Prognostic significance of Klotho expression in patients with renal cell carcinoma.

INTRODUCTION: Various molecular markers have been investigated in renal cell carcinoma (RCC) without significant reliability. We analyzed Klotho (tumor suppressive protein) expression in RCC to investigate its association with tumor-stage, grade, disease-free-survival (DFS) and overall-survival (OS). METHODS: Data of histologically confirmed patients of RCC with complete clinical follow-up were retrieved from Medical-Record-Library. Tissue sections of tumor and normal parenchyma were prepared from the blocks. Immunohistochemical studies for Klotho were done with commercially available kit (EPR6856, Ab181373; Abcam, Cambridge MA, USA). Klotho expression was scored between 0-3 and grouped into weak/absent (0, 1) and moderate/strong (2, 3). Tumors stages and grades were grouped into low stage (I and II) and high stage (III and IV) and into low grade (grade 1 and 2) and high grade (grade 3 and 4) according to WHO/ISUP grading. The histopathologists were blinded as to the clinical and follow-up data. Various prognostic factors were analyzed with respect to Klotho expression. Kaplan-Meier curves were created for DFS and OS. RESULTS: Fifty-four patients of mean age 55.15 ± 13.34 years and M:F ratio of 1.8:1 were included. Normal renal tissue had strong expression of Klotho in all. In tumor tissue 20 (37%) had negative, 7 (13%) had weak, 14 (25.9%) had moderate and 13 (24.1%) had strong Klotho expression. Significantly more patients had absent/weak Klotho expression with higher grade (16/24 (66.7%) vs 7/25 (28%); p = 0.007), higher stage (22/33 (66%) vs 5/21 (23.8%); p = 0.002), LVI (12/14 (85.7%) vs 2/14 (14.3%); p = 0.002), sinus-fat-invasion (16/21 (76.2%) vs 5/21 (23.8%); p = 0.002), renal-vein-involvement (14/18 (77.8%) vs 4/18 (22.2%); p = 0.004), necrosis (17/26 (65.3%) vs 9/26 (34.6%); p = 0.029) and metastasis (8/9 (88.9%) vs 1/9 (11.1%); p = 0.01). Median DFS and OS were significantly lower in patients with weak/absent Klotho expression (12 vs 23 months, p = 0.023 and 15 vs 33 months, p = 0.006 respectively). Kaplan-Meier curves showed lower estimated DFS and OS in patients with weak/absent expression. CONCLUSIONS: We conclude that Klotho expression in renal tumor could be a good prognostic marker in patients with RCC.

Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting.

Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erß), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen. Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERß. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERß positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERß-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERß-negative group (log-rank test P = 0.035). Conclusion: AR and ERß positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERß-positive tumors recurred as compared to AR-positive and ERß-negative patients. PFS was significantly lower in ERß-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

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.

Extensively Drug-Resistant Klebsiella pneumoniae Associated with Complicated Urinary Tract Infection in Northern India.

Klebsiella pneumoniae (Kp), which is associated with hospital-acquired infections, is extensively drug-resistant (XDR), making treatment difficult. Understanding the genetic epidemiology of XDR-Kp can help determine its potential to be hypervirulent (hv) through the presence of siderophores. We characterized the genomes of 18 colistin-resistant XDR-Kp isolated from 14 patients with complicated tract infection at an Indian healthcare facility. The 18 organisms comprised the following sequence types (STs): ST14 (n = 9), ST147 (n = 5), ST231 (n = 2), ST2096 (n = 1), and ST25 (n = 1). Many patients in each ward were infected with the same ST, suggesting a common source of infection. Some patients had recurrent infections with multiple STs circulating in the ward, providing evidence of hospital transmission. ß-lactamase genes (blaCTX-M-1, blaSHV, and blaampH) were present in all isolates. blaNDM-1 was present in 15 isolates, blaOXA-1 in 16 isolates, blaTEM-1D in 13 isolates, and blaOXA-48 in 3 isolates. Disruption of mgrB by various insertion sequences was responsible for colistin resistance in 6 isolates. The most common K-type among isolates was K2 (n = 10). One XDR convergent hvKp ST2096 mutation (iuc+ybt+blaOXA-1+blaOXA-48) was associated with prolonged hospitalization. Convergent XDR-hvKp has outbreak potential, warranting effective antimicrobial stewardship and infection control.

