Painful diabetic neuropathy (PDN) is one of the most common and intractable complications of diabetes. Painful diabetic neuropathy is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, axonal degeneration, and changes in cutaneous innervation. However, the complete molecular profile underlying the hyperexcitable cellular phenotype of DRG nociceptors in PDN has not been elucidated. This gap in our knowledge is a critical barrier to developing effective, mechanism-based, and disease-modifying therapeutic approaches that are urgently needed to relieve the symptoms of PDN. Using single-cell RNA sequencing of DRGs, we demonstrated an increased expression of the Mas-related G protein–coupled receptor d (Mrgprd) in a subpopulation of DRG neurons in the well-established high-fat diet (HFD) mouse model of PDN. Importantly, limiting Mrgprd signaling reversed mechanical allodynia in the HFD mouse model of PDN. Furthermore, in vivo calcium imaging allowed us to demonstrate that activation of Mrgprd-positive cutaneous afferents that persist in diabetic mice skin resulted in an increased intracellular calcium influx into DRG nociceptors that we assess in vivo as a readout of nociceptors hyperexcitability. Taken together, our data highlight a key role of Mrgprd-mediated DRG neuron excitability in the generation and maintenance of neuropathic pain in a mouse model of PDN. Hence, we propose Mrgprd as a promising and accessible target for developing effective therapeutics currently unavailable for treating neuropathic pain in PDN.

Most of the literature on pineoblastoma consists of case reports and single-institution series. The goal of this systematic review and individual patient data (IPD) analysis was to summarize the existing literature, identify factors associated with overall survival (OS), and provide a contemporary update on prognosis for patients with pineoblastoma. Forty-four studies were identified with 298 patients having IPD. Kaplan–Meier analyses were used to report survival outcomes based on age, tumor metastases, extent of resection (EOR), adjuvant therapy, and publication year. Cox regression was performed to identify independent predictors of time to mortality. Multivariable recursive partitioning analysis was used to identify the most important subgroups associated with mortality. Patients were classified based on publication year before and after the last systematic review on this topic (pre-2012 and 2012 onwards) and compared using univariate and multivariable analyses. This study demonstrates that EOR less-than-gross total resection, metastatic presentation, adjuvant chemotherapy without radiation, and tumor presentation in children less than three years old are associated with poorer prognosis. Since 2012, the 5-year actuarial OS has improved from 32.8% to 56.1%, which remained significant even after accounting for EOR, age, and adjuvant therapy. Pineoblastoma remains a severe rare disease, but survival outcomes are improving.

Background: Lymphopenia has been associated with in-hospital, early, and late mortality. We aimed to elucidate differences in baseline characteristics in patients with lymphopenia with and without acute respiratory distress syndrome (ARDS) and determine predictors of in-hospital mortality in this patient population. Methods: Patients ≥ 18 years of age with lymphopenia were identified in the National Inpatient Sample (2017–2021) and stratified according to ARDS diagnosis. Predictors of in-hospital mortality were determined using multivariate analyses with a logistic regression model. Results: From 183,185 patients with lymphopenia, 10,420 (5.7%) had ARDS, of which 92.8% had coronavirus disease 2019. The patients with ARDS suffered from more in-hospital mortality (47% versus 6.7%, p < 0.001). ARDS increased the odds of in-hospital mortality by eight-fold (odds ratio [OR]: 7.91 [7.06–8.86], p < 0.001). Age ≥ 65 years (OR: 4.88 [3.98–5.99]), moderate/severe liver disease (OR: 2.53 [1.87–3.42]), and metastatic cancer (OR: 2.18 [1.68–2.82]) were among the strongest positive predictors of in-hospital mortality (all p < 0.001). Conclusions: Patients with lymphopenia who have ARDS have higher in-hospital mortality, likely due to the condition’s clinical course. Lymphopenia may be a marker of immune dysregulation and systemic involvement in ARDS.

Patients undergoing breast cancer surgery and reconstruction seek information using online patient education materials (OPEMs). The National Institutes of Health (NIH) and American Medical Association (AMA) recommend a sixth-grade reading level for OPEMs. In recent years, Chat Generative Pre-Trained Transformer (ChatGPT), a large language model (LLM), has shown potential utility in patient education. This study compares the readability and content quality of OPEMs on breast cancer surgery and reconstruction with ChatGPT-generated materials. Google searches were conducted in January 2025 to identify relevant OPEMs for breast cancer surgery and reconstruction. For each search term, ChatGPT 4.0 was prompted to generate patient education guides using two approaches: (1) Standard prompting and (2) simplified prompting to align with NIH/AHA recommendations (“write the guide like I am in sixth grade”). Readability and content quality metrics were assessed. Ninety-nine OPEMs and 60 ChatGPT responses (30 standard, 30 simplified) were analyzed. Median Flesch–Kincaid Grade Level (FKGL) was 10.8 for OPEMs, 10.0 for standard ChatGPT responses, and 5.8 for simplified ChatGPT responses. OPEMs and standard ChatGPT responses significantly exceeded NIH/AMA recommendations (p < 0.001). Simplified ChatGPT responses aligned with the sixth-grade level and were significantly easier to read than OPEMs and standard ChatGPT responses (p < 0.001). DISCERN scores did not significantly differ between OPEMs and standard/simplified ChatGPT responses. OPEMs on breast cancer surgery and reconstruction exceed recommended readability levels. ChatGPT, when prompted to simplify, produced materials consistent with NIH/AMA guidelines while maintaining content quality. Using ChatGPT for patient education may enhance accessibility and patient comprehension of health information.

Objective: Online patient education materials (OPEMs) are important resources for patients seeking health information. While the National Institutes of Health (NIH) and American Medical Association (AMA) recommend a sixth-grade readability level for OPEMs, commonly available material often exceeds such criteria. Large language models (LLMs), such as ChatGPT and Gemini, have emerged as tools for health education with potential applications in simplification of health material. This study assesses the utility of ChatGPT and Gemini in enhancing the readability of OPEMs for peripheral nerve surgeries. Methods: Eleven common peripheral nerve surgeries were used as online search terms. The first 20 unique search results were assessed; results were excluded if they did not include patient-facing material. ChatGPT and Gemini were instructed to rewrite the text of the OPEM at or below a sixth-grade reading level. Readability metrics were calculated for original OPEMs, alongside ChatGPT and Gemini rewrites. LLM responses were reviewed for accuracy/quality (five-point scale) and comprehensiveness (three-point scale) using predefined criteria. Results: A total of 220 websites were assessed. In total, 155 OPEMs met the inclusion criteria; 65 websites were excluded because they were academic journal articles or other provider-facing materials. The average Flesch–Kincaid grade level (FKGL) of OPEMs was 11.3, significantly greater than the NIH/AMA-sixth grade recommendations (p < 0.001). The average FKGL of ChatGPT rewrites was significantly lower than that of OPEMs (11.3 vs. 7.5, p < 0.001), as was the average FKGL of Gemini rewrites (11.3 vs. 5.6, p < 0.001). ChatGPT rewrites were of higher accuracy/quality (4.5/5.0 vs. 4.0/5.0, p < 0.001) and comprehensiveness (2.0/3.0 vs. 1.0/3.0, p < 0.001) relative to Gemini rewrites. Conclusions: The readability of online patient education materials for peripheral nerve surgery significantly exceeded NIH/AMA recommendations. ChatGPT and Gemini were able to significantly simplify the reading level of these OPEMs. LLMs may serve as tools to improve the readability of peripheral nerve surgery OPEMs.