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Introduction/ObjectivesPyoderma gangrenosum (PG) is a rare, rapidly progressive neutrophilic dermatosis commonly associated with systemic inflammatory diseases. We aimed to characterize the association of PG and inflammatory arthritis, as little is known outside of case reports and small cohort studies.MethodWe performed a systematic review in PubMed, EMBASE, and Scopus from inception to present using the terms arthritis and pyoderma gangrenosum. Patient demographics, clinical presentation, and treatment outcomes were recorded. Descriptive statistics and stratified analysis were used to compare factors of interest by type of arthritis.ResultsA total of 1399 articles were screened, and 129 patients with inflammatory arthritis and PG were included in the review. The most common types of arthritis were rheumatoid arthritis (RA) (50.4%), inflammatory bowel disease (IBD)–associated arthritis (10.9%), and psoriatic arthritis (8.5%). In the vast majority of cases, joint symptoms preceded PG, by a median of 10 years (inter-quartile range [IQR] 5–16). Corticosteroid monotherapy and biologic therapies, used alone or in combination, resulted in improvement or complete resolution of ulcers 71.4% and 67.3% of the time, respectively. Within the latter, infliximab, adalimumab, and anakinra were most successful in inducing remission overall. RA and non-RA did not differ significantly in treatment success or healing time.ConclusionsThis study shows that PG is frequently preceded by inflammatory arthritis, most commonly RA. Clinicians used a wide variety of treatment regimens with variable outcomes. While larger studies are needed to standardize the treatment of inflammatory arthritis-associated PG, this study suggests that in addition to systemic corticosteroids, biologic medications can be effective treatment options for these patients.Key Points.• Inflammatory arthritis, most commonly rheumatoid arthritis, often precedes rather than follows pyoderma gangrenosum.• Other forms of arthritis associated with PG included IBD-associated arthritis and psoriatic arthritis.• Biologic therapies, such as infliximab, adalimumab, and anakinra, were largely successful in treating arthritis-associated pyoderma gangrenosum and may play an important role in corticosteroid-sparing therapy or in a maintenance regimen for this subset of patients.• The type of inflammatory arthritis associated with pyoderma gangrenosum may not be a helpful treatment guide as it was not significantly associated with treatment outcomes or healing time.

Background Many studies examining weight trajectories have used adiposity measures shown to be problematic for trajectory analysis in children with obesity, and remission of obesity remains poorly understood. Objectives To describe weight trajectories for school-aged children, the rate of obesity remission and factors associated. Methods Children between 6 and 11 years of age with ≥3 valid height and weight measurements from an Oregon hospital-system over a minimum six-month period were included. Percent distance from the median body mass index (BMI) was used for modeling. Latent class analysis and linear mixed models were used to classify children based on their weight trajectory. Results We included 11,247 subjects with a median of 2.1 years of follow-up, with 1,614 (14.4%) classified as overweight and 1,794 (16.0%) classified as obese. Of subjects with obesity, 1% experienced remission during follow-up, whereas 23% of those with overweight moved to within a healthy weight range. Latent class analysis identified three classes within each weight-based stratum over time. The majority of children with overweight or obesity had a flat trajectory over time. Lower socioeconomic status was associated with a worsening trajectory. Latent class models using alternate measures (BMI, BMI z-scores, tri-ponderal mass index (TMI)) differed substantially from each other. Conclusions Obesity remission was uncommon using the adiposity metric of distance from the median though transition from overweight to healthy weight was more common. Children with low socioeconomic status have worse trajectories overall. The choice of adiposity metric may have a substantial effect on the outcomes.

BackgroundCheckpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response.MethodsWe evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg intravenous was given every 3 weeks for four doses with enzalutamide. The primary endpoint was prostate-specific antigen (PSA) decline of ≥50%. Secondary endpoints were objective response, PSA progression-free survival (PFS), time to subsequent treatment, and time to death. Baseline tumor biopsies were obtained when feasible, and samples were sequenced and evaluated for the expression of PD-L1, microsatellite instability (MSI), mutational and neoepitope burdens.ResultsFive (18%) of 28 patients had a PSA decline of ≥50%. Three (25%) of 12 patients with measurable disease at baseline achieved an objective response. Of the five responders, two continue with PSA and radiographic response after 39.3 and 37.8 months. For the entire cohort, median follow-up was 37 months, and median PSA PFS time was 3.8 months (95% CI: 2.8 to 9.9 months). Time to subsequent treatment was 7.21 months (95% CI: 5.1 to 11.1 months). Median overall survival for all patients was 21.9 months (95% CI: 14.7 to 28 .4 months), versus 41.7 months (95% CI: 22.16 to not reached (NR)) in the responders. Of the three responders with baseline biopsies, one had MSI high disease with mutations consistent with DNA-repair defects. None had detectable PD-L1 expression.ConclusionsPembrolizumab has activity in mCRPC when added to enzalutamide. Responses were deep and durable and did not require tumor PD-L1 expression or DNA-repair defects.Trial registration numberclinicaltrials.gov (NCT02312557).

Background The morbidity associated with advanced stage melanoma is an important consideration in the dialog surrounding early detection and overdiagnosis. Few studies have stratified melanoma patient quality of life (QoL) by stage at diagnosis. Objective We sought to investigate if melanoma stage is independently associated with changes in QoL within a large, community‐based melanoma registry. Secondarily, we investigated whether demographic factors such as age, geographic location or level of education are associated with changes in QoL in the same population. Methods 1108 melanoma patients were surveyed over a three‐month period using the QoL in Adult Cancer Survivors Survey, consisting of 47 items on a 7‐point frequency scale. Data were analysed using both descriptive statistical models and adjusted multivariate logistic regression. Results There were 677 respondents generating a 61% response rate. Overall, higher stage at diagnosis correlated with the largest decreases in QoL as it pertained to both general (p = 0.001) and Cancer‐Specific stressors (p < 0.001). Education level (p = 0.020), age (p < 0.001), rural area code designation (p = 0.020) and family history of melanoma (p = 0.017) were also independently associated with changes in QoL. Conclusion Earlier stage at melanoma diagnosis is associated with better QoL and thus represents a crucial intervention in patient care. Given our findings and the growing body of evidence surrounding morbidity in late‐stage melanoma, it is essential that QoL be included in assessing the benefits of early detection. The morbidity associated with advanced stage melanoma is an important consideration in the dialog surrounding early detection and overdiagnosis. Few studies have stratified melanoma patient quality of life by stage at diagnosis. We sought to investigate if melanoma stage is independently associated with changes in quality of life within a large, community‐based melanoma registry. We found that melanoma diagnosed at a later stage is associated with reduced quality of life as measured by distress over recurrence, finances, appearance, family, cognitive problems, fatigue, pain, sexual problems, and social avoidance. Thus, quality of life is an essential consideration in assessments of melanoma screening programs and early detection efforts.

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) presents significant diagnostic and prognostic challenges, as current biomarkers frequently fail to accurately stage disease, predict rapid metastatic recurrence (rPDAC), or assess response to neoadjuvant therapy (NAT). We investigated the potential for circulating neoplastic-immune hybrid cells (CHCs) as a non-invasive, multifunctional biomarker for PDAC. Methods: Peripheral blood specimens were obtained from patients diagnosed with PDAC. CHCs were detected by co-expression of pan-cytokeratin and CD45, normalized to 50,000 peripheral blood mononuclear cells. rPDAC was defined as metastatic recurrence within six months of margin-negative pancreatectomy. Cyclic immunofluorescence (CyCIF) analyses compared hybrid phenotypes in blood and tumors. Results: Blood samples were collected from 42 patients with PDAC prior to resection. Those with radiographically occult metastatic disease and rPDAC had higher preoperative CHC numbers compared to patients who did not (65.0 and 74.4, vs. 11.52 CHCs; p < 0.001). Patients with complete or near-complete pathologic responses to NAT had lower preoperative CHC numbers than partial and/or non-responders (1.7 vs. 13.1 CHCs; p = 0.008). When assessed longitudinally, those with partial pathologic response saw CHC levels become undetectable while on treatment but increase in the interval between NAT completion and resection. In contrast, patients with poor responses or development of metastatic disease experienced persistent CHC detection during therapy or rising levels prior to radiographic evidence of metastases. Further, in metastatic PDAC patients, treatment-induced phenotypic changes in hybrid cells mirrored those in paired metastatic tumor samples. Conclusions: CHC enumeration and phenotyping display promise as a real-time indicator of disease burden, recurrence risk, and treatment response in PDAC. CHCs have great potential as tumor-derived biomarkers to optimize therapeutic strategies and improve survival in patients with PDAC.

