Penile Strangulation: Analysis of Postextrication Follow-Up, Sequelae, and a Review of Literature.

Numerous case reports exist on penile strangulation injuries and extrication methods; however, the care and long-term consequences of penile strangulation injuries have been under-reported. Our aim is to investigate the long-term outcomes and sequalae following penile strangulation injuries. The PubMed Medline database was searched using the keyword string "penile strangulation," "penis strangulation," and "constriction" for all studies reporting outcomes of published penile strangulation injuries. Articles were evaluated for follow-up after strangulation injury, strangulating agent, extricating agent, and sequelae of injury. Fifty-six studies resulted with reports of 100 cases of penile strangulation and extrication from January 2000 to December 2019. The mean patient age was 41 (range: 3-86) years. Twenty-four (24/100) cases reported sequalae following extrication. Follow-up ranged from 2 weeks to 7 years with median follow-up time in the 7- to 12-month grouping. Metal rings comprised 36% (36/100) of strangulation agents and 50% of reported incidents were attributed to sexual activity. To our knowledge, this is the only study focusing on long-term outcomes after penile strangulation. This review provides a summary of 56 studies that document penile strangulation injuries over the last 20 years. Although a wide array of penile strangulation injuries have been documented in the literature, reports lack secondary management and long-term outcomes after removal of the strangulation device. We recommend that providers report long-term penile strangulation outcomes for future urologic evaluations after extrication.

Clinical Considerations for Patients Experiencing Acute Kidney Injury Following Percutaneous Nephrolithotomy.

Acute kidney injury (AKI) is a common postoperative outcome in urology patients undergoing surgery for nephrolithiasis. The objective of this study was to determine the prevalence of postoperative AKI and its degrees of severity, identify risk factors, and understand the resultant outcomes of AKI in patients with nephrolithiasis undergoing percutaneous nephrolithotomy (PCNL). A cohort of patients admitted between 2012 and 2019 to a single tertiary-care institution who had undergone PCNL was retrospectively analyzed. Among 417 (n = 326 patients) encounters, 24.9% (n = 104) had AKI. Approximately one-quarter of AKI patients (n = 18) progressed to Stage 2 or higher AKI. Hypertension, peripheral vascular disease, chronic kidney disease, and chronic anemia were significant risk factors of post-PCNL AKI. Corticosteroids and antifungals were associated with increased odds of AKI. Cardiovascular, neurologic complications, sepsis, and prolonged intensive care unit (ICU) stay percentages were higher in AKI patients. Hospital and ICU length of stay was greater in the AKI group. Provided the limited literature regarding postoperative AKI following PCNL, and the detriment that AKI can have on clinical outcomes, it is important to continue studying this topic to better understand how to optimize patient care to address patient- and procedure-specific risk factors.

Does kidney biopsy in pediatric lupus patients "complement" the management and outcomes of silent lupus nephritis? Lessons learned from a pediatric cohort.

BACKGROUND: Silent lupus nephritis (SLN) is systemic lupus erythematosus (SLE) without clinical and laboratory features of kidney involvement but with biopsy-proven nephritis. This study aims to describe and compare the baseline characteristics and outcomes of pediatric SLN with overt LN (OLN) and to identify associated risk factors and biochemical markers. METHODS: In this retrospective, observational study, multivariate logistic regression and receiver operating characteristic (ROC) analyses studied age, sex, race, serum complements, anti-double-stranded-DNA antibody, anti-Smith antibody, eGFR, and proliferative nephritis. RESULTS: In our cohort of 69 patients, 47 were OLN, and 22 were SLN. OLN (OR = 4.9, p = 0.03) and non-African Americans (AA) (OR = 13.0, p < 0.01) had higher odds, and increasing C3 and C4 were associated with lower odds of proliferative nephritis (OR 0.95 and 0.65 per one unit increase in C3 and C4, respectively, p < 0.01). They demonstrated a good discriminative ability to detect proliferative nephritis as assessed by the area under the ROC curve (C3 = 0.78, C4 = 0.78). C3 and C4 in proliferative SLN and OLN were comparable and significantly lower than their non-proliferative counterparts. No association was observed between age, sex, anti-double-stranded-DNA antibody, anti-Smith antibody, eGFR, and proliferative nephritis. Proliferative SLN and OLN patients received similar treatments. Adverse events were identified in the proliferative OLN only. CONCLUSIONS: Lower complement levels are associated with proliferative lesions in pediatric LN-both SLN and OLN. The non-AA population had higher odds of having proliferative nephritis than the AA. Prospective, randomized, long-term follow-up of proliferative SLN patients is needed to ascertain the beneficial effect of early diagnosis and treatment. A higher resolution version of the Graphical abstract is available as Supplementary information.

