If not now, then when? The need for new evidence in the robotic management of upper tract urothelial carcinoma.

Current guidelines recommend radical nephroureterectomy with bladder cuff excision as the standard surgical treatment for high-risk upper tract urothelial carcinoma (UTUC). While large evidence is available regarding open and laparoscopic nephroureterectomy, data focusing on robotic nephroureterectomy (RNU) in UTUC are mostly limited with mixed results, especially in locally advanced disease. In light of the recent introduction of new robotic platforms, it is of utmost importance to further investigate oncologic outcomes associated with RNU. Moreover, stronger data exploring different operative settings (i.e. robotic arms and trocars placement) for the new robotic systems are eagerly warranted. To give an answer to such open clinical questions, the Junior ERUS/Young Academic Urologist Working Group on Robot-assisted Surgery designed a multicentric project involving different high-volume centers across the world. The aim of the study will be exploring surgical and oncologic outcomes of RNU, specifically focusing on several clinical unmet needs, such as best operative setting for new robotic platforms, lymph node dissection (LDN) template and robotic bladder cuff management.

Perioperative and functional outcomes following robot-assisted partial nephrectomy: Descriptive analysis of Indian study group on partial nephrectomy database.

Introduction: There is an unmet need for high-quality data for Robot-assisted partial nephrectomy (RAPN) in the Indian population. Indian study group on partial nephrectomy (ISGPN) is a consortium of Indian centers contributing to the partial nephrectomy (PN) database. The current study is a descriptive analysis of perioperative and functional outcomes following RAPN. Methods: For this study, the retrospective ISGPN database was reviewed, which included patients who underwent RAPN for renal masses at 14 centers across India from September 2010 to September 2022. Demographic, clinical, radiological, perioperative, and functional data were collected and analyzed. Ethics approval was obtained from each of the participating centers. Results: In this study, 782 patients were included, and 69.7% were male. The median age was 53 years (interquartile range [IQR 44-62]), median operative time was 180 min (IQR 133-240), median estimated blood loss was 100 mL (IQR 50-200), mean warm ischemia time was 22.7 min and positive surgical margin rates were 2.5%. The complication rate was 16.2%, and most of them were of minor grade. Trifecta and pentafecta outcomes were attained in 61.4% and 60% of patients, respectively. Conclusions: This is the largest Indian multi-centric study using the Indian Robotic PN Collaborative database to evaluate the outcomes of robot-assisted PN, and has proven its safety and efficacy in the management of renal masses.

Determinants of substance use among young people attending primary health centers in India.

Background: Substance use is a complex condition with multidimensional determinants. The present study aims to find the prevalence and determinants of substance use among young people attending primary healthcare centers in India. Methods: A multicentric cross-sectional study was conducted across 15 states in India on 1,630 young people (10-24 years) attending primary health centers. The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) was used to capture data on substance use. The degree of substance involvement was assessed and multivariate regression analysis was conducted to determine the risk factors of substance use. Results: The prevalence of substance use was 32.8%, with a median substance initiation age of 18 years. Among the substance users, 75.5% began before completing adolescence. Tobacco (26.4%), alcohol (26.1%) and cannabis (9.5%) were commonly consumed. Sociodemographic determinants included higher age, male gender, urban residence, positive family history, northeastern state residence and lower socioeconomic class. Over 80% of users had moderate or high involvement. Conclusions: High substance use prevalence among young people in Indian healthcare centers underscores the urgency of targeted intervention. Insights on determinants guide effective prevention strategies for this complex public health issue.

Transperitoneal versus retroperitoneal robot-assisted partial nephrectomy: a systematic review and meta-analysis.

