Neoadjuvant chemotherapy does not increase peri-operative morbidity following radical cystectomy.

OBJECTIVE: To determine whether use of neoadjuvant chemotherapy (NAC) is associated with a higher risk of post-operative complications following radical cystectomy (RC) for bladder cancer (BCa). MATERIALS AND METHODS: We retrospectively reviewed records of patients undergoing RC for non-metastatic urothelial BCa at 13 tertiary care centres from 2007-2019. Patients who received NAC ('NAC + RC' group) were compared with those who underwent upfront RC ('RC alone' group) for intra-operative variables, incidence of post-operative complications as per the Clavien-Dindo classification (CDC) and rates of re-admission and re-intervention. Multivariable logistic regression analysis was performed to determine predictors of CDC overall and CDC major (grade III-V) complications. We also analysed the trend of NAC utilization over the study period. RESULTS: Of the 3113 patients included, 968 (31.1%) received NAC while the remaining 2145 (68.9%) underwent upfront RC for BCa. There was no significant difference between the NAC + RC and RC alone groups with regards to 30-day CDC overall (53.2% vs 54.6%, p = 0.4) and CDC major (15.5% vs 16.5%, p = 0.6) complications. The two groups were comparable for the rate of surgical re-intervention (14.6% in each group) and re-hospitalization (19.6% in NAC + RC vs 17.9% in RC alone, p = 0.2%) at 90 days. On multivariable regression analysis, NAC use was not found to be a significant predictor of 90-day CDC overall (OR 1.02, CI 0.87-1.19, p = 0.7) and CDC major (OR 1.05, CI 0.87-1.26, p = 0.6) complications. We also observed that the rate of NAC utilization increased significantly (p < 0.001) from 11.1% in 2007 to 41.2% in 2019, reaching a maximum of 48.3% in 2018. CONCLUSION: This large multicentre analysis with a substantial rate of NAC utilization showed that NAC use does not lead to an increased risk of post-operative complications following RC for BCa. This calls for increasing NAC use to allow patients to avail of its proven oncologic benefit.

SFPQ and Tau: critical factors contributing to rapid progression of Alzheimer's disease.

Dysfunctional RNA-binding proteins (RBPs) have been implicated in several neurodegenerative disorders. Recently, this paradigm of RBPs has been extended to pathophysiology of Alzheimer's disease (AD). Here, we identified disease subtype specific variations in the RNA-binding proteome (RBPome) of sporadic AD (spAD), rapidly progressive AD (rpAD), and sporadic Creutzfeldt Jakob disease (sCJD), as well as control cases using RNA pull-down assay in combination with proteomics. We show that one of these identified proteins, splicing factor proline and glutamine rich (SFPQ), is downregulated in the post-mortem brains of rapidly progressive AD patients, sCJD patients and 3xTg mice brain at terminal stage of the disease. In contrast, the expression of SFPQ was elevated at early stage of the disease in the 3xTg mice, and in vitro after oxidative stress stimuli. Strikingly, in rpAD patients' brains SFPQ showed a significant dislocation from the nucleus and cytoplasmic colocalization with TIA-1. Furthermore, in rpAD brain lesions, SFPQ and p-tau showed extranuclear colocalization. Of note, association between SFPQ and tau-oligomers in rpAD brains suggests a possible role of SFPQ in oligomerization and subsequent misfolding of tau protein. In line with the findings from the human brain, our in vitro study showed that SFPQ is recruited into TIA-1-positive stress granules (SGs) after oxidative stress induction, and colocalizes with tau/p-tau in these granules, providing a possible mechanism of SFPQ dislocation through pathological SGs. Furthermore, the expression of human tau in vitro induced significant downregulation of SFPQ, suggesting a causal role of tau in the downregulation of SFPQ. The findings from the current study indicate that the dysregulation and dislocation of SFPQ, the subsequent DNA-related anomalies and aberrant dynamics of SGs in association with pathological tau represents a critical pathway which contributes to rapid progression of AD.

