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This work presents the results of a study on the use of subcritical water as both solvent and reactant for the hydrolysis of corn oil without the use of acids or alkalis at temperatures of 150-280 degreesC. Corn oil hydrolysis leads to the formation of its respective fatty acids with the same efficiency of conventional methods. Fatty acids form an important group of products, which are used in a range of applications. The confirmation and identification of the hydrolysis products was done by HT-HRGC-FID and HRGC/MS.

The construction of an on-line SPE-SFE-CGC system is described. The home-made system is of low cost and of easy construction and maintenance, making possible the analysis of organic micropollutants in liquid samples such as water in a fraction of the time spent using traditional methods.

Abstract The current geriatric population in the United States accounts for approximately 12% of the total population and is projected to reach nearly 20% (71.5 million people) by 20301. With this expansion of the number of older adults, physicians will face the common complaint of rhinitis with increasing frequency. Nasal symptoms pose a significant burden on the health of older people and require attention to improve quality of life. Several mechanisms likely underlie the pathogenesis of rhinitis in these patients, including inflammatory conditions and the influence of aging on nasal physiology, with the potential for interaction between the two. Various treatments have been proposed to manage this condition; however, more work is needed to enhance our understanding of the pathophysiology of the various forms of geriatric rhinitis and to develop more effective therapies for this important patient population.

Antibody-drug conjugates (ADCs) are at the forefront of cancer therapy, combining targeted precision with potent cytotoxicity. Conceived by Paul Ehrlich in the early 1900s, the concept of a magic bullet selectively eliminating cancer cells has evolved alongside bioengineering and cancer biology advancements. ADCs consist of a monoclonal antibody, linker, and cytotoxic payload, designed to target specific antigens on tumor cells while minimizing collateral damage. Mechanistically, ADCs are internalized via endocytosis, releasing the cytotoxic payload within the lysosome, potentially affecting neighboring tumor cells. ADC development has progressed through multiple generations, each addressing limitations of its predecessors. From gemtuzumab ozogamicin to trastuzumab emtansine (T-DM1), and now to third-generation agents such as trastuzumab deruxtecan (DS-8201) and disitamab vedotin (RC48), improvements have been made in target selectivity, potency, linker stability, and reduced off-target effects. Significant success has been seen in ADCs targeting human epidermal growth factor receptor 2 and trophoblast cell-surface antigen 2 antigens, especially in patients with breast cancer, including those resistant to previous therapies. The future of ADCs includes exploring new surface antigens, bispecific antibodies, immune-activating antibodies, radiopharmaceutical-loaded ADCs, and masked ADCs for tissue-specific activation. Ongoing research aims to optimize treatment efficacy while minimizing toxicity, expanding the potential of combination therapy. ADCs represent a promising frontier in precision cancer treatment, with continued research enhancing their potential in breast cancer and beyond. This review provides a comprehensive exploration of ADCs' evolution in breast cancer therapy, offering a molecular perspective to inform clinical practice and update colleagues on this dynamic field.

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy., (© 2024. The Author(s).)

