Comparison Of Ventral Inlay and Dorsal Onlay Urethroplasty For Female Urethral Stricture.

OBJECTIVE: To compare the outcomes of Ventral inlay buccal mucosal graft urethroplasty (VIBMGU) with dorsal onlay buccal mucosal graft urethroplasty (DOBMGU) for the treatment of Female urethral stricture (FUS). MATERIAL AND METHODS: This study included women who underwent either VIBMGU or DOBMGU between January 2016 and June 2023. The preoperative American Urological Association (AUA) symptom scores, maximal urinary flow rate (Qmax), post-void residual volume (PVR) on ultrasonography, and length and location of the stricture were obtained from a prospectively maintained electronic database. The data obtained from the patient's last visit were compared with the preoperative values for this study. The primary outcome was the success rate. The secondary outcomes were changes in AUA score, PVR, and Qmax. The patient's last follow-up visit was considered for the duration of the follow-up. RESULTS: Seventy-three patients were treated for BMGU for FUS. Forty-six patients underwent VIBMGU, and 27 patients underwent DOBMGU. The median duration of follow-up was 27.5 (11.00-55.00) versus 14 (7.00-17.00) months, respectively. The success rates of VIBMGU and DOBMGU were 89.13% and 88.89%, respectively. There was a reduction in AUA scores and PVR and an improvement in Qmax postoperatively in both groups. The difference in the reduction in AUA scores between the VIBMGU and DOBMGU groups was statistically significant. The difference was not statistically significant in terms of reduction in PVR and improvement in Qmax between the 2 groups. CONCLUSION: The ventral inlay technique can provide equal results to the dorsal technique with the added advantage of vaginal sparing. This is the single largest series in the literature on FUS with the largest follow-up period of 90 months.

Long-term Sexual Function and Quality of Life in Women Following Substitution Urethroplasty.

PURPOSE: To assess the long-term quality of life (QOL) and sexual function (SF) in women who underwent either dorsal on-lay (DO) or ventral inlay (VI) urethroplasty for urethral stricture disease. METHODOLOGY: Between January 2016 and September 2022, women who underwent either dorsal on-lay (DO) or ventral inlay (VI) urethroplasties and had at least a six-month follow-up been included. Using the Female Sexual Function Index (FSFI) and WHO-QOL bref questionnaires, the QOL and SF were evaluated. Scores were compared between the two groups after being examined for internal validity. A sub-group analysis was carried out based on the procedure's success. RESULTS: With follow-up periods ranging from 6 to 86 months, 25 patients who received VI urethroplasty and 10 patients who underwent DO urethroplasty were included. Both scores demonstrated strong internal consistency. The cumulative QOL and FSFI scores were comparable in both groups (p = 0.53 and p = 0.83, respectively). Significantly high scores were noted in the physical health domain (76.5 ± 9.9 vs 62.33 ± 10.97; p = 0.03; (95% CI = 0.72-24.4)) and the environmental domain (75.75 ± 3.84 vs 66.00 ± 4.24; p = 0.01 (95% CI = 2.64-16.85) in patients with successful VI and DO urethroplasties respectively. Addictions, low socioeconomic status and protracted symptom duration were associated with low QOL scores. Old age was related to low FSFI scores. CONCLUSION: Substitution urethroplasty, despite the approach, showed good QOL and SF scores. Long symptom duration, addictions, and poor socioeconomic status were associated with low QOL whereas old age independently influenced low FSFI scores.

Intraoperative ultrasonography (IOUS)-guided vs conventional laparoscopic nephrectomy: a randomised control trial.

OBJECTIVES: To assess the efficacy of routine use of intraoperative ultrasonography (IOUS) in improving perioperative outcomes in patients undergoing IOUS-guided laparoscopic nephrectomy (IOUS-LN) and conventional laparoscopic nephrectomy (C-LN). PATIENTS AND METHODS: This was a parallel-arm, single-blinded, randomised controlled trial (CTRI/2021/12/038906). All patients undergoing LN, either for benign or malignant causes, were included. Patients undergoing partial/cytoreductive nephrectomy, with venous thrombus were excluded. In the study arm, IOUS-guided renal vascular assessment was performed after colon mobilisation and a standard LN was performed in the control arm. The primary outcome was intraoperative duration. The secondary outcomes were blood loss, need for open conversion, blood transfusion, perioperative complications, duration of Intensive Care Unit (ICU) stay and length of hospitalisation (LOH). The patients were followed for 3 months after surgery. RESULTS: A total of 104 patients were included, with 52 in each arm. Demographic characteristics were comparable in both arms. A significant reduction in the operative duration (mean [sd] 181.69 [40.8] vs 199.7 [41.8] min, P = 0.02) was seen in the IOUS-LN group. The difference in blood loss showed no significant difference when compared between both groups (median [interquartile range] 84.55 [74-105.5] vs 99.95 [78.5-111] mL, P = 0.08). On subgroup analysis, the reduction in the operative duration was significant in patients who underwent laparoscopic simple nephrectomy (LSN; mean [sd] 194.4 [42.5] vs 221.2 [36.4] min, P = 0.01), whereas comparable operative durations were seen in patients undergoing laparoscopic radical nephrectomy (LRN; mean [sd] 168.96 [35.3] vs 178.3 [35.9] min, P = 0.34). Similar conversion rates were seen in both groups (P = 0.98) along with blood transfusions (P = 0.78). The LOH, ICU stay, and complications were similar in both groups. Significantly less blood loss (P = 0.03) was noted with IOUS in patients undergoing LSN. IOUS did not influence any outcomes in patients undergoing LRN. CONCLUSION: Intraoperative ultrasonography significantly reduced the operative duration in LN, but with no significant reduction in the volume of blood loss. Significant reduction in intraoperative duration and blood loss was seen in patients who underwent LSN on subgroup analysis.

