The impact of metabolic syndrome on short term radical cystectomy complications.

PURPOSE: Radical cystectomy is a highly morbid procedure with short term perioperative complications rates cited to be as high as 60%. Short term perioperative complications have been demonstrated to be more frequent in underweight and overweight patients. We sought to evaluate the impact of metabolic syndrome on surgical outcomes. MATERIALS AND METHODS: We identified 19,071 eligible patients who underwent radical cystectomy for nonmetastatic bladder cancer using the American College of Surgeons National Surgical Quality Improvement Program database between the years 2014 to 2021. The primary exposure was the presence of metabolic syndrome (body mass index >30, hypertension, diabetes) and included 1,566 patients. Our primary outcome was the development of a post operative surgical complication with secondary outcomes of the impact on length of stay, return to operating room, readmission, and 30 day mortality. RESULTS: Metabolic syndrome was associated with an increased rate of complications following radical cystectomy (P < 0.001). Complications were demonstrated in 68% of patients with metabolic syndrome in comparison to 60% of those without. Following multivariable adjustment for relevant demographic, comorbidity, and treatment factors, compared to patients without metabolic syndrome, patients with metabolic syndrome were significantly more likely to experience a complication in the 30 days following cystectomy. Among the secondary outcomes, on multivariable analysis significant differences were found in the risk of readmission and extended length of stay. Critically, the risk of 30 day morbidity was associated with a 1.8 fold increase in those with metabolic syndrome. CONCLUSIONS: Metabolic syndrome demonstrates significantly worse perioperative outcomes following radical cystectomy for bladder cancer.

Role and Results of Constrained Insert in Computer-Assisted Primary Total Knee Arthroplasty: A Propensity-Matched Study.

Purpose: Mild ligament imbalance is often encountered in the mediolateral plane during complex primary total knee arthroplasty. A constrained (CP) polyethylene insert compatible with the primary femur is useful to manage these cases without the need to fall back on revision implants. The aim of the study was to define the correct indications of the use of a CP insert based on objective data from computer assisted surgery and to compare the early results of a CP insert with a standard posterior stabilized (PS) insert through one-to-one propensity score matching. Methods: This is a retrospective case study from a prospectively collected database. One-to-one matching without replacement was used with a caliper width of 0.2 to match the scores between CP (N = 64) and PS groups (N = 1624), resulting in equal covariate matching of PS (N = 64) and CP (N = 64) cohorts. Patients were assessed radiographically and functionally at a minimum follow-up of 3 years. Result: Average coronal and sagittal plane deformities were similar in both the group CP (varus 13.1 ± 5.2 valgus 13 ± 7.9) and the group PS (varus 13.4 ± 4.6 valgus 10.9 ± 8.6). The average residual medial lateral gap difference was significantly higher in group CP (3.8 ± 1.8) in comparison to group PS (1.3 ± 1) (P < .05). A CP insert was chosen where mild ligament imbalance of 3-5 mm persisted after medial soft tissue releases in a varus knee and in cases with residual medial collateral ligament laxity in valgus knees. Conclusions: Constrained insert used with the primary femoral component is a valuable option to handle mild ligamentous instability in complex primary total knee arthroplasty after mechanical alignment is achieved with computer navigation. Level of Evidence: III.

Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

PURPOSE: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts. METHODS: This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208). RESULTS: The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients. CONCLUSION: CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.

Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

Utilization and Timing of Cystoscopy for Hematuria Evaluation by Advanced Practice Providers and Urologists.