INTRODUCTION: Robot-assisted partial nephrectomy (RAPN) can be performed either by a transperitoneal (TP) or a retroperitoneal (RP) approach. However, the superiority of one approach over the other is not established. Hence, the primary aim of this review was to compare perioperative outcomes between these two surgical approaches. METHODS: Literature was systematically searched to identify studies reporting perioperative outcomes following TP RAPN and RP RAPN. The study protocol was registered with PROSPERO (CRD42023399496). The primary outcome was comparing complication rates between the two approaches. RESULTS: This review included 22 studies, 5675 patients, 2524 in the RP group, and 3151 in the TP group. The overall complications were significantly lower in the RP group [Odds ratio (OR) 0.80 (0.67, 0.95), p = 0.01]. However, the rate of major complications was similar between the two groups. The operative time was significantly shorter with the RP group [Mean Difference (MD)-16.7 (- 22.3, - 11.0), p = < 0.0001]. Estimated blood loss (EBL) and need for blood transfusion (BT) were significantly lower in the RP group. There was no difference between the two groups for conversion to radical nephrectomy [OR 0.66 (0.33, 1.33), p = 0.25] or open surgery [OR 0.68 (0.24, 1.92, p = 0.47] and positive surgical margins [OR 0.93 (0.66, 1.31, p = 0.69]. Length of stay (LOS) was shorter in the RP group [MD - 0.27 (- 0.45, - 0.08), p = < 0.00001]. CONCLUSIONS: RP approach, compared to TP, has significantly lower complication rates, EBL, need for BT and LOS. However, due to the lack of randomized studies on the topic, further data is required.

Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants.

PURPOSE: Midostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants. METHODS: Using sentinel dosing for participants' safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50 mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2. RESULTS: In Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (Cmax), and 3-4% decrease in total exposures (AUC). Bupropion showed a 55% decrease in Cmax and 48-49% decrease in AUCs. Pioglitazone showed a 10% decrease in Cmax and 6% decrease in AUC. In Study 2, midostaurin resulted in a 26% increase in Cmax and 7-10% increase in AUC of EES; and a 19% increase in Cmax and 29-42% increase in AUC of LVG. Midostaurin 50 mg twice daily for 28 days ensured that steady-state concentrations of midostaurin and the active metabolites were achieved by the time of CYP substrate drugs or oral contraceptive dosing. No safety concerns were reported. CONCLUSION: Midostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated.

Factors Affecting the Outcome after Surgical Clipping of Ruptured Distal Anterior Cerebral Artery (DACA) Aneurysms.

Objective The purpose of this study is to assess demographic, clinical, and unique morphological characteristics of distal anterior cerebral artery (DACA) aneurysm. The relation of outcome included Glasgow Outcome Scale (GOS) using various independent variables, Hunt and Hess clinical grade (H&H), Miller Fischer grade, intraoperative rupture, and comparison of outcomes at discharge and last follow-up. Methods Demographic data, aneurysm characteristics, and treatment outcomes were evaluated in 28 ruptured DACA aneurysms operated over a period of 13 years. Association between independent variables and dependent variables (GOS) at discharge and at last follow-up (13 years) was analyzed, and the interrelationship between these factors and outcome was evaluated. GOS was used to assess functional outcomes. Results Over a period of 13 years, 500 patients harboring ruptured intracranial aneurysms were surgically clipped, and out of them 28 patients (5.6%) had ruptured DACA aneurysms. In this series, 20 (71.4%) patients had low grade and 8 (28.6%) had high grade H&H. Out of the 28 patients, 19 (67.8%) had good recovery, 6 (21.5%) were severely disabled, and 3 (10.7%) died at the time of discharge. On the last follow-up (13 years), smoking ( p -value 0.03) and use of temporary clip ( p -value 0.00) were significant predictors for unfavorable outcome. Conclusion The results of our case series show that even with ruptured aneurysm excellent overall outcome after microsurgical clipping can be achieved, even though among cerebral aneurysms, DACA aneurysm is considered to have less favorable outcome. Alcohol consumption and use of temporary clip were the predictors for unfavorable outcome at the time of discharge. On the last follow-up, smoking and use of temporary clip were found to be the risk factors for unfavorable outcome. Although the small sample size of this study is a limitation, smoking and use of temporary clip play an important role on the overall outcome. The aim of this study was to analyze data to determine factors which may influence outcome after surgical clipping of ruptured DACA aneurysms.

