Project description:Patients with histologically proven adenocarcinoma of the rectum will receive pelvic radiotherapy to a dose of 45Gy in 25 fractions with a tumor boost to a dose of 9Gy in 5 fractions (thus total of 54Gy/30Fx to the primary tumor), combined with radio sensitizing chemotherapy. Patients will then be closely monitored, through endoscopy and imaging, for response to treatment and relapse. Salvage oncologic surgery to be offered if there is failure to achieve complete clinical response or in the event of a loco regional relapse.
Project description:AKI-dialysis patients had a higher incidence of long-term ESRD and mortality than the patients without AKI. The patients who recovered from dialysis were associated with a lower incidence of long-term ESRD and mortality than in the patients who still required dialysis.
Project description:IntroductionAfter dialysis-requiring acute kidney injury (AKI-D), recovery of sufficient kidney function to discontinue dialysis is an important clinical and patient-oriented outcome. Predicting the probability of recovery in individual patients is a common dilemma.MethodsThis cohort study examined all adult members of Kaiser Permanente Northern California who experienced AKI-D between January 2009 and September 2015 and had predicted inpatient mortality of <20%. Candidate predictors included demographic characteristics, comorbidities, laboratory values, and medication use. We used logistic regression and classification and regression tree (CART) approaches to develop and cross-validate prediction models for recovery.ResultsAmong 2214 patients with AKI-D, mean age was 67.1 years, 40.8% were women, and 54.0% were white; 40.9% of patients recovered. Patients who recovered were younger, had higher baseline estimated glomerular filtration rates (eGFR) and preadmission hemoglobin levels, and were less likely to have prior heart failure or chronic liver disease. Stepwise logistic regression applied to bootstrapped samples identified baseline eGFR, preadmission hemoglobin level, chronic liver disease, and age as the predictors most commonly associated with coming off dialysis within 90 days. Our final logistic regression model including these predictors had a correlation coefficient between observed and predicted probabilities of 0.97, with a c-index of 0.64. An alternate CART approach did not outperform the logistic regression model (c-index 0.61).ConclusionWe developed and cross-validated a parsimonious prediction model for recovery after AKI-D with excellent calibration using routinely available clinical data. However, the model's modest discrimination limits its clinical utility. Further research is needed to develop better prediction tools.
Project description:IntroductionPreemptive wait-listing of deceased donor kidney transplant (DDKT) candidates before maintenance dialysis increases the likelihood of transplantation and improves outcomes among transplant patients. Previous studies have identified substantial disparities in rates of preemptive listing, but a gap exists in examining geographic sources of disparities, particularly for sub-regional units. Identifying small area hot spots where delayed listing is particularly prevalent may more effectively inform both health policy and regionally appropriate interventions.MethodsWe conducted a retrospective cohort study utilizing 2010-2020 Scientific Registry of Transplant Recipients (SRTR) data for all DDKT candidates to examine overall and race-stratified geospatial hot spots of post-dialysis wait-listing in U.S. zip code tabulation areas (ZCTA). Three geographic clustering methods were utilized to identify robust statistically significant hot spots of post-dialysis wait-listing.ResultsNovel sub-regional hot spots were identified in the southeast, southwest, Appalachia, and California, with a majority existing in the southeast. Race-stratified results were more nuanced, but broadly reflected similar patterns. Comparing transplant candidates in hot spots to candidates in non-clusters indicated a strong association between residence in hot spots and high area deprivation (OR: 6.76, 95%CI: 6.52-7.02), indicating that improving access healthcare in these areas may be particularly beneficial.ConclusionOur study identified overall and race-stratified hot spots with low rates of preemptive wait list placement in the U.S., which may be useful for prospective healthcare policy and interventions via targeting of these narrowly defined geographical areas.
