Citations

Abstract Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder, characterized by progressive heterotopic ossification (HO) and painful soft-tissue inflammatory flare-ups. This was a post hoc analysis from a phase 2 (NCT03188666) trial in which adults with FOP received intravenous anti-activin A antibody garetosmab 10 mg/kg or placebo every 4 wk over 28 wk (Period 1), followed by a 28-wk open-label treatment and extension (Periods 2 and 3). Here we describe flare-ups, their relationship to new HO lesions, and the impact of garetosmab on flare-ups. Volume of new HO lesions was measured by CT. Patient-reported flare-ups were defined by any 2 of the following: new onset of pain, swelling, joint stiffness, decrease in movement, or perceived presence of HO. Flare-ups were experienced by 71% (17/24) of placebo-treated patients, 59% (10/17) of whom developed a new HO lesion irrespective of flare-up location; 24% of flare-ups location-matched new HO lesions. Twenty-nine new HO lesions occurred in the placebo cohort by week 28, of which 12 (41%) occurred in the same location as new or ongoing flare-ups. A higher volume of newly formed heterotopic bone (week 28) occurred in placebo-treated patients who had experienced a prior flare-up vs those without (median [Q1:Q3] of 16.6 [12.0:31.1] vs 3.2 cm3). Garetosmab was previously shown to decrease patient-reported flare-up frequency in Period 1; here, garetosmab reduced the median (Q1:Q3) duration of patient-reported flares (15.0 [6.0:82.0] vs 48.0 [15.0:1.00] d) and the severity of flare-ups vs placebo. Frequency of corticosteroid use was numerically reduced in those treated with garetosmab (40.0%) vs placebo (58.3%). In this analysis, 71% of placebo-treated adults with FOP experienced flare-ups over 28 wk, which were associated with an increased volume of newly formed heterotopic bone. Garetosmab reduced the severity and duration of flare-ups, with effects sustained during the entire trial.

Background Professional opinion polling has become a popular means of seeking advice for complex nephrology questions in the #AskRenal community on X. ChatGPT is a large language model with remarkable problem-solving capabilities, but its ability to provide solutions for real-world clinical scenarios remains unproven. This study seeks to evaluate how closely ChatGPT's responses align with current prevailing medical opinions in nephrology. Methods Nephrology polls from X were submitted to ChatGPT-4, which generated answers without prior knowledge of the poll outcomes. Its responses were compared to the poll results (inter-rater) and a second set of responses given after a one-week interval (intra-rater) using Cohen's kappa statistic (κ). Subgroup analysis was performed based on question subject matter. Results Our analysis comprised two rounds of testing ChatGPT on 271 nephrology-related questions. In the first round, ChatGPT's responses agreed with poll results for 163 of the 271 questions (60.2%; κ = 0.42, 95% CI: 0.38–0.46). In the second round, conducted to assess reproducibility, agreement improved slightly to 171 out of 271 questions (63.1%; κ = 0.46, 95% CI: 0.42–0.50). Comparison of ChatGPT's responses between the two rounds demonstrated high internal consistency, with agreement in 245 out of 271 responses (90.4%; κ = 0.86, 95% CI: 0.82–0.90). Subgroup analysis revealed stronger performance in the combined areas of homeostasis, nephrolithiasis, and pharmacology (κ = 0.53, 95% CI: 0.47–0.59 in both rounds), compared to other nephrology subfields. Conclusion ChatGPT-4 demonstrates modest capability in replicating prevailing professional opinion in nephrology polls overall, with varying performance levels between question topics and excellent internal consistency. This study provides insights into the potential and limitations of using ChatGPT in medical decision making.

AbstractBackgroundCutaneous melanoma (CM) is a significant health concern because of its high metastatic potential. Gene Expression Profile (GEP) testing, particularly the 31‐GEP test (DecisionDx‐Melanoma), has been increasingly used for risk stratification in CM patients. This study aimed to evaluate the clinical utility and performance of the 31‐GEP test in a real‐world setting.MethodsPatients with CM who underwent 31‐GEP testing from August 2014 to August 2022 at our institution were identified through searches of electronic health records. The study analyzed the influence of 31‐GEP testing on clinical decision‐making related to sentinel lymph node biopsy (SLNB), medical oncology referral, and postdiagnosis surveillance. Kaplan–Meier curves and Cox proportional hazard models were used to elucidate the test's performance, focusing on relapse‐free survival (RFS) and melanoma‐specific survival (MSS).ResultsThe study included 65 CM patients. Dermatologists ordered more than 80% of 31‐GEP tests. In 81.5% of cases, 31‐GEP results did not alter standard clinical management. SLNB decisions were unaffected in 92% of patients with pre‐SLNB 31‐GEP results. Among patients with stage I‐IIA melanoma, 25% of those with high‐risk 31‐GEP results were referred to medical oncology. Contrary to expectations, the rate of nodal metastasis was higher in low‐risk than in high‐risk 31‐GEP cases. Survival analysis showed overlapping RFS and MSS curves between different 31‐GEP classes, suggesting limited prognostic value.ConclusionsThe 31‐GEP test has a limited impact on clinical management decisions and shows limited prognostic value.

