Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial.

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7-73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4-95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9-68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. Immune-related adverse effects were exclusively associated with pembrolizumab. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects, all related to pembrolizumab. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 .

180° versus 360° Selective Laser Trabeculoplasty in Open Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis.

PRECIS: This systematic review and meta-analysis found that 360° selective laser trabeculoplasty (SLT) is significantly more effective than 180° SLT at reducing intraocular pressure at one month and one year follow-ups, without increased serious adverse event risk. PURPOSE: To determine the efficacy of 180° versus 360° selective laser trabeculoplasty (SLT) in adults with open angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: A systematic review was performed using PubMed, Embase, and Scopus databases, from 1995 to December 30, 2023, for studies comparing 180° and 360° SLT in adults with OAG and OHT (PROSPERO ID: CRD42024497832). Meta-analyses were performed to calculate nominal percent and raw reductions in IOP between treatment groups at one-month, one-year, and two-year follow-ups, as well as success rates, defined as a 20% or greater IOP reduction. RESULTS: Nine studies with 1044 eyes were included; 491 received 180°SLT and 553 received 360° SLT. At the one-month follow-up, 360° SLT reduced IOP by 3.45% more (WMD=3.45; 95% CI: 2.02-4.88; P<0.00001) and 0.87 mmHg more (WMD=0.87; 95% CI: 0.35-1.38; P=0.0010). At the one-year follow-up, 360° SLT reduced IOP by 4.33% more (WMD=4.33; 95% CI: 2.35-6.32; P<0.0001) and 1.15 mmHg more (WMD=1.15; 95% CI: 0.25-2.04; P=0.01). At two years of follow up, 360° SLT reduced IOP by 4.86% more (WMD=4.86; 95% CI: -0.32, 10.0; P=0.07) and 1.25 mmHg more (WMD=1.25; 95% CI: -0.29, 2.79; P=0.11), however the difference was not statistically significant. Compared to 360° SLT, 180° SLT had a significantly lower success rate (OR=0.50; 95% CI: 0.35-0.72; P=0.0002). There was no difference in serious complications between interventions. CONCLUSION: 360° SLT is more effective than 180° SLT at lowering IOP at one-month and one-year follow-ups as well as achieving successful IOP control without increased risk of serious complications.

The Importance of Medial Patellar Shape as a Risk Factor for Recurrent Patellar Dislocation in Adults.

BACKGROUND: Research on the cause of lateral patellar dislocation (LPD) has focused on trochlear morphologic parameters, joint alignment, and patellofemoral soft tissue forces. A paucity of information is available regarding how patellar morphologic parameters influence the risk for LPD. PURPOSE/HYPOTHESIS: The purpose was to assess whether patellar morphology is a risk factor for recurrent LPD. It was hypothesized that (1) patients with recurrent LPD would have decreased patellar width and volume and (2) patellar morphologic parameters would accurately discriminate patients with recurrent LPD from controls. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: A total of 21 adults with recurrent LPD (age, 29.7 ± 11.1 years; height, 170.8 ± 9.9 cm; weight, 76.1 ± 17.5 kg; 57% female) were compared with 21 sex- and height-matched controls (age, 27.2 ± 6.7 years; height, 172.0 ± 10.6 cm; weight, 71.1 ± 12.8 kg; 57% female). Three-dimensional axial fat-saturated magnetic resonance imaging scans were used to measure patellar medial, lateral, and total width; patellar volume; patellar medial and lateral facet length; the Wiberg index; and previously validated knee joint alignment and femoral shape measurements (eg, tibial tuberosity to trochlear groove distance, trochlear dysplasia). RESULTS: The LPD group demonstrated reduced medial patellar width (Δ = -3.6 mm; P < .001) and medial facet length (Δ = -3.7 mm; P < .001) but no change in lateral width or facet length. This resulted in decreased total patellar width (Δ = -3.2 mm; P = .009), decreased patellar volume (Δ = -0.3 cm3; P = .025), and an increased Wiberg index (Δ = 0.05; P < .001). No significant differences were found for all other patellar shape measures between cohorts. Medial patellar width was the strongest single discriminator (83.3% accuracy) for recurrent LPD. Combining medial patellar width, patellofemoral tilt, and trochlear groove length increased the discrimination to 92.9%. CONCLUSION: The medial patellar width was significantly smaller in patients with recurrent LPD and was the single most accurate discriminator for recurrent LPD, even compared with traditional trochlear shape and joint alignment measures (eg, trochlear dysplasia, patella alta). Therefore, medial patellar morphology should be assessed in patients with LPD as a risk factor for recurrence and a potential means to improve treatment.

