Search

The present work deals with surface modification and gamma (γ) irradiation treatment to improve the performance of polyester/bitumen emulsion polymer-coated jute woven textiles for geotextile applications. There are different formulations of jute used such as raw (untreated) jute textile fabrics (J0) were modified by HEMA (2-hydroxyethyl methacrylate) monomer (J1), raw jute was only coated with the blend of polyester resin/bitumen emulsion (10 %/30 %) (J2), and the HEMA-treated jute was coated with polymer blends (J3). It was revealed that the HEMA treatment increased the tensile breaking force of the polymer-coated jute textiles (J3) by 13.2 %, and moisture properties decreased by 18–24 %. Further, γ-irradiation of 2.5 and 5.0 kGy was exposed to the processed jute fabrics for the yield of improved performance. In this case, a 5.0 kGy dose of γ-irradiation demonstrated maximum improvement compared to their non-irradiated ones, which is 6.1 % and 3.7 % increase of tensile breaking force for J2 (γ) and J3 (γ), respectively, than their non-irradiated jute samples (J2 and J3), whilst the enhancement of the values were 15.4 % and 17.4 %, respectively, compared to the raw jute (J0) sample. The moisture properties were reduced by up to 60 % as a function of γ-irradiation. Further characterization of the jute fabric samples was assessed by FTIR (Fourier Transform Infrared) Spectroscopy, XRD (X-ray diffraction), TGA (Thermogravimetric Analysis), and SEM (Scanning Electron Microscopy) testing.

Abstract Cocaine/crack abstinence periods have higher risk of relapse. Abstinence as initial part of the recovery process is affected by learning and memory changes that could preserve the addictive cycle. To further understand how the interruption of cocaine/crack consumption affects neurotrophin level we performed the present systematic review and meta-analysis following the PRISMA statement (number CRD42019121643). The search formula was conducted in PubMed, Web of Science, Embase, ScienceDirect, and Google Scholar databases. The inclusion criterion was cocaine use disorder in 18 to 60-year-old people, measuring at least one neurotrophin in blood before and after a controlled abstinence period. Studies without pre-post design were excluded. Five investigations had nine different reports, four of them were subjected to a meta-analysis (n = 146). GRADE risk of bias method was followed. Individual studies reported increased peripheral brain derived neurotrophic factor (BDNF) after abstinence, evidence pooled by Hedge’s g showed no significant change in BDNF after abstinence. Relevant heterogeneity in the length of the abstinence period (12–32 days), last cocaine/crack consumption monitoring and blood processing were detected that could help to explain non-significant results. Further improved methods are suggested, and a potential BDNF augmentation hypothesis is proposed that, if true, would help to understand initial abstinence as a re-adaptation period influenced by neurotrophins such as the BDNF.

Background: Species identification in commercially processed food and feed products is one of the important issues. This study was conducted to develop a genetic method for the detection of pig and cattle species in processed food and feed products using newly designed species-specific primers targeting mitochondrial 12S rRNA gene fragments. Methods: Two sets of specific primers were designed based on the 12S rRNA gene sequences of pig and cattle species from GenBank. The primers were validated by using the DNA extracted from nine different chordates, including pig, cattle, chicken, bata fish, bat, toad, African parrot, rat, and human origin. Annealing temperature ranging from 46-54 °C for 30 seconds and template DNA 1:10 serial dilutions ranging from 10 to 0.00001 ng/µl were employed for primer annealing and sensitivity analysis. Samples were analyzed using optimized Polymerase Chain Reaction (PCR) conditions. Results: The most intense expected DNA bands of pig and cattle were produced at 50 °C. Under that optimized annealing temperature pig and cattle-specific primers did not anneal with the DNA of other chordates. Total extracted DNA 0.001 ng and 0.01 ng of pig and cattle respectively containing the mitochondrial DNA (mtDNA) was successfully detected. Conclusion: These findings indicate that the newly designed primer pairs can be used to detect pig and cattle derivatives in various processed food and feed products. DOI: 10.18502/jfqhc.8.4.8256

