Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial.

There is a critical unmet need for safe and efficacious neoadjuvant treatment for cisplatin-ineligible patients with muscle-invasive bladder cancer. Here we launched a phase 1b study using the combination of intravesical cretostimogene grenadenorepvec (oncolytic serotype 5 adenovirus encoding granulocyte-macrophage colony-stimulating factor) with systemic nivolumab in cisplatin-ineligible patients with cT2-4aN0-1M0 muscle-invasive bladder cancer. The primary objective was to measure safety, and the secondary objective was to assess the anti-tumor efficacy as measured by pathologic complete response along with 1-year recurrence-free survival.

Comparing direct medical care costs of patients with bladder cancer who received an ileal conduit vs. neobladder in the year following cystectomy.

Purpose: Bladder cancer is 1 of the most costly cancers, however there is limited research on medical care costs by type of urinary diversion. The objective of our study was to compare medical care costs of the 2 most common urinary diversions in the year following radical cystectomy.

Methods: The Bladder Cancer Quality of Life Study included patients diagnosed with bladder cancer who underwent radical cystectomy and received an ileal conduit (IC, n = 821) or neobladder (NB, n = 181) in 3 integrated health systems.

The IgLON family of cell adhesion molecules expressed in developing neural circuits ensure the proper functioning of the sensory system in mice.

Deletions and malfunctions of the IgLON family of cell adhesion molecules are associated with anatomical, behavioral, and metabolic manifestations of neuropsychiatric disorders. We have previously shown that IgLON genes are expressed in sensory nuclei/pathways and that IgLON proteins modulate sensory processing. Here, we examined the expression of IgLON alternative promoter-specific isoforms during embryonic development and studied the sensory consequences of the anatomical changes when one of the IgLON genes, Negr1, is knocked out.

Osteogenesis Imperfecta: A study of the patient journey in 13 European countries.

Introduction: Osteogenesis imperfecta (OI) is a heritable skeletal disorder and comprises various subtypes that differ in clinical presentation, with Type I considered the least severe and Types III/IV the most severe forms. The study aim was to understand the OI patient diagnostic and treatment journey across Europe.

Methods: We conducted a qualitative, descriptive study to understand the OI patient journey.

Inter-kingdom communication and the sympoietic way of life.

Organisms are now seen as holobionts, consortia of several species that interact metabolically such that they sustain and scaffold each other's existence and propagation. Sympoiesis, the development of the symbiotic relationships that form holobionts, is critical for our understanding the origins and maintenance of biodiversity. Rather than being the read-out of a single genome, development has been found to be sympoietic, based on multigenomic interactions between zygote-derived cells and symbiotic microbes.

Feasibility of a Smartphone Application for Education and Symptom Management of Patients With Renal Cell Carcinoma on Combined Tyrosine Kinase and Immune Checkpoint Inhibitors.

Purpose: Patients with advanced renal cell carcinoma (RCC) face significant challenges, stemming both from the complexities of the disease itself and the adverse effects of treatments. This study evaluated the feasibility and acceptability of a mobile health (mHealth) application tailored for education and symptom management of patients with advanced RCC receiving combined immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) therapy.

Methods: The primary end points were acceptability and feasibility.

"When does human life begin?" teaching human embryology in the context of the American abortion debate.

The Dobbs decision of the United States Supreme Court and the actions of several state legislatures have made it risky, if not outright dangerous, to teach factual material concerning human embryology. At some state universities, for instance, if a professor's lecture is felt to teach or discuss abortion (as it might when teaching about tubal pregnancies, hydatidiform moles, or eneuploidy), that instructor risks imprisonment for up to 14 years (Gyori, 2023). Some states' new censorship rules have thus caused professors to drop modules on abortion from numerous science and humanities courses.

Reprint of: Prelude to molecularization: The double gradient model of Sulo Toivonen and Lauri Saxén.

The present molecular investigations of Organizer phenomena show a remarkable connection to the earlier classical embryological studies that used transplantation as a method for making mechanistic models of induction. One of the most prominent of these connections is the dual gradient model for anterior-posterior and dorsal-ventral polarity. This paper will discuss some of the history of how transplantation experiments provided data that could be interpreted in terms of two gradients of biologically active materials.

Cost-utility of Initial Management of High-grade T1 Bladder Cancer With Intravesical BCG vs Immediate Radical Cystectomy.

Objective: To compare the cost-utility of initial management of high-grade T1 non-muscle invasive bladder cancer (HGT1 NMIBC) with intravesical BCG vs immediate radical cystectomy. High-risk NMIBC patients may climb a costly ladder of treatments, culminating in radical cystectomy for oncologic or symptomatic benefit in up to one-third. This high healthcare resource utilization presents a challenging dilemma in balancing sufficiently aggressive management with cost, toxicity, and quality-of-life.

