Factors associated with unplanned clinical encounters for ureteral stent-related symptoms.

BACKGROUND, INTRODUCTION AND AIM: Ureteral stent-related symptoms (USRS) often result in unplanned phone calls and ER visits. We hypothesize that patient factors can be identified to predict these unplanned encounters. METHODS AND MATERIALS: Retrospective analysis of indwelling ureteral stent placements from 2014 to 2019 at a single institution by CPT code was performed. Patient demographics, discharge medications, and clinical factors were evaluated using multiple logistic regression with respect to postoperative telephone and emergency room (ER) encounters for USRS. RESULTS: Of 374 patients, 75 (20.1%) had one or more encounters for USRS: 48 (12.8%) called the clinic and 39 (10.4%) returned to the ER. Chronic opioid use was predictive of calls to clinic and ER visits (OR 3.21 [CI 1.42-6.97], p < 0.01 and OR 3.64 [CI 1.45-8.98], p < 0.01). Survival analysis stratified by history of chronic opioid use and discharge opioid prescriptions demonstrated that opioid naïve patients receiving opioids at discharge had unplanned encounters sooner and more often [Calls p = 0.025, ER p = 0.041]), whereas patients with chronic opioid use returned to the ER sooner and more frequently when prescribed additional opioids (Calls p = 0.4, ER p = 0.002). CONCLUSION: Patients with a history of chronic opioid use may experience more intense USRS or have a lower threshold to seek medical care than opioid naïve patients and tend to bypass calling the clinic for the ER. Given that none of the studied medications reduced unplanned patient contact for USRS, urologists should consider upfront definitive management of urinary obstruction when appropriate.

Surgical Insights for the Management of Variant Histology in Renal Cell Carcinoma.

PURPOSE: To review the current literature regarding variant (non-clear) histology of renal cell carcinoma (RCC) and the clinical management of these renal tumors. MATERIAL AND METHODS: A PubMed database search was performed in May 2020 focusing on variant RCC, its diagnosis and associated syndromes, tumor characteristics, and options for management. RESULTS: A broad range of pathological, clinical and diagnostic characteristics amongst non-ccRCC variants were found to have an impact on the overall management of these tumors. The imaging modalities, frequency of surveillance, and timing for intervention were found to be dependent on the type of genetic alterations, type of histology, and tumor growth rates. The timing and type of surgery as well as the systemic therapy are tailored to the specific tumor type and patient. CONCLUSION: The findings of this review suggest that clinical management should be considered and adjusted for patients with non-ccRCC histological variants based on tumor subtype and genetic alterations.

Boosting NAD+ with a small molecule that activates NAMPT.

Pharmacological strategies that boost intracellular NAD+ are highly coveted for their therapeutic potential. One approach is activation of nicotinamide phosphoribosyltransferase (NAMPT) to increase production of nicotinamide mononucleotide (NMN), the predominant NAD+ precursor in mammalian cells. A high-throughput screen for NAMPT activators and hit-to-lead campaign yielded SBI-797812, a compound that is structurally similar to active-site directed NAMPT inhibitors and blocks binding of these inhibitors to NAMPT. SBI-797812 shifts the NAMPT reaction equilibrium towards NMN formation, increases NAMPT affinity for ATP, stabilizes phosphorylated NAMPT at His247, promotes consumption of the pyrophosphate by-product, and blunts feedback inhibition by NAD+. These effects of SBI-797812 turn NAMPT into a "super catalyst" that more efficiently generates NMN. Treatment of cultured cells with SBI-797812 increases intracellular NMN and NAD+. Dosing of mice with SBI-797812 elevates liver NAD+. Small molecule NAMPT activators such as SBI-797812 are a pioneering approach to raise intracellular NAD+ and realize its associated salutary effects.

Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance.

OBJECTIVE: Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme in the salvage pathway that produces nicotinamide adenine dinucleotide (NAD+), an essential co-substrate regulating a myriad of signaling pathways. We produced a mouse that overexpressed NAMPT in skeletal muscle (NamptTg) and hypothesized that NamptTg mice would have increased oxidative capacity, endurance performance, and mitochondrial gene expression, and would be rescued from metabolic abnormalities that developed with high fat diet (HFD) feeding. METHODS: Insulin sensitivity (hyperinsulinemic-euglycemic clamp) was assessed in NamptTg and WT mice fed very high fat diet (VHFD, 60% by kcal) or chow diet (CD). The aerobic capacity (VO2max) and endurance performance of NamptTg and WT mice before and after 7 weeks of voluntary exercise training (running wheel in home cage) or sedentary conditions (no running wheel) were measured. Skeletal muscle mitochondrial gene expression was also measured in exercised and sedentary mice and in mice fed HFD (45% by kcal) or low fat diet (LFD, 10% by kcal). RESULTS: NAMPT enzyme activity in skeletal muscle was 7-fold higher in NamptTg mice versus WT mice. There was a concomitant 1.6-fold elevation of skeletal muscle NAD+. NamptTg mice fed VHFD were partially protected against body weight gain, but not against insulin resistance. Notably, voluntary exercise training elicited a 3-fold higher exercise endurance in NamptTg versus WT mice. Mitochondrial gene expression was higher in NamptTg mice compared to WT mice, especially when fed HFD. Mitochondrial gene expression was higher in exercised NamptTg mice than in sedentary WT mice. CONCLUSIONS: Our studies have unveiled a fascinating interaction between elevated NAMPT activity in skeletal muscle and voluntary exercise that was manifest as a striking improvement in exercise endurance.

Surgical insights for the management of variant histology in renal cell carcinoma

ABSTRACT Purpose: To review the current literature regarding variant (non-clear) histology of renal cell carcinoma (RCC) and the clinical management of these renal tumors. Material and Methods: A PubMed database search was performed in May 2020 focusing on variant RCC, its diagnosis and associated syndromes, tumor characteristics, and options for management. Results: A broad range of pathological, clinical and diagnostic characteristics amongst non-ccRCC variants were found to have an impact on the overall management of these tumors. The imaging modalities, frequency of surveillance, and timing for intervention were found to be dependent on the type of genetic alterations, type of histology, and tumor growth rates. The timing and type of surgery as well as the systemic therapy are tailored to the specific tumor type and patient. Conclusion: The findings of this review suggest that clinical management should be considered and adjusted for patients with non-ccRCC histological variants based on tumor subtype and genetic alterations.