Kansas City University

Kyrle disease (KD) is a rare dermatologic condition characterized by hyperkeratotic papules with central keratotic plugs, often associated with systemic conditions such as diabetes and chronic kidney disease. Due to its clinical overlap with other dermatologic disorders, KD is frequently misdiagnosed. Diagnosis primarily relies on characteristic histopathological findings, with dermoscopy serving as a valuable adjunct for clinical assessment. This systematic review highlights KD’s clinical features, systemic associations, dermoscopy findings, differential diagnosis, and current treatment approaches. While some therapies have shown promise, the lack of standardized management underscores the need for further research. By consolidating the existing literature, this systematic review emphasizes the importance of a multidisciplinary approach in managing KD and calls for future studies to establish standardized diagnostic and therapeutic protocols to improve patient outcomes.

The Thulium fiber laser (TFL) is a relatively new tool for endoscopic laser lithotripsy. The Endourological Society’s T.O.W.E.R. registry sought to evaluate the stone-free rate (SFR) at 3 months following URS. A subset of the study sought to determine the association between cumulative TFL energy and SFRs. 423 patients with planned ureteroscopic lithotripsy using TFL (SOLTIVE™, Gyrus ACMI, Inc. d/b/a Olympus Surgical Technologies America) were prospectively enrolled between December 2020 and May 2023 at nine international sites. Baseline clinical characteristics and SFR data for kidney and ureteral stones were separately analyzed according to quartile cumulative TFL energy ranges. Median patient age was 58.0 (IQR: 44–67) years and maximal stone diameters were 9.9 (IQR: 7–12.9) mm and 7.4 (IQR 6.1–9.4) mm for kidney and ureteral stones, respectively. Overall SFR (no fragments) for renal and ureteral stones were 73.0% and 85.7% at 3-months. Cumulative energy levels were divided into quartiles and lower SFRs were observed with the highest quartile for kidney stones (p = 0.001), but not in ureteral stones. This correlated with kidney stone size as larger stones required more energy. The rate of adverse events related to the procedure was 1.9% (8/423). Higher stone burdens had lower stone free rates and required more cumulative laser energy. The TFL is effective in endoscopic lithotripsy. This post-marketing survey demonstrates that TFL is a safe and effective tool for endoscopic laser lithotripsy.

Background CXCR1/2 inhibitors are being implemented with immunotherapies in PDAC clinical trials. CXC-ligands are a family of cytokines responsible for stimulating these receptors; while typically secreted by activated immune cells, fibroblasts, and even adipocytes, they are also secreted by immune-evasive cancer cells. CXC-ligand release is known to occur in response to inflammatory stimuli. Adipose tissue is an endocrine organ and a source of inflammatory signaling peptides. Importantly, adipose-derived cytokines and chemokines are implicated as potential drivers of tumor cell immune evasion; cumulatively, these findings suggest that targeting CXC-ligands may be beneficial in the context of obesity. Methods RNA-sequencing of human PDAC cell lines was used to assess influences of adipose conditioned media on the cancer cell transcriptome. The adipose-induced secretome of PDAC cells was validated with ELISA for induction of CXCL5 secretion. Human tissue data from CPTAC was used to correlate IL-1β and TNF expression with both CXCL5 mRNA and protein levels. CRISPR-Cas9 was used to knockout CXCL5 from a murine PDAC KPC cell line to assess orthotopic tumor studies in syngeneic, diet-induced obese mice. Flow cytometry and immunohistochemistry were used to compare the immune profiles between tumors with or without CXCL5. Mice-bearing CXCL5 competent or deficient tumors were monitored for differential tumor size in response to anti-PD-1 immune checkpoint blockade therapy. Results Human adipose tissue conditioned media stimulates CXCL5 secretion from PDAC cells via either IL-1β or TNF; neutralization of both is required to significantly block the release of CXCL5 from tumor cells. Ablation of CXCL5 from tumors promoted an enriched immune phenotype with an unanticipatedly increased number of exhausted CD8 T cells. Application of anti-PD-1 treatment to control tumors failed to alter tumor growth, yet treatment of CXCL5-deficient tumors showed response by significantly diminished tumor mass. Conclusions In summary, our findings show that both TNF and IL-1β can stimulate CXCL5 release from PDAC cells in vitro, which correlates with expression in patient data. CXCL5 depletion in vivo alone is sufficient to promote T cell infiltration into tumors, increasing efficacy and requiring checkpoint blockade inhibition to alleviate tumor burden.