Off-clamp Versus On-clamp Robot-assisted Partial Nephrectomy: A Systematic Review and Quantitative Synthesis by the European Association of Urology Young Academic Urologists Renal Cancer Study Group.

Context: The superiority of off-clamp robot-assisted partial nephrectomy (RAPN) over the on-clamp technique has recently been questioned by randomized controlled trials comparing the two techniques. Objective: To systematically review the recent literature and perform a quantitative synthesis of data on the comparison of off-clamp versus off-clamp hilar control during RAPN. Evidence acquisition: A systematic search was performed in the PubMed, Embase, Web of Science, and Scopus databases for studies comparing off-clamp versus on-clamp RAPN in terms of perioperative and functional outcomes. The study protocol was registered in the PROSPERO database (CRD42023413160). Only prospective randomized controlled trials and retrospective matched observational studies were included. The primary outcome of the study was the percentage decrease in the estimated glomerular filtration rate (eGFR). Evidence synthesis: A total of 11 studies were included involving a total of 2483 patients (944 patients in the off-clamp and 1539 patients in the on-clamp group). There was no difference between the two groups in the percentage decline in eGFR (mean difference [MD] 0.04%, 95% confidence interval [CI] -3.7% to 3.86%; p = 0.98). There were so significant differences between the groups for length of hospital stay (p = 0.56), complications (p = 0.08), conversion to open or radical surgery (p = 0.18), estimated blood loss (p = 0.06), or need for blood transfusion (p = 0.07). The operative time was shorter in the off-clamp group (MD-21.89 min, 95% CI -42.5 to -1.27; p = 0.04) but after sensitivity analysis the difference was no longer statistically significant (p = 0.15). The positive surgical margin rate was significantly lower in the off-clamp group (odds ratio 0.6, 95% CI 0.39-0.91; p = 0.02). Conclusions: Our review revealed no clinically relevant differences in perioperative and functional outcomes between off-clamp and on-clamp RAPN. Patient summary: In this review, we compared the two methods of controlling the kidney blood vessels during robot-assisted surgery to remove part of the kidney. We noted that there was no difference between the two groups for outcomes such as complications and the decrease in kidney function after surgery.

Intramuscular hydatid cyst of paraspinal muscle: A diagnostic challenge.

Hydatid cyst is a zoonosis caused by ingestion of eggs of Echinococcus-a tapeworm. Following ingestion of the eggs, oncosphere larvae are released which penetrate the intestinal wall to invade various organs of the body including liver, lungs, and skeletal muscles via. blood vessels. Due to their contractile nature and high lactic acid content, skeletal muscles are typically not a suitable site for attachment of hydatid cyst. In our case report presented below, we report a rare case of an isolated hydatid cyst of paraspinal muscle presenting as a slow-growing asymptomatic mass in the back, posing a clinical diagnostic dilemma.

Leaf water relations and osmotic adjustment of Canada Western Red Spring wheat cultivars subjected to drought.

For wheat (Triticum aestivum ), sustained crop yield at limited soil water availability has been linked to osmotic adjustment (OA) - a physiological mechanism that aids maintenance of leaf hydration status, turgor (P ) and growth. 'Canada Western Red Spring' (CWRS) wheat cultivars are typically grown in rainfed areas with milder climates, but ongoing climate change is increasesing the frequency and intensity of drought events. The overarching goal of this study was to elucidate if commercially used CWRS cultivars ('Superb', 'Stettler', 'AAC Viewfield') have the ability for leaf OA. Measurements of leaf water relation parameters (water potential, Ψ ; solute potential, Ψ s ; stomatal conductance, g s ; relative water content, RWC) showed that all three cultivars reached zero P (= Ψ - Ψ s ) at a leaf Ψ of -1.1MPa. Prior to that, P maintenance in 'Superb' and 'AAC Viewfield' was associated with a significant reduction in leaf Ψ s and OA contributed 0.53MPa ('Superb') and 0.73MPa ('AAC Viewfield'). Our data analyses provided no support for the existence of OA in 'Stettler'. Under water deficit, leaf g s was significantly higher in 'AAC Viewfield' compared to 'Stettler'; it was intermediate in 'Superb'. Together, drought tolerance in CWRS wheat cultivars is most likely linked to the degree of OA.

