Tag: pubmed

JCO Oncol Pract. 2025 Jun 12:OP2500170. doi: 10.1200/OP-25-00170. Online ahead of print.

ABSTRACT

PURPOSE: To assess the impact and outcomes of a novel program for routine preemptive DPYD testing in fluoropyrimidine (FP)-naïve patients.

PATIENTS AND METHODS: This single-center, retrospective cohort study included adult patients who either received a systemic FP or had a DPYD test result between July 1, 2022, and June 30, 2023. Patients were categorized into preemptive or standard cohorts on the basis of the timing of their DPYD test relative to their initial FP dose. Primary outcomes measured were 90-day all-cause mortality, and FP-related hospitalizations and emergency department (ED) visits after the first FP dose. Secondary outcomes included the incidence of empiric dose reductions, FP avoidance, and dose escalation tolerability among patients with dihydropyrimidine dehydrogenase (DPD) deficiency.

RESULTS: Among 1,281 patients, 90-day all-cause mortality was 5.78% in the preemptive cohort versus 8.23% in the standard cohort (adjusted hazard ratio [HR], 0.69 [95% CI, 0.43 to 1.10]; P = .12), with a notable overrepresentation of patients treated with curative intent in the preemptive group (53.0% v 39.4%, P < .0001). Deaths attributed to DPD deficiency were one (0.18%) in the preemptive cohort and four (0.72%) in the standard cohort (not statistically significant with limited power). Hospitalizations and ED visits related to FP toxicity were paradoxically higher in the preemptive cohort (13.99% v 8.69%, adjusted HR, 1.67 [95% CI, 1.15 to 2.43]; P = .007). Among patients with DPD deficiency in the preemptive cohort, 84.6% received an empiric FP dose reduction, and dose escalation was attempted in 52.2% of these cases.

CONCLUSION: Preemptive DPYD testing did not significantly reduce treatment-related mortality, although a numerical decrease suggests potential benefits that may be substantiated with greater statistical power. Nearly half of the patients managed with a dose reduction did not undergo dose escalation.

PMID:40505058 | DOI:10.1200/OP-25-00170

Int J Surg. 2025 Jun 12. doi: 10.1097/JS9.0000000000002725. Online ahead of print.

ABSTRACT

BACKGROUND: By modulating inflammatory pathways and exerting sympatholytic effects, perioperative dexmedetomidine offers several benefits in non-transplant surgery. Its favorable impact on ischemia-reperfusion injury and perioperative renal function support the potential role of dexmedetomidine as an adjunct in transplant surgery. The evidence within various settings of kidney (KT) and liver transplantation (LT) is systematically reviewed.

METHODS: This systematic review evaluated randomized controlled trials investigating the efficacy of perioperative systemic dexmedetomidine in preventing allograft failure and/or kidney dysfunction in kidney and liver transplant recipients. Meta-analysis was performed using random or fixed effects model depending on the degree of statistical heterogeneity. Risk of bias and evidence quality were assessed.

RESULTS: Ten randomized controlled trials tested perioperative systemic dexmedetomidine in recipients of living (n = 3) or deceased donor (n = 1) kidney transplants and living (n = 5) or deceased donor (n = 1) liver transplants. With moderate to high certainty, cardiocirculatory, pulmonary or surgical complication rates did not differ between dexmedetomidine and control groups. Risk for delayed graft function was reduced with dexmedetomidine after deceased donor KT (risk ratio:0.52 [0.26-1.01]; p = 0.05) and living donor LT (risk ratio:0.35 [0.17-0.74]; p = 0.006), though this did not translate into improved long-term allograft survival within limited long-term follow-up. Rates of posttransplant acute kidney injury were decreased following these transplant modalities (risk ratio:0.40 [0.18-0.90]; p = 0.03 and 0.69 [0.50-0.95]; p = 0.02, respectively). Early postoperative serum creatinine was improved after KT and living donor LT. After living donor LT, serum parameters indicating allograft function improved with dexmedetomidine on postoperative days 1, 3, and 5. However, no such improvements were observed after deceased donor LT.

CONCLUSIONS: Current evidence suggests that perioperative dexmedetomidine may reduce delayed graft function in deceased donor KT and living donor LT while supporting overall renal recovery. However, due to limited data and moderate certainty of evidence, further large-scale multicenter trials are needed to confirm clinical applicability and assess long-term efficacy.