Provision of Kidney Disease Education Service Is Associated with Improved Vascular Access Outcomes among US Incident Hemodialysis Patients.

Background: Pre-ESKD Kidney Disease Education (KDE) has been shown to improve multiple CKD outcomes, but its effect on vascular access outcomes is not well studied. In 2010, Medicare launched KDE reimbursements policy for patients with advanced CKD. Methods: In this retrospective USRDS analysis, we identified all adult patients on incident hemodialysis with ≥6 months of pre-ESKD Medicare coverage during the first 5 years of CMS-KDE policy and divided them into CMS-KDE services recipients (KDE cohort) and nonrecipients (non-KDE cohort). The primary outcome was incident arteriovenous fistula (AVF) and the composite of incident AVF or arteriovenous graft (AVG) utilization. Secondary outcomes were central venous catheter (CVC) with maturing AVF/AVG and pure CVC utilizations. Step-wise multivariate analyses were performed in four progressive models (model 1, KDE alone; model 2, multivariate model encompassing model 1 with sociodemographics; model 3, model 2 with comorbidity and functional status; and model 4, model 3 with pre-ESKD nephrology care). Results: Of the 211,990 qualifying patients on incident hemodialysis during the study period, 2887 (1%) received KDE services before dialysis initiation. The rates of incident AVF and composite AVF/AVG were more than double (30% and 35%, respectively, compared with 14% and 17%), and pure catheter use about a third lower (40% compared with 65%) in the KDE cohort compared with the non-KDE cohort. The maximally adjusted odds ratios in model 4 for study outcomes were incident AVF use, 1.78, 99% confidence interval, 1.55 to 2.05; incident AVF/AVG use, 1.78, 99% confidence interval, 1.56 to 2.03; incident CVC with maturing AVF/AVG, 1.69, 99% confidence interval, 1.44 to 1.97; and pure CVC without any AVF/AVG, 0.51, 99% confidence interval, 0.45 to 0.58. The benefits of the KDE service were maintained even after accounting for the presence, duration, and facility of ESKD care. Conclusion: The occurrence of pre-ESRD KDE service is associated with significantly improved incident vascular access outcomes. Targeted studies are needed to examine the effect of KDE on patient engagement and self-efficacy as a cause for improvement in vascular access outcomes.

Association between nuclear grade of renal cell carcinoma and the aorta-lesion-attenuation-difference.

INTRODUCTION AND BACKGROUND: Several features noted on renal mass biopsy (RMB) can influence treatment selection including tumor histology and nuclear grade. However, there is poor concordance between renal cell carcinoma (RCC) nuclear grade on RMB compared to nephrectomy specimens. Here, we evaluate the association of nuclear grade with aorta-lesion-attenuation-difference (ALAD) values determined on preoperative CT scan. METHODS AND MATERIALS: A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate low-grade (nuclear grade 1 and 2) and high-grade (nuclear grade 3 and 4) tumors was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using ROC analysis. Sub-group analysis by histologic sub-type was also performed. RESULTS: A total of 368 preoperative CT scans in patients with RCC on nephrectomy specimen were reviewed. Median patient age was 61 years (IQR 52-68). The majority of patients were male, 66% (243/368). Tumor histology was chromophobe RCC in 7.6%, papillary RCC in 15.5%, and clear cell RCC in 76.9%. The majority, 69.3% (253/365) of tumors, were stage T1a. Nuclear grade was grade 1 in 5.46% (19/348), grade 2 in 64.7% (225/348), grade 3 in 26.2% (91/348), and grade 4 in 3.2% (11/348). Nephrographic ALAD values for grade 1, 2, 3, and 4 were 73.7, 46.5, 36.4, and 43.1, respectively (p = 0.0043). Nephrographic ALAD was able to differentiate low-grade from high-grade RCC with a sensitivity of 32%, specificity of 89%, PPV of 86%, and NPV of 36%. ROC analysis demonstrated the predictive utility of nephrographic ALAD to predict high- versus low-grade RCC with an AUC of 0.60 (95% CI 0.51-0.69). CONCLUSION: ALAD was significantly associated with nuclear grade in our nephrectomy series. Strong specificity and PPV for the nephrographic phrase demonstrate a potential role for ALAD in the pre-operative setting that may augment RMB findings in assessing nuclear grade of RCC. Although this association was statistically significant, the clinical utility is limited at this time given the results of the statistical analysis (relatively poor ROC analysis). Sub-group analysis by histologic subtype yielded very similar diagnostic performance and limitations of ALAD. Further studies are necessary to evaluate this relationship further.

