Nevin Manimala

J Clin Oncol. 2025 Apr 3:JCO2401818. doi: 10.1200/JCO-24-01818. Online ahead of print.

ABSTRACT

PURPOSE: Although multiple agents targeting PD-1 have been approved as second-line treatment for esophageal squamous cell carcinoma (ESCC), only a fraction of patients derive long-term survival. Hence, reliable predictive biomarkers are urgently needed.

METHODS: Comprehensive tumor genomic profiling and transcriptome sequencing were performed on samples from the RATIONALE-302 study. We also conducted single-cell RNA sequencing analysis on Notch1 knockdown ESCC murine models to further explore the potential molecular mechanisms underlying anti-PD-1 benefit.

RESULTS: We identified NOTCH1 mutation as a potential predictive biomarker for longer overall survival (OS) with tislelizumab versus chemotherapy (18.4 months v 5.3 months; hazard ratio, 0.35 [95% CI, 0.17 to 0.71]). At the transcriptional level, type I IFN (IFN-I)/toll-like receptor expression signatures were positively associated with OS benefit of tislelizumab, whereas B-cell and neutrophil signatures predicted unfavorable OS. Exploratory analyses showed that the presence of NOTCH1 mutation correlated with enrichment of IFN-I signatures and reduced infiltration of B cells and neutrophils. In murine models, comparative single-cell transcriptome analyses further revealed that Notch1 deficiency facilitated a more immunologically activated tumor microenvironment which potentiated anti-PD-1 treatment.

CONCLUSION: Our data provide novel insights for anti-PD-1 treatment selection using NOTCH1 mutations and may provide a rationale for combination therapy in ESCC.

PMID:40179324 | DOI:10.1200/JCO-24-01818

PLoS One. 2025 Apr 3;20(4):e0320365. doi: 10.1371/journal.pone.0320365. eCollection 2025.

ABSTRACT

BACKGROUND: Heart failure (HF) is a growing health problem and around two percent are affected in the general population. Accurate diagnostic markers that have the potential for early diagnosis of HF are lacking. This study aimed to compare the expression levels of microRNA-210-3p with biomarkers NT-proBNP, sST2, and galectin-3, in heart failure patients with preserved and reduced ejection fractions.

MATERIALS AND METHODS: The cross-sectional study was conducted on 270 hypertensive heart failure patients in the age group of 30 to 75 years of both genders. The participants with evidence of HF were recruited from the Department of Cardiology in a tertiary care hospital in Chennai, India. MicroRNA-210-3p was analyzed by qRT-PCR in a stratified sample of 80 HF patients and 20 apparently healthy individuals. Biomarkers were analyzed by ELISA. Institutional ethics committee approval and written informed consent were obtained. Statistical analysis was performed using R software (4.2.1). Based on the type of distribution of data, appropriate statistical tools were used. p-value ≤ 0.05 was considered to be statistically significant.

RESULTS: All the biomarkers including microRNA-210-3p were significantly higher in HFrEF than in HFpEF. MAGGIC score showed a positive correlation with all the biomarkers. The cut-off of microRNA-210-3p was 5.03.

CONCLUSION: All the biomarkers were significantly elevated in HFrEF compared to HFpEF. However, microRNA-210-3p could be an early marker in the diagnosis of heart failure. The strategy of employing a multi-marker approach could help in the early diagnosis as well as in stratifying the HF patients.

PMID:40179320 | DOI:10.1371/journal.pone.0320365

Neurogastroenterol Motil. 2025 Apr 3:e70037. doi: 10.1111/nmo.70037. Online ahead of print.

ABSTRACT

BACKGROUND: Gut-directed hypnotherapy has been shown to be an effective treatment for irritable bowel syndrome, but prior studies have been small with variable delivery modalities. This systematic review and meta-analysis investigates the efficacy of gut-directed hypnotherapy for irritable bowel syndrome (IBS) symptoms and the impact of delivery characteristics.