Efficacy of Low Dose Intravenous Epinephrine Infusion in Improving Perioperative Outcomes in Patients Undergoing Transurethral Resection of Prostate: A Prospective Parallel Arm Double-Blind Randomized Control Trial.

OBJECTIVE: To determine the efficacy of intraoperative low-dose intravenous epinephrine infusion in improving intraoperative bleeding and perioperative outcomes of transurethral resection of prostate (TURP) surgery. METHODS: This was a double-blinded, randomized control trial in which all patients undergoing bipolar TURP were included. Patients with uncontrolled hypertension, cardiac disease, and on anticoagulants were excluded. The study group received intravenous epinephrine, whereas the control group received normal saline at the same rate (0.05 µg/kg/min) throughout the procedure. Intraoperative blood loss was the primary outcome. The secondary outcomes were incidence of intraoperative hypotension (due to spinal anesthesia), resection time, indwelling catheter time, and length of hospitalization. RESULTS: Thirty-six patients were included in each group. Demographic and clinical profiles were comparable with an overall median prostate size of 41 (34-52) gram in both groups. The primary objective, mean intraoperative blood loss in the study group was lower than the control group but statistically insignificant (67.91+/-18.7 mL vs 75.14 +/-17.1 mL; P = .086). Incidence of intraoperative hypotension was significantly lower in the study group (8.3% vs 33.3%; P = .01). Rest of the secondary outcomes, resection time (83 (64-111.5) minutes vs 86 (68-94.75) minutes; P = .97), mean indwelling catheter time (P = .94), postoperative complications (P = .73), and length of hospitalization (P = .87) were comparable. CONCLUSION: In this first-of-its-kind trial, low-dose epinephrine infusion did not reduce intraoperative blood loss in patients undergoing TURP. However, it significantly reduced intraoperative hypotension, which complicates spinal anesthesia particularly in elderly population.

Inferior Alveolar Plus Buccal Nerve Block Decreases Postoperative Pain Scores at Buccal Mucosal Graft Harvest Site: A Retrospective Analysis.

OBJECTIVE: Postoperative pain at buccal mucosal graft (BMG) harvest site hinders the resumption of food intake. We aim to study the effect of inferior-alveolar nerve block plus buccal nerve block (IANB+BNB) on pain scores. METHODS: This was a retrospective case-control study performed in a single center from July 2021 to July 2022 (ethics committee approval: T/IM-NF/Urology/23/27). We performed IANB+BNB with a mixture of 5 mL each of 1% lignocaine and 0.25% bupivacaine and 4 mg dexamethasone, in addition to local infiltration of 2% lignocaine and (1:100000) epinephrine combination before harvesting BMG. We retrospectively compared the recorded postoperative pain scores using the visual analog scale (VAS) among patients who received and did not receive IANB+BNB. The time for resumption of pain-free diets and postoperative analgesic requirements was compared. RESULTS: The study groups included 20 patients each and were similar in age and graft size. The VAS scores at 0 hours [1.0 (1.25) vs. 2.5 (3.5); P= .043], 6 hours [2.40 (± 0.69) vs. 4.60 (± 0.97); P= .008], 12 hours [2.50 (± 0.97) vs. 4.80 (± 0.92); P= .008], and 24 hours [3.0 (1.25) vs. 4.5 (1.25); P= .002] were better in the intervention arm. However, the pain beyond the second day was similar. The IANB+BNB group resumed solid food quicker, and the cumulative paracetamol dose required was less [8.9 (± 3.03) vs. 16.2 (± 5.06) g; P= .001]. Fewer patients required opioids. CONCLUSION: Patients who received IANB+BNB had better pain scores during the first 24 hours following surgery and tolerated solid diet quicker.