Pro Re Nata Antihypertensive Medications and Adverse Outcomes in Hospitalized Patients: A Propensity-Matched Cohort Study.

[Figure: see text].

Validation of aorta-lesion-attenuation difference on preoperative contrast-enhanced computed tomography scan to differentiate between malignant and benign oncocytic renal tumors.

OBJECTIVES: We previously noted that the aorta-lesion-attenuation difference (ALAD) determined on CT scan discriminated well between chromophobe RCC and oncocytoma. The current evaluation seeks to validate these initial findings in a second cohort of nephrectomy patients. METHODS: A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for small, solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate malignant pathology from oncocytoma was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using ROC analysis. RESULTS: Twenty-one preoperative CT scans and corresponding pathology reports were reviewed and included in the validation cohort. ALAD values were calculated during the excretory and nephrographic phases. Compared to the training cohort, patients in the validation cohort were significantly older (62 versus 59 years old), had larger tumors (3.7 versus 2.7 cm), and higher stage disease (59% versus 79% T1a disease). Nephrographic ALAD was able to differentiate malignant pathology from oncocytoma in the training and validation cohorts with a sensitivity of 84% versus 73%, specificity of 86% and 67%, PPV of 98% versus 91%, and NPV of 33% versus 35%. The AUC for malignant pathology versus oncocytoma in the validation cohort was 0.72 (95% CI 0.63-0.82). Nephrographic ALAD was able to differentiate chromophobe RCC from oncocytoma in the training and validation cohorts with a sensitivity of 100% versus 67%, specificity of 86% versus 67%, PPV of 75% versus 43%, and NPV of 100% versus 84%. The AUC for chromophobe RCC versus oncocytoma in the validation cohort was 0.72 (95% CI 0.48-0.96). CONCLUSIONS: The ability of ALAD to discriminate between chromophobe RCC and oncocytoma was diminished in the validation cohort compared to the training cohort, but remained significant. The current findings support further investigation in the role of ALAD in the management of patients with indeterminate diagnoses of oncocytic neoplasm.

Association of early initiation of dialysis with all-cause and cardiovascular mortality: A propensity score weighted analysis of the United States Renal Data System.

BACKGROUND: Early initiation of maintenance hemodialysis has been associated with excess mortality in some studies, but the effects on cardiovascular (CV) mortality has not been studied. Moreover, whether the increased mortality is due to co-morbidities or early initiation of dialysis is unclear. We used a propensity score weighted analysis of the United States Renal Data System (USRDS) to examine how the estimated glomerular filtration rate (eGFR) at initiation of dialysis affects total and CV mortality. METHODS: Association between tertiles of eGFR at initiation of hemodialysis and all-cause and CV mortality were assessed in 676,196 adult patients who initiated hemodialysis between 2006 and 2014, using inverse probability of treatment weighting (IPTW) weighted multivariable regression models. RESULTS: The intermediate (eGFR 8.7 to <13.0 mL/min) and early start groups (eGFR ≥13.0 mL/min) had a 42% and 93% increased all-cause mortality, respectively compared to late (eGFR < 8.7), start group (unadjusted hazard ratio (HR) = 1.42; 95% CI, 1.41-1.43 and HR = 1.93; 95%CI, 1.91-1.94, respectively). This association was attenuated but remained significant in propensity weighted multivariable analysis (adjusted HR = 1.13; 95%CI, 1.12-1.14 for intermediate and HR = 1.37; 95%CI, 1.36-1.39, for early start, respectively). The CV mortality was similarly increased (adjusted HR = 1.08; 95%CI, 1.07-1.10 and HR = 1.23; 95%CI, 1.21-1.24, for intermediate and early start, respectively). In patients with cystic kidney disease, all-cause mortality was increased with early start, but there were no differences in CV mortality between groups. CONCLUSIONS: Early initiation of dialysis is associated with increased all-cause and CV mortality. Our observations support delaying hemodialysis according to the eGFR values.