Automated Identification of Key Steps in Robotic-Assisted Radical Prostatectomy Using Artificial Intelligence.

PURPOSE: The widespread use of minimally invasive surgery generates vast amounts of potentially useful data in the form of surgical video. However, raw video footage is often unstructured and unlabeled, thereby limiting its use. We developed a novel computer-vision algorithm for automated identification and labeling of surgical steps during robotic-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Surgical videos from RARP were manually annotated by a team of image annotators under the supervision of 2 urologic oncologists. Full-length surgical videos were labeled to identify all steps of surgery. These manually annotated videos were then utilized to train a computer vision algorithm to perform automated video annotation of RARP surgical video. Accuracy of automated video annotation was determined by comparing to manual human annotations as the reference standard. RESULTS: A total of 474 full-length RARP videos (median 149 minutes; IQR 81 minutes) were manually annotated with surgical steps. Of these, 292 cases served as a training dataset for algorithm development, 69 cases were used for internal validation, and 113 were used as a separate testing cohort for evaluating algorithm accuracy. Concordance between artificial intelligence‒enabled automated video analysis and manual human video annotation was 92.8%. Algorithm accuracy was highest for the vesicourethral anastomosis step (97.3%) and lowest for the final inspection and extraction step (76.8%). CONCLUSIONS: We developed a fully automated artificial intelligence tool for annotation of RARP surgical video. Automated surgical video analysis has immediate practical applications in surgeon video review, surgical training and education, quality and safety benchmarking, medical billing and documentation, and operating room logistics.

Navigating Now and Next: Recent Advances and Future Horizons in Robotic Radical Prostatectomy.

Robotic-assisted radical prostatectomy (RARP) has become the leading approach for radical prostatectomy driven by innovations aimed at improving functional and oncological outcomes. The initial advancement in this field was transperitoneal multiport robotics, which has since undergone numerous technical modifications. These enhancements include the development of extraperitoneal, transperineal, and transvesical approaches to radical prostatectomy, greatly facilitated by the advent of the Single Port (SP) robot. This review offers a comprehensive analysis of these evolving techniques and their impact on RARP. Additionally, we explore the transformative role of artificial intelligence (AI) in digitizing robotic prostatectomy. AI advancements, particularly in automated surgical video analysis using computer vision technology, are unprecedented in their scope. These developments hold the potential to revolutionize surgeon feedback and assessment and transform surgical documentation, and they could lay the groundwork for real-time AI decision support during surgical procedures in the future. Furthermore, we discuss future robotic platforms and their potential to further enhance the field of RARP. Overall, the field of minimally invasive radical prostatectomy for prostate cancer has been an incubator of innovation over the last two decades. This review focuses on some recent developments in robotic prostatectomy, provides an overview of the next frontier in AI innovation during prostate cancer surgery, and highlights novel robotic platforms that may play an increasing role in prostate cancer surgery in the future.

Cutaneous Ureterostomy Following Radical Cystectomy for Bladder Cancer: A Contemporary Series.

