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Mortality risk stratification in chronic kidney disease: one size for all ages?

Current National Kidney Foundation Kidney Disease Outcomes Quality Initiative staging criteria for chronic kidney disease (CKD) are intended to apply to all age groups. However, it is unclear whether different levels of estimated GFR (eGFR) have the same prognostic significance in older and younger patients. The study cohort was composed of Department of Veterans Affairs (VA) patients who were aged 18 to 100 yr and had at least one outpatient serum creatinine measurement between October 1, 2001, and September 30, 2002 (n=2583,911). Patients with ESRD were excluded. GFR was estimated using the Modification of Diet in Renal Disease equation using each patient's first outpatient creatinine measurement during the study period. The association of eGFR with survival was measured by age group. Twenty percent of cohort patients had an eGFR<60 ml/min per 1.73 m2, ranging from 3% among 18- to 44-yr-olds to as high as 49% among 85- to 100-yr-olds. Fifty-two percent (n=266,421) of cohort patients with an eGFR<60 ml/min per 1.73 m2 had "very" moderate reductions in eGFR into the 50- to 59-ml/min per 1.73 m2 range. The association of eGFR with mortality was weaker in the elderly than in younger age groups: Whereas severe reductions in eGFR were associated with an increased risk for death in all age groups, "very" moderate reductions in eGFR (50 to 59 ml/min per 1.73 m2) were associated with an increased adjusted risk for death only among patients who were younger than 65 yr. Age-related attenuation of the association of eGFR with mortality was also present among women and black patients. In the clinical setting, mortality risk stratification in elderly patients should not be based on the same eGFR cut points as for younger age groups and would benefit from finer categorization of the 30- to 59-ml/min per 1.73 m2 eGFR group.

Adolescent↗

Identification of a novel signature for prognostic stratification and integrative analyses in lung adenocarcinoma.

BACKGROUND: Recently, research has revealed that the Golgi apparatus is involved in the development process of cancer; however, the specific effect of Golgi apparatus-related genes (GAGs) in lung adenocarcinoma (LUAD) remains unclear. This study aims to construct a more concise and practical risk model in LUAD using GAG. METHODS: The gene expression profiles of patients with LUAD were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and GAGs were downloaded from the Gene Set Enrichment Analysis (GSEA) database. Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were performed to identify the prognostic GAG signature. Kaplan-Meier and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signatures. The correlation between the risk model and the immune landscape was examined using CIBERSORT and TIDE analyses. Also, the genes in the signature were assessed by single-cell RNA sequencing (scRNA-seq). RESULTS: A prognostic signature comprising 5 GAG genes (GNPNAT1, RGS20, CAV3, NTSR1, and FURIN) was established after LASSO and multi-Cox analyses. Both the Kaplan-Meier analysis and the ROC curves supported the strong predictive utility of the risk model. Specifically, the former yielded significant stratification in all three validation datasets (P=1.2001e-05, P=0.006, and P=0.04), while the latter provided further evidence of its predictive precision through the area under the curve. In addition, we found that the low-risk group responded better to immunotherapy than the high-risk group (P<0.0001). scRNA-seq analysis revealed the distribution patterns of the 5 GAG genes in cells. Finally, we assessed the situation of tumor mutation burden (TMB) and performed functional analysis based on the risk model of GAGs. CONCLUSIONS: The risk model based on GAGs can effectively stratify the prognosis of patients and predict immunotherapy responses in LUAD.

Golgi apparatus↗

Greenhouse gases in non-oxygenated and artificially oxygenated eutrophied lakes during winter stratification.