Utilization of CMS pre-ESRD Kidney Disease Education services and its associations with the home dialysis therapies.

BACKGROUND: Kidney Disease Education (KDE) has been shown to improve informed dialysis selection and home dialysis use, two long-held but underachieved goals of US nephrology community. In 2010, the Center for Medicare and Medicaid Services launched a policy of KDE reimbursements for all Medicare beneficiaries with advanced chronic kidney disease. However, the incorporation of KDE service in real-world practice and its association with the home dialysis utilization has not been examined. METHODS: Using the 2016 US Renal Data System linked to end-stage renal disease (ESRD) and pre-ESRD Medicare claim data, we identified all adult incident ESRD patients with active Medicare benefits at their first-ever dialysis during the study period (1 January 2010 to 31 December 2014). From these, we identified those who had at least one KDE service code before their dialysis initiation (KDE cohort) and compared them to a parsimoniously matched non-KDE control cohort in 1:4 proportions for age, gender, ESRD network, and the year of dialysis initiation. The primary outcome was home dialysis use at dialysis initiation, and secondary outcomes were home dialysis use at day 90 and anytime through the course of ESRD. RESULTS: Of the 369,968 qualifying incident ESRD Medicare beneficiaries with their first-ever dialysis during the study period, 3469 (0.9%) received KDE services before dialysis initiation. African American race, Hispanic ethnicity, and the presence of congestive heart failure and hypoalbuminemia were associated with significantly lower odds of receiving KDE services. Multivariate analyses showed that KDE recipients had twice the odds of initiating dialysis with home modalities (15.0% vs. 6.9%; adjusted odds ratio (aOR):95% confidence interval (CI) 2.0:1.7-2.4) and had significantly higher odds using home dialysis throughout the course of ESRD (home dialysis use at day 90 (17.6% vs. 9.9%, aOR:CI 1.7:1.4-1.9) and cumulatively (24.7% vs. 15.1%, aOR:CI 1.7:1.5-1.9)). CONCLUSIONS: Utilization of pre-ESRD KDE services is associated with significantly greater home dialysis utilization in the incident ESRD Medicare beneficiaries. The very low rates of utilization of these services suggest the need for focused systemic evaluations to identify and address the barriers and facilitators of this important patient-centered endeavor.

Improved ability to achieve target trough levels with liquid versus capsule tacrolimus in kidney transplant patients with HIV on protease inhibitor- or cobicistat-based regimens.

HIV + patients are commonly accepted for kidney transplantation. However, patients on protease inhibitor (PI)- or cobicistat (cobi)-based regimens have trouble achieving optimal tacrolimus (Tac) levels. Our study compared the ability to achieve target levels using liquid versus immediate-release capsule Tac in kidney transplant patients with HIV on PI- or cobi-based regimens. The study included four kidney transplant patients who were converted to liquid Tac due to inability to achieve acceptable drug levels on the capsule formulation. Tac trough levels were analyzed retrospectively to compare target levels before and after conversion. The individual patient time in the therapeutic range (TTR) was calculated using Rosendaal's linear interpolation method, and the difference between before and after conversion TTR was determined. In combined data, 44.63% of all Tac trough levels were within the target range after conversion to liquid Tac compared to 22.07% prior to conversion (P < .001). Furthermore, 3.31% and 7.44% of Tac trough levels were lower than 3 ng/mL or higher than 12 ng/mL, respectively, after conversion compared to 11.72% (P = .0564) and 24.14% (P < .0001) prior to conversion. The overall mean TTR was 45.1% after conversion to liquid Tac compared to 16.2% prior to conversion (P = .097). Finally, the coefficient of variation for Tac trough levels was 42.6 after conversion compared to 56.4 prior to conversion. A significantly improved ability to achieve target trough Tac levels was achieved with liquid Tac extemporaneous versus capsule formulation in kidney transplant patients with HIV taking a PI- or cobi-based regimen.

A pilot study of immunosuppression resumption following BK viremia resolution.