OBJECTIVE: To report peri-operative outcomes of a contemporary series of bladder cancer patients undergoing radical cystectomy (RC) with cutaneous ureterostomy (CU) urinary diversion at a tertiary referral center. METHODS: We retrospectively identified patients who underwent RC with CU at Mayo Clinic between 2016 and 2021. Clinicopathologic and perioperative characteristics were analyzed using standard descriptive statistics. RESULTS: A total of 31 patients underwent RC with CU at our institution. Median age was 72years and 21 were male. This was highly comorbid cohort (83% had an American Society of Anesthesiologists [ASA] Physical Status Classification System ≥3; median Charlson Comorbidity index= 8). Median time to flatus, tolerating regular diet, and length of stay were 3 (interquartile range [IQR] 3-3), 3 (IQR 3-4), and 4days (IQR 4-7), respectively. A total of 14 patients experienced a high-grade complication (Clavien-Dindo ≥3) within 30days of surgery, and 8 were readmitted. The most common 30-day complication was sepsis, which affected 13% (4/31) of patients. At 90days postsurgery, the readmission rate was 32% (10/31), most commonly for sepsis. Three patients required reoperation within 90days, including one patient who required CU revision due to stomal ischemia. One patient died within this time frame from causes unrelated to bladder cancer. CONCLUSION: In a comorbid, relatively elderly bladder cancer cohort undergoing RC, the use of CU was associated with expeditious surgery and postoperative recovery. CU represents an option for urinary diversion in high-risk patients undergoing RC. Higher rate of postoperative ureteral obstruction can be pre-emptively addressed with chronic stent placement.

Relative impact of lymph-node metastasis and seminal vesical invasion on oncologic outcomes following radical prostatectomy.

BACKGROUND: While both seminal vesicle (SVI) and lymph-node invasion (LNI) have been identified as adverse prognostic variables among men undergoing radical prostatectomy (RP), the relative impact of each of these features on subsequent oncologic outcomes has not been well defined. We assessed the impact of LNI on long-term oncologic outcomes among patients with SVI at RP. METHODS: We reviewed 19,519 patients who underwent RP and identified 2043 with SVI. Metastasis-free (MFS), cancer-specific (CSS), and overall survival (OS) were estimated for patients with SVI, stratified by the presence and number of pelvic lymph node metastases. Cox proportional hazards models were used to evaluate the independent association of the number of metastatic nodes and lymph node density with oncologic outcomes among patients with SVI, controlling for age, year of surgery, margin status, preoperative PSA, pathologic Gleason score, extraprostatic extension, and use of adjuvant therapies. RESULTS: At a median follow up of 12.1 years (IQR 7.0,18.6), 548 patients developed metastatic disease and 1331 died, including 406 who died from prostate cancer (PCa). We found that, among patients with SVI, the presence of a single positive lymph node was not associated with incrementally adverse oncologic outcomes compared to no nodal metastasis at RP, with 10-year MFS, CSS, and OS rates of 81.3% versus 78.3%(p = 0.18), 86.5% versus 89.8%(p = 0.32), and 72.8% versus 76.7%(p = 0.53), respectively. In contrast, on multivariable analyses, the presence of ≥2 metastatic nodes and a 20% lymph-node density cut off remained independently associated with worse survival. CONCLUSIONS: SVI represents an adverse pathologic feature such that the presence of a single positive pelvic lymph node did not further adversely impact prognosis. Meanwhile, a significant number of involved nodes was associated with decreased survival. These findings may aid in risk-stratification as well as clinical trial design for such high-risk patients following surgery.

Surgical Site Infections in Open and Laparoscopic Operations in Rooms With Open-floor Drainage Systems.

INTRODUCTION: Surgical site infections are common postoperative complications. Some operating rooms have open-floor drainage systems for fluid disposal during endourologic cases, although nonendoscopy cases are not always allowed in these rooms. We hypothesized that operating rooms with open-floor drainage systems would not materially affect risk of surgical site infections for patients undergoing open and laparoscopic procedures. METHODS: Patients who had surgical site infections from 2016 through 2020 were identified from data of the National Surgical Quality Improvement Program. Patients without surgical incisions, with open wounds, and with surgical site infections at surgery were excluded. The primary outcome was surgical site infection occurrence within 30 days of surgery. Multilevel multivariable logistic regression was used to estimate the observed-to-expected surgical site infection ratio for each operating room (2 with and 23 without open-floor drainage systems). RESULTS: We identified 8,419 surgical cases, of which 802 (9.5%) were performed in operating rooms with open-floor drainage systems; 166 patients (2.0%) had surgical site infections. Of the surgical site infections, 7 (4.2%) occurred in operating rooms with open-floor drainage systems. Surgical specialty, American Society of Anesthesiologists physical status, higher case acuity, dyspnea, immunosuppression, longer surgical duration, and wound classification were associated with surgical site infections (P < .05 for all). The observed-to-expected ratios of surgical site infections occurring in the 2 operating rooms with open-floor drainage systems were 0.85 and 1.15. The odds ratio of surgical site infections for urologic cases performed in room with vs without open-floor drainage systems was 1.30 (P = .65). CONCLUSIONS: Urology operating room designs often include open-floor drainage systems for water-based cases. These drainage systems were not associated with an increased risk of surgical site infections.

