSS-intermediate-1, 10.8 in I-IPSS-intermediate-2, and 6.4 in I-IPSS-high-risk patients (log-rank test <0.0001); instead, it was not reached in the I-IPSS-low-risk cohort because of the extremely low number of registered deaths. The addition of GBMF and MS to IPSS improved the efficacy for predicting the risk of death. Indeed, the sensitivity of I-IPSS was significantly higher (P < .05) than that of IPSS, considering both total deaths and 5- and 10-year mortality. This comprehensive approach allows clinicians to evaluate mutual interactions between IPSS, GBMF, and MS and identify high-risk patients with poor prognosis who may benefit from aggressive treatments. More importantly, this integrated score can be easily applicable worldwide as it only required information that represent the good clinical practice in the management of PMF patients.

Validity of St Gallen risk categories in prognostication of breast cancer patients in Southern Sri Lanka.

BACKGROUND: Although, there are many developments in the field of management, breast cancer is still the commonest cause of cancer related deaths in women in Sri Lanka. This emphasizes the need for validation of treatment protocols that are used in Sri Lanka for managing breast cancers. There are no published papers on treatment and survival of breast cancer patients in Sri Lanka. Hence this study was designed to determine the validity of St Gallen risk categories based on the survival outcomes of breast cancer patients in Southern Sri Lanka. METHOD: This retro-prospective study included all female breast cancer patients who had sought the immunohistochemistry services of our unit from May 2006 to December 2012. Patients who had neo-adjuvant chemotherapy were excluded. Patients were stratified according to the St Gallen risk categories; low-risk (LR), intermediate-risk (IR) and high-risk (HR), which is used in deciding on the adjuvant treatment. IR category was subdivided based on presence/absence of 1-3 positive-nodes (absent-IR1, present-IR2) and HR on the number of positive-nodes(1-3 lymph nodes;HR1,> 3 lymph nodes;HR2). Kaplan-Meier and Cox-regression models were used in the survival analysis. RESULTS: This study included 713breast cancer patients (LR-2%, IR1-45%, IR2-10%, HR1-13%, HR2-30%). Five year breast cancer specific survival (BCSS)wasLR-100%, IR-91%, HR-66% and the recurrence free survival (RFS) was LR-85%, IR-84%, HR-65%. BCSS and RFS curves were significantly different between the three risk categories (p < 0.001). No survival difference was evident between the IR1 and IR2 (BCSS-p = 0.232, RFS-p = 0.118). HR1 and HR2 had a distinctly different BCSS (p = 0.033) with no difference in RFS (p = 0.190). CONCLUSION: This study validates the St Gallen risk categorization of female breast cancer patients in our setting. However, the HR includes two subsets of patients with a distinct difference in BCSS.

Breast cancer histopathology is predictive of low-risk Oncotype Dx recurrence score.

BACKGROUND: Oncotype Dx is a genetic test that has been incorporated into the 2017 AJCC breast cancer staging system for ER positive, HER2-negative, lymph node-negative patients to predict the risk of recurrence. Recent data suggest that immunohistochemistry (ER, PR, HER2, and Ki-67) and histologic subtype may identify patients that will not benefit from Oncotype Dx testing. METHODS: A total of 371 patients underwent Oncotype Dx testing at our institution from 2012 to 2016. Oncotype recurrence score was categorized as low- (ORS = 0-10), intermediate- (11-25), or high risk (26-100). Invasive carcinomas were categorized based on histologic subtype as "favorable" (mucinous, tubular, cribriform, tubulolobular, and lobular) and "unfavorable" (ductal, mixed ductal and lobular, and micropapillary carcinoma). All cases were estrogen receptor positive and HER2-negative. Clinical and histologic predictors of low-risk ORS were assessed in univariate and multivariate logistic regression. RESULTS: A total of 371 patients were categorized by ORS as low risk (n = 85, 22.9%), intermediate risk (n = 244, 65.8%), and high risk (n = 42, 11.3%). The histologic subtypes with the highest percentage of high-risk ORS were invasive micropapillary (n = 4/17, 23.5%), pleomorphic lobular (n = 2/10, 20%), and ductal carcinoma (n = 28/235, 11.9%). Low-grade invasive carcinomas with favorable histology rarely had a high-risk ORS (n = 1/97, 1%). In a simple multivariable model, favorable histologic subtype (OR = 2.39, 95% CI: 1.10 to 5.15, P = 0.026), and histologic grade (OR = 1.76, 95% CI: 1.07 to 2.90, P = 0.025) were the only significant predictors of an ORS less than 11 in estrogen receptor positive, HER2-negative, and lymph node-negative patients. CONCLUSION: We question the utility of performing Oncotype Dx in subtypes of invasive carcinoma that are associated with excellent prognosis. We propose that immunohistochemistry for ER, PR, and HER2 is sufficient for patients with low-grade invasive carcinomas and can be used as a surrogate for Oncotype Dx.

