Nevin Manimala

J Clin Oncol. 2025 Jan 29:JCO2401269. doi: 10.1200/JCO-24-01269. Online ahead of print.

ABSTRACT

PURPOSE: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets EGFR exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of EGFR ex20ins+ advanced/metastatic NSCLC.

METHODS: Patients with treatment-naive EGFR ex20ins+ locally advanced/metastatic NSCLC were randomly assigned 1:1 to mobocertinib 160 mg once daily or pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by maintenance pemetrexed. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR), with planned interim analysis (IA) after approximately 70% of 227 expected PFS events.

RESULTS: A total of 354 patients were randomly assigned (mobocertinib: n = 179; chemotherapy: n = 175). Baseline characteristics were balanced between arms. At IA (cutoff: April 4, 2023), the median PFS per BICR was 9.6 months in each treatment arm (hazard ratio [HR], 1.04 [95% CI, 0.77 to 1.39]; P = .803). The primary end point crossed the prespecified futility boundary (HR > 1). The confirmed objective response rate (95% CI) per BICR was 32% (26 to 40) with mobocertinib versus 30% (24 to 38) with chemotherapy; the median duration of response was 12.0 versus 8.4 months. Quality-of-life assessments indicated clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation with mobocertinib versus chemotherapy. Grade ≥3 adverse events in >5% of patients (mobocertinib, chemotherapy) were diarrhea (20%, 1%), anemia (6%, 10%), increased lipase (6%, 0%), and decreased neutrophil count (1%, 7%).

CONCLUSION: The EXCLAIM-2 trial did not meet its primary end point. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with EGFR ex20ins+ advanced/metastatic NSCLC.

PMID:39879577 | DOI:10.1200/JCO-24-01269

Annu Rev Clin Psychol. 2025 Jan 29. doi: 10.1146/annurev-clinpsy-081423-023518. Online ahead of print.

ABSTRACT

The opioid crisis, driven by illicitly manufactured fentanyl, presents significant challenges in treating opioid use disorder (OUD) and opioid withdrawal syndrome. Fentanyl is uniquely lethal due to its rapid onset and respiratory depressant effects, driving the surge in overdose deaths. This review examines the limitations of traditional diagnostic criteria like those of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) and explores the potential of dimensional models such as the Hierarchical Taxonomy of Psychopathology (HiTOP) for a more nuanced understanding of OUD. Current treatments, including medications for OUD, are evaluated for efficacy in managing fentanyl-related OUD. Innovations in drug formulations and alternative induction methods are discussed to address the unique challenges posed by fentanyl. Psychotherapeutic and behavioral interventions, such as cognitive behavioral therapy and contingency management, are highlighted as crucial complements to pharmacotherapy. The review underscores the need for increased precision, comprehensive phenotyping, and advanced diagnostics to develop personalized treatment plans, all with the aim of improving patient outcomes and mitigating the societal impact of the opioid crisis.

PMID:39879556 | DOI:10.1146/annurev-clinpsy-081423-023518

Ann Am Thorac Soc. 2025 Jan 29. doi: 10.1513/AnnalsATS.202407-688OC. Online ahead of print.

ABSTRACT

RATIONALE: Previous studies evaluating the effect of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) on blood pressure (BP) showed variable results. Moreover, several studies recruited patients with normal or controlled BP, and compliance to antihypertensive drugs was not monitored. In addition, very few studies investigated central BP in this scenario.

OBJECTIVES: To evaluate whether OSA treatment is able to reduce central and peripheral BP in patients with uncontrolled hypertension (HTN) despite well documented use of anti-hypertensive treatment.

METHODS: The MORPHEOS is a multicenter, randomized controlled trial designed to evaluate the effects of CPAP or placebo (nasal dilator strips-NDS) for 6-months in patients with moderate-to-severe OSA and uncontrolled HTN on office BP, ambulatory BP monitoring (ABPM) and central BP (co-primary endpoints). Uncontrolled HTN was defined by ≥1 abnormal parameter in ABPM after 1-month of pill count and ≥80% adherence to medication. Pill count, adherence to CPAP or NDS and office BP was determined once a week in the first month and monthly thereafter.