Socio-economic, education, and insurance-related factors associated with the treatment completion rates in patients with nonmetastatic urinary bladder cancer: A Retrospective cohort study.

Introduction: Among urological malignancies, the diagnosis and treatment of urinary bladder cancer (UBC) incurs the highest cost per patient. Our objective was to broaden the current understanding of how demographic, socioeconomic, education, and insurance-related factors influence UBC management. Methods: Between January 2017 and December 2019, all patients with nonmetastatic bladder cancer were included. The demographic, treatment, and follow-up details were retrieved from a prospectively maintained database, and the Modified Kuppuswamy Index was used to evaluate the patients' socioeconomic level. Patients were divided into the completed treatment group, or the incomplete treatment group based on adherence to the initially intended treatment plan. Patients who presented with benign disease or metastases were not included. Results: Eighty-nine patients did not complete the initially intended course of treatment out of 132 patients who needed additional management after the initial transurethral resection. Comparable risk factors and demographic profiles existed in both groups. Patients with intermediate-risk disease are more likely to fail to adhere to the initial intended treatment (odds ratio [OR] = 0.09; 95% confidence interval [CI]: 0.02-0.30). On logistic regression analysis, upper socioeconomic status (OR = 6.8; 95% CI: 0.35-132.1) patients and patients with higher educational status of graduation or above (OR = 3.62; 95% CI: 0.75-17.43) had higher chances of treatment completion. Education status significantly impacted treatment completion on multivariate analysis (P = 0.01). Patients who utilized employer-funded insurance had better treatment compliance (OR = 4.1; 95% CI: 0.90-18.7). The compliance was unaffected by smoking, occupation, or other demographic factors. Conclusion: Patients with low economic status, low levels of education, and who need adjuvant intravesical therapy had considerably greater treatment dropout rates.

Supramolecular Chemotherapy with Cucurbit[n]urils as Encapsulating Hosts.

The cucurbit[n]urils (CB[n]) belong to the field of relatively young supramolecules which act as containers for a large variety of guests and are being explored extensively for their numerous biomedical applications. This includes drug formulation and delivery, controlled drug release, photodynamic therapy, sensing for bioanalytical purposes, etc. These supramolecular host-guest systems have distinctive recognition properties and have successfully been shown to enhance the in vitro and in vivo utility of various chemotherapeutic agents. The CB[n]s are tailored to optimize their application in payload delivery and diagnostics and in lowering the toxicity of existing drugs. This review has listed the recent studies on working mechanisms and host-guest complexation of the biologically vital molecules with CB[n] and highlighted their implementation in anticancer therapeutics. Various modifications in CB-drug inclusion compounds like CB supramolecular nanoarchitectures along with application in photodynamic therapy, which has shown potential as targeted drug delivery vehicles in cancer chemotherapy, have also been discussed.

A prospective evaluation of patient-reported outcomes during follow-up of ureteral stones managed with medical expulsive treatment (MET).

Patient-reported outcomes (PROs) for ureteral stones predominantly assess the pain. Despite the lack of evidence, multiple trials studying the efficacy of medical expulsive therapy (MET) have used PROs to define spontaneous stone passage (SSP). We aim to objectively evaluate the accuracy of PROs to predict successful SSP and the probability of patient's symptom resolution after stone passage. A single-center, prospective observational study recruiting adults with isolated, uncomplicated, ≤ 10 mm ureteral calculus was conducted. All patients received 4 weeks of MET, and SSP was confirmed by low-dose non-contrast-enhanced computed tomography (NCCT). The accuracy of PROs: "pain cessation," "decreased pain," "stone seen," and "stone capture" to predict successful SSP were evaluated in 1 month. The patient's symptom resolution rate was assessed at 1 and 4-month follow-ups. A total of 171 patients were included, and the overall SSP rate was 66.4% (n = 99). Patient-reported pain cessation, stone visualization, and stone capture were associated with successful SSP, but their accuracy was 59, 53, and 43%, respectively. Moreover, 25% of patients reporting complete pain cessation still harbored ureteral calculus. Pain resolved in 91% of patients after SSP at a 4-month follow-up. While hematuria and nausea resolved in all patients, lower urinary tract symptoms (LUTS) were not resolved in 17% of patients. We concluded that patient-reported pain cessation, stone visualization, and stone capture predict successful SSP, but confirmatory imaging is required due to the poor accuracy of these measures. The significant rates of non-pain-related symptoms indicate their significant contribution to patient morbidity. Clinical Trial Registration: Registered in Clinical Trial Registry of India (CTRI), Registration number: CTRI/2020/10/028777 (29th October 2020).

Insight into the Tubulin-Targeted Anticancer Potential of Noscapine and its Structural Analogs.