2024 Egyptian consensus statement on the role of non-statin therapies for LDL cholesterol lowering in different patient risk categories.

BACKGROUND: The new millennium has witnessed increased understanding of cardiovascular (CV) risk factors and improvement in atherosclerotic cardiovascular disease (ASCVD) management. The role of LDL cholesterol and other atherogenic lipid particles in the development of atherosclerosis is now beyond doubt. MAIN BODY: Statins have been widely used and recommended in guidelines for preventing and managing ischemic events. However, statins have side effects, and many patients do not achieve their low-density lipoprotein cholesterol (LDL-C) goals. In recent years, non-statin lipid-lowering agents have gained increasing use as adjuncts to statins or as alternatives in patients who cannot tolerate statins. This consensus proposes a simple approach for initiating non-statin lipid-lowering therapy and provides evidence-based recommendations. Our key advancements include the identification of patients at extreme risk for CV events, the consideration of initial combination therapy of statin and ezetimibe in very high-risk and extreme-risk groups and the extended use of bempedoic acid in patients not reaching LDL-C targets especially in resource-limited settings. CONCLUSIONS: Overall, this consensus statement provides valuable insights into the expanding field of non-statin therapies and offers practical recommendations to enhance CV care, specifically focusing on improving LDL-C control in Egypt. While these recommendations hold promise, further research and real-world data are needed for validation and refinement.

Soluble tumor necrosis factor receptor type 1 is an alternative marker of urinary albumin-creatinine ratio and estimated glomerular filtration rate for predicting the decline of renal function in subjects with type 2 diabetes mellitus.

BACKGROUND: Urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rates (eGFR) help predict worsening diabetic kidney disease (DKD) but have their limitations. Soluble tumor necrosis factor receptor type 1 (sTNFR1) is a biomarker of DKD. The predictive abilities of sTNFR1 and UACR plus eGFR have not been compared. METHODS: This prospective cohort study included patients with type 2 diabetes (T2D) to identify the risk factors of worsening DKD. Renal events were defined as > 30 % loss in eGFR based on consecutive tests after 6 months. The associations of sTNFR1, UACR, and eGFR levels and the risks of renal events were tested using a Cox regression model and the area under the curve (AUC) was compared between sTNFR1 levels and UACR plus eGFR using receiver-operating characteristic (ROC) analysis. The accuracy of stratification was evaluated using Kaplan-Meier analysis. RESULTS: Levels of sTNFR1 and UACR were associated with risks of > 30 % decline in eGFR after adjusting for relevant factors. The association between sTNFR1 levels and renal outcomes was independent of UACR and eGFR at baseline. The AUC of sTNFR1 level was comparable with that of combined UACR and eGFR (0.73 vs. 0.71, respectively, p = 0.72) and the results persisted for quartile groups of sTNFR1 and risk categories of Kidney Disease: Improving Global Outcomes (KDIGO) (0.70 vs. 0.71, respectively, p = 0.84). Both stratifications by sTNFR1 levels and KDIGO were accurate. CONCLUSION: sTNFR1 could be an alternative marker for identifying patients with diabetes at risk of declining renal function.

The TG/HDL-c Lipid Ratio as a Cardiovascular Risk Marker in a Mexican Urban Middle-Class Population: Do We Need a Risk Score Tailored for Mexicans?