Posterior Pole Asymmetry Analysis as a Diagnostic Tool in Glaucoma Suspects: An Electrophysiological Approach.

Purpose: Spectral domain optical coherence tomography (SD-OCT) with posterior pole asymmetry analysis (PPAA) provides a mapping of posterior pole retinal thickness with asymmetry analysis between hemispheres of each eye. We investigated whether these structural abnormalities were correlated with functional retinal ganglion cell (RGC) loss, quantified by steady state pattern electroretinogram (ssPERG), in glaucoma suspects (GS). Methods: Twenty GS (34 eyes) were enrolled in a prospective study at the Manhattan Eye, Ear, and Throat Hospital. All subjects underwent ophthalmological examination, including Humphrey visual field, Spectralis Glaucoma Module Premium Edition (GMPE) SD-OCT PPAA, and ssPERG testing. The ability of ssPERG parameters (Magnitude [Mag, µv], MagnitudeD [MagD, µv], and MagD/Mag ratio) to predict PPAA thickness (total, superior, and inferior thickness, [µm]) was tested via adjusted multivariate linear regression analysis. Results: Mag explained 8% of variance in total PPAA change (F(1,29)=6.33, B=6.86, 95% CI: 1.29-12.44, p=0.018), 8% in superior PPAA change (F(1,29)=5.57, B=6.92, 95% CI: 0.92-12.92, p=0.025), and 7.1% in inferior PPAA change (F(1,29)=5.83, B=6.80, 95% CI: 1.04-12.56, p=0.022). Similarly, MagD explained 9.7% of variance in total PPAA change (F(1,29)=8.09, B=6.47, 95% CI: 1.82-11.13, p=0.008), 10% in superior PPAA change (F(1,29)=7.33, B=6.63, 95% CI: 1.62-11.63, p=0.011), and 8.5% in inferior PPAA change (F(1,29)=7.25, B=6.36, 95% CI: 1.53-11.18, p=0.012). MagD/Mag ratio and PPAA were not significantly associated. Conclusion: To the best of our knowledge, this is the first study demonstrating a positive relationship between RGC dysfunction and retinal thickness changes between the superior and inferior hemispheres. The detection of asymmetrical structural loss, combined with functional RGC assessment using ssPERG, may be an informative tool for early glaucoma diagnosis.

Impact of Donor, Recipient, and Graft Characteristics on Corneal Transplantation Outcomes.

Purpose: Although several donor, recipient, and graft characteristics have been studied in relation to corneal transplantation outcomes, no study to our knowledge has assessed the impact of donor cooling times on postoperative outcomes longitudinally. With only one corneal graft available for every 70 needed worldwide, this study seeks to identify any factors that could alleviate this shortage. Methods: Patients undergoing corneal transplantation at the Manhattan Eye, Ear & Throat Hospital over a 2-year period were retrospectively studied. Study metrics included age, diabetic history, hypertensive history, endothelial cell density, death-to-preservation time (DTP), death-to-cooling time (DTC), and time-in-preservation (TIP). Postoperative transplantation outcomes, including best corrected visual acuity (BCVA) at 6- and 12-month follow-up visits, need for re-bubbling, and need for re-grafting, were assessed. Unadjusted univariate and adjusted multivariate binary logistic regressions were performed to determine the association of cooling and preservation parameters with corneal transplantation outcomes. Results: Among 111 transplants, our adjusted model found that DTC ≥4 hours was associated with significantly worse BCVA, but only at 6-month postoperative follow-up (odds ratio [OR]: 0.234; 95% confidence interval [CI]: 0.073-0.747; p = 0.014). By 12-month follow-up, DTC >4 hours was no longer associated with BCVA in a statistically significant manner (OR: 0.472; 95% CI: 0.135-1.653; p = 0.240). A similar trend was found at a DTC cutoff of ≥3 hours. None of the other studied parameters, including DTP, TIP, donor age, or medical history were significantly correlated with transplantation outcomes. Conclusion: Longer DTC or DTP did not have a statistically significant effect on corneal graft outcomes after one year, though short-term outcomes were improved in donor tissues with DTC below four hours. None of the other studied variables correlated with transplantation outcomes. Given the global shortage of corneal tissue, these findings should be considered when determining suitability for transplantation.