BACKGROUND: Immunosuppression reduction for BK viremia is associated with de novo humoral responses, which are a risk factor for rejection and graft loss. In this pilot project, we tested a protocol of immunosuppression resumption to standard dose after viral clearance for optimal protection against humoral immunity in patients undergoing treatment for BK viremia. METHODS: Thirty-six consecutive kidney transplant recipients who developed BK viremia from 7/1/2014 to 11/18/2016 underwent immunosuppression reduction. After 4 weeks of absent viremia, mycophenolate mofetil (MMF) was increased by 500mg/day every 2 weeks up to standard dosage, followed by increase of tacrolimus trough levels to 5-7 ng/mL. If viremia recurred during the increase, immunosuppression was reduced in this same stepwise fashion, with stepwise increase again after 2 months of negative viremia. RESULTS: Mean tacrolimus trough level (ng/mL) was 8.3 ± 2.7 at viremia onset, 5.3 ± 3.6 at resolution, and 5.6 ± 2.0 at study end date. Mean daily dose (mg) of MMF was 1574 ± 355 at onset, 910 ± 230 at resolution, and 1377 ± 451 at study end date. Only one patient developed low level viremia recurrence (peak 2875 copies/mL) during the period of immunosuppression resumption that ultimately resolved. CONCLUSIONS: The results of our pilot project indicate that following BK viremia resolution, resumption of standard immunosuppression can be achieved safely without BK viremia recurrence. Larger trials with long-term follow up are required to determine whether such an approach improves long-term graft survival.

Preventive care for patients with end-stage kidney disease: crossroads between nephrology and primary care.

Patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis (HD) might expect their nephrologists to coordinate all their healthcare needs. We performed a survey among adult patients with ESKD undergoing HD in two outpatient dialysis centers at the University of Florida to identify differences in characteristics between patients with and without primary care providers (PCP) and to explore the association of PCP utilization with adherence to preventive health measures. Of the 132 participants, 89.4% reported having a PCP. This group was more likely to be female, older, and with higher education level. Having a PCP was associated with influenza, pneumococcal, and tetanus/Tdap vaccinations as well as screening for tuberculosis, depression, hypertension, and dyslipidemia. The PCP group had statistically significant higher rates of influenza immunization (89.8% vs 71.4%, P = .04) as well as screening for hypertension (93.2% vs 64.3%, P = .04) and depression (78.8% vs 42.9%, P = .004), compared to the group without PCP, in the multivariable analysis. Having a PCP is associated with higher rates of influenza vaccination and screening for depression and hypertension. These findings could have important implications as far as identifying patients with ESKD at risk for fragmented care and potential gaps in optimal preventive care.

Prevalence and correlates of sleep apnea among US Veterans with chronic kidney disease.

The prevalence and correlates of sleep apnea (SA) among Veterans with chronic kidney disease (CKD), a population at high risk of both SA and CKD, are unknown. We performed a cross-sectional analysis of 248 Veterans (18-89 years) selected only for presence of moderate to severe CKD. All participants underwent full, unattended polysomnography, measurement of renal function and a sleepiness questionnaire. Logistic regression with backward selection was used to identify predictors of prevalent SA (apnea-hypopnea index [AHI, ≥15 events/hr] and prevalent nocturnal hypoxia [NH, % of total sleep time spent at <90% oxygen saturation]). The mean age of our cohort was 73.2 ± 9.6 years, 95% were male, 78% were Caucasian and the mean body mass index (BMI) was 30.3 ± 4.8 kg/m2 . The prevalence of SA was 39%. There was no difference in daytime sleepiness among those with and without SA. In the final model, older age, higher BMI and diabetes mellitus (DM) were associated with higher odds of SA, after controlling for age, BMI, race and sex. Higher BMI, DM, unemployed/retired status, current smoking and higher serum bicarbonate level were associated with prevalent NH. To sum, SA was common among Veterans with moderate to severe CKD. Although some traditional risk factors for SA were associated with SA in this population, sleepiness did not correlate with SA. Further study is needed to validate our findings and understand how best to address the high burden of SA among Veterans with CKD.

Renin-Angiotensin-Aldosterone System Optimization for Acute Decompensated Heart Failure Patients (ROAD-HF): Rationale and Design.