RESULTS: A total of 123 patients completed the study (NDS: n=64, CPAP: n=59). The two groups were similar at baseline. Adherence to NDS (≥80%) and CPAP (≥4h/night) were 98.3% and 81.7%, respectively. As compared to NDS, office systolic BP (Δ=-10±16mmHg, p<0.001) and diastolic BP (Δ=-7±12mmHg, p=0.001) were reduced significantly in the CPAP group. Despite the BP lowering effect of CPAP did not reach statistical differences for ABPM parameters, the rate of 24-h ABPM control (<130X80mmHg) was higher in the CPAP than in the NDS group (40.7 vs 20%; p=0.024). Central diastolic BP reduced significantly (Δ=-6±9mmHg; adjusted p=0.029).

CONCLUSIONS: CPAP improves the rates of BP control in patients with OSA and uncontrolled HTN under regular use of medications. Clinical trial registration available at www.

CLINICALTRIALS: gov, ID: NCT02270658.

PMID:39879540 | DOI:10.1513/AnnalsATS.202407-688OC

Ann Am Thorac Soc. 2025 Jan 29. doi: 10.1513/AnnalsATS.202409-906OC. Online ahead of print.

ABSTRACT

RATIONALE: Tobacco smoking is a well-established risk factor for idiopathic pulmonary fibrosis (IPF), yet the influence of early-life tobacco exposure on future IPF risk remains poorly understood.

OBJECTIVES: To test the hypothesis that early-life tobacco exposure may elevate the risk of developing IPF, with this effect potentially modified by genetic susceptibility to IPF and mediated through accelerated biological aging.

METHODS: Using data from over 430,000 participants in the UK Biobank, we performed a prospective cohort study to examine the associations of maternal smoking around birth and age of smoking initiation with IPF risk. We evaluated the combined effects and interactions between early-life tobacco exposure and genetic susceptibility to IPF, quantified using polygenic risk scores. We assessed biological aging, as measured by telomere length and phenotypic age, as potential mediators in the associations between early-life tobacco exposure and IPF risk. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: Maternal smoking around birth was associated with a higher risk of IPF (HR: 1.26; 95% CI: 1.11-1.43). Compared to never-smokers, individuals who initiated smoking in childhood (HR: 3.65; 95% CI: 3.02-4.41), adolescence (HR: 2.64; 95% CI: 2.28-3.05), and adulthood (HR: 2.09; 95% CI: 1.79-2.44) exhibited increased IPF risk (P for trend < 0.001). An additive interaction was observed between age of smoking initiation and genetic risk for IPF. Individuals with high genetic risk, maternal smoking exposure, and childhood smoking initiation had a 16-fold greater risk of IPF (HR: 16.47; 95% CI: 9.57-28.32), compared to those with low genetic risk and no tobacco exposure. Telomere length and phenotypic age each mediated approximately 10% of the effect of maternal smoking on IPF, with weaker mediation effects observed for later ages of smoking initiation.

CONCLUSION: Early-life tobacco exposure may elevate the risk of IPF, with effect modified by genetic susceptibility and partially mediated through accelerated biological aging.

PMID:39879538 | DOI:10.1513/AnnalsATS.202409-906OC

Cancer Biother Radiopharm. 2025 Jan 29. doi: 10.1089/cbr.2024.0194. Online ahead of print.

ABSTRACT

Purpose: To evaluate the use of yttrium-90 (Y90) dosimetry in predicting treatment outcomes when used following transarterial radioembolization with SIR-Spheres® (Resin Y90) in patients with hepatic tumors. Materials and Methods: This single institution retrospective analysis included 100 patients with hepatocellular carcinoma, colorectal carcinoma or other liver metastases who underwent transarterial radioembolization with resin Y90 and had imaging follow-up within one year of treatment. Mean tumor dose and mean dose to nontumor was calculated using voxel-based dosimetry software. Descriptive statistics were reported and methods of analyses included simple and multivariable linear regression, contingency table analyses, Kaplan-Meier estimation, and Cox proportional hazards models. Results: Of 100 patients included, 65 demonstrated tumor shrinkage following transarterial radioembolization. Of these, 20 (30.8%) had hepatocellular carcinoma, 22 (33.8%) had colorectal carcinoma, and 23 (35.4%) had other types of metastases. There was an association between tumor shrinkage and mean tumor dose (p = 0.0285) and mean dose to nontumor (p = 0.0028) in hepatocellular carcinoma patients, but not colorectal carcinoma, or the other subgroup. For all 100 patients, time to death and mean tumor dose was associated only in the other subgroup (p = 0.0260), but not in the hepatocellular or colorectal carcinoma groups. Time to death and mean dose to nontumor was associated in hepatocellular carcinoma patients (p = 0.0421), but not the colorectal carcinoma or other subgroup. Conclusions: Voxel-based dosimetry assessment is a tool that may be utilized to assist in predicting treatment outcomes in responders to transarterial radioembolization.

