Impact of an intergenerational program to improve loneliness and social isolation in older adults initiated at the time of emergency department discharge: study protocol for a three-arm randomized clinical trial.

BACKGROUND: Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U? intervention using peer support from similar-aged volunteers and demonstrated reduced SIL among older adults discharged from the emergency department (ED). Generativity, defined as "the interest in establishing and guiding the next generation," can provide an alternative theoretical basis for reducing SIL via intergenerational programs between members of younger and older generations. The current protocol will examine the impact of younger intergenerational volunteers providing the HOW RU? METHODS: In this randomized clinical trial, we will compare the following three arms: (1) the standard same-generation peer support HOW R U? intervention, (2) HOW R U? intervention delivered by intergenerational volunteers, and (3) a common wait-list control group. Outcome assessors will be blinded to the intervention. Trained volunteers will deliver 12 weekly telephone support calls. We will recruit participants ≥ 70 years of age with baseline loneliness (six-item De Jong loneliness score of 2 or greater) from two EDs. Research staff will assess SIL, depression, quality of life, functional status, generativity, and perceived benefit at baseline, at 12 weeks, and 24 weeks post-intervention. DISCUSSION: We hypothesize participants receiving the intergenerational intervention will show improved outcomes compared to the control group and peer support HOW R U? INTERVENTION: We also hypothesize that participants with higher perceptions of generativity will have greater reductions in SIL than their lower generativity counterparts. Aging is experienced diversely, and social interventions combatting associated SIL should reflect that diversity. As part of a program of research following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, the findings of this RCT will be used to define which intervention characteristics are most effective in reducing SIL. TRIAL REGISTRATION: ClinicalTrials.gov NCT05998343 Protocol ID:21-0074E. Registered on 24 July 2023.

Distinct Features of Plasma Ultrashort Single-Stranded Cell-Free DNA as Biomarkers for Lung Cancer Detection.

BACKGROUND: Using broad range cell-free DNA sequencing (BRcfDNA-Seq), a nontargeted next-generation sequencing (NGS) methodology, we previously identified a novel class of approximately 50 nt ultrashort single-stranded cell-free DNA (uscfDNA) in plasma that is distinctly different from 167 bp mononucleosomal cell-free DNA (mncfDNA). We hypothesize that uscfDNA possesses characteristics that are useful for disease detection. METHODS: Using BRcfDNA-Seq, we examined both cfDNA populations in the plasma of 18 noncancer controls and 14 patients with late-stage nonsmall cell lung carcinoma (NSCLC). In comparison to mncfDNA, we assessed whether functional element (FE) peaks, fragmentomics, end-motifs, and G-Quadruplex (G-Quad) signatures could be useful features of uscfDNA for NSCLC determination. RESULTS: In noncancer participants, compared to mncfDNA, uscfDNA fragments showed a 45.2-fold increased tendency to form FE peaks (enriched in promoter, intronic, and exonic regions), demonstrated a distinct end-motif-frequency profile, and presented with a 4.9-fold increase in G-Quad signatures. Within NSCLC participants, only the uscfDNA population had discoverable FE peak candidates. Additionally, uscfDNA showcased different end-motif-frequency candidates distinct from mncfDNA. Although both cfDNA populations showed increased fragmentation in NSCLC, the G-Quad signatures were more discriminatory in uscfDNA. Compilation of cfDNA features using principal component analysis revealed that the first 5 principal components of both cfDNA subtypes had a cumulative explained variance of >80%. CONCLUSIONS: These observations indicate that the distinct biological processes of uscfDNA and that FE peaks, fragmentomics, end-motifs, and G-Quad signatures are uscfDNA features with promising biomarker potential. These findings further justify its exploration as a distinct class of biomarker to augment pre-existing liquid biopsy approaches.

Predictors of sentinel lymph node metastasis in very thin invasive melanomas.