The purpose of the study is to examine the role of entrepreneur education in the relationship between entrepreneur career and entrepreneurial self-efficacy. The study serves as substantiation for the previous entrepreneurial career studies and promotes better understanding of factors prompting the antecedents to entrepreneurial behavior. There is a need for more empirical research in this aspect because reviewed literature highlighted a number of problems associated with entrepreneurial education and entrepreneurial career in many nations’ world over and particular the developing countries. The study used survey-based method and SEM-PLS is employed to achieve the research objectives of the study. The data is collected from the manufacturing firms in Pakistan.The empirical evidence on the association between entrepreneurial education, entrepreneurial self-efficacy, and entrepreneurial career with moderating effect of SEN will strengthened previously established models such as the entrepreneurial intention model, which is modification in the theory of planned behavior and entrepreneurial event theory, both of which are linked to the theory of reasoned action. It is assumed that human actions are reasoned, controlled and planned. Thus, action is possible for the consequences of the reflected behavior. The findings are in line with the proposed hypothesized results.The study could offer valuable insights into the stage of entrepreneurial education for a range of stakeholders in Pakistan at particular and the world at large. Perhaps it is among the earliest studies of this kind in Pakistan that examined the effects of entrepreneurial education on students’ attitude toward entrepreneurial career. The outcomes from this study would be of beneficial for variety of interested parties including academicians, policymakers, learning institutions, supervisory bodies and the public in general.

Background: While targeted therapies have transformed the treatment landscape of oncogene-addicted non-small cell lung cancer (NSCLC), the influence of sex on treatment outcomes remains insufficiently understood., Objectives: This systematic review aimed to investigate the impact of sex on clinical outcomes in patients with NSCLC harboring driver fusions treated with targeted therapies enrolled in clinical trials., Data Sources and Methods: A comprehensive literature search was conducted using PubMed, Embase, and relevant conference abstracts to identify phase III randomized and early clinical trials that reported sex-specific data, including progression-free survival (PFS), overall survival (OS), overall response rate, and adverse events (AEs), in patients with fusion-positive NSCLC treated with tyrosine kinase inhibitors (TKIs)., Results: This review involved 10 studies reporting PFS data and 3 studies with OS data, focusing on first-line treatments for ALK fusion (9 studies) and RET fusion-positive (1 study) NSCLC. Pooled analysis of hazard ratios (HRs) for PFS and OS in ALK inhibitors trials revealed no significant differences in survival outcomes based on sex. Additionally, none of the studies provided data on sex-based differences in response rates or toxicities, highlighting a significant knowledge gap regarding the impact of sex on secondary outcomes in targeted therapy., Conclusion: This review found no significant sex-related differences in survival outcomes among patients treated with ALK inhibitors. However, the lack of data on sex-specific response and toxicity emphasizes the need for future research to better understand the role of sex in modulating treatment outcomes and treatment decisions with TKIs., Competing Interests: E.A.—Lectures and educational activities: MSD, Janssen; Consulting, Advisory role: from Amgen and Sanofi; Travel, Accommodations: Amgen, Ipsen. D.M.: Lectures and educational activities: Astellas Pharma, PharmaMar, Roche; Travel, Accommodations: Novartis, Lilly, Bristol-Myers Squibb, Merck. D.I.—Lectures and educational activities: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, MSD, Pfizer, Pharmamar, Takeda; Consulting, advisory role: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Beigene, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, Merck, MSD, Pfizer, Pharmamar, Sanofi, Takeda; Clinical Trials: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, F. Hoffmann-La Roche, GSK, Johnson & Johnson, Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Pharmamar, Sanofi; Research Grants: AstraZeneca, BMS, F. Hoffmann-La Roche, GSK. G.L.R.—Consulting, advisory role: Merck Sharp and Dohme, Takeda, Amgen, Eli Lilly, BMS, F. Hoffmann-La Roche, Italfarmaco, Novartis, Sanofi, Pfizer, AstraZeneca. L.M.—Lectures and educational activities: Bristol-Myers Squibb, AstraZeneca, Roche, Takeda, Janssen, Pfizer, MSD, Radonova; Consulting, advisory role: Roche, Takeda, Janssen, MSD; Research Grants: Inivata, AstraZeneca, Gilead; Travel, Accommodations, Expenses: Bristol-Myers Squibb, Roche, Takeda, AstraZeneca, Janssen. All other authors declare no conflicts of interest., (© The Author(s), 2024.)