Chronic kidney disease (CKD) patients can benefit from personalized education on lifestyle and nutrition management strategies to enhance healthcare outcomes. The potential use of chatbots, introduced in 2022, as a tool for educating CKD patients has been explored. A set of 15 questions on lifestyle modification and nutrition, derived from a thorough review of three specific KDIGO guidelines, were developed and posed in various formats, including original, paraphrased with different adverbs, incomplete sentences, and misspellings. Four versions of AI were used to answer these questions: ChatGPT 3.5 (March and September 2023 versions), ChatGPT 4, and Bard AI. Additionally, 20 questions on lifestyle modification and nutrition were derived from the NKF KDOQI guidelines for nutrition in CKD (2020 Update) and answered by four versions of chatbots. Nephrologists reviewed all answers for accuracy. ChatGPT 3.5 produced largely accurate responses across the different question complexities, with occasional misleading statements from the March version. The September 2023 version frequently cited its last update as September 2021 and did not provide specific references, while the November 2023 version did not provide any misleading information. ChatGPT 4 presented answers similar to 3.5 but with improved reference citations, though not always directly relevant. Bard AI, while largely accurate with pictorial representation at times, occasionally produced misleading statements and had inconsistent reference quality, although an improvement was noted over time. Bing AI from November 2023 had short answers without detailed elaboration and sometimes just answered “YES”. Chatbots demonstrate potential as personalized educational tools for CKD that utilize layman’s terms, deliver timely and rapid responses in multiple languages, and offer a conversational pattern advantageous for patient engagement. Despite improvements observed from March to November 2023, some answers remained potentially misleading. ChatGPT 4 offers some advantages over 3.5, although the differences are limited. Collaboration between healthcare professionals and AI developers is essential to improve healthcare delivery and ensure the safe incorporation of chatbots into patient care.

AbstractA 61‐year‐old female presented with progressive plaques on the left forehead and right labia.

Abstract Background Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. Methods TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. Results Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). Conclusions Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

AbstractBackgroundAbsent “organic” disease, dyspeptic symptoms may arise from abnormal gastric sensation, accommodation, motility or emptying (GE). Extensive gastric sensorimotor evaluation is rarely undertaken because testing is prolonged, invasive, poorly tolerated or unavailable.AimsTo investigate whether gastric antral motor function, evaluated with scintigraphy, predicts GE. To explore whether motor testing with symptom recording predicts day‐to‐day symptoms in patients with dyspepsia.MethodsGE was determined using a scintigraphic solid‐meal protocol (296 kcal, 35% fat). Antral motility was estimated from 10 min of scintigraphic time‐activity curves acquired 40 min after meal consumption. An antral motility index (MI) was derived from contraction amplitude and frequency. Intra‐gastric distribution of the meal on scintograms at 1 h (IGD1) was determined. Meal‐induced symptoms were evaluated by questionnaire. Patients completed the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI‐DD) for 14 days.ResultsTwelve healthy participants and 23 prospectively recruited patients completed the study. Nine patients had delayed, and 2 had rapid, GE. In univariate analysis MI explained 42% of GE half‐time. In multivariate analysis MI and GE half‐time explained 25% of the variance in meal‐induced symptoms. While scintigraphic evaluation of gastric motor function with symptom recording explained 80% of the variance in the GCSI‐DD, meal‐induced symptoms were the only significant predictor. However, among patients with delayed GE, MI, GE half‐time, IGD1, and meal‐induced symptoms all significantly predicted GCSI‐DD.ConclusionsAntral motility predicts GE. In exploratory analyses, only meal‐induced symptoms predicted daily symptoms among patients with dyspepsia. However, motor function also predicted symptoms in patients with delayed GE.