Background: Atrophic pseudoarthrosis is a serious complication with an incidence of 5-10 % of bone fractures located in the diaphysis of long bones. Standard treatments involve aggressive surgical procedures and re-interventions requiring the use of autografts from the iliac crest as a source of bone-forming biological activity (Standard of Care, SoC). In this context, regenerative ex vivo expanded osteogenic cell-based medicines could be of interest. Particularly, Mesenchymal Stromal Cells (MSC) offer new prospects to promote bone tissue repair in pseudoarthrosis by providing biological activity in an osteoconductive and osteoinductive environment., Methods: We conducted a phase IIa, prospective, randomised, parallel, two-arms, open-label with blinded assessor pilot clinical trial to compare SoC vs. a tissue-engineered product (TEP), composed of autologous bone marrow (BM)-derived MSCs loaded onto allogeneic decellularised, lyophilised spongy bone cubes, in a cohort of 20 patients with non-hypertrophic pseudoarthrosis of long bones. Patients were followed up for 12 months. Radiological bone healing was evaluated by standard X-ray and computed tomography (CT) scanning. Quality of life was measured using the EUROQOL-5D questionnaire., Results: Ten patients were randomized to TEP and 10 to SoC with iliac crest autograft. Manufacturing of TEP was feasible and reproducibly achieved. TEP implantation in the bone defect was successful in all cases and none of the 36 adverse events (AE) reported were related to the treatment. Efficacy analyses were performed in the Full Analysis Set (FAS) population, which included 17 patients after 3 patients withdrew from the study. The degree of consolidation, estimated by measuring Hounsfield units (HU) on CT, showed no significant differences between the two treatment groups at 12 months post treatment (main efficacy variable) (p = 0.4835) or at 6 months., Conclusions: Although only a small number of patients were included in our study, it is notable that no significant differences were observed between the experimental treatment and SoC, thus suggesting TEP as an alternative where autograft is not available or contraindicated., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Congenital talipes equinovarus (CTEV), also known as clubfoot, is a common musculoskeletal entity that affects one to two per 1000 live births worldwide. Imaging modalities including radiography, US, and MRI have emerged as valuable tools for the diagnosis, treatment, and monitoring of CTEV. The deformity is characterized by midfoot cavus, forefoot adductus, and hindfoot varus and equinus. The Ponseti method of manipulation and serial casting is the standard treatment of CTEV. Radiography shows the anatomy, position, and relationships of the different bones of the foot. US allows accurate assessment of cartilaginous and bony structures, in addition to its inherent advantages such as absence of ionizing radiation exposure. One of the indications for US is to monitor the response to Ponseti method treatment. MRI enables visualization of bones, cartilage, and soft tissues and allows multiplanar evaluation of deformities, providing a comprehensive imaging analysis of CTEV. An integrated approach that combines clinical examination and imaging findings is essential for effective management of CTEV. The authors provide a comprehensive overview of CTEV with a review of imaging modalities to help evaluate CTEV, focusing on radiography, US, and MRI. Using this article as a guide, radiologists involved in the assessment and treatment of CTEV can contribute to the management of the condition. © RSNA, 2024 Supplemental material is available for this article.

This study aims to perform an extensive review of the literature that evaluates various factors that affect the survival rates of patients with severe combined immunodeficiency (SCID) after hematopoietic stem cell transplantation (HSCT) in developed and developing countries. An extensive search of the literature was made in four different databases (PubMed, Embase, Scopus, and Web of Science). The search was carried out in December 2022 and updated in July 2023, and the terms such as "hematopoietic stem cell transplantation," "bone marrow transplant," "mortality," "opportunistic infections," and "survival" associated with "severe combined immunodeficiency" were sought based on the MeSH terms. The language of the articles was "English," and only articles published from 2000 onwards were selected. Twenty-three articles fulfilled the inclusion criteria for review and data extraction. The data collected corroborates that early HSCT, but above all, HSCT in patients without active infections, is related to better overall survival. The universal implementation of newborn screening for SCID will be a fundamental pillar for enabling most transplants to be carried out in this "ideal scenario" at an early age and free from infection. HSCT with an HLA-identical sibling donor is also associated with better survival rates, but this is the least common scenario. For this reason, transplantation with matched unrelated donors (MUD) and mismatched related donors (mMRD/Haploidentical) appear as alternatives. The results obtained with MUD are improving and show survival rates similar to those of MSD, as well as they do not require manipulation of the graft with expensive technologies. However, they still have high rates of complications after HSCT. Transplants with mMRD/Haplo are performed just in a few large centers because of the high costs of the technology to perform CD3/CD19 depletion and TCRαβ/CD19 depletion or CD34 + selection techniques in vitro. The new possibility of in vivo T cell depletion using post-transplant cyclophosphamide could also be a viable alternative for performing mMRD transplants in centers that do not have this technology, especially in developing countries., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: In Peru, on 11 February 2023, the Ministry of Health registered 4 million patients infected with COVID-19 and around 219,260 deaths. In 2020, the SARS-CoV-2 virus was acquiring mutations that impacted the properties of transmissibility, infectivity, and immune evasion, leading to new lineages. In the present study, the frequency of COVID-19 variants was determined during 2021 and 2022 in patients treated in the AUNA healthcare network., Methods: The methodology used to detect mutations and identify variants was the Allplex™ SARS-CoV-2 Variants Assay I, II, and VII kit RT-PCR. The frequency of variants was presented by epidemiological weeks., Results: In total, 544 positive samples were evaluated, where the Delta, Omicron, and Gamma variants were identified. The Delta variant was found in 242 (44.5%) patients between epidemiological weeks 39 and 52 in 2021. In the case of Gamma, it was observed in 8 (1.5%) patients at weeks 39, 41, 43, 45, and 46 of 2021. The Omicron variant was the most frequent with 289 (53.1%) patients during weeks 49 to 52 of 2021 and 1 to 22 of 2022. During weeks 1 through 22 of 2022, it was possible to discriminate between BA. 1 ( n  = 32) and BA.2 ( n  = 82)., Conclusion: The rapid identification of COVID-19 variants through the RT-PCR methodology contributes to timely epidemiological surveillance, as well as appropriate patient management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2024 Ortiz-Gómez, Gomez, Chuima, Zevallos, Ocampo, Torres and Pinto.)

Purpose: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM., Experimental Design: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico., Results: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations., Conclusions: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM., Competing Interests: Declaration of Competing Interest Umberto Malapelle has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck, AstraZeneca, Janssen, Diatech, Novartis and Hedera unrelated to the current work. Pasquale Pisapia has received personal fees as speaker bureau from Novartis, for work performed outside of the current study. Giancarlo Troncone reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen, and Bayer unrelated to the current work. Alessandro Russo reports advisory board role/consultancy from AstraZeneca, MSD, Novartis, Pfizer, BMS, Roche, and Amgen unrelated to the current work. Andres F. Cardona discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol‐Myers Squibb, Foundation Medicine, Roche Diagnostics, Thermo Fisher, Broad Institute, BioNTech, Amgen, Flatiron Health, Teva Pharma, Rochem Biocare, Bayer, INQBox and The Foundation for Clinical and Applied Cancer Research – FICMAC; advisor role to EISAI, Merck Serono, Jannsen Pharmaceutical, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol‐Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, Guardant Health, Illumina, and Foundation for Clinical and Applied Cancer Research – FICMAC outside the submitted work. Marzia Del Re has received research grants from Astellas and AstraZeneca, consulting fees from Janssen, AstraZeneca, Astellas, discloses speaker bureau role for AstraZeneca, Astellas, Janssen, Novartis, Roche, Daiicho Sankyo, Takeda, advisory board role for Novartis, Roche, and Amgen outside the submitted work. Ashutosh Sachdeva reports consulting fees from AMBU and MERIT, advisory board role for AMBU not related to the submitted work. Fred R. Hirsch reports advisory boards consultancy for Bristol‐Myers Squibb, AstraZeneca/Daiichi, Sanofi/Regeneron, Novartis, Amgen, OncoCyte, Genentech, and Nectin Therapeutics unrelated to the current work. Christian Rolfo is a speaker for Merck Sharp and Dohme, AstraZeneca, COR2ED, Daiichi Sankyo, Physicians Education Resource, and Roche (CH); has research collaborations (nonfinancial support) with Guardant Health; advisory board activity: Archer, Inivata, Bayer U.C. LLC, Boston pharmaceutical, CEA, MD Serono, General Dynamics, MedStar, Novartis, Sanofi Genzyme‐Regeneron. Provides expert testimony to Intellisphere, scientific board for Imagene, and is a coordinating PI for MD Serono Global PI LUNG itrapid@ 024 trial. Research grant from LCRF‐Pfizer unrelated to the current work. The other authors declare no competing interest., (Copyright © 2023. Published by Elsevier Ltd.)