Introduction: Pembrolizumab stands as a first-line option for patients with advanced non-small cell lung cancer (NSCLC) and high programmed death-ligand 1 (PD-L1) expression (PD-L1 ≥50%). Several factors such as antibiotic exposure, low body mass index (BMI), certain metastatic location or poor performance status may influence outcomes., Methods: We conducted a multicenter retrospective analysis in a cohort of patients with advanced high PD-L1 expression NSCLC treated with first-line pembrolizumab in clinical practice. We sought to evaluate clinical outcomes according to several factors., Results: Among the 494 included patients, median age was 67.29 years, 77% were male, 54% and 38% were former or current smokers, respectively; 84% had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1, and 48% had a BMI of <25. 32% of patients had bone metastases, 32% brain metastases and 16% liver metastases. 35% of patients had exposure to antibiotics (AB), 44% to corticosteroids and 62% to proton pump inhibitors (PPi). With a median follow-up of 14.3 months, the median overall survival (OS) and progression-free survival (PFS) were 15.9m (95% CI 13.1 to 18.8) and 9.9m (95% CI 7.7 to 12.1), and the overall response rate (ORR) was 43%. After univariate analysis, median OS in patients with ECOG-PS 0 vs. 1 vs. 2 was 36.7m vs. 14.8m vs. 2.7m (p<0.001). Median OS in patients who received treatment with corticosteroids vs. patients without exposure was 11.4m vs. 22.3m (p<0.001). After multivariate analysis, corticosteroid exposure (HR 1.41) and ECOG-PS (HR 2.40) maintained a prognostic impact., Discussion: First-line pembrolizumab outcomes in advanced high PD-L1 expression NSCLC patients could be negatively influenced by corticosteroid exposure or poor ECOG-PS., Competing Interests: The following authors declare potential conflicts of interest outside the submitted work: DI: Consultation Honoraria: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, Merck, MSD, Pfizer, Sanofi, Takeda. Speaker Honoraria: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, MSD, Novartis, Pfizer, Takeda. Clinical Trials: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, F. Hoffmann-La Roche, GSK, Janssen, Lilly, Merck, Mirati Therapeutics, MSD, Novartis, Pfizer, Sanofi. Research grant: AstraZeneca, BMS, F. Hoffmann-La Roche, GSK. AC 12th author: AstraZeneca, Advisory Board, Personal. Bayer, Other, Personal, Speaker honoraria. Boehringer Ingelheim, Advisory Board, Personal. Bristol-Myers Squibb, Advisory Board, Personal. Janssen, Advisory Board, Personal. Lilly, Advisory Board, Personal. Merck Sharp & Dohme, Advisory Board, Personal. Novartis, Advisory Board, Personal. Pfizer, Advisory Board, Personal. PharmaMar, Invited Speaker, Personal. Regeneron, Advisory Board, Personal. Roche, Advisory Board, Personal. Sanofi, Advisory Board, Personal. Takeda, Advisory Board, Personal. Merck Sharp & Dohme, Research Grant, Institutional, Financial interest, Drug-only for Investigator-initiated trial. PI: Advisory role and/or travel compensation: Bristol‐Myers Squibb, F. Hoffmann, La Roche AG, MSD Oncology, Pfizer, Medscape, Astra Zeneca, Takeda, Amgen. JS-L: Astra Zeneca, Invited Speaker, Personal. Astra Zeneca, Advisory Board, Personal. BMS, Invited Speaker, Personal. BMS, Advisory Board, Personal. MSD, Invited Speaker, Personal. MSD, Advisory Board, Personal. Roche, Invited Speaker, Personal. Roche, Advisory board, Personal. Eisai, Invited Speaker, Personal. La Roche Posay, invited Speaker, Personal. AB: Astrazeneca advisory board and personal and invited speaker, BMS expert testimony and invited speaker, MSD invited speaker, Novartis invited speaker, Pfizer invited speaker, Personal, Piere Fabre invited speaker, Roche invited speaker and advisory board, Sanofy advisory board and invited speakerBMS, Principal Investigator, Clinical Trial CA224-1044. Pfizer, Principal Investigator, Clinical Trial C4221016. EA: Consultant or Advisory Role: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda. Speaking: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda. Co-founder: Trialing Health S.L. MC: Consultant or Advisory Role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Lilly, MSD, Takeda, Phyzer, Kyowa, Sanofi,Jansen. Speaking: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Lilly, MSD, Takeda, Kyowa, Pierre-fabre, Novocure, Sanofi, Jansen. MF: AstraZeneca, Invited Speaker, Personal. BMS, Invited Speaker, Personal. BMS, Advisory Board, Personal. Janssen, Invited Speaker, Personal. Janssen, Advisory Board, Personal. Pfizer, Invited Speaker, Personal. RG-C: Astra Zeneca, Invited Speaker, Personal; Astra Zeneca, Advisory Board, Personal; BMS, Invited Speaker, Personal; BMS, Advisory Board, Personal; Jansen, Advisory Board, Personal; Jansen, Invited Speaker, Personal; lilly, Invited Speaker, Personal; lilly, Advisory Board, Personal; MSD, Advisory Board, Personal; novartis, Invited Speaker, Personal; novartis, Advisory Board, Personal; pfizer, Invited Speaker, Personal; pfizer, Advisory Board, Personal; roche, Invited Speaker, Personal; roche, Advisory Board, Personal; Sanofi, Advisory Board, Personal; Takeda, Advisory Board, Personal; Takeda, Invited Speaker, Personal; Astra Zeneca, Steering Committee Member, Personal, Financial interest; Jansen, Steering Committee Member, Personal, Financial interest. EF: Personal honoraria for advisory board participation from Abbvie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, BMS, Eli Lilly, F. Hoffmann-La Roche, Genmab, Gilead, GSK, Janssen, Merck Serono, MSD, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, Daiichi Sankyo; personal speaker honoraria from Amgen, AstraZeneca, BMS, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Peervoice, Pfizer, Sanofi, Takeda, Touch Oncology; Board of Director role: Grifols; financial support for meeting attendance and/or travel from AstraZeneca, Janssen, Roche. MM: Advisory Board,consulting fees or sspeakin honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Helsinn Therapeutics, Eli Lilly, Immedica, Beigene, MSD, Novartis, Pfizer, F. Hoffmann-La Roche Ltd., Takeda, Sanofi, Janssen, Amgen, Cassen. Research funding institution: Bristol-Myers Squibb, AstraZeneca, F. Hoffmann-La Roche Ltd. Travel and accommodation support: AstraZeneca, F. Hoffmann-La Roche Ltd., Pfizer, MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Piedra, Martínez-Recio, Hernández, Morán, Arriola, Recuero-Borau, Cobo, Cordeiro, Mosquera, Fernández, García-Campelo, Calles, Álvarez, Zapata-García, Isla, Callejo, Iranzo, Serra-López, Barba, Sullivan, Felip and Majem.)