Concentrations of dissolved methane (CH4), carbon dioxide (CO2), and nitrous oxide (N2O) were measured in the water columns of non-oxygenated and artificially oxygenated, ice-covered eutrophied lakes in the mid-boreal zone in Finland during late winter 1997 and 1999. Sampling was conducted during winter stratification, the critical period for oxygen (O2) deficiency in seasonally ice-covered, thermally stratified lakes. Oxygen concentrations were maintained at least at a moderate level throughout the oxygenated water columns, whereas the non-oxygenated columns suffered anoxic hypolimnia. The mean concentrations of dissolved CH4 exceeding the atmospheric equilibrium were greater in the non-oxygenated water columns (20.6-154 microM) than in the oxygenated ones (0.01-1.41 microM). In contrast, the mean excess CO2 concentrations varied less between the non-oxygenated and oxygenated sites (0.28-0.47 and 0.25-0.31 mM, respectively). Oxygenated water columns had greater mean excess concentrations of N2O (0.018-0.032 microM) than the non-oxygenated ones (0.005-0.024 microM). If the accumulated greenhouse gas stores in the water columns during winter are assumed to be released to the atmosphere during the spring overturn, the global warming potentials (GWP, time horizon 100 yr) of these potential emissions at the non-oxygenated, eutrophic study sites ranged from 177 to 654 g CO2 equivalent (CO2-e) m-2 compared with 144 to 173 g CO2-e m-2 at the oxygenated sites. The increase in the accumulation of CH4 was the main reason for the higher GWP of the non-oxygenated sites. Anthropogenic eutrophication of lake ecosystems can generate increased CH4 emissions due to associated O2 depletion of their sediment and water column.

Carbon Dioxide↗

Hospital-acquired pneumonia in critically ill patients: mortality risk stratification upon onset.

STUDY OBJECTIVES: To identify, in patients experiencing hospital-acquired pneumonia (HAP), prognostic factors present at disease onset and build an algorithm capable of stratifying mortality risk upon HAP onset. DESIGN: Observational cohort from January 1994 to December 2001. SETTING: One intensive care unit (ICU) from a university-affiliated, urban teaching hospital. PATIENTS: All consecutive patients exhibiting bacteriologically documented HAP either on ICU admission or during ICU stay. INTERVENTIONS: Data collection and multivariate analysis using Chi-Square Automatic Interaction and Detection technique. RESULTS: 168 patients were studied. The overall mean mortality rate was 49.4%. Upon onset of HAP, five independent variables allowed binary stratification of mortality risk. These consisted of underlying diseases (nonfatal versus ultimately and rapidly fatal diseases), Simplified Acute Physiology Score II (less than versus > or =37), platelet count (less than versus > or =150,000/mm3), chest x-ray involvement (1 versus >1 lobe), and PaO2/FiO2 (less than versus > or =167 mm Hg). A branching algorithm consisting of these five variables identified patients with HAP at both low (<35%) and high (>75%) risk of mortality. CONCLUSION: Mortality in ICU patients with HAP may be predicted early, upon onset of HAP, by the cumulative use of prognostic factors in an algorithm.

Aged↗

A systematic approach to risk stratification and intervention within a managed care environment improves diabetes outcomes and patient satisfaction.

OBJECTIVE: To determine whether a comprehensive diabetes management program that included risk stratification and social marketing would improve clinical outcomes and patient satisfaction within a managed care organization (MCO). RESEARCH DESIGN AND METHODS: The 12-month prospective trial was conducted at primary care clinics within a MCO and involved 370 adults with diabetes. Measurements included 1) the frequency of dilated eye and foot examinations, microalbuminuria assessment, blood pressure measurement, lipid profile, and HbA(1c) measurement; 2) changes in blood pressure, lipid levels, and HbA(1c) levels; and 3) changes in patient satisfaction. RESULTS: Complete data are reported for the 193 patients who had been enrolled for 12 months; life table analysis is reported for all patients who remained enrolled at the study's end as well as for a comparative control group of 623 patients. For the 193 patients for whom 12-month data were available, the number of patients in the low-risk category (HbA(1c) <7%) increased by 51.1%. A total of 97.4% of patients with an HbA(1c) >8% at baseline had a change in treatment regimen. Patients at the highest risk for coronary heart disease (LDL >130 mg/dl) decreased from 25.4% at baseline to 20.2%. Patients with a blood pressure <130/85 mmHg increased from 23.8 to 44.6%. Of these patients, 63.0% had changes in medication. Patients and providers expressed significant increases in satisfaction with the program. CONCLUSIONS: The program was successful in initiating the recommended changes in the diabetic therapeutic regimen, resulting in improved glycemic control, increased monitoring/management of diabetic complications, and greater patient and provider satisfaction. These results should have great significance in the design of future programs in MCOs aimed at improving the care of people with diabetes and other chronic diseases.

