Citations

Background/Objectives: It is often challenging for patients to understand treatment options, their mechanisms of action, and the potential side effects of each treatment option for glomerular disorders. This study explored the ability of ChatGPT to simplify these treatment options to enhance patient understanding. Methods: GPT-4 was queried on sixty-seven glomerular disorders using two distinct queries for a general explanation and an explanation adjusted for an 8th grade level or lower. Accuracy was rated on a scale of 1 (incorrect) to 5 (correct and comprehensive). Readability was measured using the average of the Flesch–Kincaid Grade (FKG) and SMOG indices, along with the Flesch Reading Ease (FRE) score. The understandability score (%) was determined using the Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). Results: GPT-4’s general explanations had an average readability level of 12.85 ± 0.93, corresponding to the upper end of high school. When tailored for patients at or below an 8th-grade level, the readability improved to a middle school level of 8.44 ± 0.72. The FRE and PEMAT-P scores also reflected improved readability and understandability, increasing from 25.73 ± 6.98 to 60.75 ± 4.56 and from 60.7% to 76.8% (p < 0.0001 for both), respectively. The accuracy of GPT-4’s tailored explanations was significantly lower compared to the general explanations (3.99 ± 0.39 versus 4.56 ± 0.66, p < 0.0001). Conclusions: ChatGPT shows significant potential for enhancing the readability and understandability of glomerular disorder therapies for patients, but at a cost of reduced comprehensiveness. Further research is needed to refine the performance, evaluate the real-world impact, and ensure the ethical use of ChatGPT in healthcare settings.

Background/Objectives: Peri-intubation hypotension is a known complication of endotracheal intubation. In the hospital setting, peri-intubation hypotension has been shown to increase hospital mortality and length of stay. The use of prophylactic vasopressors at the time of sedation induction to prevent peri-intubation hypotension has been raised. This systematic review and meta-analysis aims to review the safety and efficacy of this practice. Methods: The study was fully registered with PROSPERO on 13 October 2022, and screening for eligibility was initiated on 20 September 2024. Randomized controlled trials, along with retrospective or prospective cohort studies, were included in the search. The terms “peri-intubation hypotension”, “vasopressors”, “intubation”, and “anesthesia induced hypotension” were used to search the title/summary in PubMed, Cochrane Library, and Google Scholar databases. An assessment of bias for each study was conducted using the Newcastle-Ottawa Quality Assessment Scale. The primary outcome was the rate of hypotension peri-intubation. Any complications secondary to hypotension or vasopressors were the secondary outcome. Results: We identified 13 studies, which were all randomized controlled studies, to include in the final analysis. The risk ratio for preventing peri-intubation hypotension was 1.6 (95% CI, 1.2–2.14) with the use of prophylactic phenylephrine while giving propofol versus no prophylactic vasopressors and 1.28 (95% CI 1.03–1.60) with the use of ephedrine. Conclusions: These findings suggest that in patients undergoing intubation in the operating room with propofol, prophylactic vasopressors given with induction for intubation decrease the odds of hypotension.

ABSTRACTPurposeThis study aimed to assess whether kidney stone burden and risk factors at the time of kidney donor evaluation were associated with a symptomatic stone event post‐donor evaluation.MethodsWe identified adults evaluated at Mayo Clinic (two sites) (2000–2011) for living kidney donation and had either a personal history or radiological evidence of kidney stone disease. We analyzed demographics, stone risk factors, stone number/size, and the committee's donation decision and reasons. A follow‐up survey (2022–2023) assessed post‐evaluation symptomatic kidney stones and related morbidity.ResultsAmong 412 potential donors with kidney stone disease, 258 donated, 75 did not donate due to kidney stones, and 79 did not donate for other reasons. Multivariable analysis showed that candidates not donating due to stones had higher body mass index (BMI), prior symptomatic kidney stones, multiple stones on imaging, bilateral kidney stones, and diameter of largest stone ≥3 mm. Of 147 who completed the survey, 26 (18%) had a symptomatic kidney stone post‐donor evaluation. Younger age (p = 0.031) and multiple stones on imaging (p = 0.02) were significant predictors of post‐evaluation symptomatic stones regardless of donation status (p = 0.41).ConclusionsStone burden on imaging and prior symptomatic stone events were associated with not donating. Younger age and stone burden on imaging were the primary risk factors for a symptomatic kidney stone event after donor evaluation.