Sexual dysfunction in Indian men undergoing Double J ureteral stenting following ureteroscopy-A prospective analysis.

This prospective study was aimed to evaluate the impact of an indwelling ureteral double-J stent on the sexual health of Indian men undergoing ureteroscopy. The first phase of the study included 30 men who were not counselled prior to stenting about possible sexual dysfunction, while in the next phase, 60 men were counselled about this. These 60 patients were assessed by a 6-point questionnaire: five questions from the International Index of Erectile Function-5 (IIEF-5) and an additional 6th question to assess pain during erection/ejaculation. Patients answered the questionnaire prior to ureteroscopy, at the time of stent removal and then 4 weeks after stent removal. A higher proportion of men in the second phase attempted sexual activity (68.3% vs. 26.7%; p < .001). Significant changes were noted in the total IIEF-5 score (mean 23.16 before vs. 15.65 after, p < .001) and individual IIEF-5 components: erection confidence (4.59 vs. 2.76, p = .017), maintenance ability (4.67 vs. 2.43, p = .006) and intercourse satisfaction (4.61 vs. 2.31, p < .001) and also the 'pain' question (2.83 post-stenting vs. 0.37 pre-stenting, p < .001). Most patients had a recovery of scores at 4 weeks after stent removal. Thus, ureteral DJ stenting leads to significant but temporary sexual dysfunction and patients need to be counselled regarding this.

Safety, feasibility, and quality of holmium laser en-bloc resection of nonmuscle invasive bladder tumors - A single-center experience.

INTRODUCTION: Conventional transurethral resection of bladder tumor (cTURBT), despite its piecemeal resection and associated limitations, remains the most widely practiced technique of TURBT. Resecting the tumor in a single piece would avoid most of the drawbacks of cTURBT. Our objective was to assess the feasibility, safety, and quality of Holmium (Ho) laser en-bloc resection (ERBT) for nonmuscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively studied 67 patients who underwent Ho laser EBRT for primary NMIBC. Data were collected regarding tumor size, number and location, intraoperative complications, and postoperative course. Patients were grouped as first 20, next 20 (21-40), and last 27 cases to assess how the quality of resection improved with increasing experience. RESULTS: The mean tumor size was 28.7 ± 7.9 mm, with 34.3% of the patients having a tumor larger than 3 cm. While 43 patients (64.17%) had a single tumor, the rest had multiple tumors, ranging from 2 to 9 in number. The mean total duration of resection was 38.7 ± 11.6 min. No case required conversion to cTURBT. No patient experienced obturator reflex or bladder perforation. Detrusor muscle was present in 85.07% of the resections. With increasing experience, requirement for bladder irrigation and the incidence of postoperative clot evacuation decreased (P < 0.0001 and P = 0.31, respectively), and the detrusor-positive rate in the specimen increased (P = 0.24). The mean duration of catheterization was 1.76 ± 0.54 days. CONCLUSION: Ho laser ERBT is safe and feasible for complete resection of NMIBCs with no risk of obturator-nerve reflex and a high rate of detrusor-positive specimens.

Predicting Mortality in Fournier Gangrene and Validating the Fournier Gangrene Severity Index: Our Experience with 50 Patients in a Tertiary Care Center in India.

