Category: Nevin Manimala

Future Oncol. 2024 Mar 6. doi: 10.2217/fon-2023-0952. Online ahead of print.

ABSTRACT

Aims: This retrospective study aims to identify a possible predictive role of KRAS mutations in non-small-cell lung cancer in response to first-line pembrolizumab, either as monotherapy or combined with chemotherapy. Methods: Patients received pembrolizumab alone (n = 213) or associated with chemotherapy (n = 81). Results: A mutation in the KRAS gene was detected in 27% of patients. In patients on pembrolizumab alone, median progression-free survival in KRAS-mutated cases was longer than in wild-type cases (11.3 vs 4.4 months; p = 0.019), whereas median overall survival did not reach statistical significance (22.1 vs 12.5 months; p = 0.119). Patients receiving chemo-immunotherapy with KRAS-positive tumors had a similar progression-free survival (9.7 vs 7.3 months; p = 0.435); overall survival data were immature. Conclusion: This study suggests a correlation between KRAS status and response to pembrolizumab.

PMID:38445372 | DOI:10.2217/fon-2023-0952

Chin Med J (Engl). 2024 Mar 6. doi: 10.1097/CM9.0000000000002982. Online ahead of print.

ABSTRACT

BACKGROUND: Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys.

METHODS: This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models.

RESULTS: A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower (P = 0.008), while the cumulative progression rate was higher (P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys (P = 0.004) in the multivariable analysis.

CONCLUSION: The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

PMID:38445358 | DOI:10.1097/CM9.0000000000002982

Stat Methods Med Res. 2024 Mar 6:9622802241233768. doi: 10.1177/09622802241233768. Online ahead of print.

ABSTRACT

The performance of individual biomarkers in discriminating between two groups, typically the healthy and the diseased, may be limited. Thus, there is interest in developing statistical methodologies for biomarker combinations with the aim of improving upon the individual discriminatory performance. There is extensive literature referring to biomarker combinations under the two-class setting. However, the corresponding literature under a three-class setting is limited. In our study, we provide parametric and nonparametric methods that allow investigators to optimally combine biomarkers that seek to discriminate between three classes by minimizing the Euclidean distance from the receiver operating characteristic surface to the perfection corner. Using this Euclidean distance as the objective function allows for estimation of the optimal combination coefficients along with the optimal cutoff values for the combined score. An advantage of the proposed methods is that they can accommodate biomarker data from all three groups simultaneously, as opposed to a pairwise analysis such as the one implied by the three-class Youden index. We illustrate that the derived true classification rates exhibit narrower confidence intervals than those derived from the Youden-based approach under a parametric, flexible parametric, and nonparametric kernel-based framework. We evaluate our approaches through extensive simulations and apply them to real data sets that refer to liver cancer patients.

PMID:38445348 | DOI:10.1177/09622802241233768

Dan Med J. 2024 Feb 8;71(3):A08230526. doi: 10.61409/A08230526.

ABSTRACT

INTRODUCTION: Tendinopathy and tendon tears of the gluteus medius and/or minimus (GMM) insertion at the greater trochanter are increasingly recognised internationally as a cause of recalcitrant lateral hip pain (LHP). The purpose of this study was to report the first Danish results of open surgical repair of GMM tears in female patients.

METHODS: In this retrospective observational study, we included 67 women (68 hips) with a mean (95% confidence interval (CI)) age of 59 (56-61) years who underwent open GMM repair between September 2018 and June 2022. All cases had magnetic resonance imaging before surgery. Pre-, three- and 12-month post-operative testing included LHP (numerical rating scale 0-10), Copenhagen Hip and Groin Outcome Score (HAGOS), Oxford Hip Score (OHS), the EuroQol-Visual Analogue Scale (EQ-VAS) and the Global Rating of Change score (GROC). Responses on GROC were considered successful if patients scored “moderately better” to “very much better”. Function of the lower limbs was assessed by the 30-second Chair-Stand-Test (CST).

RESULTS: From pre-testing to 12-month follow-up, LHP at rest and during activity decreased significantly, all HAGOS subgroups improved by 27-35 points, the OHS improved from 22 to 35 points, the EQ-VAS improved from 52 to 72 points and the mean (95% CI) number of repetitions in the CST improved by 2.4 (1.4-3.3). Success on the GROC was reported by 79% of the patients.

CONCLUSION: Open surgical repair of GMM tendon tears in women produced statistically significant improvements in patient-reported outcomes at one-year follow-up.

FUNDING: None.

TRIAL REGISTRATION: Not relevant.

PMID:38445316 | DOI:10.61409/A08230526

Eur J Ophthalmol. 2024 Mar 6:11206721241234952. doi: 10.1177/11206721241234952. Online ahead of print.