INTRODUCTION: Risk scores are essential in primary prevention to detect high-risk patients. The most common scores exclude hypertriglyceridemia and abdominal obesity in their risk assessment. We examined the triglyceride/HDL-cholesterol (TG/HDL-c) ratio as a cardiovascular (CV) risk marker in a middle-class urban Mexican population sample. AIM: Our aim was to test the concept of a scoring system reflecting Mexican population characteristics. METHODS: A total of 2602 healthy adults from the Lindavista primary prevention program were considered, evaluating gender, age, blood pressure, smoking, body mass index, waist circumference, lipid profile, and fasting glucose. According to the abnormality, a score from -3 to +3 was assigned. RESULTS: The summation of eleven variables yielded the Lindavista score (LS), which was calibrated versus the TG/HDL ratio and ACC ASCVD Risk Estimator Plus score to determine its correlation with risk categories. The TG/HDL-c ratio had a linear correlation with LS and high-risk ACC ASCVD categories. CONCLUSIONS: Compared with LS and TG/HDL-c, the ACC ASCVD system underestimates the high-risk category. The high prevalence of obesity and lipid triad in the Mexican population requires a scale that considers those traits. The TG/HDL-c ratio is a practical, easy, and economical instrument to categorize risk in Mexicans.

Prevalence and Predictors of Combined Body Mass Index and Waist Circumference Among Indian Adults.

Objective: To determine the prevalence and predictors of combined BMI-WC disease risk categories among Indian adults. Methods: The study utilizes data from Longitudinal Ageing Study in India (LASI Wave 1) with an eligible sample of 66, 859 individuals. Bivariate analysis was done to get the proportion of individuals in different BMI-WC risk categories. Multinomial logistic regression was used to identify the predictors of BMI-WC risk categories. Results: Poor self-rated health, female sex, urban place of residence, higher educational status, increasing MPCE quintile, and cardio-vascular disease increased with increasing BMI-WC disease risk level while increasing age, tobacco consumption, and engagement in physical activities was negatively associated with BMI-WC disease risk. Conclusion: Elderly persons in India have a considerable higher prevalence of BMI-WC disease risk categories which make them vulnerable to developing several disease. Findings emphasize the need of using combined BMI categories and waist circumference to assess the prevalence of obesity and associated disease risk. Finally, we recommend that intervention programs with an emphasis on urbanites wealthy women and those with a higher BMI-WC risk categories be implemented.

Hyperuricemia Predicts the Progression of Type 2 Diabetic Kidney Disease in Chinese Patients.

INTRODUCTION: Diabetic kidney disease (DKD) has a high global disease burden and substantially increases the risk of end-stage renal disease and cardiovascular events. High levels of serum uric acid (SUA), or hyperuricemia, may indicate patients with type 2 diabetes (T2D) at risk for kidney disease. METHODS: This study explored the association between SUA levels and progression of kidney disease among patients with T2D. A cross-sectional study of 993 Chinese patients aged 20-75 years with T2D and DKD was conducted. Patients were stratified by progression risk of kidney disease based on estimated glomerular filtration rate and ratio of urinary albumin to creatinine, according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Ordinal logistic regression was used to assess associations between SUA and different KDIGO risk categories. RESULTS: Among 768 patients in the final analysis, those with hyperuricemia and higher SUA were more likely to be assigned to higher KDIGO risk categories. Patients with SUA > 420 µmol/L were ninefold more likely to be in a higher KDIGO risk category than those with SUA < 300 µmol/L (odds risk 9.74, 95% confidence interval 5.47-17.33, P < 0.001). CONCLUSIONS: Hyperuricemia may be associated with higher risk of DKD progression in individuals with T2D.

Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype.