Objective Dry needling (DN) has recently been investigated as an alternative strategy to reduce muscle spasticity and improve mobility in people with multiple sclerosis (pwMS). The aim of the present review was to identify any available literature on the potential benefits of DN in pwMS. Methods A systematic literature search was conducted in the PubMed, Scopus, ScienceDirect, Embase/Ovid, CINAHL, CENTRAL, Web of Science and PEDro databases and at ClinicalTrials.gov. The search results were limited to studies published between 2000 and 2023 without language restrictions. All articles reporting on the application of DN (defined as the use of a needle to target myofascial trigger point(s) without injection) in pwMS were included. Studies related to traditional medicine were excluded. Two reviewers independently investigated the quality of reporting based on Joanna Briggs Institute critical appraisal tools. Data on the effects of DN on muscle spasticity, pain intensity, mobility and other reported outcomes in pwMS were extracted and analyzed. Results Four original articles (two case reports and two case series) and one conference paper reporting the findings of a randomized controlled trial randomized controlled trial (RCT) were included. The RCT was small (n = 16 participants) and sham-controlled with no significant differences between groups. In all four case reports/series, reduced spasticity was observed following DN treatment in pwMS. Findings with respect to other outcomes (including pain intensity, mobility, quality of life, manual dexterity and disability reduction) were mixed. Conclusion Although no firm conclusions can be drawn from these uncontrolled case reports/series, DN for pwMS appears feasible and (based on limited clinical observation) may have potential as an adjunct therapeutic method to address spasticity in pwMS. However, the quantity and quality of available data are extremely limited. There is a need for high-quality studies of DN (ideally adequately sized RCTs with a low risk of bias) to further explore its effectiveness in the MS population.

Purpose: Preclinical studies have shown that interleukin (IL)-1β blockade can modulate the tumor microenvironment (TME) to activate antitumor immunity and, in combination with immune checkpoint inhibitors (ICIs), prevent cancer growth. Our study investigates if immune biomarkers in the TME impact outcomes in patients with non–small cell lung cancer (NSCLC) treated with the IL-1β inhibitor canakinumab plus an ICI-based therapy and describes canakinumab effects on the TMEs of these patients. Methods: Exploratory analyses were conducted in two prospective trials evaluating canakinumab combined with pembrolizumab-based regimens in patients with NSCLC: CANOPY-1 (first-line setting) and CANOPY-N (neoadjuvant setting). Immunohistochemistry and transcriptomic analyses were performed on baseline tumor samples from CANOPY-1 and immunohistochemistry and multiplex immunofluorescence analyses were performed on baseline and post-treatment tumor samples from CANOPY-N. Associations with clinical outcomes were evaluated. Results: In CANOPY-1, in patients with low levels of T-cell infiltration in the tumor, the addition of canakinumab to a pembrolizumab-based regimen was associated with progression-free and overall survival improvements. Low levels of T-cell infiltration were associated with an immunosuppressive gene expression phenotype, supporting the role of low T-cell infiltration as a surrogate of an overall immunosuppressive TME. In CANOPY-N, a reduction in immunosuppressive cells in the TME was observed following canakinumab and pembrolizumab treatment. Conclusions: Our exploratory biomarker analyses from the CANOPY-1 and CANOPY-N trials suggest that IL-1β blockade may shift the TME towards an immune-activated status and that patients with immunosuppressive TME features could benefit from the addition of canakinumab to an ICI-based treatment.

Objective This article aims to review the current literature on the severity of global corneal blindness (CB), summarize the current challenges of corneal eye banks in low and middle-income countries (LMICs), and highlight key principles and opportunities for improvement in corneal eye banking in these countries. Methods In this article, we reviewed available literature pertinent to global CB and corneal transplantation (CT), and eye banking in LMICs, in addition to supplementation with personal communication with eye banking staff working in LMICs. Results CB is a major cause of global blindness and visual impairment, with numerous etiologies varying by geography, socioeconomics, and age. CT remains the mainstay in surgical intervention for CB, with a robust corneal eye banking system playing a critical role in efforts to decrease the amount of CB. Four vital functions of eye banks include consent, recovery, processing, and distribution, with challenges and opportunities present within each. Eye bank infrastructure in LMICs has had numerous successes and setbacks in the last 20 and much work remains to be done. Conclusions Much remains to be done in the aim to treat global CB, however, the establishment of ethical, efficient, and high-quality corneal eye banks with subsequent CT acts as a key pillar in the multifaceted approach. With the ultimate goal of self-sufficiency, many eye banks in LMICs lead by example in surmounting challenges shared internationally, and set the stage for others to seize the opportunity to provide tissue to cure CB.