Adult↗

Stress echocardiography for risk stratification of diabetic patients with known or suspected coronary artery disease.

OBJECTIVE: Coronary artery disease (CAD) is a leading cause of mortality and morbidity in diabetic patients; therefore, their risk stratification is a relevant issue. Because exercise tolerance is frequently impaired in these patients, pharmacological stress echocardiography (SE) has been suggested as a valuable alternative. Our aim was to evaluate the prognostic value of this technique in diabetic patients with known or suspected CAD. RESEARCH DESIGN AND METHODS: A total of 259 consecutive diabetic patients underwent pharmacological SE (dobutamine in 108 patients and dipyridamole in 151 patients) and follow-up for 24 +/- 22 months. A comparison between the prognostic value of SE and exercise electrocardiography (ECG) was made in a subgroup of 120 subjects. RESULTS: A total of 13 cardiac deaths and 13 nonfatal infarctions occurred during follow-up, and 58 patients were revascularized. Univariate predictors of outcome were known CAD, positive SE, rest and peak wall motion score index (WMSI), and peak/rest WMSI variation. Peak WMSI was the only significant and independent prognostic indicator (odds ratio 11; 95% CI 4-29, P < 0.0001) on multivariate Cox's analysis. After adjustment for the most predictive clinical and exercise ECG variables, SE provided 43% additional prognostic information (gain in X(2) = 7, P < 0.01). Moreover, positive SE was associated with a significantly lower event-free survival. CONCLUSIONS: SE effectively predicts cardiac events in diabetic patients with known or suspected CAD and adds additional prognostic information as compared with exercise ECG.

Adrenergic beta-Agonists↗

Noninvasive risk stratification prevents sudden death due to paroxysmal atrial fibrillation in hypertrophic cardiomyopathy.

Sudden death is a tragic complication of hypertrophic cardiomyopathy. We report the case of a young patient with hypertrophic cardiomyopathy in whom an episode of atrial fibrillation triggered ventricular fibrillation and cardiac arrest. A 21-year-old man with nonobstructive hypertrophic cardiomyopathy underwent cardioverter-defibrillator implantation for primary prevention of sudden death, after risk stratification with noninvasive strategies. After 6 weeks, during a moderate effort, the patient had a syncopal episode, preceded by palpitations and dizziness, and terminated by the cardioverter-defibrillator. Device interrogation revealed an episode of atrial fibrillation with high ventricular response, spontaneously followed by ventricular tachycardia/fibrillation. Atrial fibrillation is a potential trigger of life-threatening arrhythmias and sudden death in patients with hypertrophic cardiomyopathy. Clinical investigation of risk markers for sudden death should be encouraged to identify high-risk patients who may benefit from a prophylactic therapy with an implantable cardioverter-defibrillator.

Adult↗

Development of vaginal adenosis-like lesions and uterine epithelial stratification in mice exposed perinatally to diethylstilbestrol.

Pregnant ICR/JCL mice were given either four daily subcutaneous injections of 20-2000 micrograms diethylstilbestrol (DES)/day or a 4-day intravenous infusion of 20-200 micrograms DES/day starting on Day 15 of gestation. Female mice were injected with 0.01-50 micrograms DES/day for 5 days starting on the day of birth. Females given oil injections during the neonatal period and offspring of mothers given injections of an infusion of respective vehicles alone served as controls when corresponding ages were attained. Incidence of adenosis-like lesions (ADL) in the vaginal epithelium and stratification of the uterine epithelium (UST) were determined in both offspring and neonatally exposed mice at 30 days of age. Injections of 0.1-50 micrograms DES/day during the neonatal period induced ADL in the fornical epithelium of vagina (36-70%), but not UST. A high incidence of ADL (80-88%) was found in the fornical and upper-vaginal epithelia in offspring of mothers given injections of 200-2000 micrograms DES/day, and UST was encountered in 38-70% of these mice. Offspring of mothers given an infusion of 20 micrograms DES/day had low incidences of ADL (11%) and UST (22%), whereas offspring of mothers infused with 200 micrograms DES/day exhibited high incidences of ADL (71%) and UST (86%). In offspring of mothers given injections of 2000 micrograms DES/day, ADL appeared in the fornical and upper-vaginal epithelial as early as 15 days of age. Thus, the present study revealed that ADL and UST occur at a high incidence in infantile mice exposed prenatally to high doses of DES. Previous studies failed to detect such effects perhaps due to the strain of mice, methods, duration, and/or dose of DES used.