METHODS: PubMed, Embase, and Web of Science were searched. Titles and abstracts, then full text articles, were screened for inclusion criteria. Studies were extracted and assessed for bias using the Cochrane Collaboration risk-of-bias tool. A meta-analysis was performed to assess the impact of gut-directed hypnotherapy on global IBS symptoms and pain. A sub-group analysis was conducted to assess the impact of gut-directed hypnotherapy delivery characteristics on IBS-related outcomes.

RESULTS: Twelve studies in 11 papers met inclusion criteria, involving 1158 patients with IBS. Eight studies provided continuous measures sufficient for meta-analysis. On systematic review, all 12 studies found gut-directed hypnotherapy to be superior to the comparator; nine were statistically significant. On meta-analysis, gut-directed hypnotherapy improved global IBS symptoms (SMD 0.73 [-0.09-1.55], I² 93%). Gut-directed hypnotherapy with high-volume delivery and gut-directed hypnotherapy delivered in groups showed statistically significant improvement in global IBS symptoms (SMD 0.56 [0.29-0.83], I² 0%; SMD 0.41 [0.05-0.77], I² 61%). Gut-directed hypnotherapy also significantly improved pain more than its comparator groups (SMD 0.25 [0.01-0.49], I² 17%).

CONCLUSION: Gut-directed hypnotherapy may improve global symptoms of IBS. In particular, GDH improved pain symptoms compared to other standard IBS interventions. GDH delivered in groups was effective at reducing global IBS symptoms compared to standard interventions.

PMID:40179285 | DOI:10.1111/nmo.70037

Cancer Nurs. 2025 Apr 2. doi: 10.1097/NCC.0000000000001478. Online ahead of print.

ABSTRACT

BACKGROUND: Pain, anxiety, and stress are the most common symptoms experienced by patients receiving chemotherapy after breast surgery. Virtual reality (VR) can be used as a method to manage these symptoms.

OBJECTIVE: To determine the effect of VR on chemotherapy-associated stress (salivary cortisol value), anxiety, pain, and vital signs of mastectomy patients.

METHODS: A total of 62 participants were enrolled in this randomized, 2-group design. Participants in the experimental group watched videos with VR glasses during their chemotherapy treatments. Saliva samples were collected from participants in both the control and experimental groups before and immediately after their chemotherapy treatments. The Personal Information Form, state anxiety component of the State-Trait Anxiety Inventory, visual analog scale, and the patients’ vital signs were also collected.

RESULTS: The State-Trait Anxiety Inventory state anxiety component and visual analog scale scores and the stress value mean scores differed significantly between the 2 groups at the second data point. There was also a statistically significant decrease in systolic blood pressure and diastolic blood pressure after chemotherapy in the experimental group.

CONCLUSION: The use of VR in women receiving chemotherapy significantly reduced their pain, anxiety, stress and blood pressure from before to immediately following the chemotherapy infusion.

IMPLICATIONS FOR PRACTICE: VR can be an appropriate intervention to reduce pain, anxiety, and stress in patients receiving chemotherapy after mastectomy.

PMID:40179266 | DOI:10.1097/NCC.0000000000001478

Cancer Nurs. 2025 Apr 2. doi: 10.1097/NCC.0000000000001500. Online ahead of print.

ABSTRACT

BACKGROUND: Spiritual care is a crucial component of oncology nursing, addressing patients’ holistic needs. However, limited research has explored spiritual well-being, competence, practices, and barriers among oncology nurses, particularly within specific cultural and religious contexts.

OBJECTIVE: To assess spiritual well-being and its predictors, including perceived competence, practices, and barriers to providing spiritual care among oncology nurses in Oman.

METHODS: A descriptive correlational study was conducted with 422 oncology nurses from 3 cancer care centers in Muscat, Oman. Convenience sampling was used, and data were collected through validated instruments, including the Spiritual Well-being Scale, Spiritual Care Competence Scale, Nurse Spiritual Care Therapeutics Scale, and Spiritual Care Practice Questionnaire. SPSS version 27 was used for data analysis, using descriptive statistics, Pearson correlation, independent t tests, analysis of variance, and multiple linear regression.