This study from the US by the National Eczema Association aimed to determine which demographic and clinical characteristics contribute to eczema patient/caregiver motivation (or lack thereof) to participate in CTs, issues getting in/staying in a trial, and likelihood to consider participating in the future. Burden of disease was the biggest motivator for participating among both those who had (81%) and hadn’t (57%) considered participating before; lack of awareness was the biggest barrier (58%). Caregivers cited altruism less than adult patients as a reason for having considered CTs. Older age and those with less severe eczema cited eligibility concerns were preventing them from considering CTs. No differences were observed based on race/ethnicity or urban/rural location. Abstract Background Eczema clinical trials (CTs) are increasing in number, yet participation across the eczema community is low. Little is known about patient characteristics and views on motivators and barriers to CT participation (CTP). Objectives Determine factors that motivate or impede participation in eczema CT and respondent characteristics associated with these factors. Methods Qualitative thematic analysis was performed on open-ended questions from an online survey that collected respondent demographics, understanding of and experience with CTs, and drivers/barriers to CTP. Mixed-methods analysis included 924 respondents, 728 (78.8%) adults with eczema and 196 (21.2%) caregivers of children with eczema. Results A large proportion (71.8%) of respondents would potentially participate in CTs. The most common theme for why a respondent considered or would explore CTP was burden of disease (81.0% and 57.3% respectively). Among those who participated in or considered a CT, caregivers (p = 0.001) reported fewer altruistic motivations compared to adult patients, with trends towards men citing disease burden more (57.0% vs. 50.9%) and altruism less (14.5% vs. 19.2%) than women. Lack of awareness (57.7%) was the most common reason for never having considered a CT. Among those who never considered CTP, age (p = 0.012) and eczema severity at its worst (p = 0.002) were associated with reasons why they never participated. Specifically, older and less severe patients had greater perceptions of eligibility as a barrier to CTP. Caregivers more commonly cited fear of CT risks (20% vs. 11.4%) compared to adult patients who cited accessibility concerns (17.7% vs. 8.6%) as barriers to CT exploration. A subgroup of respondents that never considered CTP and extremely unlikely to consider CTs cited more fears/risks/unknowns and accessibility barriers to CTP. No significant differences in motivators or barriers were observed across race/ethnic groups and urban/rural populations. Conclusions Motivating factors for CTP include greater disease burden; lack of awareness represents a large barrier. Healthcare providers are trusted intermediaries with ability to refer and inform about CTs; they have a potentially significant role in raising awareness and discussing eczema patient/caregiver perspectives related to CTP. Investigators should tailor recruitment approaches and study design where possible to address identified motivators and barriers.

Perceptual and adaptive learning modules (PALM’s) provide a large number of visual examples for evaluation and accommodate to learner performance by actively adjusting the module parameters. We developed a module for discriminating 5 inflammatory reaction patterns using the Novel Diagnostic Educational Resource (NDER) platform. The module included a 20 question pre-test, a 200 question training section, and a 20 question post-test. During the pre-test and post-test, images were displayed for an indefinite period of time with no feedback given. In the training section, images were displayed for a duration inverse to learner performance, and after submitting their response learners were immediately shown the correct answer. The performance of module participants was compared to a control group who completed pre-test and post-test only. 26 pathology and dermatology residents completed the module and were included in analysis. Pre-test and post-test scores showed an average increase of 17.1 percentage points (95% CI 13.0 to 21.2, P < 0.001). When performance on pre-test and post-test was compared between the module and control groups, module group performance increased more than control group performance by an average of 10.1 percentage points (95% CI -2.5 to 17.8, P = 0.0119). 84% (37) of participants found the module somewhat useful or very useful and 68% (30) of participants would be pretty likely or very likely to recommend to another trainee. Our findings validate the use of NDER for teaching inflammatory reaction patterns. Participants generally had favorable feedback regarding the interface and teaching potential of the module. Including a late re-test as part of the module would be beneficial in further validating future iterations. Next steps include optimizing module performance and developing module content for more advanced learners.