Small bots, big impact: solving the conundrum of cooperation in optional Prisoner's Dilemma game through simple strategies.

Cooperation plays a crucial role in both nature and human society, and the conundrum of cooperation attracts the attention from interdisciplinary research. In this study, we investigated the evolution of cooperation in optional Prisoner's Dilemma games by introducing simple bots. We focused on one-shot and anonymous games, where the bots could be programmed to always cooperate, always defect, never participate or choose each action with equal probability. Our results show that cooperative bots facilitate the emergence of cooperation among ordinary players in both well-mixed populations and a regular lattice under weak imitation scenarios. Introducing loner bots has no impact on the emergence of cooperation in well-mixed populations, but it facilitates the dominance of cooperation in regular lattices under strong imitation scenarios. However, too many loner bots on a regular lattice inhibit the spread of cooperation and can eventually result in a breakdown of cooperation. Our findings emphasize the significance of bot design in promoting cooperation and offer useful insights for encouraging cooperation in real-world scenarios.

Giant Gallstone With Gallbladder Perforation and Hepatic Abscess in an Asian Patient.

Giant gallstone with a secondary hepatic abscess is a very rare phenomenon. We recently treated a patient with a giant gallbladder (GB) stone of size 11.5 cm with a hepatic abscess who presented with features of an acute abdomen. This was subsequently managed with an open subtotal cholecystectomy and concomitant hepatic abscess drainage. To the best of our knowledge and after a thorough literature search, this is one of the largest reported gall bladder (GB) stones with wall perforation and hepatic abscess in the Asian subcontinent.

Off-clamp Versus On-clamp Robot-assisted Partial Nephrectomy: A Propensity-matched Analysis.

BACKGROUND: Partial nephrectomy is the preferred treatment option for the management of small renal masses. On-clamp partial nephrectomy is associated with a risk of ischemia and a greater loss of postoperative renal function, while the off-clamp procedure decreases the duration of renal ischemia, leading to better renal function preservation. However, the efficacy of the off- versus on-clamp partial nephrectomy for renal function preservation remains debatable. OBJECTIVE: To compare perioperative and functional outcomes following off- and on-clamp robot-assisted partial nephrectomy (RAPN). DESIGN, SETTING, AND PARTICIPANTS: This study used the prospective multinational collaborative Vattikuti Collective Quality Initiative (VCQI) database for RAPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objective of this study was the comparison of perioperative and functional outcomes between patients who underwent off- and on-clamp RAPN. Propensity scores were calculated for age, sex, body mass index (BMI), renal nephrometry score (RNS) and preoperative estimated glomerular filtration rate (eGFR). RESULTS AND LIMITATIONS: Of the 2114 patients, 210 had undergone off-clamp RAPN and others on-clamp procedure. Propensity matching was possible for 205 patients in a 1:1 ratio. After matching, the two groups were comparable for age, sex, BMI, tumor size, multifocality, tumor side, face of tumor, RNS, polar location of the tumor, surgical access, and preoperative hemoglobin, creatinine, and eGFR. There was no difference between the two groups for intraoperative (4.8% vs 5.3%, p = 0.823) and postoperative (11.2% vs 8.3%, p = 0.318) complications. Need for blood transfusion (2.9% vs 0, p = 0.030) and conversion to radical nephrectomy (10.2% vs 1%, p < 0.001) were significantly higher in the off-clamp group. At the last follow-up, there was no difference between the two groups for creatinine and eGFR. The mean fall in eGFR at the last follow-up compared with that at baseline was equivalent between the two groups (-16.0 vs -17.3 ml/min, p = 0.985). CONCLUSIONS: Off-clamp RAPN does not result in better renal functional preservation. Alternatively, it may be associated with increased rates of conversion to radical nephrectomy and need for blood transfusion. PATIENT SUMMARY: With this multicentric study, we noted that performing robotic partial nephrectomy without clamping the blood supply to the kidney is not associated with better preservation of renal function. However, off-clamp partial nephrectomy is associated with increased rates of conversion to radical nephrectomy and blood transfusion.