Importance Carcinoma of Unknown Primary (CUP) presents a clinical challenge for practitioners. The current diagnostic approach often involves extensive imaging and examinations, with variable success. We aimed to evaluate the effectiveness of Indocyanine Green (ICG) injection using the Da Vinci robot to aid in intraoperative decision making. Objectives To evaluate the diagnostic utility of ICG use during robotic surgery to aid in either the identification of the primary tumor or to delineate the extent of disease to guide excision. Methods This study involved a retrospective review of patients treated at the Massachusetts Eye and Ear who underwent robotic surgery with the utilization of Indocyanine Green (ICG) from October 1, 2022. All patients in the study were operated on using the SP model of the Da Vinci robot. Basic demographic and pathologic data were recorded. Intraoperative data points included assessing the presence of an identifiable primary tumor using white light only and documenting the confidence level of ICG localization. Results In total, 28 patients who underwent robotic surgery using ICG were identified for this study. The mean age of the cohort was 62 years. Twenty‐six patients were male, and the primary diagnosis was HPV‐related squamous cell carcinoma (SCCa) in 22 patients, HPV‐negative SCC in 5 patients, atypia in 1 patient, and metastatic papillary thyroid carcinoma in 1 patient. Nine patients had either PET‐localizing or visually identified primary tumors, and ICG was used to guide the surgical extent of resection. The remaining 19 patients had CUP. Within the patients with CUP, the primary was ultimately identified in 16 of the 19 (84.2%) patients. In regard to ICG localization, this resulted in a True Positive detection in 10 patients (52.6%), False Positive detection in 6 patients (31.6%), False Negative detection in 0 patients (0%), and True Negative detection in 3 patients (15.8%). Based on a confusion matrix of the aforementioned values, the calculated sensitivity, specificity, PPV, and NPV were 100%, 33.3%, 62.5%, and 100%, respectively. The discriminatory index of ICG in the detection of unknown primary disease was found to be 66.6%. Conclusion The integration of systemic ICG injection with the Da Vinci SP robot's real‐time imaging capabilities offers a potential option for enhancing primary tumor identification in CUP patients that adds little to no cost, time, and morbidity to the patient. This preliminary analysis suggests that the use of ICG in robotic surgery for CUP holds promise and warrants further investigation to refine surgical techniques and enhance clinical outcomes.

Nearly half of US adults have hypertension, with blood pressure (BP) uncontrolled in over two-thirds of cases. Significant disparities exist in BP control, particularly for Southern and rural-dwelling Americans. To examine the impact of patients’ relationships with families, communities, and providers on BP control efforts. Semi-structured interviews explored patient and provider experiences managing hypertension and controlling BP. Twenty-nine providers and 25 patients with hypertension were recruited from 13 high- and low-performing primary care clinics (assessed via hypertension control rates) and one cardiology clinic across two health systems in North Carolina and Kansas. A health equity framework–shaped interview guide and codebook development. Inductive and deductive coding methodologies were employed, with thematic analysis used to organize emergent themes. Patients frequently discussed the prevalence of hypertension within their families, with some detailing feelings of inevitability and/or linking their cardiovascular outcomes to family histories. Cultural expectations were often mentioned, with families’ and communities’ normative behaviors sometimes creating barriers to hypertension management. Southern and/or rural culture (e.g., diet) may pose unique challenges, as some providers cited patients’ resistance to deviate from regional norms. The importance of tailoring hypertension care to patients’ unique circumstances was often cited and linked with increased trust and patient activation, with the utilization of culturally appropriate, patient-facing resources being identified as a best practice. While providers in high-performing clinics more consistently discussed approaches to tailoring care and using culturally appropriate materials, providers in low-performing clinics more often referenced time constraints limiting personalized care and having non-inclusive resources. Effective hypertension management may be impacted by patients’ relationships, both external (e.g., family, community) and internal (e.g., providers) to healthcare. Future research should explore strategies for tailoring culturally appropriate hypertension care to patients, specifically identifying ways to overcome structural barriers that can hinder clinics’ utilization.

INTRODUCTION Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's disease (AD) diagnosis. METHODS Self‐reported medical and substance use history (i.e., problem history) was used to cluster participants from the National Alzheimer's Coordinating Center (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over 2 years. RESULTS Two thousand seven hundred fifty‐four individuals were partitioned into three subtypes: minimal (n = 1380), substance use (n = 1038), and cardiovascular (n = 336). The cardiovascular problem history subtype had significantly worse cognitive decline over a 2 year follow‐up period (p = 0.013). DISCUSSION Our study highlights the need to account for problem history to reduce heterogeneity of outcomes in AD clinical trials. Highlights Clinical data were used to identify subtypes of patients with Alzheimer's disease (AD) in the National Alzheimer's Coordinating Center dataset. Three problem history subtypes were found: minimal, substance use, and cardiovascular. The mean change in Clinical Dementia Rating Sum of Boxes (CDR‐SB) was assessed over a 2 year follow‐up. The cardiovascular subtype was associated with the worst cognitive decline. The magnitude of change in CDR‐SB was similar to recent AD clinical trials.