OBJECTIVE: To characterize differences between urologists and advanced practice providers (APPs) in the utilization of cystoscopy for hematuria. METHODS: We identified patients initially evaluated for hematuria by a urologist or urology APP between 2015 and 2020 in the MarketScan Research Databases. We determined whether they received a cystoscopy within 6 months of their urology visit and the number of days until cystoscopy. We used multivariable regression to analyze the association between these outcomes and whether the urology clinician was an advanced practice registered nurse (APRN), physician assistant (PA), or urologist. RESULTS: We identified 34,470 patients with microscopic hematuria and 17,328 patients with gross hematuria. Patients evaluated by urologists more often received a same-day cystoscopy than those evaluated by APPs (13% vs 5.8%). The odds that patients evaluated for microscopic and gross hematuria received a cystoscopy were 46.2% and 26.2% lower, respectively, if they were evaluated by an APRN vs a urologist. Patients seeing an APRN for microscopic and gross hematuria also waited approximately 7 and 14 days longer for their cystoscopy, respectively. No differences were observed for patients evaluated by PAs vs urologists. CONCLUSION: Patients evaluated for hematuria by an APRN were less likely to receive a cystoscopy and had a longer wait until the procedure compared to those evaluated by a urologist; however, no differences were observed between PAs and urologists. Better understanding APP integration into urology clinics is warranted.

Necrotizing granulomatous epididymo-orchitis post intravesical BCG administration after brachytherapy for prostate cancer.

Urothelial carcinoma of the bladder remains a challenging disease to treat. Intravesical instillation of BCG has demonstrated tremendous efficacy in preventing recurrence. BCG related necrotizing granulomatous epididymo-orchitis is rare and has not been previously linked to brachytherapy for adenocarcinoma of the prostate. We hypothesize that prior brachytherapy has a deleterious effect on the verumontanum that can result in retrograde transmission of BCG particles leading to granulomatous epididymo-orchitis. This is the first case report of necrotizing granulomatous epididymo-orchitis related to BCG in a patient status post brachytherapy for adenocarcinoma of the prostate.

Functional and oncologic outcomes of prostate capsule-sparing radical cystectomy: A systematic review and meta-analysis.

Radical cystectomy (RC) is the gold standard treatment for patients with organ-confined bladder cancer. However, despite the success of this treatment, many men who undergo orthotopic neobladder substitution develop significant erectile dysfunction and urinary symptoms, including daytime and nighttime urinary incontinence. Prostate-capsule-sparing radical cystectomy (PCS-RC) with orthotopic neobladder (ONB) has been described in the literature as a surgical technique to improve functional outcomes in appropriately selected patients. We performed a systematic review and meta-analysis of manuscripts on PCS-RC with ONB published after 2000. We included retrospective and prospective studies with more than 25 patients and compared PCS-RC with nerve-sparing or conventional RC. Studies in which the entire prostate was spared (including the transitional zone) were excluded. Comparative studies were analyzed to assess rates of daytime continence, nighttime continence, and satisfactory erectile function in patients undergoing PCS-RC compared with those undergoing conventional RC. Fourteen reports were included in the final review. Our data identify high rates of daytime (83%-97%) and nighttime continence (60%-80%) in patients undergoing PCS-RC with ONB. In comparative studies, meta-analysis results demonstrate no difference in daytime continence (RR:1.12; 95% CI: 0.72-1.73) in those undergoing PCS-RC compared to those undergoing conventional RC. Similarly, nighttime continence was similar between the 2 groups (RR:1.85; 95% CI: 0.57-6.00. Erectile function was improved in those undergoing PCS-RC (RR 5.35; 95% CI: 1.82-15.74) in the PCS-RC series. Bladder cancer margin positivity and recurrence rates were similar to those reported in the literature with conventional RC with an average weighted follow-up of 52.2 months. While several studies utilized different prostate cancer (CaP) screening techniques, the rates of CaP were low (incidence 0.02; 95% CI:0.01-0.04), and oncologic outcomes were similar to standard RC. PCS-RC is associated with improved nighttime continence and erectile function compared to conventional RC techniques. Further work is needed to standardize CaP screening before surgery, but the data suggest low rates of CaP with similar oncologic outcomes when compared to RC.

Standardization of the evaluation and surveillance of patients with BCG unresponsive high grade non-muscle invasive bladder cancer clinical trials.