Interactions between host and pathogenic microorganisms are common in nature and have a significant impact on host health, often leading to several types of infections. These interactions have evolved as a result of the ongoing battle between the host's defense mechanisms and the pathogens' invasion strategies. In this chapter, we will explore the evolution of host-pathogen interactions, explore their molecular mechanisms, examine the different stages of interaction, and discuss the development of pharmacological treatments. Understanding these interactions is crucial for improving public health, as it enables us to develop effective strategies to prevent and control infectious diseases. By gaining insights into the intricate dynamics between pathogens and their hosts, we can work towards reducing the burden of such diseases on society., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study aimed to describe pre-exposure prophylaxis (PrEP) for HIV discontinuation in adolescent men who have sex with men (aMSM) and adolescent transgender women (aTGW) and to identify factors associated with discontinuation., Methods: The PrEP1519 study included a cohort of aMSM and aTGW aged 15-19 years old, and it was conducted in three large Brazilian capital cities. For this analysis, we included adolescents who initiated PrEP. PrEP discontinuation was defined as no possession of PrEP pills for >90 days. Kaplan-Meier curves were used to analyze the probabilities of discontinuation, and survival distributions stratified by covariates were compared using log-rank or Wilcoxon tests. Cox regression models were used to estimate the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI)., Results: We included 908 adolescents, 829 (91.30%) aMSM and 79 (8.70%) aTGW, most of whom were 18-19 years (80.29%). The incidence rate of discontinuation was 75.6 per 100 person-years. The probability of discontinuation was 52.61% in the first year. The multivariate analysis demonstrated that the aTGW (aHR = 1.63; 95% CI: 1.02-1.64) and adolescents with a medium (aHR = 1.29; 95% CI: 1.02-1.64) or low (aHR = 1.65; 95% CI: 1.29-2.12) perceived risk of HIV infection had an increased risk of discontinuation, whereas the adolescents with a partner living with HIV had a lower risk of discontinuation (aHR = 0.57; 95% CI: 0.35-0.91)., Discussion: Adolescents with a high risk for discontinuation may need additional support that emphasizes the value of PrEP as a tool for HIV prevention because PrEP discontinuation was associated with a disconnect between HIV risk perception and HIV prevention., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This study analyzed the sociodemographic and behavioral characteristics of adolescent men who have sex with men (aMSM) and transgender women (aTGW) initiating oral pre-exposure prophylaxis (PrEP) in human immunodeficiency virus (HIV) prevention clinics., Methods: PrEP1519 is a prospective, multicenter, open-label PrEP demonstration cohort study of aMSM and aTGW aged 15-19 years living in three large Brazilian capital cities. For this analysis, we included adolescents who enrolled in PrEP1519 from February 2019 to August 2021. Adolescents who visited PrEP clinics were classified into four groups based on PrEP eligibility and on their decision to use PrEP: (1) ineligible for same-day PrEP initiation; (2) eligible for same-day PrEP initiation, initiated PrEP at first visit; (3) eligible for PrEP initiation, initiated PrEP after the first visit; and (4) eligible for same-day PrEP initiation but declined. The groups that were eligible for same-day PrEP initiation were compared using the Chi-square and Fisher's exact tests., Results: Of the 1,254 adolescents enrolled in the PrEP1519 study, 61 (4.9%) were considered ineligible for same-day PrEP initiation. Of the 1,193 eligible for same-day PrEP initiation, 1,113 (93.3%) initiated PrEP [1,054 initiated PrEP in the first visit (88.3%) and 59 in subsequent visits (4.9%)] and 80 (6.7%) did not. Despite 90% of the PrEP decliners reporting a low risk of HIV infection, most reported condomless anal sex in the past six months (70%)., Discussion: Same-day PrEP initiation among aMSM and aTGW was high, highlighting that this strategy was important to promote PrEP initiation among adolescents with increased vulnerability to HIV in Brazil., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Triple-negative breast cancer (TNBC) is a heterogeneous disease associated with a poor prognosis. Delaying in time to start adjuvant chemotherapy (TTC) has been related to an increased risk of distant recurrence-free survival (DRFS). We aimed to develop a prognostic model to estimate the effects of delayed TTC