This study evaluated a panel including the molecular taxonomy subtype and the expression of 27 genes as a diagnostic tool to stratify bladder cancer patients at risk of aggressive behavior, using a well-characterized series of non-muscle invasive bladder cancer (NMIBC) as well as muscle-invasive bladder cancer (MIBC). The study was conducted using the novel NanoString nCounter gene expression analysis. This technology allowed us to identify the molecular subtype and to analyze the gene expression of 27 bladder-cancer-related genes selected through a recent literature search. The differential gene expression was correlated with clinicopathological variables, such as the molecular subtypes (luminal, basal, null/double negative), histological subtype (conventional urothelial carcinoma, or carcinoma with variant histology), clinical subtype (NMIBC and MIBC), tumor stage category (Ta, T1, and T2-4), tumor grade, PD-L1 expression (high vs. low expression), and clinical risk categories (low, intermediate, high and very high). The multivariate analysis of the 19 genes significant for cancer-specific survival in our cohort study series identified TP53 (p = 0.0001), CCND1 (p = 0.0001), MKI67 (p < 0.0001), and molecular subtype (p = 0.005) as independent predictors. A scoring system based on the molecular subtype and the gene expression signature of TP53, CCND1, or MKI67 was used for risk assessment. A score ranging from 0 (best prognosis) to 7 (worst prognosis) was obtained and used to stratify our patients into two (low [score 0-2] vs. high [score 3-7], model A) or three (low [score 0-2] vs. intermediate [score 3-4] vs. high [score 5-7], model B) risk categories with different survival characteristics. Mean cancer-specific survival was longer (122 + 2.7 months) in low-risk than intermediate-risk (79.4 + 9.4 months) or high-risk (6.2 + 0.9 months) categories (p < 0.0001; model A); and was longer (122 + 2.7 months) in low-risk than high-risk (58 + 8.3 months) (p < 0.0001; model B). In conclusion, the molecular risk assessment model, as reported here, might be used better to select the appropriate management for patients with bladder cancer.

Cardiovascular Risk Profile and Lipid Management in the Population-Based Cohort Study LATINO: 20 Years of Real-World Data.

The rising prevalence of cardiovascular (CV) risk factors in Portugal has translated into more than 35,000 annual deaths due to CV diseases. We performed a multicenter observational cohort study encompassing clinical activities performed between 2000 and 2019 to characterize the CV risk profile and LDL-C management of patients in every CV risk category using electronic health records of a regional population in Portugal. We analyzed data from 14 health centers and 1 central hospital in the north of Portugal of patients between 40 and 80 years that had at least 1 family medicine appointment at these institutions. Living patients were characterized on 31 December 2019. CV risk assessment was computed according to the 2019 ESC/EAS Guidelines. Lipid-lowering therapy (LLT) and achievement of LDL-C targets were assessed. In total, the analysis included 78,459 patients. Patient proportions were 33%, 29%, 22%, and 17% for low, intermediate, high, and very high CV risk, respectively. Moderate-intensity statins were the most frequently used medication across all CV risk categories. High-intensity statins were used in 5% and 10% of high and very high CV risk patients, respectively. Ezetimibe was used in 6% and 10% of high and very high CV risk patients, respectively. LDL-C targets were achieved in 44%, 27%, 7%, and 3% of low, intermediate, high, and very high CV risk patients, respectively. For uncontrolled patients in the high and very high CV risk categories, a median LDL-C reduction of 44% and 53%, respectively, would be required to meet LDL-C targets. There are clear opportunities to optimize LDL-C management in routine clinical practice. The prescription of LLT according to CV risk represents an important missed treatment opportunity.

Evidence-based risk factors for major complications during Ramadan fasting in people with diabetes grouped under IDF-DAR risk categories.

AIM: To identify evidence-based risk factors for major complications during Ramadan fasting in people with diabetes grouped under IDF-DAR risk categories. METHODS: This prospective observational multicenter study was conducted by Baqai Institute of Diabetology and Endocrinology (BIDE) between April-June 2019. People with diabetes having intention to fast during Ramadan were recruited. Demographic data collection along with risk categorization was done during pre-Ramadan visit. Structured education was given on one- to-one basis to each of the study participants. Assessment of complications was done during post Ramadan visit. RESULTS: A total of 1045 people with diabetes participated with near equal gender distribution. Two thirds of study population was grouped into very high- and high-risk categories. Frequencies of major hypoglycemia, major hyperglycemia, hospitalization & need to break the fast were 4.4%, 10.8%, 0.8% & 3.1% respectively. On multivariate analysis, the risk factors found for major hypoglycemia during Ramadan were male gender, use of sedatives & antidepressants & having type1 diabetes mellitus, history of DKA/HHS during last 3 months for major hyperglycemia, major hypoglycemia & hospitalization for breaking of fast while older age, acute illness, and major hypoglycemia were identified factors for hospitalization. CONCLUSION: In this prospective study evidence-based risk factors for fasting related major complications were identified in people with diabetes. It is imperative to recognize these factors during pre-Ramadan risk assessment visit.

