Pembrolizumab con axitinib para personas mayores de 18 años con cáncer de riñón de células claras, metastásico, no resecable quirúrgicamente, de riesgo favorable, ECOG 0-2, y sin tratamiento sistémico previo / Pembrolizumab with axitinib for people over 18 years of age with clear cell kidney cancer, metastatic, not surgically resectable, favorable risk, ECOG 0-2, and without prior systemic treatment

INTRODUCCIÓN: Cuadro clínico: El cáncer de riñón es una de las neoplasias más frecuente en el mundo. Según el Observatorio Global del Cáncer (GLOBOCAN, por sus siglas en inglés) en 2022, se ha reportado una incidencia anual de cáncer de riñón de 2.2 % a nivel mundial y una mortalidad anual de 1.6%. El estudio mundial de carga de enfermedad 2021 reportó que, en Perú la prevalencia de cáncer de riñón fue de 16.71 casos por cada 100 000 personas, la incidencia fue de 3.71 casos nuevos por cada 100 000 personas-año, y produjo 54.01 años de vida saludables perdidos (AVISA) por cada 100 000 personas. Tecnología sanitária: El pembrolizumab es un anticuerpo monoclonal humanizado anti-PD1 que cuenta con número de registro sanitario "BE01015" por parte de la Dirección General de Medicamentos, Insumos y Drogas (DIGEMID) para el tratamiento de primera línea, en asociación con axitinib, de pacientes adultos con carcinoma de células renales avanzado. Justificación de la evaluación: Este informe de evaluación de tecnología sanitaria con evaluación multicriterio (ETS-EMC) se realizó a solicitud del Comité Farmacoterapéutico del Hospital Nacional Edgardo Rebagliati Martins (HNERM) ­ EsSalud, para responder a una solicitud de evaluación de la tecnología sanitaria de pembrolizumab. La solicitud fue presentada mediante la Carta N° 913-GRPRESSALUD-

Amivantamab en adultos con cáncer de pulmón de células no pequeñas (CPCNP) con metástasis, con mutación de inserción del exón 20 del receptor de factor de crecimiento epidérmico, y que han progresado a tratamiento de quimioterapia basada en platino / Amivantamab in adults with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor exon 20 insertion mutation, and who have progressed to platinum-based chemotherapy treatment

INTRODUCCIÓN: Cuadro clínico: El cáncer de pulmón es la más común y la principal causa de morbilidad y mortalidad por cáncer a nivel mundial. En 2020, se diagnosticaron 2 millones de casos y se registraron 1.8 millones de muertes, afectando mayormente a hombres. El cáncer de pulmón de células no pequeñas (CPCNP) representa el 85% de los casos, siendo el adenocarcinoma el subtipo histológico más frecuente. A nivel molecular, las mutaciones en el Receptor del Factor de Crecimiento Epidérmico (EGFR) es la mutación más frecuente del CPCNP y corresponden al 30-50% de la población asiática. En Perú, el 25% corresponde a las mutaciones en el gen EGFR. Sin embargo, la mutación de EGFR en la inserción del exón 20 (EGFR Ex20) es la más rara, equivale a un 4 ­ 12%. Esta mutación complica el tratamiento, ya que suelen ser resistentes a las terapias convencionales. Tecnología sanitária: El Amivantamab (Rybrevant® o JNJ-61186372) es un anticuerpo humano que se une simultáneamente a los receptores EGFR y MET en la superficie de las células cancerígenas, bloqueando ambos receptores. Esta acción interfiere con las señales necesarias para la supervivencia y el crecimiento de dichas células. Además, amivantamab activa el sistema inmunológico, induciendo a las células inmunitarias a destruir las células cancerígenas mediante citotoxicidad. Este medicamento fue aprobado por la Administración de Alimientos y Medicamentos

Pertuzumab en combinación con trastuzumab, docetaxel y carboplatino para mujeres adultas con cáncer de mama en estadio cT1-T4, ≥cN0, M0 (bien sea mayor de 2cm de diámetro o nódulo positivo), HER2+, ECOG 0-2, como tratamiento neoadyuvante / Pertuzumab in combination with trastuzumab, docetaxel and carboplatin for adult women with stage cT1-T4 breast cancer, ≥cN0, M0 (either greater than 2 cm in diameter or node positive), HER2+, ECOG 0-2, as neoadjuvant treatment

