SETD2 regulates SLC family transporter-mediated sodium and glucose reabsorptions in renal tubule.

A regulatory mechanism for SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule, is incompletely understood. Here, we report an important regulation of SLC family transporter by SETD2, a chromatin remodeling gene whose alterations have been found in a subset of kidney cancers. Kidney-specific inactivation of Setd2 resulted in hypovolemia with excessive urine excretion in mouse and interestingly, RNA-sequencing analysis of Setd2-deficient murine kidney exhibited decreased expressions of SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule. Importantly, inactivation of Setd2 in murine kidney displayed attenuated dapagliflozin-induced diuresis and glucose excretion, further supporting that SETD2 might regulate SLCfamily transporter-mediated sodium and glucose reabsorptions in renal tubule. These data uncover an important regulation of SLC family transporter by SETD2, which may illuminate a crosstalk between metabolism and epigenome in renal tubule.

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors.

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species. The degree to which LC activity is homogenous across these factors, however, has never been assessed due to the small sample size of individual studies. Here, we pool data from 20 laboratories (1,855 neurons) and show diversity across both intrinsic and extrinsic factors such as species, age, sex and brain state. We use a negative binomial regression model to compare activity from male monkeys, and rats and mice of both sexes that were recorded across brain states from brain slices ex vivo or under different anesthetics or during wakefulness in vivo. LC activity differed due to complex interactions of species, sex, and brain state. The LC became more active during aging, independent of sex. Finally, in contrast to the foundational principle that all species express two distinct LC firing modes ("tonic" or "phasic"), we discovered great diversity within spontaneous LC firing patterns. Different factors were associated with higher incidence of some firing modes. We conclude that the activity of the evolutionarily-ancient LC is not conserved. Inherent differences due to age and species-sex-brain state interactions have implications for understanding the role of LC in species-specific naturalistic behavior, as well as in psychiatric disorders, cardiovascular disease, immunology, and metabolic disorders.

Impacts of urinary tract anomalies or history of upper urinary tract surgery on outcome of mini-ECIRS (endoscopic combined intrarenal surgery).

This study assessed the impact of urinary tract anomalies or a history of upper urinary tract surgery (UTAS) on the minimally invasive endoscopic combined intrarenal surgery (mini-ECIRS) outcomes. Data from 1432 patients undergoing ECIRS for urolithiasis at three Japanese tertiary institutions between 2015 and 2021 were analyzed, with patients categorized into those with normal urinary tracts (non-UTAS) and those with UTAS (UTAS). We retrospectively examined the association between the UTAS and perioperative outcomes in mini-ECIRS. Of the 1096 cases in the final analysis, 1035 and 61 were identified as non-UTAS and UTAS, respectively. Stone-free rate (residual fragments > 2 mm, 62.8% vs. 62.7%), operation time (110.5 vs. 115.0 min), and hospital stay duration (5.6 vs. 5.7 days) showed no significant differences between non-UTAS and UTAS. The UTAS group demonstrated significantly higher rates of preoperative pyuria (86.2% vs. 71.1%), preoperative urinary tract infection (32.8% vs. 15.5%), preoperative stenting (52.5% vs. 31.0%), and preoperative nephrostomy (24.6% vs. 9.2%). However, the postoperative fever (26.3% vs. 25.0%) or septic shock (1.9% vs. 0%) were comparable between non-UTAS and UTAS. Stone burden and the number of calyces involved were significantly associated with a low stone-free rate (P < 0.001). Younger age, female sex, solitary stones, number of calyces involved, preoperative urinary tract infection, and absence of preoperative nephrostomy were identified as risk factors for perioperative complications. The UTAS was not associated with stone-free outcomes or perioperative complications. Mini-ECIRS demonstrated comparable stone-free outcomes and safety in patients with UTAS and those with normal urinary tracts.

Comparison of renal function between the artery and vein clamp and artery-only clamp in robot-assisted partial nephrectomy for moderate- to high-complexity renal masses: A propensity-matched study.