BACKGROUND: Melanomas < 0.8 mm in Breslow depth have less than a 5% risk for nodal positivity. Nonetheless, nodal positivity is prognostic for this group. Early identification of nodal positivity may improve the outcomes for these patients. OBJECTIVES: To determine the degree to which ulceration and other high-risk features predict sentinel lymph node (SLN) positivity for very thin melanomas. METHODS: The National Cancer Database was reviewed from 2012 to 2018 for patients with melanoma with Breslow thickness < 0.8 mm. Data were analysed from 7 July 2022 through to 25 February 2023. Patients were excluded if data regarding their ulceration status or SLN biopsy (SLNB) performance were unknown. We analysed patient, tumour and health system factors for their effect on SLN positivity. Data were analysed using χ2 tests and logistic regressions. Overall survival (OS) was compared by Kaplan-Meier analyses. RESULTS: Positive nodal metastases were seen in 876 (5.0%) patients who underwent SLNB (17 692). Factors significantly associated with nodal positivity on multivariable analysis include lymphovascular invasion [odds ratio (OR) 4.5, P < 0.001], ulceration (OR 2.6, P < 0.001), mitoses (OR 2.1, P < 0.001) and nodular subtype (OR 2.1, P < 0.001). Five-year OS was 75% and 92% for patients with positive and negative SLN, respectively. CONCLUSIONS: Nodal positivity has prognostic significance for very thin melanomas. In our cohort, the rate of nodal positivity was 5% overall in these patients who underwent SLNB. Specific tumour factors (e.g. lymphovascular invasion, ulceration, mitoses, nodular subtype) were associated with higher rates of SLN metastases and should be used to guide clinicians in choosing which patients will benefit from SLNB.

Association of sociodemographic characteristics with utilization of sentinel lymph node biopsy for American Joint Committee on Cancer 8th edition T1b cutaneous melanoma.

Sentinel lymph node biopsy (SLNB) is an important staging and prognostic tool for cutaneous melanoma (CM). However, there exists a knowledge gap regarding whether sociodemographic characteristics are associated with receipt of SLNB for T1b CMs, for which there are no definitive recommendations for SLNB per current National Comprehensive Cancer Network guidelines. We performed a retrospective analysis of the 2012-2018 National Cancer Database, identifying patients with American Joint Committee on Cancer staging manual 8th edition stage T1b CM, and used multivariable logistic regression to analyze associations between sociodemographic characteristics and receipt of SLNB. Among 40,458 patients with T1b CM, 23,813 (58.9%) received SLNB. Median age was 62 years, and most patients were male (57%) and non-Hispanic White (95%). In multivariable analyses, patients of Hispanic (aOR 0.67, 95%CI 0.48-0.94) and other (aOR 0.78, 95%CI 0.63-0.97) race/ethnicity, and patients aged > 75 (aOR 0.33, 95%CI 0.29-0.38), were less likely to receive SLNB. Conversely, patients in the highest of seven socioeconomic status levels (aOR 1.37, 95%CI 1.13-1.65) and those treated at higher-volume facilities (aOR 1.29, 95%CI 1.14-1.46) were more likely to receive SLNB. Understanding the underlying drivers of these associations may yield important insights for the management of patients with melanoma.

Epidemiology, management, and treatment outcomes of metastatic spinal melanoma.

Metastatic spinal melanoma is a rare and aggressive disease process with poor prognosis. We review the literature on metastatic spinal melanoma, focusing on its epidemiology, management, and treatment outcomes. Demographics of metastatic spinal melanoma are similar to those for cutaneous melanoma, and cutaneous primary tumors tend to be most common. Decompressive surgical intervention and radiotherapy have traditionally been considered mainstays of treatment, and stereotactic radiosurgery has emerged as a promising approach in the operative management of metastatic spinal melanoma. While survival outcomes for metastatic spinal melanoma remain poor, they have improved in recent years with the advent of immune checkpoint inhibition, used in conjunction with surgery and radiotherapy. New treatment options remain under investigation, especially for patients with disease refractory to immunotherapy. We additionally explore several of these promising future directions. Nevertheless, further investigation of treatment outcomes, ideally incorporating high-quality prospective data from randomized controlled trials, is needed to identify optimal management of metastatic spinal melanoma.

Perception of culturally competent care among a national sample of skin cancer patients.

Given limited information about patient experiences with cultural competency within dermatology, we sought to characterize the perception of culturally competent care among skin cancer patients in the United States. We used the 2017 National Health Interview Survey (NHIS) to identify a sample of patients with skin cancer and analyzed responses to the following questions: "How important is it for providers to understand or share your culture?" and "How often are you able to see health care providers that understand or share your culture?" For each question, we calculated the overall prevalence along with adjusted odds ratios for each sociodemographic group. Overall, 31% (95% CI 27-35%) of skin cancer patients responded that it was very or somewhat important for providers to share/understand culture. Patients with income below 200% of the federal poverty level (aOR 1.52; 95% CI 1.02-2.25), foreign-born patients (aOR 3.33; 95% CI 1.25-8.88), and patients with the highest educational attainment of a high school diploma (aOR 1.50; 95% CI 1.08-2.09) all had increased odds of placing importance on sharing/understanding culture. Furthermore, 80% (95% CI 75-85%) of skin cancer patients responded that they were able to see providers that shared/understood their culture all or most of the time, and therefore 20% of patients had access to culturally competent care only some or none of the time. Our study revealed that many (31%) skin cancer patients highly value culturally competent care, with lower-income, foreign-born patients, and patients with the highest educational attainment of a high school diploma, placing greater importance on culturally competent care. However, as many (20%) skin cancer patients have limited access to culturally competent care, future research should focus on analyzing and improving care for patient groups affected by cultural barriers.