INTRODUCTION: The long-term benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with chronic congestive heart failure are well-known, making them one of the most widely prescribed medications. However, the administration of ACEIs/ARBs in acute decompensated heart failure (ADHF) can increase the risk of morbidity and mortality secondary to worsening renal function (WRF). A decrease in estimated glomerular filtration rate (eGFR) during the treatment of ADHF has been associated with an increase in mortality proportional to the degree of WRF. AIM: The aim of our study is to determine whether withholding ACEIs/ARBs during the initial 72 h of admission in patients with ADHF will prevent WRF and allow more effective diuresis. METHODS: Four hundred and thirty patients will be randomized to the intervention (withholding ACEIs/ARBs) or control (continue/start ACEIs/ARBs) arms for 72 h. Primary outcomes include rates of acute kidney injury (AKI), patient global assessment, and change in kinetic eGFR over 72 h, while secondary outcomes include change in weight, fluid balance, change in signs and symptoms of congestion, change in renal function, change in urinary biomarkers (tissue inhibitor of metalloproteinases 2 [TIMP-2] × insulin-like growth factor-binding protein 7 [IGFBP7]), patients experiencing treatment failure, hospital length of stay (LOS), cost analysis, mortality within 30 days, and hospital readmissions over 30 days and 1 year. CONCLUSION: This prospective clinical trial will prove if withholding ACEIs/ARBs will prevent AKI in ADHF. It will help us understand the complex interactions between the heart and kidney, and delineate the best treatment strategy for ADHF. Holding ACEIs/ARBs might help preserve renal function, and decrease hospital LOS, readmission rates, and cost of care in ADHF. REGISTRATION: ClinicalTrials.gov identifier: NCT03695120.

Opioid Safety and Concomitant Benzodiazepine Use in End-Stage Renal Disease Patients.

Background: Opioid use is common in end-stage renal disease (ESRD) patients. However, safety of individual opioids and concomitant benzodiazepine use has not been studied. Objective: To study the epidemiology of opioid and concomitant benzodiazepine use in ESRD population. To study the clinical safety profile of individual opioids in patients on hemodialysis. Design: Retrospective analysis of the U.S. Renal Data System. A comprehensive review of the current literature was performed to update currently used opioid safety classification. Participants: ESRD patients ≥18 years on hemodialysis who were enrolled in Medicare A and B and Part D between 2006 and 2012, excluding those with malignancy. Main Measures: Hospital admission with diagnosis of prescription opioid overdose within 30, 60, and 90 days of prescription; death due to opioid overdose. Results: Annually, the percentage of patients prescribed any opioid was 52.2%. Overall trend has been increasing except for a small dip in 2011, despite which the admissions due to opioid overdose have been rising. 30% of those who got a prescription for opioids also got a benzodiazepine prescription. 56.5% of these patients received both prescriptions within a week of each other. Benzodiazepine use increased the odds of being on opioids by 3.27 (CI 3.21-3.32) and increased the odds of hospitalization by 50%. Opioids considered safe such as fentanyl and methadone were associated with 3 and 6 folds higher odds of hospitalization within 30 days of prescription. Hydrocodone had the lowest odds ratio (1.9, CI 1.8-2.0). Conclusions: Concurrent benzodiazepine use is common and associated with higher risk of hospitalization due to opioid overdose. Possible opioid-associated hospital admission rate is 4-5 times bigger in ESRD population than general population. Current safety classification of opioids in these patients is misleading, and even drugs considered safe based on pharmacokinetic data are associated with moderate to very high risk of hospitalization. We propose a risk-stratified classification of opioids and suggest starting to use them in all ESRD patients.

External Validation of the qSOFA Score in Emergency Department Patients With Pneumonia.