among TNBC risk subgroups., Materials and Methods: We analyzed 687 TNBC patients who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). Database was randomly divided to create a discovery set (n=344) and a validation set (n=343). Univariate and multivariate Cox regression models were performed to identify prognostic factors for DRFS. Risk stratification was implemented through two models developed based on proportional hazard ratios from significant clinicopathological characteristics. Subpopulation treatment effect pattern plot (STEPP) analysis was performed to determine the best prognostic cut-off points for stratifying TNBC subgroups according to risk scores and estimate Kaplan-Meier differences in 10-year DRFS comparing TTC (≤30 vs.>30 days)., Results: In univariate analysis, patients aged ≥70 years (HR=4.65; 95% CI: 2.32-9.34; p=<0.001), those at stages pT3-T4 (HR=3.28; 95% CI: 1.57-6.83; p=0.002), and pN2-N3 (HR=3.00; 95% CI: 1.90-4.76; p=<0.001) were notably associated with higher risk. STEPP analysis defined three risk subgroups for each model. Model N°01 categorized patients into low (score: 0-31), intermediate (score:32-64), and high-risk (score: 65-100) cohorts; meanwhile, Model N°02: low (score: 0-26), intermediate (score: 27-55), and high (score: 56-100). Kaplan-Meier plots showed that in the discovery set, patients with TTC>30 days experienced a 17.5% decrease in 10-year DRFS rate (95%CI=6.7-28.3), and the impact was more remarkable in patients who belong to the high-risk subgroup (53.3% decrease in 10 years-DRFS rate). Similar results were found in the validation set., Conclusions: We developed two prognostic models based on age, pT, and pN to select the best one to classify TNBC. For Model N°02, delayed adjuvant chemotherapy conferred a higher risk of relapse in patients ≥70 years and who were characterized by pT3/T4 and pN2/N3. Thus, more efforts should be considered to avoid delayed TTC in TNBC patients, especially those in high-risk subgroups., 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 Morante, Ferreyra, Pinto, Valdivieso, Castañeda, Vidaurre, Valencia, Rioja, Fuentes, Cotrina, Neciosup and Gomez.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required., Methods: This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026., Discussion: The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research., Trial Registration: The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: There is an increasing amount of data from Latin America on the characterization of BRCA variants; however, there is limited information from Peru. We conducted a retrospective study to describe germline pathogenic/likely pathogenic(P/LP) variants and variants of uncertain/unknown significance (VUS) in the BRCA1 and BRCA2 genes in Peru, in patients with breast and ovarian cancer, candidates for treatment with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors., Methods: The patients were evaluated during the period 2019-2021. Genomic DNA was isolated from peripheral blood samples and targeted sequencing was performed using the Ampliseq BRCA panel. Genetic variant interpretation was carried out in accordance with the recommendations of the American College of Medical Genetics and ClinVar. During this period, 525 patients (143 with breast cancer and 382 with ovarian cancer) were studied., Results: We found that 14.7% (21/143) of breast cancer patients and 20.7% (79/382) of ovarian cancer patients were carriers of P/LP variants in BRCA1/2. The most frequent pathogenic variants detected in BRCA1 were c.2105dupT (BIC: 2224insT, n=12, 18.75%), c.68&#95;69delAG (BIC: 185delAG, n=6, 9.38%), c.140G>T and c.815&#95;824dupAGCCATGTGG (n=5, 7.81%), while in BRCA2 were c.8023A>G (n=6, 16.67%), c.6024dupG (BIC: 6252insG, n=4, 11.11%), and c.9235delG (BIC: 9463delG, n=3, 8.33%). Regarding VUS, we found that 6.99% (10/143) of breast cancer patients and 7.33% (28/382) of ovarian cancer patients were carriers of a VUS in BRCA1/2. For BRCA1, the most frequent VUS was c.93C>G (n=2), and for BRCA2, c.5465A>T (n=4), c.3101T>C (n=3), c.205C>A and c.437T>C (n=2)., Conclusion: We found a frequency of 14.7% germline mutations in breast cancer patients and 20.7% in ovarian cancer patients. The most recurrent mutations were BRCA1 c.2105dupT and BRCA2 c.8023A>G. We found that BRCA2 c.8023A>G, c.6024dupG, and c.9235delG were not previously reported in Peruvian patients. BRCA1 c.2344dupA is a novel mutation that has not been previously reported in any database. The frequency of VUS in our cohort was 7.2%., 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 Ferreyra, Rosas, Cock-Rada, Araujo, Bravo, Doimi, Casas, Clavo, Pinto and Belmar-López.)