ABSTRACT

PURPOSE: To compile real-time data on the preferred mydriasis practice patterns for retinopathy of prematurity (ROP) screening in Europe.

METHODS: A cross-sectional online survey was conducted from December 2022 to January 2023, using a self-report online questionnaire which was distributed via email to the members of the European Pediatric Ophthalmological Society and the Greek National ROP Task Force. A six-week period of recruitment was determined, and a reminder email was sent after two weeks. Descriptive statistics were used to explore the data, which was summarized with frequencies and percentages.

RESULTS: Sixty-six responses were recorded (response rate: 29.5%), representing practices in 55 Neonatal Intensive Care Units from 21 European countries. In 94.5%, the applied mydriatic regimen consists of phenylephrine with at least one muscarinic antagonist, either tropicamide or cyclopentolate. The concentration of phenylephrine ranges from 0.5% to 5%, of tropicamide from 0.25% to 1%, and of cyclopentolate from 0.2% to 1%. The most commonly used regimen (43.6%) contains phenylephrine 2.5% and tropicamide 0.5%, administered either combined or separately. About 54.5% of the reported mydriatic solutions are non-commercial, in-house preparations. Systemic adverse events, including oxygen desaturation, bradycardia and cardiopulmonary arrest were reported in 14.5%.

CONCLUSION: There is considerable heterogeneity in the applied mydriatic regimens for ROP screening in Europe, reflecting the absence of universal guidelines. The wide use of in-house preparations underlines the gap in the pharmaceutical industry. Concern should be raised against the wide use of undiluted commercial drugs, that reach adult dose, in the fragile population of preterm infants.

PMID:38445304 | DOI:10.1177/11206721241234952

J Agromedicine. 2024 Mar 6:1-12. doi: 10.1080/1059924X.2024.2325708. Online ahead of print.

ABSTRACT

OBJECTIVES: The objectives of this study on the forestry and logging workforce are to: 1) Analyze causes of injuries/fatalities to inform future intervention studies focused on risk mitigation, 2) determine whether there are any trends or associations between work-related risk factors and workplace injuries/fatalities over a 16-year period (2003-2019), and 3) identify knowledge gaps related to injuries and fatalities for future studies to address.

METHODS: Data on fatalities, injuries, and illnesses of the forestry and logging workforce from the United States Bureau of Labor Statistics were analyzed. Correlation analysis (p < .05) was conducted to assess the relationship between causes of forestry and logging workforce fatalities by cause of fatality in the United States. Injury and fatality rates were calculated for each year (fatalities: 2003-2018; injuries: 2005-2019) and time span-specific incidence rates were calculated by cause.

RESULTS: Contact with objects and equipment was the primary cause of injuries and fatalities in the forestry and logging workforce during the study period. Transportation-related incidents ranked second as the cause of fatalities, while the category of falls, slips, and trips was the second leading cause of injuries.

CONCLUSION: Gaps in occupational health and safety identified by this study should be collaboratively addressed by researchers and the forestry industry.

PMID:38445302 | DOI:10.1080/1059924X.2024.2325708

Forensic Sci Int Synerg. 2024 Feb 28;8:100459. doi: 10.1016/j.fsisyn.2024.100459. eCollection 2024.

ABSTRACT

The article by Maseme, Gardner and Mahomed discusses the need for clarifications and amendments to South Africa’s legal framework, particularly the Protection of Personal Information Act (POPIA), 4 of 2013, which governs broad consent for biobank research. The authors emphasise the importance of addressing conflicts between POPIA and the ethical standards stipulated by the Department of Health. The article calls for collaboration between the forensic science community and the Academy of Science of South Africa, to develop a uniform code of conduct, as per the requirements of POPIA. The authors stress the imperative of a DNA statistical population profile database for diverse representation in forensic science. The article highlights the significance of voluntary informed consent and compliance with ISO/IEC 17025 standards, with a view to mitigating potential risks and ethical concerns.

PMID:38445266 | PMC:PMC10912828 | DOI:10.1016/j.fsisyn.2024.100459

Front Neurosci. 2024 Feb 20;18:1358998. doi: 10.3389/fnins.2024.1358998. eCollection 2024.

ABSTRACT

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects over 50 million elderly individuals worldwide. Although the pathogenesis of AD is not fully understood, based on current research, researchers are able to identify potential biomarker genes and proteins that may serve as effective targets against AD. This article aims to present a comprehensive overview of recent advances in AD biomarker identification, with highlights on the use of various algorithms, the exploration of relevant biological processes, and the investigation of shared biomarkers with co-occurring diseases. Additionally, this article includes a statistical analysis of key genes reported in the research literature, and identifies the intersection with AD-related gene sets from databases such as AlzGen, GeneCard, and DisGeNet. For these gene sets, besides enrichment analysis, protein-protein interaction (PPI) networks utilized to identify central genes among the overlapping genes. Enrichment analysis, protein interaction network analysis, and tissue-specific connectedness analysis based on GTEx database performed on multiple groups of overlapping genes. Our work has laid the foundation for a better understanding of the molecular mechanisms of AD and more accurate identification of key AD markers.