BACKGROUND: Pneumonia is the leading cause of sepsis. In 2016, the 3rd International Consensus Conference for Sepsis released the Quick Sepsis-Related Organ Failure Assessment (qSOFA) to identify risk for poor outcomes in sepsis. OBJECTIVE: We sought to externally validate qSOFA in emergency department (ED) patients with pneumonia and compare the accuracy of qSOFA to systemic inflammatory response syndrome score (SIRS), Confusion, Respiratory Rate and Blood Pressure (CRB), Confusion, Respiratory Rate, Blood Pressure and Age (CRB-65), and DS CRB-65, which is based on the CRB-65 score and includes two additional items-presence of underlying comorbid disease and blood oxygen saturation. METHODS: A subgroup analysis of U.S. Critical Illness and Injury Trials Group (USCIITG-Lung Injury Prevention Study [LIPS]; ClinicalTrials.gov ID: NCT00889772) prospective cohort. The primary outcome was in-hospital mortality. Secondary outcomes were measures of intensive care unit (ICU) utilization. Sensitivity, specificity, and area under the curve (AUC) were reported. RESULTS: From March to August 2009, 5584 patients were enrolled; 713 met inclusion criteria. Median age was 61 years (interquartile range 49-75 years). SIRS criteria had the highest sensitivity for death (89%) and lowest specificity (25%), while CRB had the highest specificity (88%) and lowest sensitivity (31%), followed by qSOFA (80% and 53%, respectively). This trend was maintained for the secondary outcomes. There was no significant difference in the AUC for death using qSOFA (AUC 0.75; 95% confidence interval [CI] 0.66-0.84), SIRS (AUC 0.70; 95% CI 0.61-0.78), CRB (AUC 0.71; 95% CI 0.62-0.80), CRB-65 (AUC 0.71; 95% CI 0.63-0.80), and DS CRB-65 (AUC 0.73; 95% CI 0.64-0.82). CONCLUSIONS: In this multicenter observational study of ED patients hospitalized with pneumonia, we found no significant differences between qSOFA and SIRS for predicting in-hospital death. In addition, several popular pneumonia-specific severity scores performed nearly identically to qSOFA score in predicting death and ICU utilization. Validation is needed in a larger sample.

High dose vitamin D supplementation does not rescue bone loss following Roux-en-Y gastric bypass in female rats.

Postoperative bone loss and increased fracture risk associated with Roux-en-Y gastric bypass (RYGB) have been attributed to vitamin D/calcium malabsorption and resultant secondary hyperparathyroidism (HPT). Adequate vitamin D supplementation (VDS), particularly in an older female population, reduces incidence of secondary HPT but the effect on bone loss and fracture risk remains unclear. To investigate whether VDS corrects the RYGB bone phenotype, 41 obese adult female rats were randomized to RYGB with 1000 IU (R1000) or 5000 IU (R5000) vitamin D/kg food or a sham surgical procedure with either paired (PF) or ad libitum (AL) feeding. Bone turnover markers, urinary calcium/creatinine ratio (CCR), and serum calciotropic and gut hormones were assessed throughout a 14-week postoperative period. Femurs were analyzed by micro-computed tomography (µCT), three-point bending test, and histomorphometry. 1000 IU animals had low 25­hydroxyvitamin D (25(OH)D), high serum parathyroid hormone (PTH), and very low urine CCR levels. 5000 IU corrected the 25(OH)D and secondary HPT but did not increase urine CCR or serum levels of 1,25­dihydroxyvitamin D (1,25(OH)D) significantly between RYGB groups. Compared to sham animals at 14 weeks, RYGB animals had significantly higher serum osteocalcin (OCN) and C-terminal telopeptide (CTX) levels. The gut hormone peptide tyrosine tyrosine hormone (PYY) was higher in the RYGB groups, and leptin was lower. µCT and biomechanical testing revealed RYGB females had decreased cortical and trabecular bone volume and weaker, stiffer bone than controls. Histomorphometry showed decreased bone volume and increased osteoid volume with increased mineral apposition rate in RYGB compared to controls. No differences in bone phenotype were identified between 1000 IU and 5000 IU groups, and osteoclast numbers were comparable across all four groups. Thus, in our model, 5000 IU VDS corrected vitamin D deficiency and secondary HPT but did not rescue RYGB mineralization rate nor the osteomalacia phenotype. Longer studies in this model are required to evaluate durability of these detrimental effects. Our findings not only underscore the importance of lifelong repletion of both calcium and vitamin D but also suggest that additional factors affect skeletal health in this population.

Long-term Recurrence Rates in Uric Acid Stone Formers With or Without Medical Management.