OBJECTIVE: To identify factors that dictate morbidity and mortality in patients with Fournier's Gangrene and validate the Fournier gangrene severity index (FGSI). MATERIALS AND METHODS: We prospectively studied 50 patients with FG from January 2016 to December 2016 pertaining to their presenting signs, intraoperative findings, and postoperative wound management and outcome. We also checked the power of the FGSI to predict the outcome of the patients in terms of mortality. Receiver operating characteristic curve was used to determine the optimum cutoff of FGSI score to predict mortality. Principle component analysis was performed to check for the possibility of reduction in the number of factors included in the FGSI. RESULTS: The mean age at presentation was 53 ± 16 years with a mortality rate of 24%. Factors associated with mortality were increasing age (p = 0.0001), presence of diabetes (p = 0.002), bed-ridden status (p = 0.001), alcoholic liver disease (p = 0.005), altered international normalized ratio (p > 0.005), late presentation (p = 0.001), and a FGSI score of > 9 at admission (p = 0.004). The mean FGSI score among survivors was 4.39 ± 3.80 compared to 14.22 ± 3.93 among those who died. The area under the curve FGSI score to predict mortality at a cutoff of 9 was 0.961 (95% CI 0.910-1.000). CONCLUSION: Increasing age, diabetes, alcoholic liver disease, bed-ridden status, delayed hospital presentation, and an altered international normalized ratio at presentation are associated with higher mortality in FG. The FGSI at admission should be used to identify patients with serious prognosis requiring intensive care.

Visible Light Photocatalysis for the Generation and Use of Reactive Azolyl and Polyfluoroaryl Intermediates.

Photocatalysis offers several mechanistically unique pathways that are not rivaled by mainstream catalysis. Primarily, the ability to convert photochemical energy into single electron oxidation and reduction events provides a new dimension for chemists to consider when choosing how to activate a molecule or approach a complex synthesis. Since most organic molecules do not absorb light in the visible region, they are impervious to direct visible light photochemistry, which provides an opportunity for photocatalysis in which a visible light absorbing compound can serve as a mediator. In this Account, we discuss the consequences of catalyst mediated, photoinduced electron transfer to several classes of reducible arenes. While the bulk of the work discussed within this Account utilizes iridium-based photocatalysts, in principle the chemistry is not limited to this class of photocatalyst, and the principles should be more general. Instead, this Account focuses largely on the consequences of single electron transfer to poly- and perfluorinated arenes and 2-halo azoles. Electron transfer converts these stable molecules into reactive intermediates whose behavior often depends entirely on the identity of the halogen that undergoes substitution. The result is both diverse chemistry and an alternative way of thinking about the chemical reactivity of these motifs. Specifically, we discuss our efforts and those of others to develop strategies for the generation of radicals or radical anions from perfluoroarenes and azoles and the behavior of these intermediates as implied by reactions in which they participate. The divergent pathway is illustrated by 2-bromoazoles, which yield azolyl radicals and can be utilized for addition to π-bonds, while use of the 2-chloroazole substrate leads to an entirely different reaction profile. Under the appropriate reaction conditions, the reactive and transient intermediates are useful coupling partners and often provide unrivaled access to new chemical space. The odd electron species can form challenging bonds with minimal prefunctionalization of the coupling partner. For instance, some of the intermediates can be utilized for C-H functionalizations to selectively make crowded amines or to synthesize biarenes substituted at every ortho position. While photocatalysis is not the only manner of accomplishing electron transfer, the catalytic generation of the reactive species in which the concentration of the transient odd electron species is kept low, provides a synthetic handle that can be used to improve reaction outcomes. This is elegantly demonstrated in a number of examples in which redox sensitive groups located on substrates survive the reaction. In addition, the underlying basic concepts associated with radical anion fragmentation are reviewed and provide the backdrop for discussion throughout the Account.

Application of capillary immunoelectrophoresis revealed an age- and gender-dependent regulated expression of PrPC in liver.

The cellular prion protein (PrPC) is a glycoprotein, anchored to the plasma membrane and abundantly expressed in the central nervous system. The expression of PrPC in the peripheral tissues is low and only little information is available on its functions in the nonneuronal tissues. The antioxidant function of PrPC during the activation of hepatic stellate cells has already been reported. Therefore, the aim of the study was to expand our knowledge on the functions of PrPC by detailed characterization of its expressional profile in the liver. In a combined strategy by using capillary immunoelectrophoresis and standard techniques, we have shown a sexually dimorphic expression of PrPC in mice and human liver tissues. Further, we showed a significant age-dependent upregulation of PrPC expression in the liver of 14- and 9-month-old mice as compared to 3 months of age. Therefore, this study may provide new insights into the gender-specific role of PrPC in the liver, which may further be linked to its protective role against oxidative stress during aging. In addition, the current study also shows an application of immunoelectrophoresis with a low coefficient of variation to analyze the miniscule amount of PrPC in the mouse liver tissue.

