Obesity Paradox in Patients Hospitalized with Community Acquired Sepsis: Does Age Make a Difference?

BACKGROUND: Higher body mass index (BMI) has been shown to be a protective factor from mortality in sepsis patients. Yet, whether this effect is different in the very elderly is currently unknown. OBJECTIVES: To investigate the relationship between BMI and sepsis outcomes in patients older and younger than 80 years of age. METHODS: A retrospective analysis of consecutive patients admitted with sepsis to Shamir Medical Center, Israel, was conducted. We compared patients older than and younger than 80 years of age with a BMI higher and lower than 25 kg/m² for hospitalization outcomes. RESULTS: Patients older than 80 years presented with multiple co-morbidities compared to younger patients, but with no difference between BMI groups. Similarly, hospitalization outcomes of functional deterioration, discharge to long-term care facilities, and readmission were not significantly different between BMI groups in the same age category. Mortality was significantly different between BMI groups in patients older than 80 years of age, with higher mortality in BMI < 25 kg/m²: in-hospital mortality (23.4% vs. 14.9%, P < 0.001), 30-day mortality (27.6% vs. 17.9%, P < 0.001), and 90-day mortality (43.4% vs. 28.9%, P < 0.001). This difference was not significant between the groups younger than 80 years old. On logistic regression, BMI over 25 kg/m² was protective in all mortality categories. Nevertheless, there was no significant interaction between age over 80 years to BMI over 25 kg/m² in all mortality outcomes. CONCLUSIONS: Among patients hospitalized with sepsis, higher BMI is a protective factor against mortality in both elderly and younger patients.

Management of Upper Tract Urothelial Carcinoma in a Double Collecting System Kidney.

Upper tract urothelial carcinoma (UTUC) in a duplex collecting system (DCS) is a relatively uncommon presentation with unclear management guidelines. Herein, we retrospectively reviewed all published cases of DCS with UTUC aiming to suggest personalized clinical care options for future cases. We conducted a systematic search for all cases of UTUC in DCS from published literature using the following keywords: UTUC, urothelial carcinoma (UC), collecting duct carcinoma, and DCS. The cases were summarized based on demographics, clinical presentation, predisposing risk factors, tumor location, management, and follow-up. We present an additional case based on our experience with a 69-year-old female with high-grade (HG) UTUC of the upper moiety in complete DCS. The patient underwent a robotic upper pole hemi-nephroureterectomy (hemi-NU) with a common sheath distal ureterectomy and a bladder cuff, followed by lower pole ureteral reimplantation. Overall, 34 patients with 35 renal units of UTUC in DCS were included and analyzed. To conclude, UTUC of DCS is rare and underreported. Hence, it is difficult to define a standard treatment. Although hemi-NU has been previously described, to the best of our knowledge, this is the first case report of robot-assisted hemi-NU for complete DCS with single-moiety UC.

Targeting HIF-1 for prostate cancer: a synthesis of preclinical evidence.

INTRODUCTION: Hypoxia-inducible factor (HIF) mediates multiple intracellular processes that drive cellular metabolism and induce proliferation. Dysregulated HIF expression is associated with oncogenic cellular transformation. Moreover, high HIF levels correlate with tumor aggressiveness and chemoresistance, indicating the vital effect of HIF-1α on tumorigenicity. Currently, widespread in-vitro and in-vivo research is focusing on targeting HIF with drugs that have already been approved for use by the FDA, such as belzutifan, in renal cell carcinoma. HIF inhibition is mostly associated with tumor size reduction; however, drug toxicity remains a challenge. AREA COVERED: In this review, we focus on the potential of targeting HIF in prostate cancer (PC) and summarize the scientific background of HIF activity in PC. This finding emphasizes the rationale for using HIF as a therapeutic target in this malignancy. We have listed known HIF inhibitors that are being investigated in preclinical studies and their potential as anticancer drugs for PC. EXPERT OPINION: Although HIF-targeting agents have been investigated for over a decade, their use in therapy-resistant cancers remains relevant and should be explored further. In addition, the use of naturally occurring HIF inhibitors should be considered as an add-on therapy for the currently used regimens.

Neoadjuvant 177Lu-PSMA-I&T Radionuclide Treatment in Patients with High-risk Prostate Cancer Before Radical Prostatectomy: A Single-arm Phase 1 Trial.