Animals↗

Cardiac risk stratification before noncardiac surgery.

The history and the physical examination remain the most important elements in cardiac risk stratification of patients prior to noncardiac surgery. Indications for further cardiac tests and interventions are usually the same as in the nonsurgical setting. No test should be performed unless the results will affect patient management. In many cases, noninvasive testing is being replaced by prophylactic medical therapy, a topic explored in the next article in this supplement.

Health Status↗

Incurring greater health care costs: risk stratification of employees with bipolar disorder.

PURPOSE: To compare the costs of employees with bipolar disorder with other employee cohorts and to assess cost differences among employees with bipolar disorder of varying severity. METHODS: Retrospective data analysis comparing employees with bipolar disorder (cohort 1) with employees without bipolar disorder (cohort 2), employees with other mental disorders (cohort 3), and employees with no mental disorders (cohort 4). Sick leave, short-term disability, long-term disability, and workers' compensation data were used to compare annual lost time and work-absence costs from January 1, 2001, through December 31, 2002. For bipolar disorder severity and risk stratification, quintiles were identified based on total medical and prescription drug costs and analyzed for many health benefits cost categories. RESULTS: Cohort 1 was the most costly in nearly every health benefits cost category. All comparisons between cohort 1 and cohorts 2, 3, and 4 yielded significant (p ≤ .05) differences except for sick leave costs in cohorts 1 and 3. The aggregate health benefits costs for the highest-cost cohort 1 quintile were $70,616, or 21 times greater than the health benefits costs for the lowest-cost quintile ($3385). Medical comorbidity costs accounted for most of this difference ($51,495; p ≤ .05). CONCLUSION: Employees with bipolar disorder are the most costly in nearly every health benefits category, with a small minority (2.4%) accounting for 20% of the costs. Employers need to identify and target high-risk ("high cost") employees with bipolar disorder and coexisting conditions that use resources more frequently for appropriate interventions that may include early screening and diagnosis, appropriate treatment, and/or behavioral strategies for improved adherence. These strategies have the potential to improve quality of patient care and reduce costs.

Journal Article↗

Liquid Biopsy of HPV Cell-Free DNA Enables Blood-Based Early Detection and Molecular Stratification of HPV-Associated Cancer and Precancer Stages.

Liquid biopsies targeting circulating tumor DNA enable noninvasive cancer detection but lack sensitivity in pre- and early- cancer stages, where clinical benefits would be greatest. Human papillomavirus (HPV) causes six cancer types, accounting for 5% of all cancers worldwide. Targeting HPV cell-free (cf)DNA offers a compelling opportunity to overcome current liquid biopsy constraints due to its unique tumor-specific origin, lack of sequence homology to the human genome, and the high viral-to-human copy ratio per cell. Utilizing HPV-associated anal cancer and precancer as a model, here we applied a custom, multi-feature HPV whole-genome liquid biopsy to biobanked and prospective screening cohorts spanning the HPV infection-precancer-cancer continuum. HPV cfDNA was detected years before cancer diagnosis and as early as the infection stage, with increasing detection as stages advanced. Genomic hallmarks of HPV malignancy, including HPV integration, PIK3CA mutations, and 3q amplification, were detected exclusively in cancer, while precancers exhibited distinct HPV genotypes. Fragmentomics analysis of HPV cfDNA revealed stage-informative signatures reflecting viral epigenetic changes during carcinogenesis. A unified classifier incorporating genomic and fragmentomics features achieved a mean AUC of 0.77 for identifying cancer and high-grade precancer, stages requiring clinical intervention. Together, these findings demonstrate the feasibility of blood-based screening and molecular risk stratification for HPV-associated cancer and precancer.