Potential role of 68Ga-PSMA PET/CT in metastatic renal cell cancer: A prospective study.

PURPOSE: Prostate-specific membrane antigen (PSMA), in addition to its utility in prostate cancer, is also an angiogenic imaging marker for hypervascular tumors like renal cell carcinoma (RCC). Our study aims to assess the potential role of 68Ga-PSMA-11 positron emission tomography (PET)/CT in metastatic RCC and compare it with contrast-enhanced computed tomography (CECT). METHODS: Biopsy-proven RCC patients with known or suspected distant metastases who underwent 68Ga-PSMA-11 PET/CT for staging/restaging were prospectively recruited. Those patients who had undergone 18F-FDG PET/CT within six weeks of 68Ga-PSMA PET/CT were also included retrospectively for comparative analysis. A patient-based and lesion-based analysis was done to compare the lesion detection rates of CECT, 68Ga-PSMA-11 PET and 18F-FDG PET. PET-based quantitative parameters were also compared between both the PET modalities. Impact of baseline parameters on survival was assessed using Cox regression analysis. A p-value of < 0.05 was considered significant. RESULTS: Thirty-seven patients with median age 60 years ± 13 years (range = 26-76 years) were included in the study. Twenty-seven patients had clear cell (cc) RCC, six had papillary RCC (pRCC), and one each had an eosinophilic variant of ccRCC, collecting duct RCC, translocation RCC and poorly differentiated RCC. 68Ga-PSMA-11 PET performed better in detecting marrow and equivocal bone lesions and worse in detecting liver lesions compared to CECT. 68Ga-PSMA-11 PET-based angiogenic tumor burden estimation using Total Lesion-PSMA (TL-PSMA) and PSMA-Total volume (PSMA-TV) had a prognostic impact on the survival of patients. 68Ga-PSMA-11 PET also detected more lesions and showed significantly higher SUVmax than 18F-FDG PET. CONCLUSION: 68Ga-PSMA-11 PET/CT performs better than CECT and 18F-FDG PET/CT in metastatic evaluation and has prognostic value in the management of clear cell RCC.

Accuracy of combined multi-parametric MRI and PSMA PET-CT in diagnosing localized prostate cancer: newer horizons for a biopsy-free pathway.

INTRODUCTION: Prostate-specific antigen (PSA) is a reliable biomarker for identification of prostate cancer, although a biopsy is still the gold standard for detecting prostate cancer. Similar to higher PIRADS lesions on MRI, the maximal standard uptake value (SUV max) on PSMA PET is linked to a higher likelihood of prostate cancer. Can an mpMRI in conjunction with PSMA PET Scan accurately predict prostate cancer and further trigger omission of biopsy similar to other solid organ urological malignancies? METHODS: Ga-68 PSMA PET and mpMRI were performed for each patient who was a part of this retrospective study. The PET-positive lesion's maximum standardized uptake value (SUVmax) was recorded. Prostate biopsies were performed on patients who had PSMA PET avid lesions and a PIRADS score of 4 or 5. Robot-assisted radical prostatectomy (RARP) was afterward performed on patients who had cancer on their prostate biopsy. The prostatectomy specimen's histopathological information was recorded. Cutoff values and correlations between the variables were determined using the ROC curves and Pearson's correlation test. RESULT: On the basis of suspicious DRE findings or elevated PSA, 70 men underwent mpMRI and PET scans. PIRADS 4 patients had a median (IQR) SUVmax of 8.75 (11.95); whereas, PIRADS 5 patients had an SUVmax of 24.5 (22). The mean SUVmax for patients whose biopsies revealed no cancer was 6.25 ± 1.41. With an AUC of 0.876 on the ROC curve, it was found that there was a significant positive correlation between the results of the mpMRI and PET scans and those of the histopathological investigation. A SUVmax ≥ 8.25 on PSMA PET for a PIRADS 4/5 lesion on mpMRI will aid in correctly predicting malignancy, with a sensitivity of 82.8% and specificity of 100%. CONCLUSION: The findings of this study were positive and indicated that patients with a high suspicion of prostate cancer on mpMRI and PSMA PET (PIRADS ≥ 4 and SUVmax ≥ 8.25). This study substantiates the fact that a combination of mpMRI and PSMA PET can accurately predict localized prostate cancer.

[177Lu]Lu-PSMA-617 Versus Docetaxel in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: Final Survival Analysis of a Phase 2 Randomized, Controlled Trial.