The development of immune checkpoint inhibitors (ICIs) has changed the therapeutic paradigm of lung cancer (LC), becoming the standard of treatment for previously untreated advanced non-small cell lung cancer (NSCLC) without actionable mutations. It has allowed the achievement of durable responses and resulted in significant survival benefits. However, not all patients respond; hence, molecular biomarkers are needed to help us predict which patients will respond. With this objective, a prospective observational study was designed, including a cohort of 55 patients with NSCLC who received ICIs. We studied whether biomarkers such as TCRβ and specific cytokines involved in the regulation of T cell activity were related to the immunotherapy response. In the survival analysis, it was found that patients with higher TCRβ clonality, lower TCRβ evenness, higher TCRβ Shannon diversity and lower TCRβ convergence had higher overall survival (OS) and progression-free survival (PFS). However, no statistically significant association was observed. Regarding cytokines, those patients with higher levels of IL-2 and IL-15 presented statistically significantly shorter OS and PFS, respectively. In fact, in the multivariable analysis, the high IL-15 level increased the risk of death by three times. Although the sample size was small and more studies are needed to confirm our results, our study reveals promising markers of responses to ICIs.

Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Cervical cancer is a public health problem in our country and worldwide. Less than 25% of cases are diagnosed in the early stages, where survival is more remarkable than 90% at five years. Here, we review surgical treatment in the early stages of cervical cancer., Methodology: A literature review was carried out in the MEDLINE database. The search was mainly limited to the English language, with priority given to systematic reviews with or without meta-analysis and randomized studies. However, only retrospective or observational evidence was found for some topics., Results: The standard treatment for early-stage cervical cancer is hysterectomy, and its radical nature will depend on the tumor size, lymphovascular permeation, and tumor-specific prognostic factors. Furthermore, the type of surgery (hysterectomy or trachelectomy) will rely on the patient's desire to preserve fertility. Nodal evaluation is indicated as part of the treatment from stage IAI with PLV. However, the sentinel lymph node is more relevant in the treatment. The incidental finding of cervical cancer after a hysterectomy requires a multidisciplinary evaluation to determine the therapeutic approach. Less radical surgery has been described as oncologically safe in low-risk groups., Conclusion: Surgical treatment in its early stages has evolved in recent decades, making it more individualized and seeking less morbidity in patients without compromising their survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nájera-Muñoz, Hernández-Romero, Isla-Ortiz and Salcedo-Hernández.)