PMID:40505055 | DOI:10.1097/JS9.0000000000002725

Int J Surg. 2025 Jun 1;111(6):4056-4059. doi: 10.1097/JS9.0000000000002386. Epub 2025 Apr 3.

ABSTRACT

BACKGROUND: Large language models (LLMs) have demonstrated potential in medical diagnostics, but their accuracy in complex cases remains a subject of investigation. DeepSeek-R1, an open-source model with advanced reasoning capabilities, has gained global attention. This study evaluates the diagnostic performance of DeepSeek-R1 compared to GPT-4 in complex clinical cases.

MATERIALS AND METHODS: A historical control study was conducted using 100 clinicopathologic cases from the New England Journal of Medicine (NEJM), published between 18 August 2022, and 30 January 2025. Each case was processed using DeepSeek-R1 with a structured diagnostic prompt. The model’s performance was assessed based on final diagnosis accuracy, differential diagnosis inclusion rate, ranking of correct diagnoses, and differential quality scores. Results were statistically compared to previously published GPT-4 performance data using chi-square, Mann-Whitney U, and t-tests.

RESULTS: DeepSeek-R1 correctly matched the final diagnosis in 35% of cases (35/100), which was comparable to GPT-4’s accuracy (39%; P = 0.634). However, DeepSeek-R1 included the correct diagnosis in its differential list in 48% of cases, significantly lower than GPT-4 (64%; P = 0.036). DeepSeek-R1 generated longer differential diagnoses (11.9 ± 2.0 vs. 9.0 ± 1.4; P = 0.000004) but maintained a similar mean rank for correct diagnoses (1.8 ± 2.2 vs. 2.5 ± 2.5; P = 0.288566) and equivalent differential quality scores (4.2 ± 0.10 vs. 4.2 ± 1.3; P = 0.099667).

CONCLUSION: DeepSeek-R1 exhibits diagnostic accuracy comparable to GPT-4 while generating more diverse differential diagnoses. Its open-source nature and innovative reasoning strategies may enhance medical AI applications. Future studies should explore real-world clinical integration and refinement of differential diagnosis prioritization.

PMID:40505040 | DOI:10.1097/JS9.0000000000002386

Anesth Analg. 2025 Jun 12. doi: 10.1213/ANE.0000000000007582. Online ahead of print.

ABSTRACT

BACKGROUND: The right ventricle-pulmonary artery (RV-PA) coupling ratio provides an assessment of RV function indexed to PA afterload. A low preoperative RV-PA ratio has been associated with increased mortality after transcatheter procedures. In patients undergoing cardiac surgery, we hypothesized that a lower preoperative RV-PA ratio is independently associated with a higher risk of major morbidity and operative mortality (MMOM).

METHODS: We conducted a retrospective cohort study of adult patients who underwent coronary artery bypass graft and/or valve surgery (aortic, mitral, and tricuspid). The RV-PA ratio was calculated using the ratio of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP). The primary outcome was MMOM as defined by the Society of Thoracic Surgeons (STS). The Youden index was used to determine the optimal cutoff to classify into low versus high TAPSE/PASP ratio groups. Multivariable analysis was performed to test the association of TAPSE/PASP ratio with MMOM and other clinical outcomes with P- value <0.05 used for statistical significance.

RESULTS: One hundred and twenty-four (14.3%) of the 868 patients who met inclusion criteria had the primary outcome of MMOM. Patients in the low TAPSE/PASP group were more likely to have MMOM (90 (22.0%) vs 34 (7.4%); P < .001) as well as longer intensive care unit length of stay (ICU-LOS), hospital LOS (H-LOS), and mechanical ventilation time (MVT). By multivariable analysis, TAPSE/PASP ratio <0.52 mm/mm Hg was associated with a significant increase in the risk of MMOM (odds ratio [OR] 1.77, 95% confidence interval [CI], 1.10-2.83, P = .018). In the analyses of secondary outcomes, for every 0.1 mm/mm Hg increase in TAPSE/PASP ratio, there was a 4% reduction in ICU-LOS and MVT, and a 3% reduction in H-LOS.