PMID:39879533 | DOI:10.1089/cbr.2024.0194

J Am Coll Health. 2025 Jan 29:1-10. doi: 10.1080/07448481.2024.2446441. Online ahead of print.

ABSTRACT

Objective: This research effort developed, implemented, and evaluated an inexpensive poster campaign designed to influence on-campus mental health culture and stigma. Participants: 124 students at a Californian graduate-only university participated in the evaluation. Methods: A single-group, pretest-posttest, quasi-experimental design tested the effect of exposing graduate students to posters carrying attribution-based messages. The campaign lasted for seven weeks in 2023. Results: Although not all outcomes were influenced, statistically significant increases in perceptions of mental health culture and willingness to disclose mental health struggles to peers and faculty were detected with medium effect sizes. There were also statistically significant increases in visits to an intervention website advertised exclusively on campaign materials. No backfiring effects were detected, an issue that campaigns must be vigilant about. Conclusion: Given the low cost of implementation, this mental health campaign represents an inexpensive, low-effort approach that can favorably influence graduate student perceptions of campus mental health culture and willingness to disclose.

PMID:39879525 | DOI:10.1080/07448481.2024.2446441

Arq Bras Cardiol. 2025 Jan 27;122(1):e20240213. doi: 10.36660/abc.20240213. eCollection 2025.

ABSTRACT

BACKGROUND: There is still a significant population of patients with embolic stroke of Undetermined Source (ESUS) whose specific attributable cause of the stroke remains unknown.

OBJECTIVES: Our research aimed to assess clinical, electrocardiogram, laboratory, and echocardiographic parameters that may predict the propensity of paroxysmal atrial fibrillation (PAF).

METHODS: We enrolled seventy-five ESUS patients who were in sinus rhythm at the time of stroke diagnosis to undergo in-hospital 7-day Holter monitoring, testing for Pro-BNP, and a standard echocardiographic examination. For statistical analysis, a P-value < 0.05 was considered significant.

RESULTS: The average age of the 75 ESUS patients was 58 years old. 60% of the patients were male, and the most prevalent concomitant condition was hypertension (53.3%). Forty patients had atrial cardiopathy, and 15 patients had PAF episodes. Hypertension and the E/e- > 12 were independent predictors of atrial cardiopathy, with p-values of 0.001 and 0.02, respectively. In patients with atrial cardiopathy, multivariable regression analysis was performed; PTFV > 5000 Mv.ms, LA volume index > 34 ml/m2, and ejection fraction < 45% were significant independent predictors of AF with significant p values of 0.001, < 0.001, and 0.001 respectively.

CONCLUSIONS: In ESUS patients, atrial cardiopathy was prevalent. Hypertension and an E/e- ratio greater than 12 were independent predictors for it. Multivariable regression analysis identified PTFV1 > 5000 mV.ms, LA volume index > 34 ml/m2, and ejection fraction < 45% as independent predictors for new-onset atrial fibrillation.

PMID:39879513 | DOI:10.36660/abc.20240213

Arq Bras Cir Dig. 2025 Jan 27;37:e1868. doi: 10.1590/0102-6720202400074e1868. eCollection 2025.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has overloaded healthcare systems worldwide. Other diseases, such as neoplasms, including gastric cancer, remained prevalent and had their treatment compromised.

AIMS: The aim of this study was to evaluate the impact of the COVID-19 pandemic on the treatment of gastric cancer and adherence to the recommended preoperative COVID-19 screening protocol.

METHODS: A retrospective study evaluated patients diagnosed with gastric adenocarcinoma who underwent surgical treatment between 2015 and 2023.

