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Oncologic Anthropology and the African Diaspora: Twenty-Year Anniversary Report, International Center for the Study of Breast Cancer Subtypes (ICSBCS)
No full textThe International Center for the Study of Breast Cancer Subtypes (ICSBCS) has played a vital role in defining and overcoming many inequities that exist in breast cancer treatment and outcome on a global basis through capacity-building programs that improve the management of breast cancer patients across the African diaspora. ICSBCS activities also fill critical gaps in disparities research related to the genetics of ancestry. Over the past 20 years, ICSBCS teams have spearheaded landmark studies documenting the relevance of genetic African ancestry to breast cancer risk, while also improving the quality of care delivered to patients in diverse communities. Herein, the achievements and future goals of this international, multi-institutional breast cancer research and outreach program are summarized
RSV Vaccine Effectiveness Against Hospitalization Among US Adults Aged 60 Years or Older During 2 Seasons
No full textIMPORTANCE: Respiratory syncytial virus (RSV) vaccines for adults aged 60 years or older became available in 2023. One dose is recommended for all adults aged 75 years or older and those aged 60 to 74 years at increased risk of severe RSV; however, duration of protection is unknown.
OBJECTIVE: To evaluate RSV vaccine effectiveness against RSV-associated hospitalization among adults aged 60 years or older during 2 RSV seasons.
DESIGN, SETTING, AND PARTICIPANTS: A total of 6958 adults aged 60 years or older were included in this test-negative, case-control study if they were hospitalized with acute respiratory illness at any of 26 hospitals in 20 US states during the October 1, 2023, to March 31, 2024, or October 1, 2024, to April 30, 2025, RSV seasons and had respiratory virus testing within 10 days of illness onset. Case patients tested positive for RSV only; control patients tested negative for RSV, SARS-CoV-2, and influenza. Demographic and clinical data were obtained through patient interview and electronic health records.
EXPOSURES: Receipt of 1 RSV vaccine dose at least 14 days before illness onset.
MAIN OUTCOMES AND MEASURES: Multivariable logistic regression was used to compare the odds of RSV vaccination among hospitalized cases and controls. Models were adjusted for age, sex, race and ethnicity, geographic region, and calendar month and year. Vaccine effectiveness was estimated as (1 - adjusted odds ratio) × 100%. Analyses were stratified by timing of RSV vaccine receipt (same vs prior season) relative to illness onset.
RESULTS: Of 6958 adults aged 60 years or older, 821 (11.8%) were RSV cases and 6137 (88.2%) were controls. A total of 1438 patients were Black (20.1%) and 4314 were White (62.0%); 3534 were female (50.8%). Median age was 72 years (IQR, 66-80 years) and 1829 adults (26.3%) were immunocompromised. A total of 63 cases (7.7%) and 966 controls (15.7%) were vaccinated. Estimated vaccine effectiveness against RSV-associated hospitalization was 58% (95% CI, 45%-68%) during 2 seasons and 69% (95% CI, 52%-81%) for same-season vaccination vs 48% (95% CI, 27%-63%; P = .06) for prior-season vaccination. Estimated vaccine effectiveness during 2 seasons was significantly lower among immunocompromised adults (30%; 95% CI, -9% to 55%) than immunocompetent adults (67%; 95% CI, 53%-77%; P = .02) and among those with cardiovascular disease (56%; 95% CI, 32%-72%) vs without (80%; 95% CI, 62%-90%; P = .03).
CONCLUSIONS AND RELEVANCE: Respiratory syncytial virus vaccines prevented RSV-associated hospitalization during 2 seasons, although effectiveness was lower in patients with immunocompromise and cardiovascular disease than in those without these conditions. Ongoing monitoring is needed to determine the optimal RSV revaccination interval
Personalized survival predictions in chromophobe renal cell carcinoma: development of a machine learning-based web tool
No full textPURPOSE: Chromophobe renal cell carcinoma (ChRCC) is a rare subtype of renal cancer, characterized by distinct clinical and genetic features. Existing studies on ChRCC are limited, and there is a critical need to explore the prognostic factors and treatment outcomes in this patient population. We used machine learning (ML) to build prognostic models and developed the first predictive web-based tool for survival.