Complete and Uneventful Recovery in a Case of Lymphocytic Hypophysitis Causing a Third Nerve Palsy.

Lymphocytic hypophysitis (LH) is a neuroendocrine disorder characterised by autoimmune inflammation of the pituitary gland with resultant pituitary dysfunction. Rarely, the presenting symptom can be diplopia due to irritation of the third, fourth, or sixth cranial nerves secondary to cavernous sinus involvement of the mass or increased intracranial pressure. We describe the case of a healthy, 20-year-old female with a pupillary sparing third nerve palsy, who was subsequently diagnosed with LH after an endoscopic transsphenoidal biopsy of the mass. She was treated with hormone replacement therapy and corticosteroids, resulting in full resolution of symptoms with no recurrence to date. To our knowledge, this is the first report of a third nerve palsy due to definitive biopsy proven LH. Despite its rarity, the unique presentation and favourable evolution of this case should aid clinicians in its timely recognition, appropriate workup, and treatment.

CENTRAL RETINAL VEIN OCCLUSION FOLLOWING BNT162B2 (PFIZER-BIONTECH) COVID-19 MESSENGER RNA VACCINE.

PURPOSE: Coronavirus disease 2019 has had a wide-ranging public health impact, contributing to at least five million deaths globally at the time of this report. Although thromboembolic events following coronavirus disease 2019 vaccination have been an ongoing concern, only a limited number of ophthalmic manifestations have been reported to date. METHODS: A detailed history, hypercoagulable workup, best-corrected visual acuity (BCVA), Humphrey visual field, dilated fundus examination, and multimodal imaging including optical coherence tomography, fundus fluorescein angiography, and fundus photography were obtained. RESULTS: A 27-year-old woman was diagnosed with central retinal vein occlusion a few days after her first dose of the BNT162b2 (Pfizer-BioNTech) coronavirus disease 2019 vaccine. Detailed elicitation of her history and a full hypercoagulable workup did not reveal any primary risk factors that could have explained her disease process. After the patient received the second dose, her symptoms deteriorated significantly and worsening peripapillary hemorrhage were seen on dilated fundus examination. The patient was treated with intravitreal injections of ranibizumab and followed closely, which showed improvement in her central retinal vein occlusion. CONCLUSION: Given the chronology of the patient's condition, it is believed that the central retinal vein occlusion that occurred as a result of the first dose was exacerbated by an intense immunological reaction after the second dose. The severity of this complication, despite its rarity, must be emphasized and weighed in but should not preclude the extensive benefits of vaccination.

Robotic Arm-Assisted versus Manual Total Knee Arthroplasty: A Propensity Score-Matched Analysis.