There are multiple ongoing and planned clinical trials that are evaluating novel therapies to treat patients with BCG-unresponsive high grade nonmuscle invasive bladder cancer (NMIBC). Importantly, there is considerable variation in surveillance strategies between these clinical trials, specifically with regards to the use of advanced imaging, enhanced cystoscopy, and mandatory biopsies, which could impact landmark efficacy assessments of investigational agents. To present guideline recommendations for the standardization of cystoscopic evaluation, surveillance, and efficacy assessments for patients with BCG-unresponsive NMIBC participating in clinical trials. On September 29, 2023 at the annual meeting of the International Bladder Cancer Network, a breakout session was convened, during which representatives from various disciplines discussed potential guidance statements with opportunity for discussion and comment. A set of statements regarding use of white light and enhanced cystoscopy were developed to help guide a pragmatic approach to surveillance and efficacy assessments of patients in clinical trials. The use of "for cause" and "mandatory" biopsies was also addressed. A standard approach to evaluation of patients within the context of clinical trials is necessary to accurately assess the efficacy of novel agents, especially within single arm trials that lack an appropriate comparator. Additionally, the utilization and timing of mandatory biopsies is critical, as these biopsies may impact both disease evaluations and the determination of duration of response.

Bladder-Preserving Trimodality Therapy With Capecitabine.

INTRODUCTION: Many patients with muscle-invasive bladder cancer are poor candidates for radical cystectomy or trimodality therapy with maximal transurethral resection of bladder tumor (TURBT) and chemoradiotherapy with cisplatin or mitomycin C. Given the benefit of chemotherapy in bladder-preserving therapy, less-intense concurrent chemotherapy regimens are needed. This study reports on efficacy and toxicity for patients treated with trimodality therapy using single-agent concurrent capecitabine. MATERIALS AND METHODS: Patients deemed ineligible for radical cystectomy or standard chemoradiotherapy by a multidisciplinary tumor board and patients who refused cystectomy were included. Following TURBT, patients received twice-daily capecitabine (goal dose 825 mg/m2) concurrent with radiotherapy to the bladder +/- pelvis depending on nodal staging and patient risk factors. Toxicity was evaluated prospectively in weekly on-treatment visits and follow-up visits by the treating physicians. Descriptive statistics are provided. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS: Twenty-seven consecutive patients met criteria for inclusion from 2013 to 2023. The median age was 79 with 9 patients staged cT3-4a and 7 staged cN1-3. The rate of complete response in the bladder and pelvis was 93%. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival at 2 years were estimated as 81%, 65%, 91%, 75%, and 92%, respectively. There were 2 bladder recurrences, both noninvasive. There were 7 grade 3 acute hematologic or metabolic events but no other grade 3+ toxicities. CONCLUSION: Maximal TURBT followed by radiotherapy with concurrent capecitabine offers a high rate of bladder control and low rates of acute and late toxicity.

Effective population size in simple infectious disease models.

Almost all models used in analysis of infectious disease outbreaks contain some notion of population size, usually taken as the census population size of the community in question. In many settings, however, the census population is not equivalent to the population likely to be exposed, for example if there are population structures, outbreak controls or other heterogeneities. Although these factors may be taken into account in the model: adding compartments to a compartmental model, variable mixing rates and so on, this makes fitting more challenging, especially if the population complexities are not fully known. In this work we consider the concept of effective population size in outbreak modelling, which we define as the size of the population involved in an outbreak, as an alternative to use of more complex models. Effective population size is an important quantity in genetics for estimation of genetic diversity loss in populations, but it has not been widely applied in epidemiology. Through simulation studies and application to data from outbreaks of COVID-19 in China, we find that simple SIR models with effective population size can provide a good fit to data which are not themselves simple or SIR.

Purple urine bag syndrome: An unusual manifestation of urinary tract infection, our experience at a tertiary care center.