RESULTS: Nurses exhibited high spiritual well-being (mean, 102.1 [SD, 14.7]) and moderate spiritual care competence (mean, 96.1 [SD, 19.1]), yet spiritual care practices were infrequent (mean, 37.6 [SD, 13.1]). Major barriers included beliefs about the privacy of patients’ spirituality (59.5%) and lack of time (54.7%). Higher competence and prior oncology training were significantly associated with greater spiritual well-being.

CONCLUSIONS: Although oncology nurses in Oman report high spiritual well-being, barriers such as time constraints and role perceptions hinder spiritual care practices.

IMPLICATIONS FOR PRACTICE: Targeted education and training programs are essential to enhance spiritual care delivery. Addressing systemic challenges, including time management and role clarity, can foster a supportive environment for integrating spiritual care into oncology nursing.

PMID:40179262 | DOI:10.1097/NCC.0000000000001500

Neuropsychol Rehabil. 2025 Apr 3:1-18. doi: 10.1080/09602011.2025.2475544. Online ahead of print.

ABSTRACT

ABSTRACTThe benefits of assistive technology (AT) have been well established to positively support participation within disability. Clinicians have an important role in guiding clients to choose goal-centred AT. This study aims to explore (i) the frequency and types of AT prescribed by clinicians and (ii) real-world implementation of AT by clinicians, employing the ISO 9999 framework, and the challenges involved with AT prescription. An online survey was circulated to brain injury clinicians within New South Wales (NSW). Data were exported into IBM SPSS Statistics v.27 for analysis. Free text responses were analysed using a mixed-methods content analysis. A total of 31 AT products were reported 131 times by clinicians. The most frequently reported AT category was mainstream technology (n = 81), used amongst all professions. Using the ISO 9999 framework, the most reported class use of AT was “communication and information management” (n = 77/131). Challenges around AT implementation were funding acquisition, customizability of AT and time constraints with training. NSW clinicians have demonstrated varied use of AT to support cognitive, physical and communication functions. However, with the rapidly advancing nature of AT, there needs to be quicker approaches to generate high-quality evidence to support its use.

PMID:40179258 | DOI:10.1080/09602011.2025.2475544

Ultrasound Obstet Gynecol. 2025 Apr 3. doi: 10.1002/uog.29216. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the accuracy of fetal biparietal diameter (BPD) measurement in comparison with crown-rump length (CRL) measurement for pregnancy dating at 11-13 weeks’ gestation.

METHODS: This was a retrospective multicenter cohort study performed in five maternity units in Spain, the UK, Belgium and Bulgaria between January 2011 and December 2019. We included all women who attended a routine ultrasound examination at 11 + 0 to 13 + 6 weeks who had a singleton pregnancy with a viable non-malformed fetus/neonate and ultrasound-derived measurements for both CRL and BPD, along with a comprehensive record of pregnancy outcomes. We developed a formula for pregnancy dating based on BPD using data from pregnancies conceived via in-vitro fertilization (IVF) by applying a simple linear regression. We validated this formula both internally and externally and compared it with the most commonly used formulae (Robinson’s CRL-based and Kustermann’s BPD-based formulae) through utilization of the Euclidean distance, relative absolute error and mean squared error. We also examined the rate of induction of labor for post-term pregnancy based on dating using each of the formulae.

RESULTS: A total of 49 492 women were included in the study, comprising 47 223 (95.4%) who conceived spontaneously and 2269 (4.6%) who conceived via IVF. In the internal validation performed using data from IVF pregnancies, our newly developed formula showed no significant difference when compared with the true gestational age calculated using conception date, with a mean difference of 0.0006 (95% CI, -0.09 to 0.09) days. In contrast, the mean difference of Kustermann’s BPD-based formula was -0.31 (95% CI, -0.46 to -0.17) days and the mean difference of Robinson’s CRL-based formula was -1.78 (95% CI, -1.88 to -1.68) days. In the external validation using data from spontaneously conceived pregnancies, with dating using Robinson’s formula as the reference for ‘true’ gestational age, both our formula and Kustermann’s formula resulted in underestimation of gestational age, with significant mean differences of -1.25 (95% CI, -1.28 to -1.22) days and -0.96 (95% CI, -0.98 to -0.93) days, respectively. The largest differences compared with Robinson’s formula-based dating results were observed between 11 + 0 and 12 + 0 weeks. Dating the pregnancy using Robinson’s formula led to 8.1% of pregnancies identified as requiring induction after 41 + 3 weeks, compared with 6.8% (P < 0.001) and 7.0% (P < 0.001) when applying our formula and Kustermann’s formula, respectively.