CONCLUSIONS: TAPSE/PASP ratio <0.52 mm/mm Hg was associated with a significant increase in the risk of MMOM. Low preoperative TAPSE/PASP ratio was also associated with longer ICU-LOS, H-LOS, and MVT, even when adjusting for STS risk score for MMOM and cardiopulmonary bypass time.

PMID:40505025 | DOI:10.1213/ANE.0000000000007582

Lab Med. 2025 Jun 12:lmaf015. doi: 10.1093/labmed/lmaf015. Online ahead of print.

ABSTRACT

INTRODUCTION: Colorectal cancer (CRC) is known to have an association with circular RNAs (circRNAs) and immune checkpoint factors. This study sought to examine the expression levels of hsa_circ_0000284 and hsa_circ_0004771 molecules and the programmed cell death 1 protein (PD-1) and ecto-5′-nucleotidase (CD73) immune checkpoints in the peripheral blood of patients with CRC as well as the ratios of circular to linear forms of homeodomain-interacting protein kinase 3 (HIPK3) and nuclear receptor interacting protein 1 (NRIP1).

METHODS: Real-time polymerase chain reaction (PCR) and flow cytometry were used to assess quantitatively the expression level of circRNAs, CD73, and PD-1 in blood samples from patients with CRC and healthy control individuals. The expression of CD73 and PD-1 molecules was analyzed using FlowJo software, and the expression levels of circRNAs, CD73, and PD-1 were calculated with real-time PCR analysis.

RESULTS: Real-time PCR analysis revealed a statistically significant increase in the linear form of hsa_circ_0004771 (linNRIP1) and PD-1 gene expression in patients’ blood compared with control individuals. In addition, the circHIPK3:linHIPK3 and circNRIP1:linNRIP1 ratios are statistically significantly higher in patients than in healthy control individuals. The flow cytometry assessment indicated a statistically significant increase in PD-1 on the surface of lymphocytes and monocytes and an increase in CD73 on the granulocytes of patients compared with the healthy control individual.

DISCUSSION: Based on these findings, hsa_circ_0000284, hsa_circ_0004771, PD-1, and CD73 were statistically significantly increased in our cancer group. If further research were done, these blood markers could potential be biomarkers for CRC progression.

PMID:40505000 | DOI:10.1093/labmed/lmaf015

Diabetes Care. 2025 Jun 12:dc250595. doi: 10.2337/dc25-0595. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the concordance of glycated albumin, fructosamine, 1,5-anhydroglucitol (1,5-AG), and hemoglobin A1c (HbA1c) with continuous glucose monitor (CGM) metrics of hyperglycemia and glycemic control in a diverse population of adults with type 2 diabetes.

RESEARCH DESIGN AND METHODS: This was a pooled cross-sectional analysis of 552 adults, ages 30 to 97 years old, with diabetes. Participants wore a CGM for up to 2 weeks, and we evaluated the agreement between blood biomarkers (glycated albumin, fructosamine, and 1,5-AG) with CGM-defined metrics of hyperglycemia and glycemic control.

RESULTS: Of the 552 participants (mean age 74 years, 53% women, 36% Black), the median of mean CGM glucose was 132 mg/dL, and participants spent on average 84% of their time in range (70-180 mg/dL). CGM mean glucose was strongly related to HbA1c (r = 0.72), glycated albumin (r = 0.64), and fructosamine (r = 0.64) but weakly related to 1,5-AG (r = 0.46). Results were similar for time above range (>180 mg/dL). Glycated albumin and fructosamine performed similarly to HbA1c in the detection of target time in and above range (c-statistics ranged from 0.85 to 0.94).

CONCLUSIONS: Glycated albumin and fructosamine had similar associations with CGM-defined metrics of hyperglycemia compared with HbA1c. These three biomarkers performed similarly in the detection of time above range and in range. Our results provide evidence for the utility of glycated albumin and fructosamine as alternate measures of hyperglycemia.

PMID:40504990 | DOI:10.2337/dc25-0595

Environ Health Perspect. 2025 Jun 12. doi: 10.1289/EHP15725. Online ahead of print.