INTRODUCTION The utility of blood‐based biomarkers for discriminating Alzheimer's disease (AD)‐related versus non‐AD‐related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability of blood markers to detect and discriminate variation in performance across multiple cognitive domains in a cognitively unimpaired sample. METHODS Participants (n = 648, aged 69.9 ± 3.8, 71% female) underwent a comprehensive cognitive assessment and assays for plasma‐based biomarkers amyloid beta (Aβ)1‐42/1‐40 by mass spectrometry, phosphorylated tau (p‐tau) 181 and 217, p‐tau217/Aβ1‐42, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). RESULTS Greater p‐tau217 was exclusively associated with poorer episodic memory performance (β = −0.11, SE = 0.04, p = .003), and remained so after covarying for NfL. Higher NfL was non‐specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p‐tau217. DISCUSSION Blood‐based biomarkers may differentiate non‐AD‐related versus AD‐related cognitive deficits. This characterization will be important for early intervention and disease monitoring for AD. Highlights There is heterogeneity in the causes of cognitive decline in aging. AD‐related blood biomarkers may help characterize these causes. Elevated p‐tau217 was exclusively associated with poorer episodic memory. Elevated NfL was associated with poorer cognition in a broad range of domains. Blood biomarkers may help differentiate AD‐ and non‐AD‐related cognitive deficits.

Reflection exercises have been used within anatomy education to evaluate empathy, humanism, and professionalism. A typical reflection exercise consists of directed prompts to guide the student's reflection as it relates to the experience and/or research question. The aim of this study was to utilize reflections through an open‐ended format to enable students to explore their experience participating in donor dissection as they form their professional identity. The “Seven Questions” exercise was developed to create an imaginary discourse between the medical student and their donor. Students were prompted to provide seven questions they would like to ask their donor, if still living, and provide a 2–3 sentence explanation as to their interest, meaning, and/or purpose of each question. Submissions (n = 418) were evaluated using thematic analysis and four themes were identified: body donation, career development, patient history, and donor gestalt. The theme of body donation included questions specific to the decision to donate one's body for medical education, sharing one's decision with family and electing educational vs. organ donation. The career development theme included questions focused on the donor's previous experience with physicians, hesitation regarding student dissection, and advice for the student dissector. The third theme, patient history, included inquiries related to social history, review of systems, and family history. The final theme of donor gestalt focused on the donor's self‐care and legacy. Student responses suggest that dissection and the donor experience organically support students modeling physician behaviors and should be considered as an educational opportunity to aid in developing physician identity.

Objective This study aims to evaluate the prognostic impact of surgical margin status in HPV‐related oropharyngeal squamous cell carcinoma (OPSCCa) and examine the potential for revising surgical margin standards in HPV+ OPSCCa. Study Design A retrospective cohort study. Setting This study was conducted across 4 tertiary oncology centers. Methods Charts of patients treated from 2010 to 2022 for HPV+ OPSCCa were reviewed. Eligible patients underwent surgery without adjuvant treatment for nonrecurrent, nonmetastatic HPV+ OPSCCa. Demographic, oncologic, treatment, and outcome data were collected. Patients with prior head and neck radiation or adjuvant therapy were excluded. Local control, locoregional recurrence (LRR), disease‐free survival (DFS), and overall survival (OS) were compared based on surgical margins using the Kaplan–Meier method. Results Among 194 qualified cases, with a median follow‐up of 41.63 months, most cases were pT1 (64.43%) or pT2 (34.54%). Recurrence occurred in 8.76% of patients, with most salvaged successfully. Analysis on univariable and multivariable modeling determined that margins less than 1 mm were considered close, and those ≥1 mm were considered clear. On multivariable modeling, surgical margins of <1 mm were associated with a hazard ratio of 3.69 (95% confidence interval [CI] 1.47‐9.30) for LRR and 2.95 (95% CI 1.41‐6.16) for DFS when compared to cases where margins were clear by 1 mm or greater. Conclusion In this multi‐institutional cohort of early‐stage HPV+ OPSCCa treated surgically without adjuvant therapy, margins <1 mm were associated with worse LRR and DFS. This suggests that traditional definitions of close margins in HPV‐negative disease may not apply to HPV+ OPSCCa, warranting a revised definition for surgical margin standards.