RESULTS: A total of 769 patients with gastric cancer were evaluated and organized into two groups: (i) pre-COVID group and (ii) COVID group. The pre-COVID group consisted of 527 patients operated on between 2015 and 2019, and the COVID group consisted of 242 patients from 2020 to 2023. The average number of surgical procedures per year in the pre-COVID group was 105 and 81 in the COVID group. There was a statistically significant difference between ASA classification (p=0.002) and clinical staging (p=0.015), which were worse in the COVID group. We observed an increase in diagnostic surgeries (p=0.026), with an increase in the minimally invasive route (p<0.001). In patients undergoing curative surgery, there was a greater indication for postoperative ICU (p=0.022) and neoadjuvant chemotherapy (p<0.001). There was no difference in 30- and 90-day mortality.

CONCLUSIONS: The surgical and oncological outcomes for patients operated on during the pandemic remained uncompromised, even though many presented with more advanced initial stages and poorer clinical performance. High adherence to protocols and a low rate of complications related to coronavirus indicate that surgeries were performed safely during this period.

PMID:39879512 | DOI:10.1590/0102-6720202400074e1868

Braz J Biol. 2025 Jan 27;84:e284867. doi: 10.1590/1519-6984.284867. eCollection 2025.

ABSTRACT

One of the biggest public health problems globally is that of iron deficiency anemia. The present research aimed to determine the effect of prebiotics along with iron fortification on iron biomarkers in female anemic rats as some evidence suggests that prebiotics convert increase the solubility of iron, thereby enhancing its absorption. A total of 126 Sprague Dawley rats were fed with sixteen different types of fortified feed containing prebiotics (Inulin + Galacto Oligosaccharides) and Iron Fortificants (Sodium Ferric Ethylenediaminetetraacetate + Ferrous Sulphate). The duration of the trials was 3 months aimed at determining the effect of iron fortification and prebiotics on different iron biomarkers including Hemoglobin (Hb), Hematocrit, Red Blood Cell (RBC) count, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC). The trials resulted in statistically significant improved iron biomarkers among female anemic rats (P-value < 0.05). It was concluded that iron fortification and prebiotics in combination were able to increase the levels of iron biomarkers in female anemic rats.

PMID:39879502 | DOI:10.1590/1519-6984.284867

Braz J Biol. 2025 Jan 27;84:e284742. doi: 10.1590/1519-6984.284742. eCollection 2025.

ABSTRACT

Leishmaniasis, caused by the Leishmania parasite, remains a persistent public health challenge in Pakistan. Despite control efforts, the disease prevalence continues to rise, particularly among pediatric populations. Understanding prevalence patterns and transmission dynamics is critical for effective control strategies. This study aims to analyze leishmaniasis prevalence data from January 2016 to July 2023 in Pakistan. Specific objectives include assessing temporal trends, demographic patterns, and geographical hotspots of transmission, while emphasizing the need for enhanced surveillance and research for targeted interventions. Retrospective analysis was conducted on leishmaniasis prevalence data collected from multiple healthcare facilities across Pakistan. Data included results from diagnostic tests on suspected cases, encompassing both pediatric and adult patients. Descriptive statistical analysis was employed to evaluate prevalence rates, demographic characteristics, and geographical distribution of positive cases. Analysis revealed an increasing trend in leishmaniasis prevalence over the study period. Initially, from 2016 to 2020, a positivity rate of 27% was observed exclusively among pediatric patients in Islamabad, with no adult cases. Subsequently, from 2017 to 2022, the positivity rate increased to 42%, affecting both pediatric and adult populations in Islamabad, Rawalpindi, and Swat. Notably, between July 2022 and July 2023, the positivity rate surged to 56%, primarily impacting adult males in the identified hotspots. The study provides evidence of rising leishmaniasis prevalence in Pakistan, particularly among pediatric patients. Identified hotspots suggest localized transmission, warranting targeted interventions. Enhanced surveillance and research efforts are crucial for understanding disease dynamics and implementing effective control measures. Priority should be given to vulnerable populations and high-burden regions to mitigate leishmaniasis impact in Pakistan.

PMID:39879501 | DOI:10.1590/1519-6984.284742