Journal Article↗

Clinico-pathologic features of chronic myeloid leukemia and risk stratification according to Sokal score.

OBJECTIVE: To compile the clinical and haematological parameters of chronic myeloid leukemia (CML) and risk stratification according to Sokal score in our population. DESIGN: A descriptive analysis. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, during the period from August 1997 to August 2005. SUBJECTS AND METHODS: All patients with diagnosis of chronic myeloid leukemia treated as outpatient in haematology clinic, or admitted in haem-oncology wards in The Aga Khan University Hospital were included. Records were retrospectively analyzed for clinicopathologic features. Risk groups were assigned as per Sokal scoring. RESULTS: During the 8 years study period, 245 patients with chronic myeloid leukemia were analyzed, the median age of presentation was 35 years (range 11-73); with male to female ratio 1.69:1. At the time of diagnosis, 178 patients (72.6%), 48 (19.7%) and 17 (7.8%) of patients were in chronic, accelerated and blast phase of the disease respectively. Abdominal fullness was the frequent clinical presentation followed by fever. Laboratory parameters revealed mean hemoglobin 10.0 g/dl (range 4.6-15), mean total leukocyte count 168 x 10(9)/L (35-959) and mean platelets 408 x 10(9)/L (range 30-2335). The mean size of spleen at the time of presentation was 9.2 cm below the left subcostal margin. A large number of patients (46.2%) were in high risk group according to Sokal score i.e. > 1.2. CONCLUSION: CML occurred more commonly at younger age in this series. Most of these patients were in high risk group according to Sokal score.

Adolescent↗

[Value of exercise test for risk stratification acute myocardial infarction].

OBJECTIVES: To assess the prognostic value of predischarge exercise testing (ET) in patients hospitalized for acute myocardial infarction (AMI). CONTEXT: Department of Cardiology in a reference hospital for Interventional Cardiology METHODS: Between January 1990 and December 1994, 178 patients hospitalized for AMI were discharged and referred to the outpatient clinic (mean follow up, 1049 +/- 612 days). Eighty-two percent of these patients were men, mean age--56 +/- 12 years. Patients that did not perform predischarge ET (Group A, n 77) were retrospectively compared with those who did (Group B, n = 101). In relation to demographic and clinical characteristics; we analysed cardiac events (CE) and death during the first 18 months after discharge in both groups. In group B patients, we studied the relation of ET parameters (duration of exercise, occurrence of exercise-induced ischaemia and arrhythmias, maximum heart rate, blood pressure response, rate pressure product and severity score) to CE and death during the first 18 months after AMI. RESULTS: The proportion of patients aged 70 years or older was greater in group A (23% vs 3%, P < 0.001). In this group, there was a greater prevalence of recurrent ischaemia (51% vs 29%, P < 0.001) and left ventricular dysfunction (42% vs 25%, P < 0.05). Group A patients were also submitted to less thrombolysis (45% vs 62%, P < 0.05) and to revascularization procedures (25% vs 41%, P < 0.05). In group B patients, the incidence of CE did not differ with respect to duration of ET, rate pressure product or maximum heart rate. Incidence of CE was greater in patients with exercise-induced ischaemia (38% vs 15%, P < 0.05), severity score > 2 (45% vs 18%, P < 0.02) and inadequate rise (< 30 mmHg) in systolic blood pressure (39% vs 13%, P < 0.02). The total incidence of CE and revascularization was also greater in patients with exercise-induced ischaemia (88% vs 49%, P < 0.001), severity score > 2 (95% vs 56%, P < 0.02) and inadequate rise in systolic blood pressure (93% vs 45%, P < 0.001). CONCLUSIONS: In patients without indication for ET as part of risk stratification after AMI, clinical characteristics were more severe as defined by age greater than 70 years, residual ischaemia and left ventricular dysfunction. Patients that performed ET had smaller risk, except when presenting exercise-induced ischaemia, severity score > 2 and inadequate rise in systolic blood pressure.

Adult↗

Stratification, competition and risk distribution: health insurance in Germany and the United States.