CONCLUSION: Pregnancy dating based on ultrasound measurement of fetal BPD between 11 + 0 and 13 + 6 weeks’ gestation is a reliable alternative to dating based on fetal CRL. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

PMID:40179227 | DOI:10.1002/uog.29216

Sci Prog. 2025 Apr-Jun;108(2):368504251330037. doi: 10.1177/00368504251330037. Epub 2025 Apr 3.

ABSTRACT

ObjectiveTo assess medication appropriateness using the medication appropriateness index (MAI) criteria, the prevalence of potentially inappropriate medication (PIM) prescribing, and factors associated with increased PIM use in elderly ambulatory patients with cirrhosis.MethodsA cross-sectional study of 70 elderly ambulatory patients with cirrhosis (≥65 years old), from January to December 2021. Two clinical pharmacists evaluated medication appropriateness using the MAI tool. Data were analyzed using SPSS version 27.0. Descriptive statistics were used to present patient demographics, clinical characteristics, and MAI responses. Regression analysis was used to identify predictive factors for PIM prescribing. The kappa statistic was used to assess interrater agreement.ResultsAll participants had at least one medication with ≥ 1 inappropriate MAI criterion, with the most common issue being incorrect treatment duration (18%). Of 610 evaluated medications, 44.1% were classified as PIMs. The mean MAI scores per patient and per medication were 15.97 (±10.48) and 1.83 (±3.18), respectively, consistent with other studies. However, the prevalence of PIMs was higher, likely due to the specific disease population studied, as this is the first study to evaluate medication appropriateness in cirrhotic patients. Good interrater agreement was observed (kappa = 0.74), indicating good interrater reliability. Increased inappropriate prescribing was associated with the number of medications, age and severe renal impairment.ConclusionsPIMs are common in elderly patients with cirrhosis, highlighting the need for better prescribing practices to ensure medication safety. Involving clinical pharmacists with geriatrics expertise and using medication appropriateness tools can reduce PIMs and drug-related problems. Further, healthcare team training is essential to improve prescribing practices. Assessing PIMs in this population could enhance clinical outcomes, reduce adverse drug reactions, and lower healthcare costs. Incorporating comprehensive medication management into routine care for elderly cirrhotic patients is a key strategy to improve patient safety and quality of life.

PMID:40179219 | DOI:10.1177/00368504251330037

Science. 2025 Apr 4;388(6742):eadx8687. doi: 10.1126/science.adx8687. Epub 2025 Apr 3.

NO ABSTRACT

PMID:40179204 | DOI:10.1126/science.adx8687

Science. 2025 Apr 4;388(6742):eadt0548. doi: 10.1126/science.adt0548. Epub 2025 Apr 4.

ABSTRACT

Whether a gut-joint axis exists to regulate osteoarthritis is unknown. In two independent cohorts, we identified altered microbial bile acid metabolism with reduced glycoursodeoxycholic acid (GUDCA) in osteoarthritis. Suppressing farnesoid X receptor (FXR)-the receptor of GUDCA-alleviated osteoarthritis through intestine-secreted glucagon-like peptide 1 (GLP-1) in mice. GLP-1 receptor blockade attenuated these effects, whereas GLP-1 receptor activation mitigated osteoarthritis. Osteoarthritis patients exhibited a lower relative abundance of Clostridium bolteae, which promoted the formation of ursodeoxycholic acid (UDCA), a precursor of GUDCA. Treatment with C. bolteae and Food and Drug Administration-approved UDCA alleviated osteoarthritis through the gut FXR-joint GLP-1 axis in mice. UDCA use was associated with lower risk of osteoarthritis-related joint replacement in humans. These findings suggest that orchestrating the gut microbiota-GUDCA-intestinal FXR-GLP-1-joint pathway offers a potential strategy for osteoarthritis treatment.

PMID:40179178 | DOI:10.1126/science.adt0548