Exposure to airborne particulate matter (PM) has been attributed to millions of deaths annually. However, the PM components responsible for observed health effects remain unclear. Oxidative potential (OP) has gained increasing attention as a key property that may explain PM toxicity. Using online measurement methods that impinge particles for OP quantification within seconds, we reveal that 60 to 99% of reactive oxygen species (ROS) and OP in secondary organic aerosol and combustion-generated PM have a lifetime of minutes to hours and that the ROS activity of ambient PM decays substantially before offline analysis. This implies that current offline measurement methods substantially underestimate the true OP of PM. We demonstrate that short-lived OP components activate different toxicity pathways upon direct deposition onto reconstituted human bronchial epithelia. Therefore, we suggest that future air pollution and health studies should include online OP quantification, allowing more accurate assessments of links between OP and health effects.

Enucleation is indicated for an ocular malignancy, a blind painful eye, a disfiguring blind eye, or as sympathetic ophthalmia prophylaxis. The procedure is performed under general anesthesia and includes detaching the extraocular muscles and severing the optic nerve. An implant or dermis fat graft is usually inserted to restore orbital volume. When the socket is healed, the patient may be fitted for an ocular prosthesis.

Repair of full thickness upper eyelid defects is indicated to restore ocular protective functions and cosmesis. While small defects may be closed primarily, larger defects often require flaps or grafts or both. While the anterior lamella may be replaced by skin, mucous membrane is required for the internal posterior lamella lining of the eyelid to maintain ocular surface health and comfort. This chapter details a systematic approach for reconstruction of upper eyelid defects.

Background Breast cancer (BC) continues to be a major health concern with 250,000 new cases diagnosed annually in the USA, 75% of which are hormone receptor positive (HR+), expressing estrogen receptor alpha (ER) and/or the progesterone receptor (PR). Although ER-targeted therapies are available, 30% of patients will develop resistance, underscoring the need for new non-ER/estrogen-based treatments. Notably, HR+BCs exhibit poor lymphocyte infiltration and contain an immunosuppressive microenvironment, which contributes to the limited efficacy of immunotherapies in HR+BC. In this study, we demonstrate that PR/progesterone signaling reduces major histocompatibility complex (MHC) Class I expression, facilitating immune evasion and escape from immune-based clearance of PR+tumors. Methods To determine the effect of PR/progesterone on MHC Class I expression, we treated human and mouse mammary tumor cell lines with progesterone and/or interferon (IFN) and measured expression of genes involved in antigen processing and presentation (APP), as well as surface MHC Class I expression. We used the OT-I/SIINFEKL model antigen system to measure the impact of progesterone on immune cell-mediated killing of modified tumor cells. We also analyzed two large BC clinical cohorts to determine how PR expression correlates with APP gene expression and MHC Class I expression in ER-positive tumors. Results In vitro, we show that PR/progesterone signaling reduces APP gene expression and MHC class I expression in human and breast mammary tumor cell lines. PR-mediated attenuation of APP/MHC Class I expression is more pronounced in the presence of IFN. In immune cell killing assays, PR-expressing mammary tumor cells treated with progesterone are protected from immune-mediated cytotoxicity. We demonstrate that PR expression in vivo prevents immune-mediated rejection of xenoantigen-modified mammary tumor cell lines through mechanisms involving MHC Class I expression and CD8 T cells. Data analysis of two large BC cohorts reveals lower APP gene expression and MHC Class I expression in ER/PR-positive tumors compared with ER-positive/PR-negative tumors. These findings show that HR+BCs, specifically PR+tumors, downregulate APP/MHC class I machinery through PR/progesterone signaling. Use of pharmacological PR/progesterone inhibitors may reverse these effects in patients with BC, thereby improving immunosurveillance and response to immunotherapies.

Research at the Juniper Gardens Children’s Project (JGCP) has demonstrated that students’ rate of growth in academic achievement from classroom instruction is influenced by their engagement in academic behaviors. This contribution to the Special Issue discusses two universal interventions teachers can use to accelerate academic responding and reduce/prevent inappropriate social behavior in the classroom. These are ClassWide Peer Tutoring (CWPT) and ClassWide-Function Related Intervention Teams (CW-FIT). Both use group reinforcement contingencies and peer-mediated instruction procedures to promote increased opportunities to respond to the curriculum and active participation. Both were developed through a program of research involving single case, small group, and randomized control trials over multiple studies and years. Implications are discussed.