Progression of Chronic Kidney Disease Risk Categories and Risk of Cardiovascular Disease and Total Mortality: Coronary Artery Risk Development in Young Adults Cohort.

Background Previous studies of worsening chronic kidney disease (CKD) based on declining estimated glomerular filtration rate (eGFR) or increasing urine albumin-creatinine ratio (UACR) are limited to later middle-age and older adults. We examined associations of CKD progression and incident cardiovascular disease (CVD) and mortality in younger adults. Methods and Results We studied 4382 adults in CARDIA (Coronary Artery Risk Development in Young Adults) initially aged 27 to 41 years and prospectively over 20 years. Five-year transition probabilities across CKD risk categories were based on eGFR and UACR measured at each exam. Proportional hazards models predicted incident CVD and all-cause mortality by time-varying CKD risk category, adjusting for demographics and CVD risk factors. Progression of CKD risk categories over 20 years occurred in 28.7% (1256/4382) of participants, driven by increases in UACR, but including 5.8% (n=255) with eGFR<60 mL/min per 1.73 m2 or UACR ≥300 mg/g. Compared with eGFR ≥60 and UACR <10, demographic and smoking-adjusted hazard ratios for CVD were 1.62 (95% CI, 1.21-2.18) for low CKD risk (eGFR ≥60 with UACR 10-29) and 13.65 (95% CI, 7.52-24.79) for very high CKD risk (eGFR <30 or eGFR 30-44 with UACR 30-299; or eGFR 30-59 with UACR ≥300). Corresponding hazard ratios for all-cause mortality were 1.42 (95% CI, 1.08-1.88) and 14.75 (95% CI, 9.97-21.82). Although CVD associations were attenuated after adjustment for mediating CVD risk factors, all-cause mortality associations remained statistically significant. Conclusions Among young to middle-aged adults, progression to higher CKD risk category was common. Routine monitoring eGFR and UACR holds promise for prevention of CVD and total mortality.

Cardiovascular event risk estimation among residents of a rural setting in Bayelsa state, Nigeria.

Cardiovascular diseases (CVD) are a leading cause of death worldwide. There is a rising prevalence of CVDs in Nigeria, including in rural communities. The present study assessed the total CVD risk among two rural communities in Bayelsa State, South-south Nigeria. Adults aged ≥ 40 years in 264 randomly selected households in two rural communities in Bayelsa State were interviewed in this descriptive cross-sectional survey. Using a structured questionnaire, data on socio-demographic characteristics, anthropometry, blood pressure (BP) and random blood sugar measurements were obtained. The WHO/ISH risk assessment chart for the African sub-region was used to estimate the 10-year total risk of fatal or non-fatal CVD events using five predictor variables: age, gender, smoking, systolic BP, and coexistence of diabetes mellitus (DM). Of the 264 participants, majority was men (70.1%) and married (93.2%). Mean age was 50.9±8.1 years. Most participants were overweight (53.4%), add salt to food on table (97.0%), lead a sedentary lifestyle (79.2%) and greater than a third of participants (36.7%) were known hypertensive patients. Using the WHO/ISH risk prediction chart for Africa, 90.0% and 10.0% of the study population had low and moderate risk, respectively of developing cardiovascular events in 10 years. As the age of participants increases, the 10-year risk of a cardiovascular event increased (X 2-48.9; P-0.001). History of hypertension (X 2-20.0; P-0.001), DM (X 2-5.87; P-0.016) and smoking (X 2-23.42; P-0.001) were significantly related to the level of 10-year cardiovascular event risk. Sex showed no significant relationship. There is a high prevalence of several cardiovascular risk factors in this rural population, though the 10-year risk of CV event is still low. CVD risk in rural communities requires awareness, monitoring and an integrated approach in their prevention, detection, and treatment.

Value of Coronary Calcium Scoring in Symptomatic and Asymptomatic Coronary Artery Disease Patients.