BACKGROUND: High-risk localized prostate cancer (HRLPC) has a substantial risk of disease progression despite local treatment. Neoadjuvant systemic therapy before definitive local therapy may improve oncological outcomes by targeting the primary tumor and micrometastatic disease. OBJECTIVE: To evaluate whether a lutetium-177 prostate-specific membrane antigen radioligand (LuPSMA) can be safely administered to patients with HRLPC before robot-assisted radical prostatectomy (RARP) and to describe immediate oncological outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was an open-label, single-arm clinical trial. Patients with HRLPC and elevated radioligand uptake on PSMA positron emission tomography/computed tomography were enrolled. Two or three LuPSMA radioligand doses (7.4 GBq) were given at 2-wk intervals. RARP with lymph node dissection was performed 4 wk after the last LuPSMA dose. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The rate of surgical complications, operative parameters, changes in functional and quality-of-life measures, and immediate oncological outcomes (histological findings and biochemical response) were measured. Data were analyzed descriptively. RESULTS AND LIMITATIONS: Fourteen patients participated (median age 67 yr). Prostate-specific antigen decreased by 17% (interquartile range [IQR] 9-50%) after two LuPSMA doses and 34% (IQR 11-60%) after three doses. Thirteen patients underwent RARP with no identifiable anatomical changes or intraoperative complications. Four patients (30%) had postoperative complications (pneumonia, pulmonary embolism, urinary leak with urinary tract infection). At 3 mo postoperatively, 12 patients (92%) required one pad or less. Final whole-mount pathology showed positive surgical margins (PSMs) in seven patients (53%) and downgrading to International Society of Urological Pathology grade group 3 in three patients (23%). Treatment-related effects included a clear vacuolated cytoplasm and pyknotic nuclei. CONCLUSIONS: LuPSMA followed by RARP appears to be surgically safe. While oncological outcomes are pending, continence recovery seems to be unaffected by LuPSMA treatment. PATIENT SUMMARY: We evaluated outcomes for patients with aggressive localized prostate cancer who received treatment with a radioactive agent before surgical removal of their prostate. This approach appears to be safe and feasible, but its therapeutic efficacy is still unknown.

The association of diabetes and hyperglycemia with sepsis outcomes: a population-based cohort analysis.

The independent association of diabetes and hyperglycemia on the outcomes of sepsis remains unclear. We conducted retrospective cohort analyses of outcomes among patients with community-onset sepsis admitted to Shamir Medical Center, Israel (08-12/2016). Statistical associations were queried by Cox and logistic regressions, controlled for by matched propensity score analyses. Among 1527 patients with community-onset sepsis, 469 (30.7%) were diabetic. Diabetic patients were significantly older, with advanced complexity of comorbidities, and were more often exposed to healthcare environments. Despite statistically significant univariable associations with in-hospital and 90-day mortality, the adjusted Hazard Ratios (aHR) were 1.21 95% CI 0.8-1.71, p = 0.29 and 1.13 95% CI 0.86-1.49, p = 0.37, respectively. However, hyperglycemia at admission (i.e., above 200 mg/dl (was independently associated with: increased in-hospital mortality, aHR 1.48 95% CI 1.02-2.16, p = 0.037, 30-day mortality, aHR 1.8 95% CI 1.12-2.58, p = 0.001), and 90-day mortality, aHR 1.68 95% CI 1.24-2.27, p = 0.001. This association was more robust among diabetic patients than those without diabetes. In this study, diabetes was not associated with worse clinical outcomes in community-onset sepsis. However, high glucose levels at sepsis onset are independently associated with a worse prognosis, particularly among diabetic patients. Future trials should explore whether glycemic control could impact the outcomes and should be part of the management of sepsis, among the general adult septic population.

A "resistance calculator": Simple stewardship intervention for refining empiric practices of antimicrobials in acute-care hospitals.

OBJECTIVE: In the era of widespread resistance, there are 2 time points at which most empiric prescription errors occur among hospitalized adults: (1) upon admission (UA) when treating patients at risk of multidrug-resistant organisms (MDROs) and (2) during hospitalization, when treating patients at risk of extensively drug-resistant organisms (XDROs). These errors adversely influence patient outcomes and the hospital's ecology. DESIGN AND SETTING: Retrospective cohort study, Shamir Medical Center, Israel, 2016. PATIENTS: Adult patients (aged >18 years) hospitalized with sepsis. METHODS: Logistic regressions were used to develop predictive models for (1) MDRO UA and (2) nosocomial XDRO. Their performances on the derivation data sets, and on 7 other validation data sets, were assessed using the area under the receiver operating characteristic curve (ROC AUC). RESULTS: In total, 4,114 patients were included: 2,472 patients with sepsis UA and 1,642 with nosocomial sepsis. The MDRO UA score included 10 parameters, and with a cutoff of ≥22 points, it had an ROC AUC of 0.85. The nosocomial XDRO score included 7 parameters, and with a cutoff of ≥36 points, it had an ROC AUC of 0.87. The range of ROC AUCs for the validation data sets was 0.7-0.88 for the MDRO UA score and was 0.66-0.75 for nosocomial XDRO score. We created a free web calculator (https://assafharofe.azurewebsites.net). CONCLUSIONS: A simple electronic calculator could aid with empiric prescription during an encounter with a septic patient. Future implementation studies are needed to evaluate its utility in improving patient outcomes and in reducing overall resistances.