OBJECTIVE: Artery and vein (AV) clamps can control venous bleeding in the surgical field and prevent carbon dioxide embolism, especially when large veins are expected to open. However, whether AV clamps cause more renal damage than artery-only (AO) clamps remains unclear. This study aimed to compare renal function and blood loss in surgeries using AO and AV clamps based on high RENAL nephrometry scores (RNS) in robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed the medical records of 500 patients who underwent RAPN between March 2016 and December 2021. We performed 1:1 propensity matching for these patients. RESULTS: A total of 340 patients with pathological malignancies who were followed up for at least 12 months were included in this analysis. A total of 291 patients with AO clamping and 49 patients with AV clamping were included. Overall, the AV clamp group had higher total RNSs and larger diameters than the AO clamp group. Propensity score-matched analysis included 37 patients in each clamp group. The median warm ischemia times of the AV and AO clamps were 25 and 22 min, respectively, with no significant difference. There were no statistically significant differences between the groups in the amount of blood loss, rate of acute kidney injury (AKI), or renal function at 1, 3, or 12 months post-RAPN. CONCLUSION: Compared with the AO clamp, the AV clamp did not have a detrimental impact on blood loss or renal dysfunction. Consequently, AV clamps may be considered for patients presenting with moderate-to-high-complexity RNSs.

Addition of Mucoadhesive Agent to Enzymatically Polymerized Caffeic Acid-Based Nasal Vaccine Formulation Attenuates Antigen-Specific Antibody Responses in Mice.

Mucosal vaccination is a promising strategy for combating infectious diseases caused by pathogenic microbes, as it can generate antigen-specific immune responses in both systemic and mucosal compartments. In our recent study, we developed a nasal vaccine system for Streptococcus pneumoniae infections in mice using enzymatically polymerized polyphenols such as caffeic acid. However, the efficacy of this mucosal vaccine system is approximately 70%, indicating a need for improvement. To address this issue, we hypothesized that incorporating a mucoadhesive agent that enhances mucosal absorption into a polyphenol-based mucosal vaccine system would improve vaccine efficacy. Contrary to our expectations, we found that adding a mucoadhesive agent, hydrophobically modified hydroxypropylmethylcellulose, to the vaccine system reduced the stimulation of antigen-specific antibody responses in both the mucosal (more than 90% reduction; P < 0.05) and systemic compartments (more than 80% reduction; P < 0.05). Although the addition of the mucoadhesive agent may have interfered with the interaction between the mucosal epithelium and the vaccine system, the underlying mechanism remains unclear, and further research is needed to fully understand the mechanisms involved.

Enzalutamide Prolonged the Duration of Drug Use in Comparison to Abiraterone Acetate and Cabazitaxel after Upfront Docetaxel: A Large Japanese Database Study.

INTRODUCTION: In the United States, a total of 268,490 men were found to have prostate cancer in 2022, thus making it the most common cancer in men, accounting for 27% of all cancers in the male population. Among all cancers in men, it was the fifth leading cause of death, with 34,500 deaths and a mortality rate of 11%. In 2019, the total number of cases was 94,748, making it the leading cancer in males, accounting for 11% of all male cancers. In terms of mortality, it ranked seventh, with 13,217 deaths and a mortality rate of 1.6%. However, new treatment options for metastatic castration-sensitive prostate cancer (mCSPC) have emerged. Docetaxel has been shown to be effective for both mCSPC and castration-resistant prostate cancer (CRPC). Upfront docetaxel has not been approved in Japan, nor has it been validated in large-scale studies. Furthermore, several agents can be used after docetaxel treatment, but it is unclear which is the most effective. We used a large Japanese health insurance database to determine which agent would be the most effective as a next-line therapy in patients who had received docetaxel. MATERIALS AND METHODS: We used data from medical institutions using the Diagnosis Procedure Combination (DPC), which provides a comprehensive evaluation of medical classifications. The Medical Data Vision database covers approximately 23% of DPC hospitals in Japan. This study analyzed 2938 patients with mCSPC who received docetaxel, followed by CRPC, between April 2008 and December 2021. The study focused on three agents: enzalutamide, abiraterone acetate, and cabazitaxel. Other agents were excluded due to the small number of patients. The following data were analyzed: age, date of CRPC diagnosis, presence of bone metastasis, drug type, and prognosis. RESULTS: This study included 1997 patients with CRPC after upfront docetaxel therapy for mCSPC (enzalutamide [ENZ] group, n = 998; abiraterone acetate [ABI] group, n = 617; and cabazitaxel [CBZ] group, n = 382). The overall survival (OS) time from drug initiation was 456 days in the enzalutamide group, which was significantly longer than that in the cabazitaxel group (p = 0.017, HR 0.94) (ENZ: ABI p = 0.54, HR 0.94; ABI: CBZ p = 0.14, HR 0.75). OS was also compared for the third-line drug in the group that received enzalutamide as the second-line drug, the group that used abiraterone acetate as the third-line drug (ENZ-ABI group), and the group that used abiraterone acetate as the second-line drug. OS from the start of the third-line drug was compared between the ENZ-ABI group and the ABI-ENZ group, which received enzalutamide as the third-line drug, but showed no significant difference (269 vs. 281 days, p = 0.85; HR 1.03). CONCLUSION: ENZ was shown to prolong OS relative to cabazitaxel after the cessation of docetaxel. ENZ was associated with a longer duration of drug use than ABI and CBZ.

