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Prevalence of High-Risk Human Papillomavirus in Squamous Cell Carcinomas of the Lacrimal Sac
No full textLacrimal sac malignancies are rare, with squamous cell carcinoma (SCC) being the most common type. High-risk human papillomavirus (HR-HPV) is a known driver of SCC in the oropharynx and other head and neck sites. This study investigated the prevalence of HR-HPV in primary lacrimal sac SCC using p16 immunohistochemistry and RNA in situ hybridization.
The pathology databases of the Florida Lions Eye Bank Ocular Pathology Laboratory and the Department of Pathology and Laboratory Medicine at the University of Miami Miller School of Medicine were reviewed for cases of primary lacrimal sac SCC with sufficient tissue for HR-HPV testing. P16 positivity was defined as strong, diffuse staining in >70% of tumor cells. RNA in situ hybridization was used to detect transcriptionally active HR-HPV.
Fifteen patients (mean age 63 years; 7 men and 8 women) with nonkeratinizing, papillary lacrimal sac SCC were identified. Twelve cases (80%) were positive for both p16 and HR-HPV by RNA in situ hybridization. All 3 HR-HPV negative cases were also p16-negative. Among HR-HPV-positive patients, 92% were Caucasian, with equal gender distribution. The most common presenting symptoms were epiphora (83%), erythema/edema (42%), and pruritus (33%). Most patients were treated with surgery and multimodal therapy. At follow-up (range 5-83 months), 92% of HR-HPV-positive patients were alive.
Primary lacrimal sac SCCs are frequently associated with HR-HPV and typically show nonkeratinizing, papillary morphology. p16 is a reliable surrogate marker for transcriptionally active HR-HPV in these tumors, supporting a potential etiologic role and diagnostic utility
Robotic-Assisted Simultaneous Bilateral Native Nephrectomy and Living Donor Kidney Transplantation
No full textSimultaneous bilateral nephrectomy and living donor kidney transplantation (LDKT) is often indicated for autosomal dominant polycystic kidney disease (ADPKD) with end-stage kidney disease (ESKD). Robotic-assisted surgery offers a minimally invasive alternative to open approaches and may reduce perioperative morbidity and length of stay.
Four adults with ADPKD/ESKD underwent fully robotic-assisted simultaneous bilateral nephrectomy/LDKT (RASBN/LDKT) at a single high-volume transplant center. All procedures used an intra-abdominal approach with a Pfannenstiel incision and GelPort for native kidney extraction and allograft introduction. Clinical, perioperative, and functional outcomes were recorded prospectively and analyzed retrospectively.
Median total operative time was 462.5 min (range, 401-544 min). Median length of stay was 3.5 days (range, 3-5 d). There were no intraoperative or postoperative vascular, urological, or surgical complications, and no conversions or hand assistance were required. All recipients had immediate graft function without delayed graft function (no hemodialysis in the first postoperative week). Kidney allograft function remained stable through 12 mo after transplant.
Robotic-assisted simultaneous bilateral nephrectomy/LDKT is feasible and safe in carefully selected ADPKD/ESKD recipients, providing excellent early clinical outcomes and expanding the role of minimally invasive techniques for complex scenarios
Mitigating chronic respiratory disease through the lens of multimorbidity: the MARES mixed-methods study protocol
No full textChronic respiratory diseases (CRDs), such as asthma and chronic obstructive pulmonary disease (COPD), are among the leading non-communicable diseases (NCDs) worldwide. However, diagnosing CRDs in low-income and middle-income countries (LMICs) remains challenging due to limited access to spirometry and trained professionals. Aggravating the burden, CRDs often coexist with other NCDs, increasing healthcare costs, reducing quality of life and elevating mortality. These challenges highlight the need for simple case-finding approaches for CRDs, such as the COPD in Low-Income and Middle-Income Countries Assessment (COLA-6) questionnaire, to support prompt identification and appropriate care within NCD services in LMICs.
To evaluate the discriminative accuracy, feasibility and implementation of the COLA-6 questionnaire in identifying and managing CRDs in Brazilian Primary Healthcare (PHC) services for NCDs.