Robot-assisted partial nephrectomy in morbidly obese patients: a VCQI database study.

To compare perioperative outcomes following robot-assisted partial nephrectomy (RAPN) in patients with morbid obesity (body mass index (BMI > 40 kg/m2)) and non-obese patients. Using the Vattikuti Collective quality initiative (VCQI) database for RAPN, data for morbidly obese and non-obese patients was obtained. Propensity scores were calculated for two treatment groups (morbidly obese vs. non-obese) for the following variables i.e. age, sex, tumor size, RNS, surgical access (retroperitoneal/transperitoneal) and estimated glomerular filtration rate (eGFR) to ensure comparability. The primary outcome for the study was comparison of trifecta between the two groups. In this study, 158 morbidly obese patients were matched with 158 non-obese patients undergoing RAPN. Two groups matched well for age, sex, tumor size, eGFR and RNS. There was no difference between two groups for ischemia time, blood loss, blood transfusion, conversion to radical nephrectomy, length of stay, intraoperative and postoperative complications. Operative time was longer in morbidly obese patients (median 210 min vs. 120 min, p = 0.000). On pathological analysis, malignant tumors were more likely in the morbidly obese group (83.1% vs.73.4%, p = 0.018). Trifecta outcomes were comparable between the two groups (60.1% vs. 63.3%, p = 0.563). The Median duration of follow-up was 12 months (1-96 months). The morbidly obese group had significantly higher day one creatinine (1.25 ± 0.7 vs. 1.07 ± 0.37, p = 0.001) and significantly lower day one eGFR (62.1 ± 19 vs. 69.2 ± 21, p = 0.018). However, there was no difference between the two groups for the last follow-up creatinine and eGFR. RAPN in morbidly obese patients is associated with equivalent perioperative outcomes compared to non-obese patients.

Trifecta and pentafecta outcomes following robot-assisted partial nephrectomy in a multi-institutional cohort of Indian patients.

Introduction: The literature on studies reporting trifecta or pentafecta outcomes following robot-assisted partial nephrectomy (RAPN) in Indian patients is limited. The primary aim of this study was to report and evaluate the factors predicting trifecta and pentafecta outcomes following RAPN in Indian patients using the multicentric Vattikuti collective quality initiative (VCQI) database. Methods: From the VCQI database for patients who underwent RAPN, data for Indian patients were extracted and analyzed for factors predicting the achievement of trifecta and pentafecta following RAPN. Trifecta was defined as the absence of complications, negative surgical margins, and warm ischemia period shorter than 25 min or zero ischemia. Pentafecta covers all the trifecta criteria as well as >90% preservation of estimated glomerular filtration rate (eGFR) and no stage upgrade of chronic kidney disease at 12 months. Results: In this study, among 614 patients, the trifecta was achieved in 374 patients (60.9%) and pentafecta was achieved in 24.2% of the patients. Patients who achieved trifecta had significantly higher mean age (54.1 vs. 51.0 years, P = 0.005), body mass index (BMI) (26.7 vs. 26.03 kg/m2, P = 0.022), and smaller tumor size (38.6 vs. 41.4 mm, P = 0.028). The preoperative eGFR (84.2 vs. 91.9 ml/min, P = 0.012) and renal nephrometry score (RNS) (6.96 vs. 7.87, P ≤ 0.0001) were significantly lower in the trifecta group. Comparing patients who achieved pentafecta to those who did not, we noted a statistically significant difference between the two groups for tumor size (36.1 vs. 41.5 mm, P = 0.017) and RNS (6.6 vs. 7.7, P = 0.0001). On multivariate analysis, BMI and RNS were associated with trifecta outcomes. Similarly, only RNS was identified as an independent predictor of pentafecta. Conclusions: RNS and BMI were independent predictors of the trifecta. At the same time, RNS was identified as an independent predictor of pentafecta following RAPN.