Issues of unequal risk distribution among sickness funds are given increasing attention in the current discussions on the reform of the statutory health insurance system in Germany. This paper examines the structural determinants of risk distribution and points toward the links between social stratification, competition, health risk and insurance status. A model showing the links between basic structural determinants is presented. Using health survey data from Germany and the U.S., statistical analyses are conducted. The results support the model and indicate its applicability for both health care systems. The paper concludes by indicating the relevance of such findings for health policy and future research.

Economic Competition↗

Applying risk assessment models in non-surgical patients: effective risk stratification.

Pulmonary embolism and deep vein thrombosis are serious complications of non-surgical patients, but scarcity of data documenting prophylaxis means antithrombotic therapy is rarely used. Prediction of risk is complicated by the variation in the medical conditions associated with venous thromboembolism (VTE), and lack of data defining risk in different groups. Accurate risk assessment is further confounded by inherited or acquired factors for VTE, additional risk due to medical interventions, and interactions between risk factors. Acquired and inherited risk factors may underlie thromboembolic complications in a range of conditions, including pregnancy, ischaemic stroke, myocardial infarction and cancer. Risk stratification may be feasible in non-surgical patients by considering individual risk factors and their cumulative effects. Current risk assessment models require expansion and modification to reflect emerging evidence in the non-surgical field. A large on-going study of prophylaxis with low-molecular-weight heparin in non-surgical patients will clarify our understanding of the components of risk, and assist in developing therapy recommendations.

Drug-Related Side Effects and Adverse Reactions↗

Simplifying the Waterston's stratification of infants with tracheoesophageal fistula.

The survival of infants with tracheoesophageal fistula was stratified by David J. Waterston et al. in 1962. This classification has been used as a guide to direct the timing of operative intervention in these infants. This study examines the current applicability of this classification system. The hospital records of 64 infants with esophageal atresia and/or tracheoesophageal fistula were reviewed. The survival rate was analyzed as a function of the infants' risk stratification, birth weight, and additional anomalies. Twenty-three infants were in Waterston Group A, 20 infants in Group B, and 21 infants in Group C. The survival of all infants was 81 per cent. Six infants died after recognition of severe anomalies and withdrawal of care, four infants died of cardiopulmonary arrest, and two infants died of sepsis. The survival of infants in both Groups A and B was 100 per cent, in contrast to 43 per cent survival in Group C. Only infants who weighed <1800 g or had severe additional anomalies were at risk of dying. Therefore, the classification of infants with esophageal atresia and/or tracheoesophageal fistula may be simplified by combining Waterston's Groups A and B into a single risk stratum.

Esophageal Atresia↗

[Usefulness of troponin T and troponin I in the diagnosis and prognostic stratification of patients with ischemic cardiopathy attending an emergency service].

BACKGROUND: Diagnostic of chest pain in the emergency services supposes a serious problem. This study wants objective if the new non enzymatic markers of myocardial necrosis (T troponin and I troponin) may be an aid for the diagnostic and prognostic stratification of patients with myocardial ischemia. PATIENTS AND METHODS: 82 successive patients who went to the emergency room for chest pain were studied. Electrocardiogram and blood samples were obtained at 0,4, and 12 house of admission. A clinic-evolutive study was performed at discharge, and they were classified in 3 categories: a) myocardial infarction, b) unstable angina (Braunwald classification) and no coronary pains. RESULTS: In the 27 patients with myocardial infarction the markers of troponin group were more sensitive than creatinine kinase to determine myocardial necrosis at 4 hours of admission. Of 41 patients with unstable angina, 34% were of Braunwald III-B class. Troponin group markers discriminate a group of high risk patients, 70% of the patients that need an emergency coronarography for bad clinical evolution were troponin group marker positive. CONCLUSIONS: The use in the emergency room of troponin necrosis markers (T and I troponin) allows to optimize the sanitary resources, detecting quickly the patients with acute myocardial infarction and discriminate a group of high risk of patients with angina.

Aged↗

Cardiac risk stratification of patients undergoing peripheral vascular surgery.

Approximately 50% of patients with peripheral vascular disease have severe coronary artery disease. Several ways of predicting the postoperative risk of major cardiac events in peripheral vascular patients have been suggested. Among preoperative tests, echocardiography is now receiving greater favor for risk stratification.

Coronary Disease↗