Background: Immune checkpoint inhibitors (ICIs) have been proposed as the standard first-line and subsequent treatment for metastatic non-small cell lung cancer (NSCLC). This study analyzed whether patients with good lung immune prognostic index (LIPI) have a better response to ICIs and the relationship between immune-related adverse events (irAEs) and response in clinical practice., Methods: This was an observational, retrospective, single-center study. Patients with stage IV NSCLC between 2016 and 2021 were included in the study. Toxicity was assessed according to The Common Terminology Criteria for Adverse Events. Response assessment was performed according to RECIST 2.0 and immuno-related criteria. Descriptive and survival analyses were conducted. Degree of toxicity and response to treatment (based on treatment and histology) were assessed. LIPI and response were assessed. LIPI included dNLR (absolute neutrophil count/(white blood cell count - absolute neutrophil count)) ≥ 3 and lactate dehydrogenase (LDH) greater than the upper limit of normal. Patients were stratified into good (G), intermediate (I), and poor (P) prognostic groups., Results: A total of 168 patients were included (130 men and 38 women, mean age 64.3 years). ICI use in the first- or second-line treatment was 65% and 35%, respectively. Fifteen (9%) patients showed complete response (CR), 50 (30%) showed partial response (PR), 39 (22%) had stable disease (SD), 45 (28%) had progressive disease (PD), and 19 (11%) were not evaluated (NE). Patients with good prognostic LIPI (dNLR < 3 and normal LDH levels) showed a better response. Progression-free survival (PFS) was 19 months in G, 6 months in I, and 2 months in P. Overall survival (OS) was 27 months in G, 8 months in I, and 3 months in P. One hundred fourteen patients died (56% G, 76% I, 93% P). Patients with adenocarcinoma were 116 (77 with irAEs G1-4 (13 CR, 31 PR, 21 SD, eight PD, and four NE)), and without were 39 (three PR, six SD, 21 PD, and nine NE). Fifty-two patients had squamous carcinoma (27 with irAEs G1-4 (two CR, 12 PR, nine SD, and four PD)), and 25 did not (four PR, three SD, 12 PD, and six NE)). IrAEs appearance was observed in longer PFS (19 vs. 2 months) and OS (27 vs. 4 months; P < 0.0001)., Conclusions: LIPI was a positive predictor of response to ICI. The presence of irAEs is associated with a better immune response. In contrast, the absence of toxicity predicted a worse prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright 2024, Moratiel Pellitero et al.)

Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host-microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients' microbial gut ecosystems were rich and diverse, and the intestinal barrier's integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.

Inherited mutations in the CHEK2 gene have been associated with an increased lifetime risk of developing breast cancer (BC). We aim to identify in the study population the prevalence of mutations in the CHEK2 gene in diagnosed BC patients, evaluate the phenotypic characteristics of the tumor and family history, and predict the deleteriousness of the variants of uncertain significance (VUS). A genetic study was performed, from May 2016 to April 2020, in 396 patients diagnosed with BC at the University Hospital Lozano Blesa of Zaragoza, Spain. Patients with a genetic variant in the CHEK2 gene were selected for the study. We performed a descriptive analysis of the clinical variables, a bibliographic review of the variants, and a cosegregation study when possible. Moreover, an in-depth bioinformatics analysis of CHEK2 VUS was carried out. We identified nine genetic variants in the CHEK2 gene in 10 patients (two pathogenic variants and seven VUS). This supposes a prevalence of 0.75% and 1.77%, respectively. In all cases, there was a family history of BC in first- and/or second-degree relatives. We carried out a cosegregation study in two families, being positive in one of them. The bioinformatics analyses predicted the pathogenicity of six of the VUS. In conclusion, CHEK2 mutations have been associated with an increased risk for BC. This risk is well-established for foundation variants. However, the risk assessment for other variants is unclear. The incorporation of bioinformatics analysis provided supporting evidence of the pathogenicity of VUS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alonso, Menao, Lastra, Arruebo, Bueso, Pérez, Murillo, Álvarez, Alonso, Rebollar, Cruellas, Arribas, Ramos, Isla, Galano-Frutos, García-Cebollada, Sancho and Andrés.)