Background: Purple urine bag syndrome (PUBS) is an unusual condition in which a purple discoloration of urine and bag occurs in people with urinary catheters. People with purple urine usually do not complain of any symptoms. The purple discoloration of the urine bag is often the only finding, frequently noted by caregivers. Materials and methods: This prospective observational study was conducted at our tertiary care institute from June 2018 to May 2020. A total of 46 patients with PUBS were included in this study. The objective of our study was to record the prevalence of each predisposing factor and to correlate the pathological mechanism through which the PUBS is manifested. Results: The mean age of PUBS patients was 67.4years and 67.4% were males. Most patients of PUBS (60.9%) had a urethral catheter, while there was percutaneous nephrostomy in 26.1% patients and 13% patients had a percutaneous suprapubic cystostomy catheter. Among the patients, 69.65% were bedridden or in an institutionalized situation, 73.9% were suffering from chronic constipation, 21.7% were associated with dementia, and 47.8% were cerebrovascular accidents with hemiparesis patients. In addition, 93.5% of patients presented with alkaline urine and 3 patients with acidic urine. The most common bacteria isolated in urine culture were E coli and Pseudomonas. Conclusions: Urinary catheter associated urinary tract infection and PUBS is most commonly documented in females, but our study showed that it is more common in males. The appearance of a purple bag does not depend on the material and type of the catheter or the catheterization method. In addition, no correlation was found between the microorganisms isolated from the environment and patients' urine.

The "Wind Surf" Deformity-Correcting Fixed Flexion Deformity and Hyperextension in Bilateral CAS TKA.

Severe knee arthritis can result in complex coronal and sagittal angular deformities. Windswept deformity is used to describe a varus deformity and contralateral valgus deformity. We recognized a new sagittal pattern at the time of computer-assisted surgery (CAS) in total knee arthroplasty (TKA) in which one knee has a fixed flexion deformity (FFD), while the contralateral knee has a hyperextension deformity. We propose to define it as "wind surf" deformity mimicking the opposite pull of the wind and a surfer. The incidence of "wind surf" deformity in this series was 0.96% among a cohort of 2,291 bilateral TKAs performed between 2013 and 2018. Twenty-two patients were identified with an FFD of 5° to 20° on one knee and recurvatum of -5° to -20° on the contralateral knee. Additional bone resection and soft-tissue releases were performed for the FFD with a goal to maintain residual 1° to 3° of flexion. Minimal bone resection and soft-tissue disruption were performed on the knee with hyperextension with a goal to maintain 5° to 7° of flexion. These opposite strategies applied with the help of CAS prevented recurrence resulting in satisfactory clinical results at 2-year follow-up. The "wind surf" deformity variant should be identified in patients presenting with severe knee arthritis to guide surgical treatment, prevent recurrence, and obtain favorable clinical patient outcomes.

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Patients with Bacillus Calmette­Guérin (BCG)­unresponsive non­muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell­activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan­Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan­Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer­specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

Management of Lateral Femoral Condyle Non-union with Autogenous Bone Graft in CAS Total Knee Arthroplasty.

Introduction: Neglected distal femur fractures often present with significant uncontained bone defects of the lateral femoral condyle (LFC) leading to a valgus deformity and lateral compartment arthritis. Case Report: Bone defect can be managed with the help of autogenous bone graft harvested from a distal femur cut and shaped in the form of an augment. The objective of using bone graft along with the primary femur was to restore bone stock in a young patient and prevent the use of an augment with a revision femur and intramedullary rod. Conclusion: The use of computer navigation helped in getting accurate components and overall alignment thus facilitating compression at the bone graft site and early union.

Model-based intensification of CHO cell cultures: One-step strategy from fed-batch to perfusion.

There is a growing interest in continuous processing of the biopharmaceutical industry. However, the technology transfer from traditional batch-based processes is considered a challenge as protocol and tools still remain to be established for their usage at the manufacturing scale. Here, we present a model-based approach to design optimized perfusion cultures of Chinese Hamster Ovary cells using only the knowledge captured during small-scale fed-batch experiments. The novelty of the proposed model lies in the simplicity of its structure. Thanks to the introduction of a new catch-all variable representing a bulk of by-products secreted by the cells during their cultivation, the model was able to successfully predict cellular behavior under different operating modes without changes in its formalism. To our knowledge, this is the first experimentally validated model capable, with a single set of parameters, to capture culture dynamic under different operating modes and at different scales.