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4 + helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αβ) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade., Competing Interests: Author VN-C has served as a speaker, consultant, and/or instructor for: AbbVie, Eli Lilly and Company, Galapagos, Janssen, Moonlake, Novartis, Pfizer, and UCB Pharma; and has received grant and/or research support from AbbVie and Novartis. Author LP has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sandoz, Sanofi, and UCB. Author SV has received speaker’s honoraria and participated in projects sponsored by Bayer, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Roche, Sanofi and UCB. Author JR has received consultancy and/or speaker’s honoraria from Abbvie, UCB, Janssen, Novartis, Pfizer, Amgen and Lilly and/or participated in clinical trials and/or research projects sponsored by Pfizer, Novartis and Janssen. Author ML-V has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, Kyowa Kirian, LEO Pharma, Lilly, Novartis, and UCB. Author CF-C has received consultancy and/or speaker’s honoraria and participated in clinical trials and/or research projects sponsored by AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, the Spanish Society of Rheumatology and UCB. Author RA has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, Almirall, Amgen, Galápagos, Gebro, Janssen, Lilly, MSD, Nordimet, Novartis, Pfizer and UCB. Author JP has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by Janssen, Novartis, Pfizer, MSD, Lilly, Amgen, BMS, AbbVie, and UCB. Author EG-A has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, MSD, Roche, Amgen, Janssen, Lilly, Novartis, Pfizer and UCB. Author PZ has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, Celgene, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer and UCB. Author BJ has received consultancy fees from Amgen, UCB and Janssen; has received speaker’s honoraria from Lilly, Abbvie and Janssen; has participated in clinical trials and/or research projects sponsored by Janssen, Lilly, Bristol Myers Squibb, Abbvie; has received support for attending congress from Novartis, Pfizer, UCB. Author JG has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by Novartis, UCB, Pfizer, BMS, MSD, AbbVie, Lilly, Janssen, AstraZeneca and Galápagos. Author XJ has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, Lilly, MSD, Nordic Pharma, Novartis, Pfizer and UCB. Author RB has received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD. Author SA has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, Almirall, Janssen, LEO Pharma, Lilly, Novartis and UCB. Author JS has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, UCB, Novartis, Amgen, Pfizer and Janssen-Cilag. Author RQ has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by Novartis, Janssen, UCB, Pfizer, Amgen, MSD, Eli-Lilly and AbbVie. Author JC has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials and/or research projects sponsored by AbbVie, Almirall, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Lilly, Novartis, Pfizer, Sandoz and UCB., (Copyright © 2023 Navarro-Compán, Puig, Vidal, Ramírez, Llamas-Velasco, Fernández-Carballido, Almodóvar, Pinto, Galíndez-Aguirregoikoa, Zarco, Joven, Gratacós, Juanola, Blanco, Arias-Santiago, Sanz Sanz, Queiro and Cañete.)