Objective: Liquid biopsy (LB) is a non-invasive technique to detect genetic alterations by next-generation sequencing (NGS) when tissue biopsy is not available. This study aims to estimate in the Spanish setting, the cost-effectiveness of using FoundationOne Liquid CDx (F1L CDx), a novel blood-derived LB test based on NGS, versus non-molecular diagnosis (non-mDx) in patients with advanced non-small cell lung cancer (NSCLC) in whom tissue sampling is not feasible., Methods: A joint model was developed combining a decision-tree with partitioned survival models to calculate the costs and health outcomes over a lifetime horizon, comparing F1L CDx in LB versus non-mDx. Only direct costs (expressed in € of 2023) were included and a 3% discount rate for future costs and effects was considered. Health outcomes were expressed in Life Years (LYs) and Quality-Adjusted Life Years (QALYs). Utilities and treatment efficacy were obtained from the literature. An expert panel of 11 Spanish oncologists determined the treatment allocation and validated all model inputs and assumptions. Several sensitivity analyses were performed to assess the robustness of the results., Results: In a hypothetical cohort of 1,000 patients, LB using F1L CDx would detect 386 alterations, so those patients could be treated with targeted therapies or enrolled in clinical trials. Cost-effectiveness results showed that F1L CDx provides greater effectiveness than non-mDx (+383.95 LYs and +305.94 QALYs), with an additional cost of €2,898,308. The incremental cost-utility ratio was €9,473/QALY gained. The probabilistic sensitivity analysis confirmed the robustness of the cost-effectiveness results., Limitations: Various limitations inherent to cost-effectiveness analyses were described., Conclusion: LB with F1L CDx test is a cost-effective strategy in Spain for patients with advanced NSCLC without tissue sample available for molecular diagnosis, improving the personalized treatment of these patients.

Background: Hospital readmission is a quality metric of hospital care and has been studied in ovarian carcinoma, but its evaluation has several limitations. Also, emergency room (ER) readmission is considered an adverse effect because it represents patient costs. Therefore, our objective was to determine the rate of ER readmission, its causes, and associated factors., Methods: A retrospective study of 592 patients with ovarian carcinoma who underwent upfront surgery, neoadjuvant therapy, or surgery for recurrent disease. An analysis of factors associated with ER readmission, hospital readmission, and surgical complications was performed, including multivariate analysis to assess for case-mix factors., Results: Of 592 patients, the median age was 51 years, and the predominant type of treatment was the neoadjuvant approach (52.9%); 46% underwent upfront surgeries and six surgeries for recurrence. The ratio to ER readmission was 11.8% (70 patients), of whom 12 patients were admitted more than once. The factors associated with ER readmission were prolonged surgery, intraoperative bleeding, extended hospital stay, the time of the day when the surgery was performed, and post-surgical complications. The hospital readmissions were 4.2%, and the overall morbidity was 17.6%. In the multivariate analysis, the only factor associated with ER readmission was the presence of surgical complications (OR = 39.01). The factors independently associated with hospital readmission were the entrance to the intensive care unit (OR = 1.37), the presence of surgical complications (OR = 2.85), and ER readmission (OR = 1.45)., Conclusion: ER readmission is an adverse event representing the presence of symptoms/complications in patients. Evaluating the ER readmission independently of the readmission to the hospital is critical because it will allow modifying medical care behaviors to prevent patients from unnecessarily returning to the hospital after a hospital discharge to manage preventable medical problems., Trial Registration: researchregistry7882., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Our study aims to evaluate the impact of different factors on cancer-related cognitive impairment in patients who undergo chemotherapy., Methodology: Prospective longitudinal single-centre study that included patients with breast and colon carcinoma who underwent chemotherapy as part of their treatment. Clinical and genetic characteristics of the patients (single nucleotide polymorphisms, SNPs) were collected. Patients' neurocognitive status was assessed using eleven validated tests at three time points: before chemotherapy (M0 - baseline), between one and four weeks after completing chemotherapy (M1), and between 24-30 weeks after completing chemotherapy (M2)., Results: Sixty-two patients were included in this study; 82% were female, median age was 56 years (range 30-74), and 64.5% had been diagnosed with breast cancer. Overall, better cognitive results at M0 were associated with age < 55 years, higher educational level, absence of comorbidities, and the CC variant rs471692 (TOP2A). Significant decline was found between M0 to M1 in the Rey Auditory Verbal Learning Test and the Letter and Number test, with evidence of recovery in M2 compared to M0 regarding the following test: Visual Memory, Functioning Assessment Short Test (FAST), Digit Symbol Substitution and Cube. In the multivariate analysis, being =55 years of age, adjuvant chemotherapy, presence of comorbidities, tobacco and alcohol use, and GT variant rs1800795 were associated with cognitive decline between M0 and M1., Conclusion: Being =55 years of age, female, presence of comorbidities and basic education level are related to a higher risk of cognitive impairment after chemotherapy.