Do Uro-Oncology Day Care Procedures Need to Be Differed during COVID-19 Pandemic?-An Experience from Tertiary Cancer Care Center.

Mahendra PalBackground The SARS-CoV-2 virus pandemic has affected millions all over the world in very short span and changed the way how health care system work across the globe. It is essential to continue cancer treatment in spite of such pandemics. Various recommendations were proposed for cancer management based on risk stratification, however, in urological malignancies, day care procedures (DCPs) are a part of complete spectrum of cancer care and standard operating procedures (SOPs) for day care procedures (DCPs)in oncology is lacking at present. Materials and Methods This is an institutional review board approved retrospective observational analytical study performed in tertiary cancer care center, with aim to assess the impact of COVID-19 on Uro-oncology day care procedures (U-DCPs)in terms of changes in appointments and actual U-DCPs performed, demographic changes such as sex ratio and age wise attendance in pre and post lockdown period and to provide a SOPs to accomplishU-DCPsefficiently in pandemics. Results There was 67.89% and 68.16% reduction in total numbers of appointment and performed U-DCPs. A statistically significant difference was found in cystoscopy, intravesicalinstallation and miscellaneous UDCPs. Overall, 4.45% reduction and 4.52% increase in male and female patients underwent UDCPs respectively, M:F ratio reduced from 3.58:1 to 2.79:1 and 30% to 50% reduction in overall patient statistics in post lockdown compare to pre lockdown procedures. For various age groups there was a statistically significant change in the number for males underwent cystoscopy in (p<0.001), Intravesical therapies (p<0.001) and miscellaneous procedures(p< 0.004). Conclusion We are now coming up to the fact that effective management of healthcare system during pandemics require establishment and effective implementation of standard protocols. Routine major urological surgical care is continued using a tiered standard of protocols (SOPs) and adequate precautions. This study may provide an insight into impact of COVID-19 on UDCPs and what precautions and strategies can be institutionalized so that the patients and the health care workers remain protected from contracting infection while in performing DCPs during pandemic or similar circumstances.

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial.

PURPOSE: The POP-RT phase 3 randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiation therapy versus prostate-only radiation therapy for high and very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. METHODS AND MATERIALS: Late urinary toxicity and the cumulative severity of each symptom during the follow-up period were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15, V65, V68Gy) in the approved radiation therapy plans was compared with urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. RESULTS: Complete combined data for late urinary symptoms and dosimetry was available for 193 of 224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for whole pelvic radiation therapy and prostate-only radiation therapy (5.2% vs 4.1%, P = .49), and grade 2 toxicity was 31.3% versus 22.7%, respectively (P = .12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior transurethral resection of prostate, grade 2+ acute urinary toxicity, low bladder dose (V10Gy), and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. CONCLUSIONS: During long-term follow-up, whole pelvic radiation therapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiation therapy. The long-term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

Clinical Profile and Outcomes of Carcinoma Penis Patients Receiving Systemic Therapy at an Indian tertiary care Center: A Retrospective Observational Study.