[Real-World Experience and Complications with Intermittent Balloon Catheters : A Predictor Analysis].

Intermittent balloon catheterization with a reusable and temporary balloon catheter that could be implanted and removed by the patient was developed in Japan in 1995. Although the intermittent balloon catheter has the potential to improve the patient's quality of life (QOL), appropriate information and guidelines are needed to prevent complications such as hematuria and urinary tract infection. This study aimed to assess the real-world practice, complications, and problems associated with the use of intermittent balloon catheters and provide useful information for future medical care. We conducted a questionnaire survey on patients with spinal cord lesions who currently use or have used intermittent balloon catheters in the past. Seventy-six patients with spinal cord lesions who visited Kanagawa Rehabilitation Hospital from August 2020 to March 2021 and gave consent for participating in this study were included. QOL scores before and after intermittent balloon catheter use showed significant improvement after use. Forty-six of the 76 (61.3%) patients had complications. Overall complications were significantly associated with male sex and possibly linked to non-traumatic spinal cord lesions.

[A case of recurrent Campylobacter fetus meningitis, occurring two months after the |initial infection was successfully treated].

A 43-year-old man was admitted to our department due to fever and headache. The cerebrospinal fluid analysis confirmed bacterial meningitis. Campylobacter species were isolated from blood cultures on the third day of admission. The patient was treated with meropenem (MEPM) and discharged on the 17th day. However, he experienced a recurrence of meningitis and was readmitted on the 68th day, initiating MEPM therapy. Campylobacter fetus was isolated from cerebrospinal fluid cultures on the 74th day. MEPM was continued until the 81st day, followed by one month of minocycline (MINO) therapy. The patient had an uneventful recovery without further recurrence. This case highlights the potential for recurrence of Campylobacter fetus meningitis approximately two months after the resolution of the initial infection. In addition to carbapenem therapy for at least two weeks, the adjunctive administration of MINO may be beneficial.

Long-term clinical course of two rare cases of synovitis-acne-pustulosis-hyperostosis-osteomyelitis syndrome involving only unilateral femur.

Synovitis-acne-pustulosis-hyperostosis-osteomyelitis (SAPHO) syndrome is characterised by aseptic osteitis and is often complicated by pustular dermatitis, such as palmoplantar pustulosis or acne. Although bone lesions are most found in the anterior thoracic region or spine, femoral lesions are not well documented in the literature. There is no established treatment for this condition, and few reports have described its long-term course. Here, we describe two cases of SAPHO syndrome involving the femur and discuss their long-term follow-up. A 40-year-old man (Case 1) presented with right thigh pain. Fifteen years after the initial diagnosis, the pain could be controlled with minomycin, salazosulfapyridine, and methotrexate. X-rays of the femur showed gradual cortical thickening. Although there were waves of pain, it gradually improved with the adjustment of drugs 25 years following the initial diagnosis. A 35-year-old man (Case 2) with right thigh pain was prescribed salazosulfapyridine and methotrexate; however, these were ineffective. Alendronate and guselkumab also proved ineffective. Ultimately, infliximab was started 9 years following disease onset, and pain became manageable. X-rays of the femur showed cortical thickening. SAPHO syndrome can be managed with drug therapies, such as nonsteroidal anti-inflammatory drugs, methotrexate, and conventional synthetic disease-modifying antirheumatic drugs; however, there are occasional treatment-resistant cases.

Predictors of postoperative storage symptoms in male patients with lower urinary tract symptoms: A retrospective analysis of prostate surgery for benign prostatic enlargement.