Introduction: There are currently three first-line immunotherapy options used as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand 1 (PD-L1) expression (≥50%). This manuscript aims to evaluate the available data on atezolizumab (AT), cemiplimab (CEMI), and pembrolizumab (PEMBRO) and to study the results obtained during pivotal trials, especially regarding patient subgroups., Methods: Nominal group and Delphi techniques were used. Eight Spanish experts in lung cancer (the scientific committee of the project) analyzed the use of immunotherapy monotherapy as first-line treatment in patients with NSCLC and high PD-L1 expression. The expert scientific committee formulated several statements based on a scientific review and their own clinical experience. Subsequently, 17 additional Spanish lung cancer experts were selected to appraise the committee's statements through two Delphi rounds. They completed a Delphi round via an online platform and voted according to a scale from 1 (strongly disagree) to 10 (strongly agree). The statements were approved if ≥70% of experts voted 7 or more., Results: A total of 20 statements were proposed covering the following areas: (1) general characteristics of pivotal clinical trials; (2) overall main outcomes of pivotal clinical trials; and (3) subgroup analysis. All statements reached consensus in the first round., Conclusions: AT, CEMI, and PEMBRO as monotherapy can be considered the standard of care in patients with advanced NSCLC and high PD-L1 expression (≥50%). Moreover, some differences noted among the drugs analyzed in this document might facilitate treatment decision-making, especially in clinically relevant patient subgroups, when using PD-1/PD-L1 inhibitors. The high level of agreement reached among experts supports the proposed statements.

To describe access to complete treatment in women with cervical cancer and state-sponsored insurance versus no insurance. We conducted a retrospective observational study. The source population consisted of women treated for cervical cancer from January 2000 to December 2015 in a tertiary care hospital. We included 411 women with state-sponsored insurance and 400 without insurance. We defined access to cervical cancer treatment as complete treatment (according NCCN/ESMO (National Comprehensive Cancer Network/European Society for Medical Oncology) standards) and timely initiation of treatment (less than 4 weeks). Clinical and sociodemographic characteristics were described and analyzed with logistic regression using complete treatment as the main outcome. A total of 811 subjects were included, the median age was 46 (IQR (Interquartile range) 42-50) years. Most of them were married (36.1%), unemployed (50.4%), and had completed primary school (44.0%). The most common clinical stages at diagnosis were II (38.2%) and III (24.7%). In the adjusted regression model, being married (OR (odds ratio): 4.3, 95% CI (confidence interval): 1.74-10.61) and having paid employment (OR: 2.79, 95% CI: 1.59-4.90) or state-sponsored insurance (OR: 1.54, 95% CI: 1.04-2.26) were positively associated with the possibility of having a complete treatment. Women with insurance were likely to be younger and receive timely treatment compared with uninsured women. Complete treatment was associated to insurance status and advanced stages of cervical cancer. State-sponsored insurance improves access to complete treatment. Government policies are needed to avoid social and economic inequity and provide better management of cervical cancer in our country., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The COVID-19 pandemic disrupted the preventive services for cervical cancer (CC) control programs in Mexico, which will result in increased mortality. This study aims to assess the impact of the pandemic on the interruption of three preventive actions in the CC prevention program in Mexico., Methods: This study is a retrospective time series analysis based on administrative records for the uninsured population served by the Mexican Ministry of Health. Patient data were retrieved from the outpatient service information system and the hospital discharge database for the period 2017-2021. Data were aggregated by month, distinguishing a pre-pandemic and a pandemic period, considering April 2020 as the start date of the pandemic. A Poisson time series analysis was used to model seasonal and secular trends. Five process indicators were selected to assess the disruption of the CC program, these were analyzed as monthly data (N=39 pre-pandemic, N=21 during the pandemic). HPV vaccination indicators (number of doses and coverage) and diagnostic characteristics of CC cases were analyzed descriptively. The time elapsed between diagnosis and treatment initiation in CC cases was modeled using restricted cubic splines from robust regression., Results: Annual HPV vaccination coverage declined dramatically after 2019 and was almost null in 2021. The number of positive Papanicolaou smears decreased by 67.8% (90%CI: -72.3, -61.7) in April-December 2020, compared to their expected values without the pandemic. The immediate pandemic shock (April 2020) in the number of first-time and recurrent colposcopies was -80.5% (95%CI:-83.5, -77.0) and -77.9% (95%CI: -81.0, -74.4), respectively. An increasing trend was observed in the proportion of advanced stage and metastatic CC cases. The fraction of CC cases that did not receive medical treatment or surgery increased, as well as CC cases that received late treatment after diagnosis., Conclusions: Our analyses show significant impact of the COVID-19 pandemic with declines at all levels of CC prevention and increasing inequalities. The restarting of the preventive programs against CC in Mexico offers an opportunity to put in place actions to reduce the disparities in the burden of disease between socioeconomic levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cruz-Valdez, Palacio-Mejía, Quezada-Sánchez, Hernández-Ávila, Galicia-Carmona, Cetina-Pérez, Arango-Bravo, Isla-Ortiz, Aranda-Flores, Uscanga-Sánchez, Madrid-Marina and Torres-Poveda.)