Geographic disparities in access to immunotherapy clinical trials for metastatic melanoma.

Survival outcomes for metastatic melanoma have drastically improved with the advent of immunotherapy. Access to ongoing immunotherapy clinical trials has become increasingly important to patients with advanced disease. We sought to quantify geographic disparities in access to these trials by U.S. division, region, urban/rural status, and median income. We searched ClinicalTrials.gov for interventional immunotherapy trials for metastatic melanoma from 2015 to 2021 and identified U.S. zip codes for each participating trial site. ArcGIS was used to calculate the one-way driving time from each zip code to the nearest treatment center. Melanoma burden in each zip code outside a 60 min driving radius was calculated by multiplying population by the corresponding state's cancer-specific mortality rate. χ2 tests were used to test for significance between census regions, divisions, and urban vs. rural zip codes, while logistic regression was used to quantify risk of poor access with median income. Across 148 trials, 4844 treatment centers were located in 1102 unique zip codes. 9010 zip codes were located greater than one-hour driving time from the nearest clinical trial. Southern regions were most likely to have poor access of all regions (p < 0.001), and rural status also significantly correlated with poor access (p < 0.001). For every $10,000 increase in median income, the likelihood of a zip code being within 60 min from a trial increased by 1.315. While immunotherapy continue to improve survival outcomes for metastatic melanoma, geographic access to clinical trials investigating these therapies remains a challenge for a significant proportion of the U.S. population.

T-Cell Mediated Immunity in Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and frequently lethal skin cancer with neuroendocrine characteristics. MCC can originate from either the presence of MCC polyomavirus (MCPyV) DNA or chronic ultraviolet (UV) exposure that can cause DNA mutations. MCC is predominant in sun-exposed regions of the body and can metastasize to regional lymph nodes, liver, lungs, bone, and brain. Older, light-skinned individuals with a history of significant sun exposure are at the highest risk. Previous studies have shown that tumors containing a high number of tumor-infiltrating T-cells have favorable survival, even in the absence of MCPyV DNA, suggesting that MCPyV infection enhances T-cell infiltration. However, other factors may also play a role in the host antitumor response. Herein, we review the impact of tumor infiltrating lymphocytes (TILs), mainly the CD4+, CD8+, and regulatory T-cell (Tregs) responses on the course of MCC, including their role in initiating MCPyV-specific immune responses. Furthermore, potential research avenues related to T-cell biology in MCC, as well as relevant immunotherapies are discussed.

Imaging ligands targeting glypican-3 receptor expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality. Early detection of HCC is important since potentially curative therapies exist in the initial stages of HCC; no curative therapies exist for late-stage HCC. However, the initial detection of HCC remains challenging due to the lack of symptoms during the early stage of the disease. Other methods of screening and detecting HCC, including blood serum tests and conventional imaging methods, remain inadequate due to genetic differences between patients and the high background activity of liver tissues. Thus, there is a need for an accurate imaging agent for the diagnosis, staging, and prognosis of HCC. Glypican-3 (GPC3) is an oncofetal receptor responsible for regulating cell division, growth, and survival. GPC3 is a clinically relevant biomarker for imaging and therapeutics, as its expression is HCC tumor-specific and absent from normal and other pathological liver tissues. The development of novel GPC3-targeting imaging agents has encompassed three classes of biomolecules: peptides, antibodies, and aptamers. These biomolecules serve as constructs for diagnostic imaging (demonstrating potential as positron emission tomography [PET], single-photon emission tomography [SPECT], and optical imaging agents) and HCC treatment delivery. More than 20 unique ligands have been identified in the literature as showing specificity for the GPC3 receptor. Although several ligands are currently under clinical investigation as therapies for HCC, clinical translation of GPC3-targeting ligands as imaging agents is lacking. This review highlights the current landscape of ligands targeting GPC3 and describes their promising possibilities as imaging agents for HCC.