BACKGROUND: Penile cancer is a rare malignancy with scant data on the impact of systemic therapy on outcomes. METHODS: Retrospective observational study of patients with a histological diagnosis of carcinoma penis treated with systemic therapy at the Tata Memorial Centre (Mumbai, India) between August 2010 and February 2018. Primary objective was overall survival (OS); secondary objectives included assessment of clinical characteristics, treatment approaches, and toxicity profiles. RESULTS: We included 91 patients with penile carcinoma who received systemic therapy at our center. Intent of therapy was curative in 71 patients (78%), and palliative in 20 (22%). Median age was 57 years (interquartile range [IQR], 50-65.5) for curatively treated patients and 58.5 years (IQR, 44-65.2) for those with advanced disease. Common presenting symptoms were lumps (70%), and pain (57%). Neoadjuvant chemotherapy (NACT) with paclitaxel + platinum was administered to 19 patients (20.9%), of which 7 (37%) attained complete or partial response. Six patients (31.5%) underwent R0 surgery post-NACT. All 71 patients underwent primary surgery; 47 (66.2%) undergoing partial penectomy. Of the 20 patients treated with palliative first-line chemotherapy, 4(20%) attained a partial response. Median OS of patients treated in curative and palliative settings was 33.8 months (95% CI, 17.2-not recorded) and 11.4 months (95% CI, 9.53-23.3), respectively. CONCLUSIONS: Patients with penile cancer treated with systemic therapy have poor outcomes. Little over a third of the patients respond to neoadjuvant chemotherapy and those with advanced disease have poor survival despite systemic therapy, emphasizing the need for early detection and optimum management of primary and nodal disease.

Late Urinary Toxicity After Extreme or Moderate Hypofractionated Prostate Radiation Therapy in Patients With Prior Transurethral Resection of Prostate.

PURPOSE: To study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiation therapy. METHODS AND MATERIALS: Patients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity-modulated radiation therapy (moderate hypofractionated radiation therapy [MHRT], stereotactic body radiation therapy [SBRT]), were included in this study. Severity and duration of urinary symptoms observed during serial follow-up after at least 3 months from radiation therapy were graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 using information from a prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analyzed with univariable and multivariable binary logistic regression. RESULTS: A total of 203 eligible patients were included (MHRT = 114, 64-68 Gy/25#; SBRT = 89, 35-37.5 Gy/5#). Median time from TURP to radiation therapy was 10 months (IQR, 7-16 months), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17 cc (IQR, 0.5-1.35 cc), whereas in MHRT and SBRT groups it was 1.03 cc (IQR, 0.4-1.15 cc) and 1.27 cc (IQR, 0.5-1.4 cc), respectively. At a median follow-up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n = 17) and 23.2% (n = 47), respectively. Grade 3 symptoms were observed at median 29 months (IQR, 19-62 months) after radiation therapy completion, lasting for a median duration of 8 months (IQR, 2-14 months). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiation therapy, fraction size, prostate volume, TURP to radiation therapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. CONCLUSIONS: In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiation therapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiation therapy.

A Glimpse at the Quinoline-Hybridization Approach for the Development of New Antimalarials.

One of the most fatal infectious diseases, malaria, still poses a threat to about half of the world's population and is the leading cause of death worldwide. The use of artemisinin-based combination therapy has helped to significantly reduce the number of deaths caused by malaria, but the emergence of drug resistance threatens to undo this gain. In a bid to boost adherence, several new combination therapies with effectiveness against drug-resistant parasites are currently being tested in clinical settings. Nevertheless, notwithstanding these gains, malaria must be completely eradicated by a concerted international effort on several fronts. Quinoline-based compounds were the cornerstone of malaria chemotherapy until recently when resistance to these drugs severely hampered efforts to achieve a "Zero Malaria" world. The inappropriate use of available antimalarials is one of the factors responsible for resistance development and treatment failure, warranting the search for new chemical entities and alternative approaches to combat this threat. A vast number of solutions have emerged and one of them, quinoline-hybridization, is an effective method for introducing structural diversity, resulting in molecules with improved biological activities, reduced drug resistance, fewer drug-drug interactions, and improved safety and pharmacokinetic profiles. Choosing the ideal target combination and achieving a balanced activity toward them while preserving drug-like properties are the key challenges in the development of molecular hybrids. This review examines the highlights of quinoline hybridization, with some of the hybrids exhibiting remarkable in vitro and in vivo activities, emphasizing that it is a useful method for developing new anti-malarial lead compounds.