OBJECTIVE: To determine if medical therapy affects long-term clinical outcomes in uric acid stone formers (UASF). METHODS: We identified 53 UASF who had complete stone clearance following stone procedure by computed tomography (CT) and had ≥1 postoperative 24-hour urine collection and a clinical follow-up ≥6 months with a surveillance CT scan. Patients were divided into "adherent to medical therapy" (compliance with potassium citrate ± allopurinol verified by computerized pharmacy data) or nonadherent groups. Primary outcomes were CT stone recurrence rate and need for surgical stone intervention. RESULTS: We found 28 of 53 (53%) adherent and 25 of 53 (47%) nonadherent individuals (14 declined medication, 11 intolerant). With median follow-up of 24 months, no significant differences were noted between groups in regards to stone recurrence (32%; P = .99) or in 24-hour urine pH compared to baseline or follow-up (range 5.46-5.62; P = 0.06). Adherent patients, however, had smaller CT stone recurrence sizes (6.3 ± 3.8 vs 11.8 ± 6.2 mm, P = .02), were 28% less likely to require stone surgery compared to those without therapy (P <.01), and trended toward longer time intervals without recurrence (23.1 ± 18.8 vs 10.5 ± 7.5 months, P = .10) compared to nonadherents. Study confounders included a variety of medication dosages and adherences, limited nonadherent follow-up, and small study number. CONCLUSION: UASF adherent to medical therapy had smaller recurrence sizes and fewer surgical interventions vs nonadherent, highlighting the protective role of potassium citrate in UA stone disease. The comparable urine pH and stone recurrence rates between groups, however, underscore areas for improvement in future UA stone prevention strategies.

What do the US advanced kidney disease patients want? Comprehensive pre-ESRD Patient Education (CPE) and choice of dialysis modality.

Improvement in Home Dialysis (HoD) utilizations as a mean to improve the patient reported and health services outcomes, has been a long-held goal of the providers and healthcare system in United States. However, measures to improve HoD rates have yielded limited success so far. Lack of patient awareness of chronic kidney disease (CKD) and its management options, is one of the important barriers against patient adoption of HoD. Despite ample evidence that Comprehensive pre-ESERD Patient Education (CPE) improves patient awareness and informed HoD choice, use of CPE among US advanced CKD patients is low. Need for significant resources, lack of validated data showing unequivocal and reproducible benefits, and the lack of validated CPE protocols proven to have consistent efficacy in improving not only patient awareness but also HoD rates in US population, are major limitations deterring adoption of CPE in routine clinical practice. We recently demonstrated that if a structured, protocol based CPE is integrated within the routine nephrology care for patients with advanced CKD, it substantially improves informed HoD choice and utilizations. However, this requires establishing CPE resources within each nephrology practice. Efficacy of a stand-alone CPE model, independent of clinical care, has not been examined till date. In this report we report the efficacy of our structured CPE protocol, delivered outside the realm of routine nephrology care-as a stand-alone patient education program, in a geographically distant region, and show that: when provided opportunity for informed dialysis choice, a majority of advanced CKD patients in US would prefer HoD. We also show that initiating CPE leads to accelerated growth in HoD utilizations and reduces disparities in HoD utilizations, goals for system improvements. Finally, the reproducibility of our structured CPE protocol with consistent efficacy data suggest that initiating such programs at institutional levels has the potential to improve informed dialysis selection and HoD rates across any similar large healthcare institute within US.

Clock gene expression is altered in veterans with sleep apnea.

Clock gene dysregulation has been shown to underlie various sleep disorders and may lead to negative cardio-metabolic outcomes. However, the association between sleep apnea (SA) and core clock gene expression is unclear. We performed a cross-sectional analysis of 49 Veterans enrolled in a study of SA outcomes in veterans with chronic kidney disease, not selected for SA or sleep complaints. All participants underwent full polysomnography and next morning whole blood collection for clock gene expression. We defined SA as an apnea-hypopnea index ≥15 events/h; nocturnal hypoxemia(NH) was defined as ≥10% of total sleep time spent at <90% oxygen saturation. We used quantitative real-time PCR to compare the relative gene expression of clock genes between those with and without SA or NH. Clock genes studied were Bmal1, Ck1δ, Ck1ε, Clock, Cry1, Cry2, NPAS2, Per1, Per2, Per3, Rev-Erb-α, RORα, and Timeless. Our cohort was 90% male, mean age was 71 yr (SD 11), mean body mass index was 30 kg/m2 (SD 5); 41% had SA, and 27% had NH. Compared with those without SA, Per3 expression was reduced by 35% in SA ( P = 0.027). Compared with those without NH, NPAS2, Per1, and Rev-Erb-α expression was reduced in NH (50.4%, P = 0.027; 28.7%, P = 0.014; 31%, P = 0.040, respectively). There was no statistical difference in expression of the remaining clock genes by SA or NH status. Our findings suggest that SA or related NH and clock gene expression may be interrelated. Future study of 24 h clock gene expression in SA is needed to establish the role of clock gene regulation on the pathway between SA and cardio-metabolic outcomes.