METHODS: The SEER database (2000-2020) was used for this study\u27s analysis. To identify the prognostic variables, we conducted Cox regression analysis and constructed prognostic models using five ML algorithms to predict the 5-year survival. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to validate the accuracy and reliability of ML models. We also performed Kaplan-Meier survival analysis.
RESULTS: Our study analyzed 10,700 patients with ChRCC and identified metastasis and tumor size as significant predictors of survival. Subtotal nephrectomy was associated with the highest survival rates. Chemotherapy and radiotherapy were infrequently used but were associated with worse survival outcomes, particularly in patients with metastasis. The developed ML models demonstrated high accuracy in predicting survival, and a web-based tool offered real-time survival predictions based on patient-specific data.
CONCLUSION: Our study identified key prognostic factors and developed a machine learning-based web tool for personalized survival predictions. Metastasis and tumor size are critical in determining patient outcomes, with subtotal nephrectomy showing the highest survival rate
Evolving treatment strategies in meningioma: from traditional approaches to emerging therapies
No full textBACKGROUND: Meningiomas are the second most prevalent adult central nervous system neoplasm, developing from arachnoid cap cells. While most are benign (WHO Grade I), atypical (Grade II), and anaplastic (Grade III), meningiomas portray aggressive behavior, higher relapse rates, and resistance to standard treatments.
OBJECTIVE: To study the progression of treatment strategies for meningiomas, underscoring emerging treatments and challenges, especially in recurrent and high-grade subtypes.
METHODS: A narrative review was conducted, identifying studies from the PubMed, Scopus, and Google Scholar databases (2000-2025). Keywords included meningioma, surgery, radiotherapy, targeted therapy, immunotherapy, and PRRT. Included studies addressed conventional or novel treatments for meningiomas.
RESULTS: Surgical resection continues as the gold standard, with the extent of removal impacting recurrence. Radiotherapy, comprising fractionated and stereotactic techniques, plays a vital role when surgery is incomplete or not possible. Chemotherapy demonstrates limited benefit. Advances in molecular profiling have shown genetic drivers (e.g., NF2, TRAF7, AKT1) and hormonal receptors as clinical targets. Emerging options include mTOR inhibitors (everolimus), anti-angiogenic agents (bevacizumab), PD-1/PD-L1 inhibitors (pembrolizumab), and peptide receptor radionuclide therapy (PRRT). Drug delivery treatments like convection-improved delivery show promise in improving CNS penetration. Nonetheless, resistance mechanisms, the absence of validated biomarkers, and insufficient trial data pose significant challenges.