OBJECTIVES: This study investigated the effects of prostate surgery on storage symptoms in male patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE). This study aimed to identify patient characteristics associated with improved, unchanged, and deteriorated post-surgical storage symptoms and to identify the risk factors for non-improvement or deterioration. METHODS: A retrospective analysis of 586 prostate surgeries performed between 2016 and 2022 at Yokosuka Kyosai Hospital was conducted on patients with LUTS and at least one storage symptom preoperatively. Patients with active urinary tract infection, prostate/bladder cancer, urethral strictures, or dementia were excluded. The study enrolled 230 patients and assessed storage symptoms using the International Prostate Symptom Score (IPSS). RESULTS: Overall, storage symptoms improved, remained unchanged, and deteriorated in 87.0%, 5.7%, and 7.4% of patients, respectively. The patients in the deteriorated group were significantly older, whereas those in the no-change group had smaller prostate volumes. Patient-reported outcome scores (IPSS, IPSS-QoL, and BII) were significantly higher in the improved group. The predictors of non-improvement included low IPSS storage score, cardiovascular disease, and diabetes mellitus. Predictors of deterioration included advanced age and low IPSS storage score. CONCLUSIONS: Patients with severe LUTS showed greater postoperative improvement in storage symptoms. A low IPSS storage score predicted non-improvement and deterioration. Advanced age, low IPSS storage score, and a history of cardiovascular disease and diabetes mellitus were identified as key predictors. Awareness of these factors may guide preoperative counseling and improve decision-making in prostate surgery, ensuring more personalized and effective treatment strategies.

Impact of chronic kidney disease stages on surgical and functional outcomes in robot-assisted partial nephrectomy for localized renal tumors.

The influence of chronic kidney disease stage on robot-assisted partial nephrectomy outcomes remains underexplored. This study aimed to assess the impact of chronic kidney disease stage on functional and surgical outcomes of robot-assisted partial nephrectomy and identify preoperative predictors of significant postoperative 1-year renal-function loss (RFL). Clinical data of 408 patients who underwent robot-assisted partial nephrectomy at Yokohama City University Hospital between 2016 and 2023 were retrospectively reviewed. The da Vinci Surgical System was applied in all patients, and outcomes assessed included surgical parameters, postoperative estimated glomerular filtration rate, trifecta and pentafecta achievements, and complications. Significant RFL was defined as estimated glomerular filtration rate reduction ≥ 25% from baseline. Higher chronic kidney disease stages correlated with older age, hypertension, diabetes, and solitary kidneys. Postoperative estimated glomerular filtration rate decline was most pronounced in patients with chronic kidney disease stages 4-5. Although the chronic kidney disease stage did not significantly affect most surgical parameters, pentafecta achievement was higher in patients with chronic kidney disease stage 3 than in those with stages 4-5. Two patients required hemodialysis after robot-assisted partial nephrectomy. Multivariable logistic regression analysis showed that preoperative hemoglobin level and maximum tumor diameter were significant predictive factors for significant RFL. In conclusion, preoperative CKD stage did not influence on surgical outcome except for pentafecta achievement. RAPN may be feasible for patients with CKD stages 4-5 because of no rapid progression to hemodialysis induction and no procedure-related mortality. Preoperative hemoglobin levels and tumor diameter emerged as predictors of significant RFL.

Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan.

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.

Enfortumab vedotin prolongs overall survival in metastatic urothelial carcinoma following pembrolizumab therapy in real-world data.

OBJECTIVE: In December 2021, enfortumab vedotin (EV), an antibody-drug conjugate directed against nectin-4, was approved in Japan as a new treatment after platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. This study evaluated, using real-world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). MATERIALS AND METHODS: Fifty-five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non-EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. RESULTS: The median (range) follow-up period after pembrolizumab discontinuation was 6.3 (0.7-31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non-EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non-EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non-EV group; hazard ratio 0.26; 95% confidence interval 0.16-0.41; p < 0.001) was an independent prognostic factor for OS. CONCLUSION: EV prolonged OS in mUC following pembrolizumab therapy in real-world data.

The effect of the conduit size on middle-term outcomes in patients with extracardiac total cavopulmonary connection.