The purpose of this study was to compare (1) operative time, (2) in-hospital pain scores, (3) opioid medication use, (4) length of stay (LOS), (5) discharge disposition at 90-day postoperative, (6) range of motion (ROM), (7) number of physical therapy (PT) visits, (8) emergency department (ED) visits, (9) readmissions, (10) reoperations, (11) complications, and (12) 1-year patient-reported outcome measures (PROMs) in propensity matched patient cohorts who underwent robotic arm-assisted (RA) versus manual total knee arthroplasty (TKA). Using a prospectively collected institutional database, patients who underwent RA- and manual TKA were the nearest neighbor propensity score matched 3:1 (255 manual TKA:85 RA-TKA), accounting for various preoperative characteristics. Data were compared using analysis of variance (ANOVA), Kruskal-Wallis, Pearson's Chi-squared, and Fisher's exact tests, when appropriate. Postoperative pain scores, opioid use, ED visits, readmissions, and 1-year PROMs were similar between the cohorts. Manual TKA patients achieved higher maximum flexion ROM (120.3 ± 9.9 versus 117.8 ± 10.2, p = 0.043) with no statistical differences in other ROM parameters. Manual TKA had shorter operative time (105 vs.113 minutes, p < 0.001), and fewer PT visits (median [interquartile range] = 10.0 [8.0-13.0] vs. 11.5 [9.5-15.5] visits, p = 0.014). RA-TKA had shorter LOS (0.48 ± 0.59 vs.1.2 ± 0.59 days, p < 0.001) and higher proportion of home discharges (p < 0.001). RA-TKA and manual TKA had similar postoperative complications and 1-year PROMs. Although RA-TKA patients had longer operative times, they had shorter LOS and higher propensity for home discharge. In an era of value-based care models and the steady shift to outpatient TKA, these trends need to be explored further. Long-term and randomized controlled studies may help determine potential added value of RA-TKA versus manual TKA. This study reflects level of evidence III.

Prevalence, Predictors, and Oncologic Outcomes of Pelvic Organ Involvement in Women Undergoing Radical Cystectomy.

CONTEXT.­: In women, radical cystectomy includes removal of the bladder, uterus, fallopian tubes, ovaries, and anterior vaginal wall, yet contiguous extension of urothelial carcinoma to all pelvic organs is rare and routine removal may be unnecessary. OBJECTIVE.­: To study pelvic organ involvement in women at radical cystectomy and investigate oncologic outcomes. DESIGN.­: Women with bladder cancer who underwent radical cystectomy at the Mayo Clinic and University of Toronto (1980-2018) were evaluated. Cancer-specific survival (CSS) was estimated with the Kaplan-Meier method; comparisons were made with the log-rank test. Associations with CSS were evaluated with Cox proportional hazard modeling. RESULTS.­: A total of 70 women with pT4a and 83 with pT3b cancer were studied. Organs involved were vagina (n = 41 of 70; 58.6%), uterus (n = 26 of 54; 48.1%), cervix (n = 15 of 54; 27.8%), fallopian tubes (n = 10 of 58; 17.2%), and ovaries (n = 7 of 58; 12.1%); 22 of 58 patients (37.9%) had >1 organ involved. Of 70 with pT4a cancer, 64 were available for survival analysis by 3 pelvic organ groups: vaginal only, vaginal and/or cervical/uterine, and vaginal and/or cervical/uterine and/or fallopian tubes/ovarian involvement. Three-year CSS for vaginal involvement only was 39%; it was 14% if cervical/uterine involvement, and <1% if fallopian tube/ovarian involvement was included (P = .02). Among 20 women with pT4aN0/Nx and vaginal involvement only, 3-year CSS for vaginal involvement was 50%, whereas among 48 women with pT3bN0/Nx cancer, 3-year CSS was 58%, P = .70. CONCLUSIONS.­: Isolated vaginal involvement should be separated from uterine and/or adnexal extension of urothelial carcinoma at pathologic staging. Direct ovarian extension is rare and routine removal may be unnecessary.

Perioperative and Oncologic Outcomes Associated with Simultaneous Radical Cystectomy and Nephroureterectomy.

OBJECTIVE: To compare the perioperative and oncologic outcomes associated with RCNU to a matched cohort undergoing RC alone. Simultaneous radical cystectomy and nephroureterectomy (RCNU) for synchronous upper tract and bladder urothelial carcinoma is an uncommon procedure. Sparse literature exists comparing outcomes in patients treated with radical cystectomy (RC) alone versus RCNU. METHODS: Adults treated with RCNU for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) between 1980 and 2020 were identified. Patients were matched 2:1 to patients undergoing RC alone for UCB based on age (+/- 5 years), gender, BMI (+/- 5), Charlson Comorbidity Index, pathologic staging (stage ≤pT2 vs >pT2), and receipt of neoadjuvant chemotherapy. Outcomes included overall survival (OS), recurrence free survival (RFS), cancer specific survival (CSS), 30-day complications, length of stay (LOS), operative time, and estimated blood loss (EBL). RESULTS: A total of 39 patients undergoing RCNU were identified and matched to 74 patients undergoing RC. There were no significant differences in LOS, EBL, or 30-day complication rates. Operative time was significantly longer in the RC cohort. OS (HR 0.58, CI 0.35-0.97, P = .036) was significantly better for patients undergoing RC alone, while no significant difference was noted in RFS (HR 0.65, 0.34-1.24) and CSS (HR 0.58, CI 0.31-1.08, P = .08). CONCLUSIONS: Patients undergoing RCNU had significantly lower OS compared to a matched group of patients undergoing RC alone. Perioperative outcomes between the groups did not differ significantly. This data can inform patient counseling for treatment of this rare disease state.