CONCLUSION: Management of severe aggressive meningiomas is evolving with novel molecular and immunotherapeutic strategies. A multidisciplinary treatment strategy combining surgery, radiation, and targeted therapies, facilitated by further clinical trials and biomarker research, is necessary to enhance patient outcomes
Fibroblasts Attenuate Anti-Tumor Drug Efficacy in Tumor Cells via Paracrine Interactions with Tumor Cells in 3D Plexiform Neurofibroma Cultures
No full textPlexiform neurofibromas (hereafter called pNF1) are often diagnosed in early childhood and occur in about 30% of neurofibromatosis type 1 (NF1) patients. pNF1 exhibits aggressive growth along a nerve in the body and has substantial potential for progression to malignant peripheral nerve sheath tumors that are rarely curable. There are two recently FDA-approved drugs, selumetinib and mirdametinib, for pNF1 patients who have symptomatic and inoperable plexiform neurofibromas; however, these treatments achieve only approximately 30% tumor shrinkage. Fibroblasts, the most abundant cell types within the pNF1 tumor microenvironment, are implicated in pNF1 growth and invasion; however, how fibroblasts affect a drug response of pNF1 remains poorly understood. In the present study, we focused on contributions of fibroblasts to the drug resistance in pNF1 via their secretome. We employed our established three-dimensional (3D) culture system incorporating human pNF1 tumor cells (Nf1(-/-)) and primary fibroblasts (Nf1(+/-)) grown in our patented microfluidic culture chips for monocultures and parallel cocultures in which 3D pNF1 structures and fibroblasts share their secretome without direct cell-to-cell contact. Three-dimensional pNF1 structures in 3D parallel cocultures with fibroblasts exhibited greater drug resistance than ones in monocultures. We found that pNF1 tumor cells showed increased P-glycoprotein expression when incubated with fibroblast-derived conditioned media or parallel cocultured with fibroblasts, compared to control conditions. Pharmacological inhibition of P-glycoprotein partially restored drug sensitivity. Additionally, fibroblasts showed higher resistance to selumetinib and mirdametinib than pNF1 tumor structures, likely due to elevated P-glycoprotein levels. This study is the first to define precise roles of fibroblasts in pNF1 drug resistance, emphasizing the potential of fibroblast-targeted therapies as a promising approach to improve pNF1 treatment outcomes
Engineered miR-214 enriched Schwann cell-derived extracellular vesicles amplify therapeutic efficacy for peripheral neuropathy in T2D mice
No full textExtracellular vesicles (EVs) derived from healthy Schwann cells (SC-EVs) ameliorate peripheral neuropathy in diabetic mice and rescue sciatic nerve function in Schwann cell Dicer knockout mice in part via SC-EV cargo miRNAs. Among these miRNAs, miR-214 repairs nerve damage. The present study investigated whether engineered SC-EVs with elevated miR-214 (214-EVs), further amplify the therapeutic effect of naïve SC-EVs (naïve-EVs) on reducing diabetic peripheral neuropathy (DPN) in a mouse model of high-fat diet (HFD)-streptozotocin (STZ) induced type 2 diabetes. Compared to naïve-EVs, 214-EVs significantly improved motor and sensory nerve conduction velocity of the sciatic nerve and thermal latency, which were associated with increased intraepidermal nerve fiber density, axonal diameter, and myelin thickness in the sciatic nerve. Quantitative RT-PCR and Western blot analyses of sciatic nerve tissues showed that, compared to naïve-EVs, 214-EVs significantly increased miR-214 levels and downregulated axonal inhibitory protein PTEN and the myelination inhibitory protein cJUN. Furthermore, 214-EVs markedly suppressed neuroinflammation by decreasing CD68 + macrophages and inactivating the TLR4/NF-κB signaling pathway. Collectively, our findings demonstrate that miR-214-enriched SC-EVs are superior to naïve-EVs to ameliorate DPN and represent a promising EV-based therapeutic strategy
Are We Choosing and Training the Best Surgeons?
No full textThe U.S. orthopaedic surgery residency match is among the most competitive in medicine; in 2024, 40% of applicants were unmatched. This drives applicants to differentiate themselves, while residency programs aim to evaluate candidates holistically. In order to understand the process that is used to select and educate the best surgeons, we examined medical student advising, the role of national organizations, and programmatic practices for resident selection. Effective career advising is essential for attracting and supporting highly qualified applicants. Exposure through preclinical courses, clerkships, and accessible mentorship enhances interest in orthopaedics among applicants with an array of experiences, skills, and backgrounds. National initiatives (e.g., the Orthopaedic Residency Information Network [ORIN]) provide centralized resources to address disparities in information access, although further standardization and consolidation are needed. Collaboration among national stakeholders is necessary to ensure fairness in the match process and to attract the best applicants. Initiatives like preference signaling have shown promise, increasing interview rates at preferred programs and better aligning applicants with residency opportunities. However, barriers such as limited access to research, costly away rotations, and expensive applications disproportionately affect underrepresented groups, highlighting the need for systemic changes. Resident selection practices must evolve to counter the inefficiencies and biases. Holistic review processes, structured interviews, and mission-driven scoring can improve alignment with program values. Programs must consider their setting and their population and also consider applicants who demonstrate an understanding of, and have an interest in caring for, that community. Improving orthopaedic residency selection requires collaborative efforts across organizations, advisors, and programs to refine processes and ensure the selection and training of those who will advance clinical orthopaedics and the science of orthopaedic surgery and also meet the needs of all patient populations
Outcomes for Stress Incontinence Procedures for Men and Women With Neurogenic Lower Urinary Tract Dysfunction: A Multicenter Neurogenic Bladder Research Group Study
No full textOBJECTIVE: To compare the efficacy and durability of procedures to treat stress urinary incontinence (SUI) in male and female patients with neurogenic lower urinary tract dysfunction.