ABSTRACT Pneumocystis jirovecii pneumonia (PJP) remains a significant cause of morbidity and mortality during AIDS. In AIDS, the absence of CD4 immunity results in exuberant and often fatal PJP. In addition, organism clearance requires a balanced macrophage response since excessive inflammation promotes lung injury and respiratory failure. Corticosteroids given in addition to antibiotics significantly improve outcomes during PJP. However, concerns exist that corticosteroids further suppress immunity and increase co-infections. New strategies to promote killing and clearance of Pneumocystis while balancing lung inflammation are required. Prior studies have shown that innate immunity to Pneumocystis is mediated by C-type lectin receptors (CLRs) on macrophages and involves downstream CARD9 activation. CARD9 can be targeted by a novel specific small molecule inhibitor (BRD5529) that significantly reduces inflammatory signaling by macrophages. CARD9 serves as the central intracellular molecule through which Dectin-1, Dectin-2, Mincle, and other CLRs signal. Dectin-1 CLR is activated through its own intracytoplasmic domain, whereas other innate CLRs (e.g., Dectin-2 and Mincle) require interactions with a common Fc-gamma receptor (FcγR) accessory chain to mediate responses. We now observe that mice double deficient in both Dectin-1 and Fcer1g (which lack the FcγR gamma chain) exhibit markedly reduced organism clearance compared with Card9 −/− infected animals. These mice also possess deficiencies in immunoglobulin (Ig) Fc receptors directly mediating antibody responses, further implicating altered humoral responses in Pneumocystis killing. We further demonstrate in the Pneumocystis pneumonia (PCP) mouse model that BRD5529 administration successfully suppresses inflammatory cytokines. Our data support that innate immune responses through the CLR-CARD9 axis and humoral response act together to mediate effective responses resulting in optimal organism killing and generation of host inflammatory responses. Furthermore, host lung inflammation during PCP may be successfully reduced with a novel CARD9 small molecule inhibitor. IMPORTANCE Pneumocystis pneumonia (PCP) causes severe respiratory impairment in hosts with suppressed immunity, particularly those with CD4 deficiencies, such as HIV. In addition to lymphocytic immunity, both innate and humoral immunities also participate in host defense against Pneumocystis . In the current studies, we defined the relative roles of CLR receptor-mediated inflammation, as well as FcgR-related inflammation and clearance of Pneumocystis organisms. Our studies reveal important roles for CLR activities for inducing lung inflammation, which can be ameliorated with a novel small molecule inhibitor of the CARD9 adaptor protein that is necessary for CLR signaling. In contrast, FcgR has a dominant role in organism clearance, underscoring an integral role of humoral responses for the elimination of this infection.

ABSTRACTBackgroundData are limited on the natural history and symptom patterns of cyclic vomiting syndrome (CVS), a disorder of gut–brain interaction characterized by recurrent stereotypical vomiting, retching, and nausea episodes.MethodsA 6‐month, observational, remote study prospectively assessed symptom patterns in adults with CVS using an electronic daily diary. Patients recorded their disease experience, including CVS symptoms and associated severity, in the daily diary. The study defined a CVS episode start as the first day of 5 or more vomiting and/or retching (V + R) events. Episode end was defined as the first day of ≥ 7 (prespecified main analysis) or ≥ 4 (sensitivity analysis) days without any diary V + R events.Key ResultsEighty‐eight of 93 (94.6%) enrolled patients (62 female; mean age, 37.7 years) had daily diary data recorded during the study; 61 (69.3%) patients had at least one episode. In the prespecified main analysis, 191 episodes (median, 0.6 per 30 diary days) were reported (median duration, 3.0 days); 17.8% of the episodes lasted > 10 days. In the sensitivity analysis, 248 episodes (median, 0.7 per 30 diary days) were reported (median duration, 2.0 days). Thirteen of 88 (14.8%) patients with diary data had interepisodic V + R (reported V + R events without meeting the threshold for study‐defined episode). Other CVS‐related (non‐V + R) symptoms (most frequently nausea, abdominal pain, and sweating) were reported more frequently during the episode versus the interepisodic period.Conclusions and InferencesThis prospective longitudinal study shows marked heterogeneity of CVS episodes and highlights the need to better define and characterize episodes in these patients.