The prostate-specific membrane antigen (PSMA) inhibitor [177Lu]Lu-PSMA-617 has been previously demonstrated to be noninferior to docetaxel in achieving a biochemical response in chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Here, we report the final analysis of overall survival (OS) for a phase 2 randomized, controlled trial. Methods: Forty chemotherapy-naïve, PSMA-positive metastatic castration-resistant prostate cancer patients were randomly assigned to [177Lu]Lu-PSMA-617 (n = 20) or docetaxel (n = 20). Thirty-five patients received treatment per the protocol. Survival analysis was done using Kaplan-Meier curves and the Cox regression model. Results: The mean follow-up duration was 33.4 mo. In intention-to-treat analysis, the median OS for the [177Lu]Lu-PSMA-617 and docetaxel arms was 15.0 mo (95% CI, 9.5-20.5 mo) and 15.0 mo (95% CI, 8.1-21.9 mo), respectively (P = 0.905). In per-protocol analysis, the median OS was 19.0 mo (95% CI, 12.3-25.7 mo) versus 15.0 mo (95% CI, 8.1-21.9 mo), respectively (P = 0.712). No significant difference in OS was observed between the 2 arms across the analyzed subgroups. Conclusion: Long-term outcomes with [177Lu]Lu-PSMA-617 administered earlier in the prechemotherapy setting are comparable to those with docetaxel.

Preoperative Predictors for the Presence of Motile Spermatozoa in the Epididymis and Patency of Anastomosis during Microsurgical Vasoepididymal Anastomosis in Patients with Obstructive Azoospermia.

Background: Following microsurgical vaso-epididymal anastomosis (VEA), anastomotic patency with sperm returning to the ejaculate is not always present and may even be delayed. The presence of motile spermatozoa is highly suggestive of future patency following surgery. Aims: We prospectively analyse the factors that could predict motile spermatozoa at the epididymis intraoperatively and predictors of patency in patients with obstructive azoospermia (OA) undergoing microsurgical VEA. Settings and Design: Department of Urology of a tertiary care centre in Northern India. It is a prospective observational study. Materials and Methods: Over a 2-year period (July 2019 to June 2021), 26 patients with idiopathic OA were enrolled in the study. Twenty patients underwent microsurgical VEA. Patients were divided into two groups based on the presence/absence of intraoperative motile spermatozoa. Statistical Analysis Used: Analysis of preoperative and intraoperative factors was done using the Mann-Whitney U-test, Chi-squared test and Fischer exact test. Results: Out of 20 patients, 5 (group 2) had intraoperative motile spermatozoa in the epididymal fluid and 15 (group 1) had nonmotile spermatozoa. Low luteinising hormone (LH) levels (P = 0.01) and high testosterone levels (P = 0.05) were the predictive of presence of motile spermatozoa in epididymal fluid. Mean follow-up was 9 months (6-18 months). Predictors of higher patency were grade 2 epididymis (firm, turgid and tense) (P = 0.003), low LH levels (P = 0.03), low sertoli cell index (P = 0.006), high sperm-Sertoli index (P = 0.002) and better surgeon satisfaction (P = 0.01). Conclusion: Low LH levels and high testosterone levels may be predictive of the presence of motile spermatozoa in epididymal fluid. Firm, turgid and tense epididymis, low Sertoli cell index, high sperm-Sertoli index and surgeon satisfaction suggest a greater chance of success after VEA for idiopathic azoospermia.

Epididymo-orchitis Presenting as Bilateral Hydrocele in a Young Adult.

We present a case of young patient who presented with a progressive scrotal swelling and low-grade fever. An ultrasound of the scrotum revealed multiple small well-defined hypoechoic lesions in both testes with bulky epididymis and bilateral hydrocele. The final diagnosis was confirmed on cytology. The typical imaging findings may help to reach the diagnosis and to plan the further management in such cases.

U-DAVIS-Deep Learning Based Arm Venous Image Segmentation Technique for Venipuncture.