The Multimorbidity Approach for REspiratory Solutions (MARES) study consists of three work packages to be conducted in PHC services in São Carlos/SP and São Paulo/SP, Brazil.MARES-1: A cross-sectional observational study enrolling 859 individuals with at least one NCD receiving care in PHC. The COLA-6 questionnaire will be administered by the research team and compared with quality-assured spirometry. The Chronic Airways Assessment Test (CAAT), Asthma Control Questionnaire (ACQ-7) and fractional exhaled nitric oxide (FeNO) will also be assessed. The diagnostic performance of COLA-6 for identifying CRDs-including COPD, asthma, preserved ratio impaired spirometry, restriction and overlaps-will be assessed using area under receiver operating characteristic curves and 95% CIs.MARES-2: A cross-sectional observational study enrolling 20 healthcare professionals (physicians, physiotherapists, community health agents and nurses) from five PHC services. These professionals will apply the COLA-6 during routine NCD care to a total sample of 1000 patients. Qualitative interviews will be conducted to explore barriers and facilitators to the implementation of COLA-6, using deductive thematic analysis.MARES-3: A longitudinal, prospective observational study in which patients from MARES-1 and MARES-2 will be reassessed at 6-month follow-up. A total sample of 473 participants with abnormal spirometry, a diagnosis of CRD or high risk for CRDs is expected. Participants will undergo spirometry, and a subset will be interviewed to explore their healthcare experiences through qualitative thematic analysis. Access to diagnostic and treatment services in Brazil will be assessed. Changes in spirometry values, FeNO, CAAT and ACQ-7 scores from baseline to 6 months in patients from MARES-1 will be analysed.
This study has been approved by the Ethics Committees of Federal University of São Carlos and University of Santo Amaro (UNISA). Ethical approval was also granted by the University College London. Results will be disseminated through peer-reviewed medical journals and presentations at international conferences. Results will improve identification of CRDs, addressing a significant gap in current PHC settings.
NCT07050823/NCT07093021/NCT07134855
Chapter 42 - Sleep and health equity
No full textThis chapter explores relationships between sleep health dimensions, social determinants, and associated health outcomes. We draw from the emerging and promising definition of sleep health developed by Buysse (2014) to formulate recommendations for advancing the concept of sleep health equity, which we argue is essential for reducing sleep health disparities and promoting equitable individual sleep health and ultimately as well at the population level
Chapter 7 - Race, socioeconomic position and sleep
No full textThe objective of this chapter is to describe the current landscape in health disparities science in the United States. After providing a brief overview of health disparities, we summarized the available influential published studies on inadequate sleep duration, poor sleep quality, and a group of commonly reported sleep disorders including insomnia, Obstructive Sleep Apnea, Narcolepsy, Restless Leg Syndrome, and Periodic Limb Movement. Overall, despite the heterogeneity in methodology measures and study population, black men and women report the shortest objective sleep duration relative to their white counterparts; while specific Hispanic subgroups may have been particularly at high risk for sleep disordered breathing. Several critical gaps remain with respect to other racial/ethnic groups and sexual minorities. Overall, we underlined the complex relationship between SES measures and perceived sleep health that may vary by racial/ethnic background. Finally, after exploring the potential influence on sleep health among minorities of acculturation, discrimination, worry and risk perception, and sleep opportunity, we later identified gaps in the literature and provided suggestions for future inquiry, including importance of personalized efficacious treatments adapted to the needs of vulnerable populations, and inclusion of sexual minorities
Chapter 20 - Sleep health and diabetes: The role of sleep duration, quality, disorders, and circadian rhythm on diabetes
No full textThe current chapter extensively examines the role of sleep health as both a risk and protective factor in relation to diabetes outcomes. It offers a comprehensive review of the existing literature, exploring how various aspects of sleep health, including duration, quality, sleep architecture (such as spindles, rapid eye movement sleep, and slow wave sleep), sleep disorders (such as insomnia and obstructive sleep apnea), and circadian rhythm, influence the likelihood of developing diabetes and its associated cardiometabolic complications, such as unhealthy glucose levels, poor glycemic control, insulin resistance, and elevated hemoglobin A1c levels. Conversely, we also highlight evidence suggesting that certain sleep parameters, when optimized, could potentially mitigate the risk of diabetes and related cardiometabolic outcomes. To provide a thorough understanding of the mechanisms underlying the relationship between sleep and diabetes, we draw upon a wide range of research and evidence, including epidemiological, observational, clinical trials, and experimental studies. By elucidating both the risk and protective effects of sleep health, this chapter aims to inform strategies for diabetes prevention and management in clinical practice and population health management
Rada Photography Mid-Century Architecture and Culture in South Florida and the Caribbean.
