The Evolution of Nadofaragene Firadenovec: A Review and the Path Forward.

BACKGROUND: The intravesical gene therapy nadofaragene firadenovec (rAd-IFNα/Syn3) was FDA approved in 2022 for non-muscle invasive bladder cancer (NMIBC) unresponsive to frontline treatment with BCG, and the first gene therapy developed for bladder cancer. This non-replicating recombinant adenovirus vector delivers a copy of the human interferon alpha-2b gene into urothelial and tumor cells, causing them to express this pleotropic cytokine with potent antitumor effects. OBJECTIVE: To provide a historical overview describing how several decades of preclinical and clinical studies investigating the role of interferon in the treatment of bladder cancer ultimately led to the development of gene therapy with nadofaragene for NMIBC. METHODS: We conducted a review of the literature using PubMed, Google Scholar, and ClinicalTrials.gov to summarize our knowledge of the evolution of interferon-based therapy in NMIBC. RESULTS: The FDA approval of this therapy represents an important landmark in urologic oncology and several decades of research dedicated to the study of interferon's direct and indirect antitumor properties in NMIBC. The data gathered from the phase 1, 2, and 3 clinical trials continue to provide additional insights into the precise mechanisms underlying both the efficacy of and resistance to nadofaragene. CONCLUSIONS: Nadofaragene leverages the cytotoxic, anti-angiogenic, and immune-modulatory roles of interferon to effectively treat NMIBC that is resistant to BCG. Ongoing studies of resistance mechanisms and prognostic biomarkers have been promising; these will ultimately improve patient selection and allow for the modulation of factors in the tumor or immune microenvironment to further increase therapeutic response.

Do Skills Naturally Transfer Between Multiport and Single-Port Robotic Platforms? A Comparative Study in a Simulated Environment.

Introduction and Objective: With introduction of the da Vinci single-port (SP) system, we evaluated which multiport (MP) robotic skills are naturally transferable to the SP platform. Methods: Three groups of urologists: Group 1 (5 inexperienced in MP and SP), Group 2 (5 experienced in MP without SP experience), and Group 3 (2 experienced in both MP and SP) were recruited to complete a validated urethrovesical anastomosis simulation using MP followed by SP robots. Performance was graded using both GEARS and RACE scales. Subjective cognitive load measurements (Surg-TLX and difficulty ratings [/20] of instrument collisions camera and EndoWrist movement) were collected. Results: GEARS and RACE scores for Groups 1 and 3 were maintained on switching from MP to SP (Group 3 scored significantly higher on both systems). Surg-TLX and difficulty scores were also maintained for both groups on switching from MP and SP except for a significant increase in SP camera movement (+7.2, p = 0.03) in Group 1 compared to Group 3 that maintained low scores on both. Group 2 demonstrated significant lower GEARS (-2.9, p = 0.047) and RACE (-5.1, p = 0.011) scores on SP vs MP. On subanalysis, GEARS subscores for force sensitivity and robotic control (-0.7, p = 0.04; -0.9, p = 0.02) and RACE subscores for needle entry, needle driving, and tissue approximation (-0.9, p = 0.01; -1.0, p = 0.02; -1.0, p < 0.01) significantly decreased. GEARS (depth perception, bimanual dexterity, and efficiency) and RACE subscores (needle positioning and suture placement) were maintained. All participants scored significantly lower in knot tying on the SP robot (-1.0, p = 0.03; -1.2, p = 0.02, respectively). Group 2 reported higher Surg-TLX (+13 pts, p = 0.015) and difficulty ratings on SP vs MP (+11.8, p < 0.01; +13.6, p < 0.01; +14 pts, p < 0.01). Conclusions: The partial skill transference across robots raises the question regarding SP-specific training for urologists proficient in MP. Novices maintained difficulty scores and cognitive load across platforms, suggesting that concurrent SP and MP training may be preferred.

Improving Rates of Immediate Postoperative Intravesical Chemotherapy with Gemcitabine for Low-Grade Bladder Cancer: An Implementation Analysis.

INTRODUCTION: We sought to demonstrate how an implementation science framework can be used to increase rates of postoperative intravesical chemotherapy with gemcitabine in patients with low-grade, nonmuscle-invasive bladder cancer, thereby improving the quality of cancer care. METHODS: An audit performed at 2 University of Rochester Medical Center hospitals involved in the SWOG S0337 trial identified low usage rates of postoperative intravesical chemotherapy once study accrual closed. The Consolidated Framework for Implementation Research guided an evaluation of barriers to adoption of this evidence-based practice. Methods employed included an online survey of urologists' perceptions of postoperative gemcitabine, face-to-face interviews with key stakeholders and direct observation of utilization processes. Subsequent implementation strategies were mapped to identified barriers; educational training for urologists and support staff and refining workflow processes were critical aspects of the intervention. Repeat usage audits measured practice change at 1 year. RESULTS: The pre-intervention rate of appropriate use of intravesical gemcitabine was 11% at Strong Memorial Hospital and increased to 78% after 4 months and 88% after 12 months. The pre-intervention rate was 37% at Highland Hospital and increased to 82% after 4 months and 94% after 12 months. Over the period audited, 8 patients received gemcitabine who ultimately had nonlow-grade histology. CONCLUSIONS: Implementation science can be used to improve the impact of evidence-based findings in urological practice. The Consolidated Framework for Implementation Research has been used extensively in the literature and was adapted for postoperative intravesical chemotherapy with gemcitabine. This approach is feasible, generalizable, and results in durable practice change.

Spectrum of disease in HIV-positive patients presenting to a tertiary care hospital: a retrospective, cross-sectional review in Kumasi, Ghana.

BACKGROUND: HIV remains a significant public health dilemma in West and Central Africa. HIV-related morbidity and mortality are unjustly high, yet little is known about the spectrum of complicating comorbidities in HIV-positive patients who are admitted to hospitals in these regions. METHODS: This study involved a retrospective chart review to determine the common comorbidities and mortality rate of HIV-infected patients admitted over a six month period to the internal medicine service at the Komfo Anokye Teaching Hospital (KATH), a tertiary care center in Ghana. Patients admitted with a known or new HIV diagnosis from January to July 2016 were included. Data were collected regarding the number of new versus known cases admitted, the most common presenting complaints, final admitting diagnoses, and causes of mortality in these patients. RESULTS: During the six-month study period, 250 HIV-positive patients were admitted to KATH, and 245 of these individuals had valid survival time recorded. Of these patients, 145/245 (59.2%) were female. Median age of patients included in the study was 42 years old (IQR 35-51). The mortality rate for HIV patients admitted to the hospital was 35.5% (87 patients). One hundred and forty-five (59.4%) patients had a known history of HIV documented in their patient charts, while the remaining patients were newly diagnosed with HIV during their inpatient stay. Pulmonary tuberculosis predominated among diagnostic findings, with 40.4% of HIV-infected patients diagnosed with the condition while admitted. Patients presenting with neurological symptoms on admission were 2.14 (95% CI: 1.27-3.61) times more likely to die than those without neurological symptoms (p = .004). CONCLUSIONS: Over 40% of HIV-positive patients admitted to KATH were newly diagnosed with HIV at admission. While pulmonary tuberculosis was the most common co-morbidity, patients presenting with neurological symptoms were at higher risk of death. This study suggests that enhanced outpatient screening is needed for early diagnosis and prompt HAART initiation, as well as increased access to diagnostic modalities and treatment for HIV-positive patients with neurological symptoms.