AIM AND OBJECTIVE: The study aimed to estimate the relationship between Coronary Calcium Scoring (CCS) and the presence of different degrees of obstructive coronary artery disease (CAD) to avoid unnecessary examinations and hence unnecessary radiation exposure and contrast injection. BACKGROUND: Coronary Calcium Scoring (CCS) is a test that uses x-ray equipment to produce pictures of the coronary arteries to determine the degree of its narrowing by the build-up of calcified plaques. Despite the lack of definitive data linking ionizing radiation with cancer, the American Heart Association supports widely that practitioners of Computed tomography Coronary Angiography (CTCA) should keep "patient radiation doses as low as reasonably achievable but consistent with obtaining the desired medical information". METHODS: Data obtained from 275 CTCA examinations were reviewed. Radiation effective doses were estimated for both CCS and CTCA, and measures to keep them as low as possible were presented. CCS and Framingham risk estimates were compared to obtain the final results of CTCA to detect sensitivity and specificity of each one in detecting obstructive lesions. RESULTS: CCS is a strong discriminator for obstructive CAD with high sensitivity and specificity and correlates well with the degree of obstruction even more than Framingham risk estimate, which has high sensitivity and low specificity. CONCLUSION: CCS helps to reduce the effective radiation dose if properly evaluated to skip unnecessary CTCA if obstructive lesions are unlikely, and this as a test does not use contrast material, thus harmful effect on the kidney will be avoided as most of the coronary atherosclerotic patients have renal problems.

[Risk stratification of emergencies during the COVID-19 pandemic within the emergency department]. / Risikostratifizierung von Notfällen während der COVID-19-Pandemie in der Zentralen Notaufnahme.

BACKGROUND: The COVID-19 pandemic represents a complex challenge for medical staff within emergency departments (ED) of hospitals at all care levels. Beside regular emergency care, rapid detection and isolation of COVID-19 cases are obligatory for prevention of internal viral transmission and efficient medical staff protection. METHODS: In this study a model of risk stratification for suspected SARS-CoV­2 and COVID-19 cases was developed on the basis of epidemiologic criteria of the Robert-Koch Institute including five risk categories (RC). The model was implemented in a hospital of basic and regular care level. By combination of risk categories with specific isolation, hygienic and personal protection procedures all areas of the ED were restructured. In a retrospective study all inpatient cases (n = 491) were re-evaluated during a 4-week interval (26 March-26 April 2020). RESULTS: In the study population 25 SARS-CoV­2 positive cases (5.2%) were identified. These cases were categorized according to the risk stratification model as follows: RC I-confirmed SARS-CoV­2 infection 36% (n = 9), RC II-reasonable suspected cases 32% (n = 8), RC III-differential diagnostic cases 12% (n = 3), RC IV-low probability 8% (n = 2) and RC V-no evidence 12% (n = 3). No viral transmission was detected during the whole period within medical staff and patients of the ED. CONCLUSIONS: Introduction of COVID-19 risk categories within the ED permits central control of important hygienic processes with respect to SARS-CoV­2 infection probability. By continuous re-evaluation of case definitions local outbreaks can be used to adapt criteria within the risk categories. Risk stratification of COVID-19 cases allows for a strict separation of COVID-19 and non-COVID-19 emergencies and thus ensures effective infection prevention of medical staff and patients.

Expression Patterns of Coagulation Factor XIII Subunit A on Leukemic Lymphoblasts Correlate with Clinical Outcome and Genetic Subtypes in Childhood B-cell Progenitor Acute Lymphoblastic Leukemia.

BACKGROUND: Based on previous retrospective results, we investigated the association of coagulation FXIII subunit A (FXIII-A) expression pattern on survival and correlations with known prognostic factors of B-cell progenitor (BCP) childhood acute lymphoblastic leukemia (ALL) as a pilot study of the prospective multi-center BFM ALL-IC 2009 clinical trial. METHODS: The study included four national centers (n = 408). Immunophenotyping by flow cytometry and cytogenetic analysis were performed by standard methods. Copy number alteration was studied in a subset of patients (n = 59). Survival rates were estimated by Kaplan-Meier analysis. Correlations between FXIII-A expression patterns and risk factors were investigated with Cox and logistic regression models. RESULTS: Three different patterns of FXIII-A expression were observed: negative (<20%), dim (20-79%), and bright (≥80%). The FXIII-A dim expression group had significantly higher 5-year event-free survival (EFS) (93%) than the FXIII-A negative (70%) and FXIII-A bright (61%) groups. Distribution of intermediate genetic risk categories and the "B-other" genetic subgroup differed significantly between the FXIII-A positive and negative groups. Multivariate logistic regression confirmed independent association between the FXIII-A negative expression characteristics and the prevalence of intermediate genetic risk group. CONCLUSIONS: FXIII-A negativity is associated with dismal survival in children with BCP-ALL and is an indicator for the presence of unfavorable genetic alterations.