OBJECTIVES: The 18- and 16-mm conduits in extracardiac total cavopulmonary connection (eTCPC) were reported to be optimal based on energy loss and flow stagnation at the relatively early phase. However, because the artificial conduit lacks growth potential, we have recently encountered some cases in which the conduit needs to be changed several years after eTCPC. These cases prompted us to reconsider the surgical strategy for eTCPC. METHODS: We reviewed our 20-year single-centre experience with eTCPC patients (n = 256) to compare the 18-mm conduit (n = 195) and 16-mm conduit (n = 61) in terms of mortality and morbidity. RESULTS: The 16-mm conduit was used significantly more frequently in patients whose main chamber was right ventricle (P < 0.001). There was also a significant difference in preoperative inferior vena cava pressure (P = 0.008). There was a significant difference in the actuarial rate of freedom from late-occurring complications, including mortality, between the 2 groups (P = 0.003). There was a significant difference in the actuarial rate of reoperation-free survival (P = 0.042); however, there was no significant difference in resurgical intervention for the conduit (P = 0.333). In multivariate analysis, preoperative inferior vena cava pressure was an independent predictor for late-occurring complications (hazard ratio 1.19; P = 0.026). Conduit size (18 or 16 mm) itself was not an independent predictive factor for late-occurring complications (P = 0.690). CONCLUSIONS: The mid-term clinical outcomes in patients who underwent eTCPC were excellent with low mortality. Preoperative inferior vena cava pressure was the only predictive risk factor for postoperative morbidity, and the 16 mm conduit was not predictive thereof.

Surgical proficiency in laparoscopic radical cystectomy with extracorporeal urinary diversion and its adequacy for the execution of robot-assisted radical cystectomy with intracorporeal urinary diversion.

INTRODUCTION: The number of facilities adopting intracorporeal urinary diversion (ICUD) using robots instead of extracorporeal urinary diversion (ECUD) is increasing. However, guidance on how to introduce robot-assisted radical cystectomy (RARC) + ICUD in each urological institute remains unclear. This study aimed to verify the feasibility of the transition from laparoscopic radical cystectomy (LRC) + ECUD to RARC + ICUD. METHODS: We retrospectively analyzed 26 consecutive patients who underwent ICUD with an ileal conduit after RARC between 2018 and 2020 (RARC + ICUD early group). We then compared these patients with 26 consecutive patients who underwent ECUD with an ileal conduit after LRC between 2012 and 2019 (LRC + ECUD late group) at Yokohama City University Hospital. RESULTS: In the RARC + ICUD early group compared with the LRC + ECUD late group, the median total operation time was 516 versus 532.5 min (P = .217); time to cystectomy, 191 versus 206.5 min (P = .234); time of urinary diversion with an ileal conduit, 198 versus 220 min (P = .016); postoperative maximum C-reactive protein levels, 6.98 versus 12.46 mg/L (P = .001); number of days to oral intake, 3 versus 5 days (P = .003); length of hospital stay, 17 versus 32 days (P < .001). The postoperative complication rates (within 90 days) were 23.1% and 42.3% in the RARC + ICUD early and LRC + ECUD late groups, respectively (P = .237). Clavien-Dindo classification ≥3 was noted in 1 and 4 patients in the RARC + ICUD early and LRC + ECUD late groups, respectively (P = .350). CONCLUSION: Regarding perioperative outcomes, the RARC + ICUD early group was not inferior to the LRC + ECUD late group. This study suggests the feasibility of a transition from LRC + ECUD to RARC + ICUD.

[A Case of Testicular Torsion of Retractile Testis Requiring Orchidectomy].

We report a case of testicular torsion in an 8-year-old who was referred to our hospital for right groin pain. He was diagnosed with right retractile testis during a 12-month check-up. However, instead of performing orchiopexy, he was placed under observation until the age of 5, after which he did not seek medical attention. Physical examination revealed swelling and tenderness in the right inguinal region and no palpable testis in the right scrotum. Ultrasound and computed tomography revealed right testicular torsion, and emergency surgery was performed. Intraoperative findings revealed a dark and ischemic testis that was twisted at 180°in the right inguinal region. There was no improvement in blood flow even after the testicular torsion was released; therefore, right orchidectomy with left orchiopexy was performed. Although the incidence of testicular torsion is higher in patients with an undescended testis than in those with a normally positioned scrotal position testis, reports of testicular torsion associated with a retractile testis are rare.

Impacts of Complete Endophytic Renal Tumors on Surgical, Functional, and Oncological Outcomes of Robot-Assisted Partial Nephrectomy.