Project description:The kidney is not typically the main target of severe acute respiratory syndrome coronavirus 2, but surprisingly, acute kidney injury (AKI) may occur in 4-23% of cases, whereas the dialysis management of AKI from coronavirus 2019 has not gained much attention. The severity of the pandemic has resulted in significant shortages in medical supplies, including respirators, ventilators and personal protective equipment. Peritoneal dialysis (PD) remains available and has been used in clinical practice for AKI for >70 years; however, it has been used on only a limited basis and therefore experience and knowledge of its use has gradually vanished, leaving a considerable gap. The turning point came in 2007, with a series of sequential publications providing solid evidence that PD is a viable option. As there was an availability constraint and a capacity limit of equipment/supplies in many countries, hemodialysis and convective therapies became alternatives. However, even these therapies are not available in many countries and their capacity is being pushed to the limit in many cities. Evidence-based PD experience lends support for the use of PD now.
Project description:BackgroundCurrent information about acute kidney injury (AKI) epidemiology in developing nations derives mainly from isolated centers, with few quality multicentric epidemiological studies. Our objective was to describe a large cohort of patients with dialysis-requiring AKI derived from ordinary clinical practice within a large metropolitan area of an emerging country, assessing the impact of age and several clinical predictors on patient survival across the spectrum of human life.MethodsWe analyzed registries drawn from 170 hospitals and medical facilities in Rio de Janeiro, Brazil, in an eleven-year period (2002-2012). The study cohort was comprised of 17,158 pediatric and adult patients. Data were analyzed through hierarchical logistic regression models and mixed-effects Cox regression for survival comparison across age strata.ResultsSevere AKI was mainly hospital-acquired (72.6%), occurred predominantly in the intensive care unit (ICU) (84.9%), and was associated with multiple organ failure (median SOFA score, 11; IQR, 6-13). The median age was 75 years (IQR, 59-83; range, 0-106 years). Community-acquired pneumonia was the most frequent admission diagnosis (23.8%), and sepsis was the overwhelming precipitating cause (72.1%). Mortality was 71.6% and was higher at the age extremes. Poor outcomes were driven by age, mechanical ventilation, vasopressor support, liver dysfunction, type 1 cardiorenal syndrome, the number of failing organs, sepsis at admission, later sepsis, the Charlson score, and ICU admission. Community-acquired AKI, male gender, and pre-existing chronic kidney disease were associated with better outcomes.ConclusionsOur study adds robust information about the real-world epidemiology of dialysis-requiring AKI with considerable clinical detail. AKI is a heterogeneous syndrome with variable clinical presentations and outcomes, including differences in the age of presentation, comorbidities, frailty state, precipitation causes, and associated diseases. In the cohort studied, AKI characteristics bore more similarities to upper-income countries as opposed to the pattern traditionally associated with resource-limited economies.
Project description:BACKGROUND:Acute kidney injury requiring dialysis (AKI-D) is associated with high mortality. Information about its epidemiology is nonetheless sparse in some countries. The objective of this study was to assess its epidemiology and prognosis in metropolitan France. METHODS:Using the French hospital discharge database, the study focused on adults hospitalized in metropolitan France between 2009 and 2014 and diagnosed with AKI-D according to the codes of the French common classification of medical procedures. Crude and standardized incidence rates (SIR) by gender and age were calculated. We explored the changes in patients' characteristics, modalities of renal replacement therapy (RRT), in-hospital care, and mortality, along with their determinants. Trends over time in the SIR for AKI-D, its principal diagnoses, and comorbidities were analyzed with joinpoint models. RESULTS:Between 2009 and 2014, the AKI-D SIR increased from 475 (95% CI, 468 to 482) to 512 per million population (95% CI, 505 to 519). AKI-D was twice as high in men as women. Median age was 68 years. Over the study period, the AKI-D SIR steadily increased in all age groups, particularly in the elderly. The most common comorbidities were cardio-cerebrovascular diseases (64.8%), pulmonary disease (42.2%), CKD (33.8%), and diabetes (26.0%); all of these except CKD increased significantly over time. In 2009, heart failure (17.2%), sepsis (17.0%), AKI (13.0%), digestive diseases (10.7%), and shock (6.6%) were the most frequent principal diagnoses, with a significant increase in heart failure and digestive diseases. The proportion of patients with at least one ICU stay and continuous RRT increased from 80.3% to 83.9% and from 56.9% to 61.8% (p<0.001), respectively. In-hospital mortality was high but stable (47%) and higher in patients with an ICU stay. CONCLUSIONS:This is the first exhaustive study in metropolitan France of the SIR for AKI-D. It shows this SIR has increased significantly over 6 years, together with ICU care and continuous RRT. In-hospital mortality is high but stable.