Arm Venous Segmentation plays a crucial role in smart venipuncture. The difficulties faced in locating veins for intravenous procedures can be diminished using computer vision for vein imaging. To facilitate this, a high-resolution dataset consisting of arm images was curated and has been presented in this study. Leveraging the ability of Near Infrared Imaging to easily detect veins, ambient lighting conditions were created inside a small enclosure to capture the images. The acquired images were annotated to create the corresponding masks for the dataset. To extend the scope and assert the usability of the dataset, the images, and corresponding masks were used to train an image segmentation model. In addition to using basic preprocessing and image augmentation based techniques, a U-Net based algorithmic architecture has been used to facilitate the task of segmentation. Subsequently, the results of performing image segmentation after applying the preprocessing methods have been compared using various evaluation metrics and have been visualised in the study. Furthermore, the possible applications of the presented dataset have been investigated in the study.

Robot-assisted partial nephrectomy for moderate to highly complex renal masses. A systematic review and meta-analysis.

Introduction: Multiple studies have been published recently assessing feasibility of robot-assisted partial nephrectomy (RAPN) for moderate to highly complex renal masses. Some studies have even compared partial nephrectomy (PN) performed through various modalities such as open PN (OPN) versus RAPN and laparoscopic PN (LPN) versus OPN. The primary aim of this review was to analyze perioperative outcomes such as warm ischemia time (WIT), duration of surgery, estimated blood loss (EBL), complications, blood transfusion, length of stay, and margin status following RAPN for complex renal masses. Another objective was to compare perioperative outcomes following various surgical modalities, i.e., OPN, LPN, or RAPN. Methods: Literature search was conducted to identify studies reporting perioperative outcomes following RAPN for moderate (Radius, Endophytic/Exophytic, Nearness, Anterior/posterior location [RENAL] score 7-9 or Preoperative Aspects of Dimension used for anatomic classification [PADUA] score 8-9) to high complexity renal masses (RENAL or PADUA score ≥ 10). Meta-analysis of robotic versus OPN and robotic versus LPN was also performed. Study protocol was registered with PROPSERO (CRD42019121259). Results: In this review, 22 studies including 2,659 patients were included. Mean duration of surgery, WIT, and EBL was 132.5-250.8 min, 15.5-30 min, and 100-321 ml, respectively. From pooled analysis, positive surgical margin, need for blood transfusion, minor and major complications were seen in 3.9%, 5.2%, 19.3%, and 6.3% of the patients. No significant difference was noted between RAPN and LPN for any of the perioperative outcomes. Compared to OPN, RAPN had significantly lower EBL, complications rate, and need for transfusion. Conclusions: RAPN for moderate to high complexity renal masses is associated with acceptable perioperative outcomes. LPN and RAPN were equal in terms of perioperative outcomes for complex masses whereas, OPN had significantly higher blood loss, complications rate, and need for transfusion as compared to RAPN.

Whole genome sequencing and in vitro activity data of Escherichia phage NTEC3 against multidrug-resistant Uropathogenic and extensively drug-resistant Uropathogenic E. coli isolates.

This data article describes the whole-genome sequencing and in vitro activity data of Escherichia phage NTEC3 isolated from a community sewage sample in Chandigarh, India. The phage NTEC3 was active against multi-drug-resistant (MDR) and extensively drug-resistant (XDR) biofilm-forming Uropathogenic Escherichia coli (UPEC) strains. The genome of this phage was linear, double-stranded, and 44.2 kb long in size. A total of 72 ORFs (open reading frames) were predicted and 30 ORFs were encoded for functional proteins. The phage belonged to the Kagunavirus genus of the Siphoviridae family. Phylogenetic analysis using DNA polymerase was performed to understand the phage evolutionary relationships. Genes encoding for lysogeny, virulence, toxins, antibiotic resistance, and the CRISPR/CRISPR-like system were not found during screening. The annotated genome was deposited in Genbank under the accession number OK539620.

A phase II study of neoadjuvant chemotherapy followed by organ preservation in patients with muscle-invasive bladder cancer.