Objective: Complete endophytic renal tumors (CERTs) are the most challenging for robot-assisted partial nephrectomy (RAPN). This study aimed to determine the impact of CERT on outcomes of RAPN. Methods: All RAPN cases for localized renal tumor undertaken at Yokohama City University Hospital between 2016 and 2023 were enrolled. Tumor characteristics and surgical, functional, and oncologic outcomes of RAPN were compared between CERT and non-CERT groups. Results: Consecutive 666 patients were enrolled, and 76 (11.4%) were identified as CERT (3 points of "E" score). CERT showed smaller tumor diameters (p < 0.001), more predominant hilar tumor (p = 0.029), higher "N" scores (p < 0.001) and "L" scores (p = 0.006) than non-CERT. The CERT group showed longer warm ischemia times (p < 0.001), more frequent positive surgical margins (p = 0.028), and relatively lower trifecta achievement rates (p = 0.101) than the non-CERT group. In multivariable analysis, the CERT was an independent predictor for trifecta achievement but not for pentafecta achievement. Conclusions: CERT was associated with longer warm ischemia time, positive surgical margin, and lower trifecta achievement, but not with surgical complication and pentafecta achievement in RAPN. This study suggested that CERT had limited influence on long-term renal functional preservation; however, it had strong impacts on short-term surgical outcome.

Sodium glucose cotransporter 2 inhibitor suppresses renal injury in rats with renal congestion.

Renal congestion is an issue of cardiorenal syndrome in patients with heart failure. Recent clinical and basic studies suggest a renoprotective potential of sodium-glucose cotransporter (SGLT) 2 inhibitors. However, the effect on renal congestion and its mechanism is not fully understood. Thus, we aimed to clarify the effect of SGLT inhibition in a renal congestion model. Renal congestion was induced in the left kidney of male Sprague-Dawley rats by ligation of the inferior vena cava between the renal veins. The SGLT2 inhibitor tofogliflozin or vehicle was orally administered daily from the day before IVC ligation until two days after surgery. On the third postoperative day, both the right control kidney and the left congested kidney were harvested and analyzed. Kidney weight and water content was increased, and renal injury and fibrosis were observed in the left congested kidney. Kidney weight gain and hydration were improved with tofogliflozin treatment. Additionally, this treatment effectively reduced renal injury and fibrosis, particularly in the renal cortex. SGLT2 expression was observed in the congested kidney, but suppressed in the damaged tubular cells. Molecules associated with inflammation were increased in the congested kidney and reversed by tofogliflozin treatment. Mitochondrial dysfunction provoked by renal congestion was also improved by tofogliflozin treatment. Tofogliflozin protects against renal damage induced by renal congestion. SGLT2 inhibitors could be a candidate strategy for renal impairment associated with heart failure.

Predicting Prostate Surgery Outcomes from Standard Clinical Assessments of Lower Urinary Tract Symptoms To Derive Prognostic Symptom and Flowmetry Criteria.

BACKGROUND: Assessment of male lower urinary tract symptoms (LUTS) needs to identify predictors of symptom outcomes when interventional treatment is planned. OBJECTIVE: To develop a novel prediction model for prostate surgery outcomes and validate it using a separate patient cohort and derive thresholds for key clinical parameters. DESIGN, SETTING, AND PARTICIPANTS: From the UPSTREAM trial of 820 men seeking treatment for LUTS, analysis of bladder diary (BD), International Prostate Symptom Score (IPSS), IPSS-quality of life, and uroflowmetry data was performed for 176 participants who underwent prostate surgery and provided complete data. For external validation, data from a retrospective database of surgery outcomes in a Japanese urology department (n = 227) were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Symptom improvement was defined as a reduction in total IPSS of ≥3 points. Multiple logistic regression, classification tree analysis, and random forest models were generated, including versions with and without BD data. RESULTS AND LIMITATIONS: Multiple logistic regression without BD data identified age (p = 0.029), total IPSS (p = 0.0016), and maximum flow rate (Qmax; p = 0.066) as predictors of outcomes, with area under the receiver operating characteristic curve (AUC) of 77.1%. Classification tree analysis without BD data gave thresholds of IPSS <16 and Qmax ≥13 ml/s (AUC 75.0%). The random forest model, which included all clinical parameters except BD data, had an AUC of 94.7%. Internal validation using the bootstrap method showed reasonable AUCs (69.6-85.8%). Analyses using BD data marginally improved the model fits. External validation gave comparable AUCs for logistic regression, classification tree analysis, and random forest models (all without BD; 70.9%, 67.3%, and 68.5%, respectively). Limitations include the significant number of men with incomplete baseline data and limited assessments in the external validation cohort. CONCLUSIONS: Outcomes of prostate surgery can be predicted preoperatively using age, total IPSS, and uroflowmetry data, with prognostic thresholds of 16 for IPSS and 13 ml/s for Qmax. PATIENT SUMMARY: This study identified key preoperative factors that can predict outcomes of prostate surgery for bothersome urinary symptoms, including which patients are at risk of a poor outcome.