Background: Atezolizumab has recently been approved for first-line treatment of high PD-L1 expression metastatic Non-Small-Cell Lung Cancer (NSCLC) patients with no EGFR or ALK mutations, on the basis of the IMpower110 trial. This study aims to estimate the cost-effectiveness of atezolizumab compared with pembrolizumab among these patients in Spanish settings, based on the results of the two cut-offs of the IMpower110 study., Methods: A three-state partitioned-survival model was adapted to Spanish settings to calculate health outcomes and costs over a lifetime horizon. Clinical data for atezolizumab were collected from the interim and the exploratory results (data cut-off: Sept'18 and Feb'20, respectively) of the IMpower110 trial while a network meta-analysis was used to model pembrolizumab treatment. Utility data were collected from the trial. Direct medical costs were considered based on resources identified by experts. Costs and outcomes were discounted at 3% per year. Health outcomes were expressed as cost per Life Year (LY) and cost per Quality-Adjusted Life Year (QALY). Both deterministic and probabilistic sensitivity analyses were performed to assess the robustness of results., Results: Over a lifetime horizon, the incremental results showed that atezolizumab generated similar health outcomes (LYs and QALYs) to pembrolizumab, with minimal differences depending on the cut-off used (+ 0.70 and + 0.42 LYs and QALYs with Sept'18 cut-off and - 0.80 and - 0.72 LYs and QALYs with Feb'20 cut-off). However, for both cut-offs, atezolizumab produced meaningfully less costs than pembrolizumab (€ - 54,261 with Sept'18 cut-off and € - 81,907 with Feb'20 cut-off). The sensitivity analyses carried out confirmed the robustness of the base-case results., Conclusions: The cost-effectiveness analysis, comparing the two cut-off of IMpower110, shows that atezolizumab provides similar health gains to pembrolizumab but at a lower cost for the first-line treatment of metastasic NSCLC patients in Spain., (© 2023. The Author(s).)

The PMS2 gene is involved in DNA repair by the mismatch repair pathway. Deficiencies in this mechanism have been associated with Lynch Syndrome (LS), which is characterized by a high risk for colorectal, endometrial, ovarian, breast, and other cancers. Germinal pathogenic variants of PMS2 are associated with up to 5% of all cases of LS. The prevalence is overestimated for the existence of multiple homologous pseudogenes. We report the case of a 44-year-old woman diagnosed with breast cancer at 34 years without a relevant cancer family history. The presence of pathogenic variant NM&#95;000535.7:c.1A > T, (p.Met1Leu) in PMS2 was determined by next-generation sequencing analysis with a panel of 322 cancer-associated genes and confirmed by capillary sequencing in the patient. The variant was determined in six family members (brothers, sisters, and a son) and seven non-cancerous unrelated individuals. Analysis of the amplified region showed high homology of PMS2 with five of its pseudogenes. We determined that the variant is associated with the PMS2P1 pseudogene following sequence alignment analysis. We propose considering the variant c.1A > T, (p.Met1Leu) in PMS2 for reclassification as not hereditary cancer-related, given the impact on the diagnosis and treatment of cancer patients and families carrying this variant.

(1) Despite the effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer, there is a lack of knowledge about predictive biomarkers. The objective of our study is to analyze different subsets of T-lymphocytes and natural killer (NK) cells as predictive biomarkers in a cohort of patients with nonsmall cell lung cancer (NSCLC) treated with ICI. (2) This is an observational, prospective study with 55 NSCLC patients treated with ICI. A total of 43 T and NK cell subsets are analyzed in peripheral blood, including the main markers of exhaustion, differentiation, memory, activation, and inhibition. (3) Regarding the descriptive data, Granzyme B+CD4+ Treg lymphocytes stand out (median 17.4%), and within the NK populations, most patients presented cytotoxic NK cells (CD56+CD3-CD16+GranzymeB+; median 94.8%), and about half of them have highly differentiated adaptive-like NK cells (CD56+CD3-CD16+CD57+ (mean 59.8%). A statistically significant difference was observed between the expression of PD1 within the CD56 bright NK cell subpopulation (CD56+CD3-CD16-PD-1+) ( p = 0.047) and a better OS. (4) Circulating immune cell subpopulations are promising prognostic biomarkers for ICI. Pending on validation with a larger sample, here we provide an analysis of the major circulating T and NK cell subsets involved in cancer immunity, with promising results despite a small sample size.