ABSTRACT

BACKGROUND: Diarrheal diseases remain a leading cause of mortality and morbidity among under-five children in South Asia. In rural Bangladesh, deep tubewells that tap into low-arsenic deep aquifers have been installed to provide microbially safe and arsenic-free drinking-water at source. However, unlike more widely used shallow tubewells, deep tubwells are sparsely distributed, and households often travel farther for drinking-water consumption from such wells. Hence, benefits from deep tubewells may be abated by higher levels of microbial contamination during water handling and storage that could increase the risk of diarrheal diseases.

OBJECTIVES: We examined the association between deep tubewell use and diarrheal disease risk in under-five children and investigated the role of social and environmental factors on modifying the association.

METHODS: We implemented community diarrheal disease surveillance across households with under-five children using deep and shallow tubewells in Matlab, Bangladesh from March 2018 to October 2019. We used Generalized Estimating Equations (GEE) to measure the association between deep tubewell use compared to shallow tubewell use on diarrheal disease prevalence.

RESULTS: Children in households using deep tubewells had diarrheal disease prevalence 0.83 times that of children in households using shallow tubewells (95% Confidence interval (CI): 0.71-0.96). Protective effects of deep tubewell use on diarrhea risk were observed among children in households that drank from wells within their household compound (Risk ratio (RR) =0.70, 95% CI: 0.54-0.91), were in flood-prone areas (RR=0.83, 95% CI: 0.75-0.92), and used unimproved latrines (RR=0.62, 95% CI: 0.43-0.89). Deep tubewell use was more protective against diarrhea than shallow tubewell use during the dry season (RR = 0.71, 95% CI: 0.52-0.97).

CONCLUSIONS: Despite concerns, using deep tubewells may not translate to higher diarrhea risk among under-five children, and may reduce diarrhea further especially in social and environmental contexts associated with higher groundwater microbial contamination. https://doi.org/10.1289/EHP15725.

PMID:40504602 | DOI:10.1289/EHP15725

Transl Vis Sci Technol. 2025 Jun 2;14(6):24. doi: 10.1167/tvst.14.6.24.

ABSTRACT

PURPOSE: To develop a methodology for analyzing dynamic corneal images using pixel intensity tracking and hue, saturation, and value (HSV) color space transformation, aiming to quantify and visually interpret corneal responsiveness to mechanical stimulation.

METHODS: This study utilized the OCULUS Corvis ST device to obtain dynamic corneal images from two subject groups (young and older individuals). To ensure accurate pixel tracking, segmentation and registration techniques were implemented. To counteract potential biases due to alterations in curvature and eye retraction caused by the air-puff mechanical stimulus, the last 30 frames available post-stimulus were used for analysis. Pixel intensity tracking calculations were then performed in the frequency domain to compute H, S, and V values for each pixel within the overall region of interest. Additionally, corneal biomechanical parameters from the Corvis ST were extracted to examine their relationship with HSV values.

RESULTS: The HSV transformation provided a quantitative visual interpretation of corneal dynamics, with reddish vibrant areas indicating higher responsiveness to mechanical stimulation and dull blue areas indicating lower responsiveness. Additionally, significant differences were found between the young and older groups in each of the three HSV channels (all P < 0.001). Four biomechanical parameters showed statistically significant differences between groups (P < 0.05), but no statistically significant correlation with HSV values was found.

CONCLUSIONS: The HSV methodology effectively visualizes and quantifies corneal responsiveness to mechanical stimulation, offering a new approach for assessing corneal dynamics.

TRANSLATIONAL RELEVANCE: HSV color space analysis has the potential to enhance the diagnosis and management of conditions in which corneal dynamics are affected.

PMID:40504568 | DOI:10.1167/tvst.14.6.24

Oncologist. 2025 Jun 4;30(6):oyaf123. doi: 10.1093/oncolo/oyaf123.

ABSTRACT

BACKGROUND: CDK4/6 inhibitors (CDK4/6i) are cornerstone therapies in Hormone Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Breast Cancer (BC) and emerging evidence suggests that they may influence immune function, potentially enhancing antitumor immunity but also triggering autoimmune reactions. This study aims to investigate the prevalence of autoimmune diseases (AD) in patients with HR+/HER2- BC to identify potential predictive biomarkers and to assess the impact of AD on disease progression.