Cancer is known as a notorious disease responsible for threatening millions of lives every year. Natural products which act by disrupting the microtubule assembly and dynamics have proven to be highly successful as anticancer agents but their high toxicity owing to lower selectivity has limited their usage. Recently, Noscapine (NOS), a known anti-tussive, has come out to be an effective anti-tubulin candidate with far lesser toxicity. Since its first report as an anti-mitotic agent in 1998, NOS has been extensively studied and modified by various groups of researchers to optimize its anti-tubulin activity. In this review, the recent advancements about the potential of these therapeutic candidates against various cancers have been compiled and analyzed for their inhibitory mechanism in distinct health conditions. It has been observed that the non-polar substitutions (e.g., halides, aryl groups) at specific sites (9-position and N-sites of isoquinoline ring; and modification of a methoxy group) have an enhanced effect on efficacy. The mechanistic studies of NOS and its modified analogs have shown their inhibitory action primarily through interaction with microtubules dynamics thus disrupting the cell-cycle and leading to apoptosis. This review highlights the latest research in the field by providing a rich resource for the researchers to have a hands-on analysis of NOS analogs and the inhibitory action in comparison to other microtubule disrupting anti-cancer agents. The article also documents the newer investigations in studying the potential of noscapine analogs as possible anti-microbial and antiviral agents.

Efficacy of PCNL in the resolution of symptoms of nephrolithiasis.

Patients undergo Percutaneous Nephrolithotomy (PCNL) for the resolution of pain, but at times, other symptoms such as hematuria, dysuria, nausea, emotional distress, and anxiety are also the presenting symptoms. While pain resolution after successful surgery is generally the focus, the resolution rate of other symptoms after surgery is not described. Our study aims to determine the efficacy of PCNL for the resolution of other symptoms. Patients aged > 18 years who underwent PCNL from September 2019 to 2021 were interviewed face-to-face and asked questions regarding their symptoms before and 3 months after the surgery. Their response was noted on an 11-point Numerical-Rating-Scale (NRS) of 0-10. The primary outcome was symptom resolution rate at 3 months after PCNL. The secondary outcomes were rate of resolution of gross hematuria, dysuria, anorexia and nausea, emotional distress and anxiety, work interference, and daily routine activities. Only patients who had complete stone clearance in a single sitting were included. Of the total 110 patients, almost half (45.45%) of the patients reported having one or more symptoms at or after 3 months of surgery. The reduction in proportion of patients and mean difference in preoperative and postoperative NRS scores of symptoms were statistically significant. Symptoms that persisted were mild and posed slight discomfort to the patient. Complete resolution of all the symptoms may not be achieved even in patients who have complete clearance after PCNL, and a few symptoms can persist, however, only mild. Appropriate preoperative counselling of the patients is, therefore, essential.

Necrotizing Fasciitis of the Breast Following a Core-Needle Biopsy.

Necrotizing fasciitis (NF) is an aggressive rapidly spreading infection of the skin and the subcutaneous tissue. Its occurrence in the breast is extremely rare especially after routine procedures like core-needle biopsy. We present the case of a 35-year-old non-lactating female who presented with swelling and a necrotic patch with pus discharge over her right breast following a core needle biopsy. She was immediately treated with aggressive debridement and culture-specific intravenous antibiotics following which she had an uneventful recovery. It is quintessential to diagnose the condition and initiate the treatment as early as possible to prevent the progression of the disease to sepsis and multi-organ dysfunction.

Template-Mediated Detoxification of Low-Molecular-Weight Amyloid Oligomers and Regulation of Their Nucleation Pathway.

Amyloid tetramer, the most toxic low-molecular-weight (LMW) amyloid oligomer, leads to synaptic dysfunction and plays a vital role in pathophysiology of Alzheimer's disease (AD). Hence, their kinetic inhibition may be regarded as a potential therapeutic strategy against AD. However, because of their dynamic, metastable nature, not much information has been gathered about them. Herein, amyloid tetramers have been isolated from a mixture pool of low- and high-molecular-weight amyloid oligomers. Kinetics of such tetrameric species has been studied in an in vitro model and inhibition of the fibrillation of the species has been achieved by means of a novel isatin functionalized polyfluorene derivative (PFIS). Isatin interacts with tetramers noncovalently to modulate its fibrillation by forming stable polymer-peptide coaggregates. In parallel to this, hydrophobic PFIS forms spherical nanoparticle in water that provides an external surface, which functions to modulate nucleation pathway of the oligomers. The polymer-peptide coaggregates are nontoxic in nature. Hence, these observations offer a potential strategy to suppress neurotoxicity of a LMW oligomer by forming nontoxic coaggregates. In parallel to this, our methodology also provides a potential strategy to observe and regulate nucleation pathway of the oligomers as well.