Effect of hyperthermic intraperitoneal chemotherapy on survival and recurrence rates in advanced gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Around 5-20% of patients who undergo surgery for advanced gastric cancer (AGC), which invades into the muscularis propria or beyond, have peritoneal carcinomatosis. The peritoneal recurrence rate is 10-54%, which is associated with a poor prognosis. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in AGC with and without peritoneal carcinomatosis is not clearly defined. METHODS: The authors conducted a meta-analysis, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, of the clinical trials and high-quality nonrandomized studies evaluating the role of HIPEC in AGC over the last 10 years. The studies were searched in PubMed, EMBASE, MEDLINE, and Cochrane databases between January 2011 to December 2021. Clinical data including overall survival, recurrence free survival, overall recurrence rate, peritoneal recurrence rate, and complications analyzed using RevMan 5.4. RESULTS: Six randomized controlled trials and 10 nonrandomized studies, comprising a total of 1700 patients were included. HIPEC was associated with significantly improved OS at 3 [odd ratio (OR) 1.89, 95% CI: 1.17-3.05] and 5 years (OR 1.87, 95% CI: 1.29-2.71). HIPEC was associated with reduced overall recurrence (OR 0.49, 95% CI: 0.31-0.80) and peritoneal recurrence (OR 0.22, 95% CI: 0.11-0.47). HIPEC was not associated with increased complications. The occurrence of postoperative renal dysfunction was significantly higher in the HIPEC group (OR 3.94, 95% CI: 1.85-8.38). CONCLUSION: The role of HIPEC in AGC has evolved over the past decade. HIPEC may improve survival rates and reduce recurrence rates in patients with AGC, without significant increase in complications and with a favorable impact on 3 and 5-year survival.

Structural insights into actin isoforms.

Actin isoforms organize into distinct networks that are essential for the normal function of eukaryotic cells. Despite a high level of sequence and structure conservation, subtle differences in their design principles determine the interaction with myosin motors and actin-binding proteins. Therefore, identifying how the structure of actin isoforms relates to function is important for our understanding of normal cytoskeletal physiology. Here, we report the high-resolution structures of filamentous skeletal muscle α-actin (3.37 Å), cardiac muscle α-actin (3.07 Å), ß-actin (2.99 Å), and γ-actin (3.38 Å) in the Mg2+·ADP state with their native post-translational modifications. The structures revealed isoform-specific conformations of the N-terminus that shift closer to the filament surface upon myosin binding, thereby establishing isoform-specific interfaces. Collectively, the structures of single-isotype, post-translationally modified bare skeletal muscle α-actin, cardiac muscle α-actin, ß-actin, and γ-actin reveal general principles, similarities, and differences between isoforms. They complement the repertoire of known actin structures and allow for a comprehensive understanding of in vitro and in vivo functions of actin isoforms.

The protein actin is important for many fundamental processes in biology, from contracting muscle to dividing a cell in two. As actin is involved in such a variety of roles, human cells have slightly different versions of the protein, known as isoforms. For example, alpha-actin is vital for contracting muscle, while beta- and gamma-actin drive cellular processes in non-muscle cells. In order to carry out its various functions, actin interacts with many other proteins inside the cell, such as myosin motors which power muscle contraction. These interactions rely on the precise chain of building blocks, known as amino acids, that make up the actin isoforms; even subtle alterations in this sequence can influence the behavior of the protein. However, it is not clear how differences in the amino acid sequence of the actin isoforms impact actin's interactions with other proteins. Arora et al. addressed this by studying the structure of four human actin isoforms using a technique called cryo-electron microscopy, where the proteins are flash-frozen and bombarded with electrons. These experiments showed where differences between the amino acid chains of each isoform were located in the protein. Arora et al. then compared their structures with previous work showing the structure of actin bound to myosin. This revealed that the tail-end of the protein (known as the N-terminus) differed in shape between the four isoforms, and this variation may influence how actin binds to others proteins in the cell. These results are an important foundation for further work on actin and how it interacts with other proteins. The structures could help researchers design new tools that can be used to target specific isoforms of actin in different types of laboratory experiments.