METHODS: A retrospective multi-institutional review by the Neurogenic Bladder Research Group of male and female patients with neurogenic lower urinary tract dysfunction who underwent urethral bulking injection (UBI), sling placement, or artificial urinary sphincter (AUS) for SUI between 2012 and 2020 was performed. The primary outcome was time to procedural failure, defined as return to baseline preoperative SUI symptoms and/or needing additional procedures for SUI. Men and women were analyzed separately, and univariate and multivariable models were constructed.
RESULTS: Forty-five males and 35 females were included. The majority had a diagnosis of spina bifida (men-60%, female-28%) or spinal cord injury (men-15%, female-5%). Median age for males was 33 years with median post-operative follow-up of 627 days. Six-month failure rates and median time to failure were: UBI-53% and 5.3 months; sling-21% and 42 months; AUS-21%. Median age for females was 44 years with median post-operative follow-up of 363 days. Six-month failure rates and median time to failure were: UBI-68% and 2.6 months; sling-50% and 7.3 months. Prior bladder reconstruction and spinal cord injury were associated with failure in males; prior urethral surgery was associated with failure in females.
CONCLUSION: SUI surgery outcomes differ between males and females with shorter failure-free survival with UBI compared to AUS and sling in males, while UBI and sling placement both demonstrated short failure-free survival in females
Radiotherapy Resources in Central Asia: An International Atomic Energy Agency Update
No full textPURPOSE: Radiation therapy is crucial in cancer treatment. However, low- and middle-income countries (LMICs), including Central Asia (Kazakhstan, Uzbekistan, Turkmenistan, Kyrgyzstan, Tajikistan), face increasing challenges because of limited radiation oncology resources, compounded by diverse health care systems and vast geography.
METHODS: A longitudinal, registry-based review analyzed the state of radiation oncology resources in Central Asia to assess current conditions and future needs, considering projected regional growth. Data were sourced from the Directory of Radiotherapy Centres (DIRAC) and GLOBOCAN 2020. A simple linear regression evaluated the relationship between machine capacity rate and Gross National Income (GNI) per capita.
RESULTS: As of 2022, the region has 75 megavoltage machines and 35 brachytherapy (BT) units, with all but two being high-dose rate BT. The number of megavoltage units per million population varies, ranging from 0.1 to 0.2 in Tajikistan, Kyrgyzstan, and Uzbekistan, and it is 2.3 in Kazakhstan. A significant correlation between GNI per capita and machine capacity was found (R(2) = 0.89, P = .014), indicating that higher GNI correlates with increased machine capacity. By 2030, a minimum of 115 megavoltage machines will be needed to meet demand, but only 75 are available as of 2022.
CONCLUSION: While progress has been made, there remain significant challenges to ensuring equitable access to radiation therapy across Central Asia, underscoring the need for additional resources to meet growing demands
Decreasing Patient Falls and Staff Workload through Enhanced Safety Rounds
No full texthttps://scholarlycommons.henryford.com/nursresconf2025/1008/thumbnail.jp