Associations between sodium-glucose co-transporter 2 (SGLT-2) inhibitors and urologic diseases: implications for lower urinary tract symptoms from a multi-state health system analysis.

OBJECTIVE: To analyze the frequency of new urologic visits and urologic diagnoses in patients prescribed sodium-glucose co-transporter-2 inhibitors (SGLT-2is). MATERIAL AND METHODS: Records from a multi-state health system between 2014 and 2022 were reviewed to identify patients referred for outpatient urology evaluation within 2 years of diabetes medication prescription. Patients were stratified by the prescription of SGLT-2is or another diabetes medication. Frequency of urology visits within 1-year, urologic diagnoses, and prescriptions to treat lower urinary tract symptoms (LUTS) were compared. Patients were stratified by whether they had achieved HbA1c goal (≥7% or <7%) following treatment as well as by sex. Multivariable logistic regression was performed to determine if SGLT-2 use independently predicted outcomes of interest. RESULTS: 163,827 patients met inclusion criteria. Use of SGLT-2is was associated with a higher frequency of early urologic referral, balanitis/balanoposthitis, overactive bladder, urinary frequency, urgency, and need for LUTS medications in males with HbA1c ≥7%. Females on SGLT-2is with HbA1c ≥7% also had higher rates of urinary incontinence. In those with HbA1c <7%, only balanitis/balanoposthitis and urinary incontinence were higher in the SGLT-2i cohorts for males and females, respectively. Multivariable analysis found SGLT-2i use as predictive of early urology referral, balanitis/balanoposthitis, urinary urgency, frequency, overactive bladder, and need for LUTS medications in males. Multivariable analysis of females demonstrated similar results. CONCLUSIONS: SGLT-2is may lead to worse urologic outcomes and increased utilization of urologic care relative to other diabetic medications. Future studies are necessary to identify which patients are at highest risk of adverse urologic outcomes.

Single Port Robotic Kidney Autotransplantation: Initial Case Series and Description of Technique.

PURPOSE: Minimally invasive kidney autotransplantation (KAT) has demonstrated reduced morbidity, however multiport robotic approach required patient repositioning and multiple sets of incisions. We present our initial series of single-port (SP) robotic KAT, ideal for multi-quadrant surgeries, and aim to evaluate feasibility and safety of the novel approach. METHODS: Between 2018 and 2022, 8 consecutive patients underwent SP KAT using the DaVinci SP platform. Patient clinicopathologic variables and perioperative outcomes were recorded. Indications for KAT include complex or recurrent ureteral stricture, ureteral avulsion, and chronic visceral pain due to multiple etiologies. RESULTS: All SP KATs were successfully performed without repositioning or conversion to open. Operative times ranged from 366 to 701 minutes, warm and cold ischemia times between 4 to 10 minutes and 86 to 209 minutes, respectively. Median hospital length of stay was 3 days. At a median of 13 months follow-up, latest postoperative GFRs were stable, ranging from +23% to -10%. There were no complications. CONCLUSION: We demonstrate our single port, multiquadrant robotic kidney auto transplantation technique performed though a single incision further reducing surgical morbidity. All cases were completed successfully without conversion or loss of graft function. All patients reported resolution of flank pain and no radiological evidence of urinary obstruction on follow up.

Direct activation of PP2A for the treatment of tyrosine kinase inhibitor-resistant lung adenocarcinoma.

Although tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy in advanced lung adenocarcinoma (LUAD) patients with pathogenic alterations in EGFR, most patients develop acquired resistance to these agents via mechanisms enabling the sustained activation of the PI3K and MAPK oncogenic pathways downstream of EGFR. The tumor suppressor protein phosphatase 2A (PP2A) acts as a negative regulator of these pathways. We hypothesize that activation of PP2A simultaneously inhibits the PI3K and MAPK pathways and represents a promising therapeutic strategy for the treatment of TKI-resistant LUAD. After establishing the efficacy of small molecule activators of PP2A (SMAPs) in a transgenic EGFRL858R model and TKI-sensitive cell lines, we evaluated their therapeutic potential in vitro and in vivo in TKI-resistant models. PP2A activation resulted in apoptosis, significant tumor growth inhibition, and downregulation of PI3K and MAPK pathways. Combination of SMAPs and TKI afatinib resulted in an enhanced effect on the downregulation of the PI3K pathway via degradation of the PP2A endogenous inhibitor CIP2A. An improved effect on tumor growth inhibition was observed in a TKI-resistant xenograft mouse model treated with a combination of both agents. These collective data support the development of PP2A activators for the treatment of TKI-resistant LUAD.