PMID:38445255 | PMC:PMC10912539 | DOI:10.3389/fnins.2024.1358998

Perioper Med (Lond). 2024 Mar 5;13(1):15. doi: 10.1186/s13741-024-00370-2.

ABSTRACT

BACKGROUND: Intravenous lidocaine could be a potential alternative adjuvant to propofol-based sedation for gastroscopy in elderly patients. This study aimed to evaluate the effect of intravenous lidocaine on the median effective dose (ED50) of propofol induction dose in elderly patients undergoing painless gastroscopy.

METHODS: The study included 70 patients aged ≥ 60 years undergoing painless gastroscopy with 64 randomly assigned to either group L (2% lidocaine 1.5 mg/kg, n = 31) or group N (equal volume normal saline, n = 33). All patients received propofol induction following 0.1 μg/kg intravenous sufentanil. The Dixon “up-and-down” sequential method was used, with a 1.5 mg/kg initial induction dose of propofol followed by a 0.1 mg/kg sequential variable dose. The primary endpoint was the ED50 of the propofol induction dose. The total propofol dose, recovery time, adverse events, and local anesthetic intoxication reactions were also recorded.

RESULTS: The ED50 of propofol induction dose was 0.670 (95% confidence interval [CI] 0.216-0.827) mg/kg in group L and 1.118 (95% CI 0.803-1.232) mg/kg in group N. There was a statistically significant difference between the two groups (p < 0.001). The incidence of hypotension and propofol injection pain were lower in group L than in group N (p < 0.05). Furthermore, the orientation recovery time in group L was shorter compared to group N (p < 0.05). None of the participants in group L observed local anesthetic intoxication reactions after receiving lidocaine.

CONCLUSIONS: The administration of intravenous lidocaine to elderly patients undergoing painless gastroscopy resulted in a significant 40% reduction in the ED50 of propofol induction dose, which may be related to the decreased incidence of hypotension and injection pain, as well as the improved post-gastroscopy orientation recovery.

TRIAL REGISTRATION: ChiCTR, ChiCTR2200065530. Registered on 08 November 2022.

PMID:38444044 | DOI:10.1186/s13741-024-00370-2

BMC Rheumatol. 2024 Mar 5;8(1):11. doi: 10.1186/s41927-024-00381-y.

ABSTRACT

BACKGROUND: To describe the evidence of methotrexate (MTX) initiation strategies in patients with rheumatoid arthritis (RA) and, in the case of non-responders, analyse the efficacy and safety of route and dose optimisation.

METHODS: We conducted a comprehensive scoping review of randomised controlled trials according to PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O’Malley. PubMed, EMBASE, and Cochrane were searched without language restriction, and hand searches of relevant articles were examined.

RESULTS: We identified 1,367 potentially eligible studies, of which 12 were selected based on the titles and abstracts and then on the full-length articles. In naïve-MTX patients, a linear dose-response relationship for starting dose was found between 5 mg/m2/week (7.5-10 mg/week) and 10 mg/m2/week (15-22 mg/week), without toxicity correlation. A higher initial dose of MTX (25 mg vs. 15 mg) was more effective, resulting in fewer dose increases due to ineffectiveness and more dose reductions due to higher remission rates. There was also a trend towards increased gastrointestinal toxicity. Comparing different routes of administration of MTX, subcutaneous MTX showed a statistically higher ACR20 response (85%) in comparison with oral MTX (77%) (p < 0.05). The clinical efficacy and safety of accelerated and conventional start MTX regimens were comparable between 7.5 and 15 mg with a 2,5 mg dose increase every two weeks. In RA patients who have failed the initial treatment with MTX, the stepwise increase in MTX doses is associated with a higher ACR20 response and sustained remission rate than other strategies. In MTX non-responders, optimisation to SC MTX was associated with improvements in ACR20 and ACR50 rates with similar toxicity between groups. In the early RA patients subgroup, SC MTX showed higher ACR20 response rates than oral MTX, and intensive oral methods have a much higher sustained remission rate, shorter mean time to remission, and better clinical disease activity measures than conventional treatments.

CONCLUSIONS: Higher starting doses of MTX and initial subcutaneous MTX made better performance in improving the ACR20 response, although the clinical effectiveness and safety of other MTX start regimens are comparable. This scoping review provides evidence in support of optimising MTX treatment in terms of route and dose prior to concluding that MTX treatment in RA patients has failed.

PMID:38444043 | DOI:10.1186/s41927-024-00381-y