Project description:BackgroundFor patients with Acute Kidney Injury (AKI), a strong and graded relationship exists between AKI severity and mortality. One of the most severe entities of AKI is Dialysis-Requiring Acute Kidney Injury (D-AKI), which is associated with high rates of mortality and end-stage renal disease (ESRD). For this high-risk population group, there is a lack of evidence regarding optimal post-AKI care. We propose that post-AKI care through the combined efforts of the nephrologist and the multidisciplinary care team may improve outcomes. Our aim here is to study for survivors of dialysis-requiring acute kidney injury, the effects of implementing early comprehensive kidney care.MethodsThis is a retrospective longitudinal cohort study of Taiwanese through analyzing the National Health Insurance Research Database (NHIRD). We included patients with acute dialysis during hospitalization from January 1, 2015 to December 31, 2018. Propensity match was done at 1:1, including estimated glomerular filtration rate (eGFR) based on CKD-EPI which was performed due to large initial disparities between these two cohorts.ResultsAfter the propensity match, each cohort had 4,988 patients. The mean eGFR based on CKD-EPI was 27.5 ml/min/1.73 m2, and the mean follow-up period was 1.4 years.The hazard ratio for chronic dialysis or ESRD was 0.55 (95% CI, 0.49-0.62; p < 0.001). The hazard ratio for all-cause mortality was 0.79 (95% CI, 0.57-0.88; p < 0.001). Both outcomes favored early comprehensive kidney care.ConclusionsFor survivors of dialysis-requiring acute kidney injury, early comprehensive kidney care significantly lowered risks of chronic dialysis and all-cause mortality.
Project description:IntroductionThe pathophysiology of acute kidney injury (AKI) involves damage to renal epithelial cells, podocytes, and vascular beds that manifests into a deranged, self-perpetuating immune response and peripheral organ dysfunction. Such an injury pattern requires a multifaceted therapeutic to alter the wound healing response systemically. Mesenchymal stromal cells (MSCs) are a unique source of secreted factors that can modulate an inflammatory response to acute organ injury and enhance the repair of injured tissue at the parenchymal and endothelial levels. This phase Ib/IIa clinical trial evaluates SBI-101, a combination product that administers MSCs extracorporeally to overcome pharmacokinetic barriers of MSC transplantation. SBI-101 contains allogeneic human MSCs inoculated into a hollow-fiber hemofilter for the treatment of patients with severe AKI who are receiving continuous renal replacement therapy (CRRT). SBI-101 therapy is designed to reprogram the molecular and cellular components of blood in patients with severe organ injury.MethodsThis study is a prospective, multicenter, randomized, double-blind, sham-controlled, study of subjects with a clinical diagnosis of AKI who are receiving CRRT. Up to 32 subjects may be enrolled to provide 24 evaluable subjects (as a per protocol population). Subjects will receive CRRT in tandem with a sham control (0 MSCs), or the low- (250 × 106 MSCs) or high-dose (750 × 106 MSCs) SBI-101 therapeutic.ResultsThe study will measure dose-dependent safety, renal efficacy, and exploratory biomarkers to characterize the pharmacokinetics and pharmacodynamics of SBI-101 in treated subjects.ConclusionThis first-in-human clinical trial will evaluate the safety and tolerability of SBI-101 in patients with AKI who require CRRT.