No full textThis is the first critical biography of the life and work of Annette and Rudi Rada, two photographers who captured the rise of Tropical Modern architecture in South Florida and the Caribbean during the mid-twentieth century
Development and Application of a Monoallelic HLA-DRB1 B Cell Immunopeptidomic Platform for Biotherapeutic Immunogenicity Risk Assessment
No full textImmunogenicity remains a challenge in biotherapeutic development. Current immunopeptidomic approaches that use monocyte derived dendritic cells suffer from donor variability and ambiguity in peptide-HLA restriction due to multiallelic expression. This dissertation describes the development of a monoallelic HLA-DRB1 B cell platform that addresses these limitations.Fifteen monoallelic HLA-DRB1 B cell lines were engineered from Raji cells through CRISPR-mediated knockout of endogenous HLA-DRB alleles, integration of a B cell receptor capable of binding human IgG, and stable transfection with individual HLA-DRB1 alleles. The platform proved to be both sensitive and reproducible, recapitulating peptide clusters observed with dendritic cells while allowing allelic specificity. Investigation of infliximab lead to the identification of a novel peptide cluster limited to B cells. Through immunoprecipitation of HLA-DR peptides of a CRISPR mediated knockout of HLA-DO from this cell line, it was determined that the differential presentation was not due to exclusive expression of HLA-DO in B cells versus dendritic cells. An additional infliximab cluster was identified from both HLA-DR and HLA-DP using HLA-DR and HLA-DP specific antibodies, respectively. Despite the peptides sharing identical sequences, the peptide showed a reproducible ability to activate T cells in HLA-DR expressing donors, but not those with HLA-DP. This coincides with predicted binding registers and non-germline residues in T cell receptor exposed regions.The outcome of this thesis establishes a validated platform for allele-specific immunopeptidomic analysis and demonstrates the importance of allele contextualization in immunogenicity risk assessment strategies. The platform provides a foundation for more precise population risk stratification and informed deimmunization strategies in biotherapeutic development
Clinical Trial Termination or Withdrawal in Head and Neck Squamous Cell Carcinoma
No full textInnovative clinical trials (CTs) are needed to address the rising incidence of head and neck squamous cell carcinoma (HNSCC). Despite adequate trial initiation, HNSCC CTs experience high failure rates, and the factors driving these trends remain unclear.
To assess the characteristics associated with failure (termination or withdrawal) in CTs for the treatment of HNSCC.
HNSCC CTs were identified on ClinicalTrials.gov from January 1, 2000, to December 31, 2024, and trial failures were defined as early termination or withdrawal. Trial characteristics were compared between failed CTs and completed CT controls. Data were analyzed from June to August 2025.
The primary outcome was trial failure. The association between failure and CT characteristics, including phase, enrollment, funding source, intervention type, and age-eligibility criteria, was analyzed using descriptive statistics and multivariable regression models.
A total of 692 matched trials were analyzed, including 346 trial failures and 346 completed control trials. The overall leading reasons for failure were strategic decisions (defined as nonscientific, sponsor-driven choices; 102 trials [29.5%]) and poor recruitment (90 trials [26.0%]). The reasons for failure varied by trial characteristics. Strategic decisions were the predominant reason for failure in phase 1 trials, industry-sponsored trials, and immunotherapy and targeted therapy trials. In contrast, poor recruitment was a more common reason in later-phase trials, non-industry-sponsored trials, and trials investigating chemotherapy, radiation, chemoradiation, combination treatments, and supportive care. Temporal analysis revealed a growing failure rate among CTs since 2000. Increased log-transformed actual enrollment safeguarded against trial failure, whereas industry funding was an independent risk factor.
In this study, HNSCC CTs were terminated early or withdrawn for a variety of reasons, most commonly due to strategic decisions or poor recruitment. Careful attention to trial characteristics associated with early failure is needed to overcome new barriers to drug development and adapt trial design to common reasons for failure