15 years of patient-reported outcomes in clinical trials leading to GU cancer drug approvals: a systematic review on the quality of data reporting and analysis.

Background: Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies.

Methods: A systematic review of the FDA archives identified GU cancer drug approvals from Feb 2007 to July 2022.

Comparative Effectiveness of Neoadjuvant Pembrolizumab Versus Cisplatin-based Chemotherapy or Upfront Radical Cystectomy in Patients with Muscle-invasive Urothelial Bladder Cancer.

Background: Recent progresses in the use of immune checkpoint inhibitor (ICI) have challenged the therapeutic standards in patients with muscle-invasive urothelial bladder carcinoma (MIBC).

Objective: To compare neoadjuvant pembrolizumab followed by radical cystectomy (RC) versus neoadjuvant chemotherapy (NAC) and RC or upfront RC, according to cisplatin eligibility.

Design, Setting, And Participants: We conducted two separate analyses for cisplatin-eligible and cisplatin-ineligible cT2-4N0M0 MIBC patients.

Interruptions in bladder cancer care during the COVID-19 public health emergency.

Background: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care.

Methods: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020.

Protocol of the Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high-grade non-muscle invasive bladder cancer.

Background: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians.

Prelude to molecularization: The double gradient model of Sulo Toivonen and Lauri Saxén.

The present molecular investigations of Organizer phenomena show a remarkable connection to the earlier classical embryological studies that used transplantation as a method for making mechanistic models of induction. One of the most prominent of these connections is the dual gradient model for anterior-posterior and dorsal-ventral polarity. This paper will discuss some of the history of how transplantation experiments provided data that could be interpreted in terms of two gradients of biologically active materials.

Factors Associated with Self-reported COVID-19 Infection and Hospitalization among Patients Seeking Care at a Comprehensive Cancer Center.

Background: COVID-19 infection severity differs by race and ethnicity, but its long-term effect on cancer-related outcomes is unknown. Therefore, information on COVID-19 history is critical to ascertain among new cancer patients in order to advance research on its impact on cancer outcomes and potentially related health disparities.

Methods: A cross-sectional study was conducted among 16,025 new patients seeking care at Moffitt Cancer Center (MCC) between 2021 and 2022.

Effectiveness of perioperative chemotherapy and radical cystectomy in treating bladder cancer.

Background: Despite abundant evidence supporting the use of perioperative chemotherapy from clinical trials, no study to date has comprehensively evaluated its use in the treatment of muscle-invasive bladder cancer (MIBC) in the real-world setting. Little is known regarding the impact of pretreatment disease stage and real-world factors such as patient comorbidities preventing timely completion of therapy on its effectiveness. This study aims to assess the usage of perioperative chemotherapy and examines its impact on pathologic downstaging rates and recurrence free survival in patients undergoing radical cystectomy.

Examining disparities in large-scale patient-reported data capture using digital tools among cancer patients at clinical intake.

Background: Patient-reported data can improve quality of healthcare delivery and patient outcomes. Moffitt Cancer Center ("Moffitt") administers the Electronic Patient Questionnaire (EPQ) to collect data on demographics, including sexual orientation and gender identity (SOGI), medical history, cancer risk factors, and quality of life. Here we investigated differences in EPQ completion by demographic and cancer characteristics.

Teaching Conservative Kidney Management and Other Palliative Care Skills in Nephrology Fellowships.

Offering and providing effective conservative kidney management (CKM) for patients with end-stage kidney disease who do not want dialysis is a foundational skill that all nephrology fellows should learn during fellowship training. However, the current educational landscape in fellowship training programs is sparse and is not recognized currently as a skill within the Accreditation Council for Graduate Medical Education (ACGME) guidelines. Moreover, there is no standardized curriculum, methods of assessment of this learning objective, and no structure for implementation within general and subspecialty nephrology training programs.

A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder.

Purpose: Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, against BCG-unresponsive carcinoma in situ (CIS).

Patients And Methods: Patients with BCG-unresponsive CIS-containing NMIBC received durvalumab IV at 1,500 mg every 4 weeks for up to 12 months.

Downstaging and Survival Associated with Neoadjuvant Immunotherapy Before Radical Cystectomy for Muscle-invasive Bladder Cancer.

Background: Neoadjuvant cisplatin-containing chemotherapy before radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer (MIBC). However, a large proportion of patients are ineligible for cisplatin. Single-arm phase 2 neoadjuvant immunotherapy trials have reported promising tumor response rates, but interpretation is limited owing to lack of a comparator arm.