Labiaplasty: Analysis of the National Surgical Quality Improvement Program Database.

BACKGROUND: Labiaplasty is an increasingly popular procedure performed for both cosmetic and pathologic etiologies. Questions have been raised regarding the efficacy of the procedure, especially for cosmetic etiologies. OBJECTIVES: The aim of this study was to examine the complication profiles of labiaplasties for both cosmetic and pathologic etiologies. METHODS: The 2005 to 2017 National Surgical Quality Improvement Program database was analyzed for patients who, according to the relevant Current Procedural Terminology code, had undergone labiaplasties. Our cohort was further separated into cosmetic and pathologic groups based on International Classification of Diseases codes. Information was collected on patient demographic characteristics, patient comorbidities, and operative variables. Outcomes of interest included surgical complications and delayed length of stay (DLOS). A univariate analysis and multivariate logistic regression were applied to determine statistically significant predictors of our outcomes of interest for both etiologies. RESULTS: There were 640 patients in the cosmetic cohort and 1919 patients in the pathologic cohort. There were no significant differences in rates of surgical complications between the 2 groups, but there was a statistically significant increase in length of stay for the pathologic group. Univariate analysis revealed operative time and plastic surgeon specialty to be predictive of DLOS in the cosmetic cohort. No covariates were implicated with multivariate analysis for either surgical complications or for DLOS in the cosmetic cohort. CONCLUSIONS: Our findings suggest that cosmetic labiaplasty is a safe and efficacious procedure with low complication rates and no predictors of adverse outcomes.

A Multimetric Readability Analysis of Online Patient Educational Materials for Submental Fat Reduction.

BACKGROUND: Patients often utilize the Internet to seek information related to their care. This study assesses the readability of online patient educational materials for submental fat reduction. METHODS: Patient educational materials from the 12 most popular websites related to submental fat reduction were downloaded and assessed for readability grade level using 10 unique scales. RESULTS: Analysis of the 12 most popular websites (and corresponding 47 articles) revealed that patient educational materials were written, on average, at an 11th grade reading level. The Flesch Reading Ease score was 48.9 (range 39.8-59.2), representing a "difficult" level of reading. Mean readability grade levels (range 9-13th grade for individual websites) were as follows: Coleman-Liau, 11.1; Flesch-Kincaid, 10.8; FORCAST, 10.8; Fry Graph, 10.1; Gunning Fog, 12.7; New Dale-Chall, 10.1; New Fog Count, 11.8; Simple Measure of Gobbledygook, 11.7; Raygor, 6.7. No website was at the 6th grade reading level for patient educational materials recommended by the American Medical Association and National Institutes of Health. CONCLUSIONS: Online patient educational materials for submental fat reduction are written well above the recommended reading level. Recognition of disparities in health literacy is necessary to enable patients to make informed decisions and become active participants in their own care. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

Evaluation of the Content of Ophthalmology Fellowship Program Web sites.

Purpose To assess the availability and content of fellowship program Web sites (FPWs) among ophthalmology subspecialties. Design This is a cross-sectional study. Subjects Web sites of all Association of University Professors of Ophthalmology-accredited fellowship programs in five subspecialties (i.e., surgical retina and vitreous; cornea, external disease, and refractive surgery; glaucoma; neuro-ophthalmology; and pediatric ophthalmology). Methods FPWs were assessed for the presence of 26 key content criteria encompassing program demographics ( n = 13), features ( n = 10), and social life ( n = 3). The presence of each content criterion as well as the content criteria groups were compared across subspecialties. Main Outcome Measures The main outcome measured is the average percentage of key content criteria present among ophthalmology fellowship Web sites. Results Among 266 accredited fellowship programs, 240 (90.2%) had Web sites. On average, Web sites reported 14.9 of 26 key content criteria (57.2%), 8.29 of 13 demographic criteria (63.8%), 5.84 of the 10 program features criteria (58.4%), and 0.705 of the 3 social life criteria (23.5%). Significant differences were identified among subspecialties in the presence of program description ( p = 0.046), hospital affiliation ( p < 0.001), names of current fellows ( p = 0.004), case diversity ( p = 0.001), and surgical statistics ( p = 0.015). The average number of key criteria differed between subspecialties ( p < 0.001). Conclusion There is significant heterogeneity in program fellowship Web site content among ophthalmology subspecialties. Information regarding social life, such as wellness programs and community information, was largely absent across all disciplines. Addressing missing information on ophthalmology FPWs may help optimize program-applicant fit.