Validated Nomogram Predicting 6-Month Survival in Pancreatic Cancer Patients Receiving First-Line 5-Fluorouracil, Oxaliplatin, and Irinotecan.

BACKGROUND: FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) is an option for fit patients with metastatic (MPC) and locally advanced unresectable (LAPC) pancreatic cancer. However, no criteria reliably identify patients with better outcomes. PATIENTS AND METHODS: We investigated putative prognostic factors among 137 MPC/LAPC patients treated with triplet chemotherapy. Association with 6-month survival status (primary endpoint) was assessed by multivariate logistic regression models. A nomogram predicting the risk of death at 6 months was built by assigning a numeric score to each identified variable, weighted on its level of association with survival. External validation was performed in an independent data set of 206 patients. The study was registered at ClinicalTrials.gov (NCT03590275). RESULTS: Four variables (performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio) were found to be associated with 6-month survival by multivariate analysis or had sufficient clinical plausibility to be included in the nomogram. Accuracy was confirmed in the validation cohort (C index = 0.762; 95% confidence interval, 0.713-0.825). After grouping all cases, 4 subsets with different outcomes were identified by 0, 1, 2, or > 2 poor prognostic features (P < .0001). CONCLUSION: The nomogram we constructed accurately predicts the risk of death in the first 6 months after initiation of FOLFIRINOX in MPC/LAPC patients. This tool could be useful to guide communication about prognosis, and to inform the design and interpretation of clinical trials.

Occurrence of Escherichia coli and faecal coliforms in drinking water at source and household point-of-use in Rohingya camps, Bangladesh.

BACKGROUND: Safe water is essential for life but unsafe for human consumption if it is contaminated with pathogenic microorganisms. An acceptable quality of water supply (adequate, safe and accessible) must be ensured to all human beings for a healthy life. METHODS: We collected and analyzed a total of 12,650 drinking water samples, for the presence of Escherichia coli and faecal coliforms, from a large habitation of the displaced Rohingya population comprising of about 1.16 million people living within 4 km2. RESULTS: We found that 28% (n = 893) water samples derived from tubewells were contaminated with faecal coliforms and 10.5% (n = 333) were contaminated with E. coli; also, 73.96% (n = 4644) samples from stored household sources (at point of use-POU) were found contaminated with faecal coliforms while 34.7% (n = 2179) were contaminated with E. coli. It was observed that a higher percentage of POU samples fall in the highest risk category than that of their corresponding sources. CONCLUSIONS: From our findings, it appears that secondary contamination could be a function of very high population density and could possibly occur during collection, transportation, and storage of water due to lack of knowledge of personal and domestic hygiene. Hence, awareness campaign is necessary, and the contaminated sources should be replaced. Further, the POU water should be treated by a suitable method.

Recent changes in pregnancy and lactation labeling: retirement of risk categories.

The rapid development and increased availability of novel pharmacologic therapies and pharmaceutical products has amplified the potential for drug exposure during pregnancy. Many drugs are beneficial for disease state management during pregnancy and provide significant fetal and maternal health benefits. However, a paucity of safety data combined with the imprecision of the current risk category system renders risk versus benefit assessment difficult. In response to decades of criticism, the U.S. Food and Drug Administration (FDA) is implementing a new pregnancy and lactation labeling rule designed to improve risk versus benefit assessment of drugs used in pregnant and nursing mothers. These recommendations will provide clear and detailed information for both patients and health care providers, and they will include three main categories: risk summary, clinical considerations, and data. The new labeling rules remove the previous letter risk categorization system (A, B, C, D, X). In this review, we summarize the upcoming FDA labeling changes and discuss their potential consequences on clinical practice.