Objective: Conservative approaches in muscle-invasive bladder cancer (MIBC) have been evolved to avoid aggressive surgery, but are limited to elderly, frail, and patients medically unfit for surgery. Our study aimed to assess the response rate of neoadjuvant chemotherapy (NACT) before radiotherapy (RT) in MIBC patients. Methods: Forty patients with urothelial carcinoma of stage T2-T4a, N0, M0 were enrolled between November 2013 and November 2015, and treated with three cycles of NACT with gemcitabine-cisplatin. Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients who achieved complete response (CR) and partial response (PR) >50% were treated with radical RT, and those who had PR <50%, stable disease (SD), and progressive disease (PD) underwent radical cystectomy (RC). Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model. Results: After NACT, 35 (87.5%) patients achieved either PR >50% or CR, and were treated with RT. Five (12.5%) patients who had PR <50%, SD, or PD underwent RC. All patients who received radiation showed CR after 6 weeks. Median follow-up was 43 months (range: 10-66 months) and median overall survival (OS) was not reached. Three-year OS, local control, and disease-free survival were 70.1%, 60.9%, 50.6%, respectively, and 50% of patients preserved their functioning bladder. Three-year OS rate was 88.9% in patients who achieved CR to NACT, 73.1% in patients with PR ≥50% and 40% in patients with PR <50%. Conclusion: NACT followed by RT provides a high probability of local response with bladder preservation in CR patients. Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.

[68 Ga]Ga-PSMA-11 Small Bowel Uptake in Crohn's Disease: Revisiting the "Non-specificity" of PSMA Ligands.

The rapidly evolving clinical utility of prostate-specific membrane antigen (PSMA) PET/CT as an imaging modality for prostate cancer (PCa) has brought to the forefront a multitude of non-prostatic diseases also exhibiting PSMA radioligand uptake. We report a case of a 71-year-old male with PCa who underwent PSMA PET/CT for recurrence evaluation. The scan demonstrated [68 Ga]Ga-PSMA-11 uptake in the distal ileum. Retrospective enquiry revealed that the patient was a known case of Crohn's disease. This case highlights an uncommon finding of PSMA radioligand uptake in the distal small bowel (non-prostatic benign pathological uptake) in a patient with known Crohn's disease, which may be misinterpreted in the evaluation of PCa.

Current practice patterns in the perioperative management of patients undergoing radical cystectomy: Results from a global survey.

OBJECTIVE: To determine current practice patterns and adherence to various components of enhanced recovery after surgery in cystectomy (ERAC) protocol for peri-operative management of radical cystectomy patients through a global survey. METHODS: A survey containing 25 questions and addressing 15 of the 22 items of the ERAC protocol was developed and disseminated through Email to the urologists with recent bladder cancer publications. The mailing list was generated by retrieving Email-ids of corresponding authors of articles using the keyword "cystectomy" in Scopus from January 2018 to October 2020. RESULTS: The survey was completed by 443 respondents across the globe. About 51.5% of respondents used some form of bowel preparation. A minority used carbohydrate loading (29.8%) and Alvimopan (13.3%). A short duration of nil by mouth was practised by 28.9%. For antibiotic prophylaxis, 51.7% used one, and 42% used two antibiotics. Duration of antibiotics was 24 hours, 48 hours, and >48 hours for 47.6%, 16.9%, and 35.4%, respectively. For peri-operative analgesia, 43.6% used non-steroidal anti-inflammatory drugs, 9.3% opioids and 40.6% combination of both. Pharmacological thrombo-prophylaxis was routinely used by 74.7% respondents. There was significant variability in ERAC and non-ERAC components according to region of practice; The open surgical approach was most commonly used in Africa (92%), whereas it was the robotic approach in North America (or America?) (41%). The use of bowel preparation was higher in Asia (58%) and Africa (65%). Alvimopan use was more common in North America (58%). Most used 1 or 2 prophylactic antibiotics but the duration was shorter (<24 hours) in the Americas and European (58%-83%) compared to Asia and Africa (15%-35%). CONCLUSION: There is high variability in the use of different ERAC components. Other than the timely removal of the abdominal drain and the use of thromboprophylaxis, the overall adherence of ERAC components is low.

Quantifying prognosis severity of COVID-19 patients from deep learning based analysis of CT chest images.

The COVID-19 pandemic has affected all the countries in the world with its droplet spread mode. The colossal amount of cases has strained all the healthcare systems due to the serious nature of infections especially for people with comorbidities. A very high specificity Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) test is the principal technique in use for diagnosing the COVID-19 patients. Also, CT scans have helped medical professionals in patient severity estimation & progression tracking of COVID-19 virus. In study we present our own extensible COVID-19 viral infection tracking prognosis technique. It uses annotated dataset of CT chest scan slice images created with the help of medical professionals. The annotated dataset contains bounding box coordinates of different features for COVID-19 detection like ground glass opacities, crazy paving pattern, consolidations, lesions etc. We qualitatively identify the severity of the patient for later prognosis stages in our study to assist medical staff for patient prioritization. First we detected COVID-19 positive patients with pre-trained Siamese Neural Network (SNN) which obtained 87.6% accuracy, 87.1% F1-Score & 95.1% AUC scores. These metrics were achieved after removal of 40% quantitatively highly similar images from the COVID-CT dataset. This reduced dataset was further medically annotated with COVID-19 features for bounding box detection. After this we assigned severity scores to detected COVID-19 features and calculated the cumulative severity score for COVID-19 patients. For qualitative patient prioritization with prognosis clinical assistance information, we finally converted this score into a multi-classification problem which obtained 47% weighted-average F1-score.