Colorectal cancer (CRC) remains one of the most prevalent and lethal cancers worldwide, prompting ongoing research into innovative therapeutic strategies. This review aims to systematically evaluate the role of gelatinases, specifically MMP-2 and MMP-9, as therapeutic targets in CRC, providing a critical analysis of their potential to improve patient outcomes. Gelatinases, specifically MMP-2 and MMP-9, play critical roles in the processes of tumor growth, invasion, and metastasis. Their expression and activity are significantly elevated in CRC, correlating with poor prognosis and lower survival rates. This review provides a comprehensive overview of the pathophysiological roles of gelatinases in CRC, highlighting their contribution to tumor microenvironment modulation, angiogenesis, and the metastatic cascade. We also critically evaluate recent advancements in the development of gelatinase inhibitors, including small molecule inhibitors, natural compounds, and novel therapeutic approaches like gene silencing techniques. Challenges such as nonspecificity, adverse side effects, and resistance mechanisms are discussed. We explore the potential of gelatinase inhibition in combination therapies, particularly with conventional chemotherapy and emerging targeted treatments, to enhance therapeutic efficacy and overcome resistance. The novelty of this review lies in its integration of recent findings on diverse inhibition strategies with insights into their clinical relevance, offering a roadmap for future research. By addressing the limitations of current approaches and proposing novel strategies, this review underscores the potential of gelatinase inhibitors in CRC prevention and therapy, inspiring further exploration in this promising area of oncological treatment.

Background: This study aimed to explore the potential associations between voice metrics of patients with PD and their motor symptoms. Methods: Motor and vocal data including the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III), Harmonic–Noise Ratio (HNR), jitter, shimmer, and smoothed cepstral peak prominence (CPPS) were analyzed through exploratory correlations followed by univariate linear regression analyses. We employed these four voice metrics as independent variables and the total and sub-scores of the UPDRS-III as dependent variables. Results: Thirteen subjects were included, 76% males and 24% females, with a mean age of 62.9 ± 10.1 years, and a median Hoehn and Yahr stage of 2.3 ± 0.7. The regression analysis showed that CPPS is associated with posture (UPDRS-III posture scores: β = −0.196; F = 10.0; p = 0.01; R2 = 0.50) and UPDRS-III postural stability scores (β = −0.130; F = 5.57; p = 0.04; R2 = 0.35). Additionally, the associations between CPPS and rapid alternating movement (β = −0.297; p = 0.07), rigidity (β= −0.36; p = 0.11), and body bradykinesia (β = −0.16; p = 0.13) showed a trend towards significance. Conclusion: These findings highlight the potential role of CPPS as a predictor of postural impairments secondary to PD, emphasizing the need for further investigation.

The treatment of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-cell ALL) has seen substantial progress over the past two decades. The introduction of BCR::ABL1 tyrosine kinase inhibitor (TKIs) has resulted in dramatic improvements in long-term survival. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), with its curative potential, has always been an integral part of the treatment algorithm of Ph+ ALL. Recently, the approval of novel therapies such as blinatumomab, inotuzumab ozogamicin and chimeric antigen receptor T-cell (CAR-T) therapy in relapse and refractory (R/R) ALL have further improved outcomes of B-cell ALL. With potent TKIs and novel targeted therapy, the treatment guidelines for Ph+ ALL are evolving rapidly. Additionally, with improved tools for detecting measurable residual disease (MRD), there has been recent interest in redefining the role of allo-HSCT for some patients. In this context, we discuss the current evidence for the utilization of allo-HSCT for Ph+ ALL, focusing on novel therapies and MRD-directed care.

Ion radiotherapy requires accurate relative biological effectiveness (RBE) calculations to account for the markedly different biological effects of ions compared to photons. Microdosimetric RBE models rely on descriptions of the energy deposition at the microscopic scale, either through radial dose distributions (RDDs) or microdosimetric probability density distributions. While RDD approaches focus on the theoretical description of the energy deposition around the ion track, microdosimetric distributions offer the advantage of being experimentally measurable, which is crucial for quality assurance programs. As the results of microdosimetric RBE models depend on whether RDD or microdosimetric distributions are used, the model parameters are not interchangeable between these approaches. This study presents and validates a method to reproduce the published reference biological and clinical dose calculations at NIRS-QST for only carbon ion radiotherapy by using the modified microdosimetric kinetic model (MKM) alongside microdosimetric distributions instead of the reference RDD approach. To achieve this, Monte Carlo simulations were performed to estimate the variation of the radiation quality within and outside the field of pristine and spread-out Bragg peaks. By appropriately optimizing the modified MKM parameters for microdosimetric distributions assessed within water spheres, we successfully reproduced the results of calculations using the reference NIRS-QST RDD, generally within 2%.