Primary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope. We have created a free, online, continuing education program (Melanoma Toolkit for Early Detection, MTED) that allows learners to choose from a variety of multimedia tools (image recognition, videos, written material, in-person seminars, self-tests, etc.) that suits their learning style and time availability. Here we present the toolkit, the development and validation of the curriculum, and report on 1-year outcomes of a nested survey study. Because the goal of the program is to maximize participation by allowing PCPs to tailor their experience to their own needs and interests, the majority of participants did not complete every element of the program. A total of 8,683 PCPs have accessed at least one element of the toolkit from 2019-2024. Participants completed a pre-survey, online training module, and post-survey that included self-reported screening behaviors, changes in confidence, and malignant and benign lesion categorization based on clinical images. A total of 139 pre-surveys and 92 post-surveys were completed, including 55 matched participants that completed both the pre- and post-training surveys. There were significant improvements in PCP confidence ( < 0.001) and malignant ( < 0.001) and benign image ( = 0.029) identification respectively. PCPs may serve as a valuable aid in skin cancer screening efforts, but additional studies are needed to evaluate the impact of these curricula in clinical practice.

Materials and methods Power analysis was performed to determine sample size. Demographics, relevant comorbidities, and routine histopathological findings of included cases Age and gender Potentially relevant comorbidities Histopathologic findings 24F PTSD, ADHD, bipolar disorder n/a 48 M fibromyalgia, stimulant use, opioid use n/a 48F PTSD, dialysis Prurigo nodularis; prurigo nodularis with scar 45F bipolar disorder Psoriasiform spongiotic dermatitis with prurigo nodularis 60 M PTSD n/a 60F fibromyalgia, bipolar disorder, opioid use, pathologic gambling Ulceration secondary to trauma; prurigo nodularis with ulceration and necrosis 66F fibromyalgia, ADHD, multiple sclerosis Sparse superificial perivascular dermatitis; suppurative folliculitis 61F depression, anxiety n/a 43F fibromyalgia Suppurative folliculitis 55F opioid use, multiple sclerosis Ulcer and irregular epidermal hyperplasia; mixed dermatitis with eosinophils and fibrosis 68F iron deficiency Epidermal hyperplasia with ulcer and underlying fibrosis; prurigo nodularis with erosion, ulcer, and scar; suppurative dermatitis and panniculitis 57F iron deficiency Lichen simplex chronicus Total RNA was extracted with RNeasy Fibrous Tissue Kit (Qiagen). Conflict of interest The authors declare that they have no conflicts of interest.

Neoadjuvant chemotherapy (NAC) improves overall survival in muscle-invasive bladder cancer (MIBC). Older patients often do not receive NAC due to its potential toxicities. We examined treatment patterns of elderly MIBC patients as well as impact of NAC on survival in this population. The National Cancer Database was queried from 2006 to 2019 for stage T2-T4a MIBC patients ≥ 80 years old. Treatment exposures (extirpative surgery; chemotherapy; radiation) were ascertained. Kaplan–Meier survival curves were generated based on treatment modalities (no treatment; radiation only; chemotherapy only; chemoradiation; surgery only; NAC with surgery). Multivariable Cox proportional hazards regression assessed associations with overall survival (OS). The cohort included 16,391 patients (mean age 86 years); 51% received treatment. MIBC treatment was less common with advancing age; patients receiving NAC then surgery were younger and had lower comorbidity scores. From 2006 to 2019, more patients received chemoradiation, while rates of NAC rose modestly. Median OS for the NAC with surgery group was 48 months versus 9 months for the no treatment group. Log-rank tests showed significantly improved survival in the NAC with surgery group compared to the surgery only group, while Cox proportional hazards regression analysis showed highest survival benefit in the NAC with surgery group. Only half of elderly MIBC patients received treatment, with fewer undergoing curative intent. NAC with surgery was associated with the greatest survival benefit. While our findings should be taken in the context of potential selection bias and patient preferences, they support NAC as part of shared-decision making regardless of age.