Characterization, genome analysis and in vitro activity of a novel phage vB_EcoA_RDN8.1 active against multi-drug resistant and extensively drug-resistant biofilm-forming uropathogenic Escherichia coli isolates, India.

AIM: We aimed to study host range, stability, genome and antibiofilm activity of a novel phage vB_EcoA_RDN8.1 active against multi-drug resistant (MDR) and extensively drug-resistant (XDR) biofilm-forming uropathogenic Escherichia coli isolates. METHODS AND RESULTS: A novel lytic phage vB_EcoA_RDN8.1 active against UPEC strains resistant to third-generation cephalosporins, fluoroquinolones, aminoglycosides, imipenem, beta-lactamase inhibitor combination and polymyxins was isolated from community raw sewage water of Chandigarh. It exhibited a clear plaque morphology and a burst size of 250. In the time-kill assay, the maximum amount of killing was achieved at MOI 1.0. vB_EcoA_RDN8.1 belongs to the family Autographiviridae, has a genome size of 39.5 kb with a GC content of 51.6%. It was stable over a wide range of temperatures and pH. It was able to inhibit biofilm formation which may be related to an endolysin encoded by ORF 19. CONCLUSIONS: The vB_EcoA_RDN8.1 is a novel lytic phage that has the potential for inclusion into phage cocktails being developed for the treatment of urinary tract infections (UTIs) caused by highly drug-resistant UPEC. SIGNIFICANCE AND IMPACT OF THE STUDY: We provide a detailed characterization of a novel lytic Escherichia phage with antibiofilm activity having a potential application against MDR and XDR UPEC causing UTIs.

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial.

PURPOSE: Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients. METHODS: This was a randomized, parallel-group, open-label, phase 2, and non-inferiority trial. Chemotherapy-naïve patients with mCRPC and high PSMA-expressing lesions on 68 Ga-PSMA-11 PET/CT were randomly assigned in 1:1 ratio to 177Lu-PSMA-617 (6.0-7.4 GBq/cycle, every 8 weeks, up to 4 cycles) or docetaxel (75 mg/m2/cycle, every 3 weeks, up to 10 cycles). The primary end-point was best prostate-specific antigen response rate (PSA-RR), defined according to Prostate Cancer Clinical Trials Working Group-3 as proportion of patients achieving ≥ 50% decline in PSA from baseline. Non-inferiority margin of - 15% was pre-specified for PSA-RR. RESULTS: Between December 2019 and March 2021, 40 of the 45 patients assessed for eligibility underwent randomization. Fifteen of 20 patients in 177Lu-PSMA-617 arm and 20/20 patients in docetaxel arm received treatment per protocol. Of these, best PSA-RR in the 177Lu-PSMA-617 arm was 60% (9/15) versus 40% (8/20) in the docetaxel arm. The difference in the PSA-RRs between the two arms was 20% (95% confidence interval, CI: - 12-47, P = 0.25), meeting the pre-specified criterion for non-inferiority in per-protocol analysis. Further, progression-free survival rates at 6 months were 30% and 20% in the 177Lu-PSMA-617 and docetaxel arms respectively (difference 10%, 95% CI: - 18-38, P = 0.50). Overall, treatment-emergent grade ≥ 3 adverse events occurred less frequently with 177Lu-PSMA-617 than with docetaxel (6/20, 30% versus 10/20, 50%, respectively, P = 0.20). Quality-of-life outcomes improved significantly in 177Lu-PSMA-617 arm compared to docetaxel arm (P < 0.01). CONCLUSION: 177Lu-PSMA-617 was demonstrated to be safe and non-inferior to docetaxel in the treatment of mCRPC and could, thus, be potentially employed earlier in the disease course rather than being solely reserved for advanced end-stage disease. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India, CTRI/2019/12/022282.