PATIENTS AND METHODS: This retrospective-prospective cohort study included consecutive HR+/HER2- BC patients treated with CDK4/6i at Humanitas Research Hospital. Clinical-pathological features, treatment data, AD occurrence, and blood test values were collected. Descriptive statistics were used to determine AD prevalence, Kaplan-Meier method to estimate progression-free survival (PFS), and log-rank test to compare survival curves.

RESULTS: 352 patients (median age: 54 years) were enrolled, of which 87.2% had metastatic disease and received palbociclib, abemaciclib, or ribociclib (45.2%, 31.0%, and 23.9%, respectively). 12.8% of patients had early BC and received abemaciclib. ADs were identified in 49 patients: most had pre-existing conditions (38 stable and 4 flaring during treatment) while 7 developed new-onset ADs. The most frequent AD were Hashimoto thyroiditis, vitiligo, and rheumatoid arthritis. In the metastatic setting, the median PFS was significantly longer in patients with AD compared to those without (P = .0013), with patients with flaring or new-onset AD showing a better PFS (P = .0015). No significant predictive biomarkers for AD evolution were found.

CONCLUSION: CDK4/6i therapy is feasible in patients with pre-existing AD. Interestingly, the onset or flaring of AD during treatment is associated with improved PFS, suggesting a potential immune activation induced by CDK4/6i. However, further robust and prospective studies are required to validate these findings and explore the underlying mechanisms.

PMID:40504547 | DOI:10.1093/oncolo/oyaf123

JAMA Oncol. 2025 Jun 12. doi: 10.1001/jamaoncol.2025.1433. Online ahead of print.

ABSTRACT

IMPORTANCE: The rising incidence of young-onset colorectal cancer (CRC) has prompted health policymakers to consider lowering the recommended starting age for screening. However, population-based evidence supporting the long-term effectiveness of early-age screening remains limited.

OBJECTIVE: To evaluate whether initiating fecal immunochemical test (FIT) screening at ages 40 to 49 years, rather than at the currently recommended age of 50 years, reduces CRC incidence and mortality.

DESIGN, SETTING, AND PARTICIPANTS: This study analyzed a community-based screening cohort of Taiwanese residents aged 40 to 49 years, categorized into 4 subcohorts based on participation in early screening (age 40 to 49 years) and continuation of nationwide regular screening (50 years and older). The cohort was followed up until 2019 to compare CRC incidence and mortality across subcohorts. To mitigate self-selection bias, a delayed screening design and efficient propensity score matching was used, restricting analyses to participants attending regular screening. To validate the findings, an extended nonadherence adjustment was applied to all 4 subcohorts. Data were collected from January 2001 to December 2019, and data were analyzed from January 2021 to December 2024.

EXPOSURES: Biennial FIT screening was initiated for the early screening group at ages 40 to 49 years and for the regular screening group at age 50 years, with follow-up continuing under Taiwan’s national screening program.

MAIN OUTCOMES AND MEASURES: Primary outcomes were CRC incidence and mortality rates, reported as cases per 100 000 person-years, with adjusted relative risks (aRRs) comparing early vs regular screening groups.

RESULTS: Of 263 125 included participants, 146 796 (55.8%) were female. A total of 39 315 participated in early and regular screening, and 223 810 participated in regular screening only. The early screening group exhibited lower CRC incidence (26.1 [95% CI, 22.3-29.9] vs 42.6 [95% CI, 40.5-44.7] per 100 000 person-years) and mortality (3.2 [95% CI, 1.9-4.6] vs 7.4 [95% CI, 6.5-8.2] per 100 000 person-years). In propensity score-matched analyses, early screening significantly reduced CRC incidence (aRR, 0.79; 95% CI, 0.67-0.94) and mortality (aRR, 0.61; 95% CI, 0.38-0.98). Findings were consistent in the extended nonadherence adjustment model, showing a 25% reduction in incidence (aRR, 0.75; 95% CI, 0.72-0.77) and a 34% reduction in mortality (aRR, 0.66; 95% CI, 0.62-0.71).

CONCLUSIONS AND RELEVANCE: This study found that initiating FIT screening at age 40 to 49 years was associated with further reduction in CRC mortality and incidence compared with starting screening at age 50 years. These results provide strong empirical support for lowering the CRC screening age, with substantial public health implications.

PMID:40504543 | DOI:10.1001/jamaoncol.2025.1433