Patterns of Utilization and Outcomes of Perioperative Chemotherapy in Patients With Locally Advanced-urothelial Bladder Cancer (LABC)-Real World Data From an Indian Tertiary Care Cancer Center.

AIM: Optimal utilization of perioperative systemic therapy in locally advanced bladder cancer (LABC) holds the key in improving the survival outcomes. We aim to analyze the oncological outcomes of clinically locally advanced urothelial bladder cancer patients treated with neoadjuvant (NACT) or adjuvant chemotherapy or without any systemic therapy in the perioperative period of radical cystectomy. METHODS & MATERIAL: We retrospectively analyzed the medical records of patients with cancer of the urinary bladder diagnosed between 2012 and 2020. The demographic profile, and the treatment received, was recorded for all patients. Oncological outcomes of the patients based on these variables were analyzed. RESULTS: Two hundred and twenty nine (229) locally advanced bladder cancer patients were included in the study. Eighty eight (38%) of them underwent upfront radical cystectomy and 141 (62%) received neoadjuvant chemotherapy (NACT). With a median follow-up of 27 months, the 2-year DFS in either of the groups was 65.4% and 67.1% respectively (P - 0.373). In the multivariate analysis, the pathological lymph nodal status and lymph vascular invasion (LVI) status influenced the DFS. The initial modality of management chosen did not affect the outcome. (HR - 0.688; 95% CI: 0.38-1.21). The commonest reason for not receiving NACT was Cisplatin ineligibility due to malignant obstructive uropathy and a subgroup analysis of this set of patients also did not show any significant difference in 2 year DFS compared to those who received NACT. CONCLUSION: A significant proportion of patients with LABC are unable to receive the recommended neoadjuvant chemotherapy and obstructive uropathy is the commonest reason for this in our centre. In our single centre series upfront radical cystectomy followed by adjuvant platinum based therapy had an outcome similar to neoadjuvant chemotherapy in LABC patients, in patients who were unable to receive the same due to various reasons.

Variations in Penile Cancer Management: Results From the Global Society of Rare Genitourinary Tumors Survey.

INTRODUCTION: There is paucity of evidence and consensus on various aspects of management of penile cancer (PeCa), which is intuitive considering the rarity of this disease. We present here the details of an online survey conducted by the Global Society of Rare Genito-urinary Tumors (GSRGT) with the aim of capturing the variations in PeCa care across different regions of the world. MATERIALS AND METHODS: An online questionnaire was developed by experts within the GSRGT and then circulated via email in English and Spanish versions to clinicians dealing with PeCa. Respondents were allowed 8 weeks to reply. RESULTS: We received 102 responses; the majority of them were from South America (37.2%) followed by North America and Asia (17.6% each). Only 11.7% of the respondents treated more than 25 patients with PeCa annually. Total penectomy is performed by 21.5% of the respondents in >50% of their patients. Less than a fifth of the experts (19.6%) responded that >50% of their patients are clinically node-negative (cN0) at presentation. For intermediate-risk cN0 patients (T1 G2 cancer), about a third of the experts chose surveillance. For invasive inguinal staging, the options of Dynamic Sentinel Lymph Node Biopsy (DSNB), Modified Inguinal Lymph Node Dissection (MILD), Superficial Inguinal Lymph Node Dissection (SILD), and Video-Endoscopic Inguinal Lymphadenectomy (VEIL) were chosen by 28.4%, 26.4%, 31.3%, and 13.7% of the respondents respectively. Considerable variation was seen in the worldwide use of these techniques. For clinically node-positive patients, respondents were in favor of giving adjuvant chemotherapy instead of neoadjuvant chemotherapy, except for cN3 patients. CONCLUSION: The results of this questionnaire objectified the variations in global practices in the management of PeCa. This serves as the baseline information which can help prioritize research areas for multinational collaborative efforts, a key mission of the GSRGT.