Intraoperative Blood Transfusion Is Associated With Increased Risk of Venous Thromboembolism After Radical Cystectomy.

PURPOSE: Our objective was to examine whether perioperative blood transfusion is associated with venous thromboembolism following radical cystectomy adjusting for both patient- and disease-related factors. MATERIALS AND METHODS: Patients who underwent radical cystectomy for bladder cancer from 1980-2020 were identified in the Mayo Clinic cystectomy registry. Blood transfusion during the initial postoperative hospitalization was analyzed as a 3-tiered variable: no transfusion, postoperative transfusion alone, or intraoperative with or without postoperative transfusion. The primary outcome was venous thromboembolism within 90 days of radical cystectomy. Associations between clinicopathological variables and 90-day venous thromboembolism were assessed using multivariable logistic regression, with transfusion analyzed as both a categorical and a continuous variable. RESULTS: A total of 3,755 radical cystectomy patients were identified, of whom 162 (4.3%) experienced a venous thromboembolism within 90 days of radical cystectomy. Overall, 2,112 patients (56%) received a median of 1 (IQR: 0-3) unit of blood transfusion, including 811 (38%) with intraoperative transfusion only, 572 (27%) with postoperative transfusion only, and 729 (35%) with intraoperative and postoperative transfusion. On multivariable analysis, intraoperative with or without postoperative blood transfusion was associated with a significantly increased risk of venous thromboembolism (adjusted OR 1.73, 95% CI 1.17-2.56, P = .002). Moreover, when analyzed as a continuous variable, each unit of blood transfused intraoperatively was associated with 7% higher odds of venous thromboembolism (adjusted OR 1.07, 95% CI 1.01-1.13, P = .03). CONCLUSIONS: Intraoperative blood transfusion was significantly associated with venous thromboembolism within 90 days of radical cystectomy. To ensure optimal perioperative outcomes, continued effort to limit blood transfusion in radical cystectomy patients is warranted.

Reports of New and Recurrent Keratitis following mRNA-based COVID-19 Vaccination.

PURPOSE: As ophthalmic side effects of messenger RNA (mRNA)-based COVID-19 vaccination are not well understood, it is crucial to document and report such instances should they occur. METHODS: In this observational case series, we report nine patients (55.6% male, mean age 58.9) who received either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccinations from January to June of 2021, and presented with symptoms of keratitis within 14 days. All patients underwent slit-lamp examination and histories were taken. RESULTS: Most subjects (66.7%) had a history of corneal inflammatory diseases and resolved under antiviral and/or steroidal treatment. Patients who reported symptoms after their second vaccine dose presented earlier than those who reported symptoms after the first dose (mean 4.4 days vs 10.5 days, respectively). CONCLUSIONS: The immunological reaction following mRNA-based COVID-19 vaccinations may trigger new-onset or reactivation of keratitis, though causality cannot be proven. Despite its rarity, clinicians should be aware of this possible complication and be prepared to treat.

Exogenous cryptococcal endophthalmitis in an immunocompetent patient.

We describe a case of exogenous cryptococcal endophthalmitis without central nervous system (CNS) involvement or systemic infection in an immunocompetent patient. An 82-year-old male with hypertension, hyperlipidemia, type 2 diabetes mellitus, and primary open-angle glaucoma with a history of left eye trabeculectomy presented with 3 months of worsening left eye pain and redness. Vitreous cultures resulted as Cryptococcus, prompting treatment with intravitreal amphotericin and further investigation. Systemic workup was unrevealing for an endogenous source, CNS involvement, or immunocompromising conditions. He was treated with an aggressive regimen of systemic antifungals, leading to subjective improvements in clinical exam and in vision.

Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer.

INTRODUCTION: Identifying neoadjuvant chemotherapy (NAC) response in patients with muscle invasive bladder cancer (MIBC) has had limited success based on clinicopathological features and molecular subtyping. Identification of chemotherapy responsive cohorts would facilitate delivery to those most likely to benefit. OBJECTIVE: Develop a molecular signature that can identify MIBC NAC responders (R) and non-responders (NR) using a cohort of known NAC response phenotypes, and better understand differences in molecular pathways and subtype classifications between NAC R and NR. MATERIALS AND METHODS: Presented are the messenger RNA (mRNA) and microRNA (miRNA) differential expression profiles from initial transurethral resection of bladder tumor (TURBT) specimens of a discovery cohort of MIBC patients consisting of 7 known NAC R and 11 NR, and a validation cohort consisting of 3 R and 5 NR. Pathological response at time of cystectomy after NAC was used to classify initial TURBT specimens as R (pT0) versus NR (≥pT2). RNA and miRNA from FFPE blocks were sequenced using RNAseq and qPCR, respectively. RESULTS: The discovery cohort had 2309 genes, while the validation cohort had 602 genes and 13 miRNA differentially expressed between R and NR. Gene set enrichment analysis identified mitochondrial gene expression, DNA replication initiation, DNA unwinding in the R discovery cohort and positive regulation of vascular associated smooth muscle cell proliferation in the NR discovery cohort. Canonical correlation (CC) analysis was applied to differentiate R versus NR. 3 CCs (CC13, CC16, and CC17) had an AUC >0.65 in the discovery and validation dataset. Gene ontology enrichment showed CC13 as nucleoside triphosphate metabolic process, CC16 as cell cycle and cellular response to DNA damage, CC17 as DNA packaging complex. All patients were classified using established molecular subtypes: Baylor, UNC, CIT, Lund, MD Anderson, TCGA, and Consensus Class. The MD Anderson p53-like subtype, CIT MC4 subtype and Consensus Class stroma rich subtype had the strongest correlation with a NR phenotype, while no subtype had a strong correlation with the R phenotype. CONCLUSIONS: Our results identify molecular signatures that can be used to differentiate MIBC NAC R versus NR, salient molecular pathway differences, and highlight the utility of molecular subtyping in relation to NAC response.

Screening Vaccinees for Non-Communicable Diseases and Risk Factors at a Covid-19 Vaccination Center in Vadodara, Gujarat.

Context: Adult population visiting COVID vaccination center is a potential teachable moment for screening and preventive advice on non-communicable diseases. Objectives: The objective of this study was to assess the proportion of vaccinees volunteering for screening and to know the proportion of newly detected hypertensives and diabetics among the screened vaccinees at COVID-19 vaccination center. Setting and Design: This descriptive, cross-sectional, operational research study was carried out at the COVID vaccination center at a medical college in central Gujarat from July to September 2021. Methods: After receiving the vaccine, the vaccinee was offered screening through a community-based assessment checklist for risk factors of non-communicable diseases, blood pressure, and blood sugar measurement. Those volunteering for this screening received a slip mentioning their risk score, blood pressure and blood sugar reading, and relevant health information and disease prevention advice. The study variables were acceptability (proportion of vaccinees volunteering for screening) and yield (newly detected hypertensives and diabetics among those screened). Results: Among vaccinees, 27.7% volunteered for risk scoring and blood pressure measurement, whereas 8.3% volunteered for blood sugar measurement. Around 15.5% of vaccinees had high-risk scores as per the community-based assessment checklist. The yield of freshly detected high blood pressure and high blood sugar was 19.3% and 10.5%, respectively. The yield was similar even among vaccinees under 30 years of age. Conclusions: Vaccinees demonstrated interest in undergoing screening for non-communicable diseases. Yield indicates that such screening is worth the effort.