INTRODUCCIÓN: Cuadro clínico: Cuadro clínico En el 2022, se reportaron 2 296 840 casos nuevos y 666 103 muertes por cáncer de mama a nivel mundial. Considerando estas cifras, el cáncer de mama ocupa el segundo lugar entre los cánceres más frecuentes y el cuarto lugar entre las causas de muerte por cáncer más frecuentes a nivel mundial. En el Perú, para el 2022, se estimaron unos 7 797 casos nuevos y 1951 muertes por cáncer de mama, con una tasa de incidencia estandarizada por edad de 39.3 casos 100 000 personas y tasa de mortalidad estandarizada por edad de 9.4 muertes 100 000 personas. En base a ello, ocupa el segundo lugar entre los cánceres más frecuentes y el séptimo lugar entre las causas de muerte por cáncer más frecuentes en el Perú. Esta neoplasia puede ser clasificada según la positividad de para la expresión del receptor 2 del factor de crecimiento epidérmico humano (HER2). La supervivencia global a los 5 años en los pacientes con cáncer de mama HER2 positivo (HER2+) es aproximadamente 77%. Además, la estimación de los años de vida saludables perdidos (AVISA) para pacientes con cáncer de mama fue de 67 060.98 (por 1000 habitantes), en el Perú, en el 2021. La elección del tratamiento para los pacientes con cáncer de mama invasivo se basa en el estado de los receptores hormonales, el estado del receptor HER2, el estadio clínico de la paciente y si la paciente cumple los criterios para recibir terapia sistémica preoperatoria. A nivel internacional, las guías de práctica clínica recomiendan el uso de regímenes terapéuticos como opcione

Ravulizumab for adults with generalized myasthenia gravis: a plain language summary of three studies.

WHAT IS THIS SUMMARY ABOUT?: Generalized myasthenia gravis (often shortened to gMG) is a rare health condition that causes muscular weakness. This summary gives an overview of three published articles that report the results of research studies of a medicine called ravulizumab, a treatment approved for adults with gMG. These studies are: The CHAMPION MG study. The CHAMPION MG extension study. A study of how the body processes and responds to ravulizumab (known as pharmacokinetics and pharmacodynamics). These studies looked at how effective and safe ravulizumab is for people with gMG. WHAT WERE THE RESULTS?: Overall, participants with gMG who received ravulizumab showed a significant and rapid improvement in their muscle strength and ability to do daily activities. These improvements were sustained for up to 60 weeks of treatment. Ravulizumab was well-tolerated overall, and no-one in the study had a meningococcal infection (a type of bacterial infection preventable with vaccination). Results from the pharmacokinetic and pharmacodynamic study support the use of ravulizumab every 8 weeks to maintain improvements in gMG. WHAT DO THE RESULTS OF THE STUDY MEAN?: Ravulizumab can be considered as a treatment option for adults with gMG who are appropriately protected against meningococcal infection before starting treatment. The drug, administered every 8 weeks, improves muscle strength and daily performance. These positive effects have been observed to persist over a long period of time.

Efficacy and safety of pembrolizumab in cervical cancer: Protocol for systematic review and meta-analysis of randomized clinical trials.

PURPOSE: This paper reports a systematic review and meta-analysis protocol that will be used to evaluate the efficacy and safety of pembrolizumab, alone or combined with bevacizumab and other therapies, in adult women with cervical carcinoma from stage IB2 onwards. METHODS: The protocol follows PRISMA-P recommendations and was registered on PROSPERO (CRD42024531233). The search will be conducted without restrictions on language and year of publication in the following databases: Pubmed, Embase, Scopus, Web of Science, Cancerlit, The World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) and Clinical Trials Registry Platform. Grey literature will be searched using the following sources: Clinicaltrials.gov, Google Scholar and Opengrey. Manual search will be carried out for the reference lists of eligible studies. The studies will be selected independently by two reviewers and all completed or ongoing randomized clinical trials that evaluated the efficacy and safety of pembrolizumab, used alone or combined with chemotherapy, radiotherapy, bevacizumab or surgery, in adult women diagnosed with cervical cancer, will be included. The data extraction will include population characteristics, type of treatment and main outcomes of studies. The methodological quality of the studies will be assessed using the Cochrane Risk of Bias 2.0. The certainty of the evidence will be rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). CONCLUSIONS: The findings will be presented in narrative summary tables and a quantitative synthesis will be conducted using the 'meta' package of R software, version 4.3.1. This future systematic review may contribute with quality evidence for clinical decision-making on the use of pembrolizumab in women with cervical cancer.

Marcación de biomoléculas con radionúclidos / Radionuclide tagging of biomolecules / Marcação de biomoléculas com radionuclídeos

Introducción: la marcación de biomoléculas con radionúclidos es una técnica fundamental en la medicina nuclear que permite la visualización y tratamiento de diversas enfermedades, especialmente el cáncer. Materiales y métodos: este trabajo aborda en detalle los métodos y aplicaciones de esta tecnología, incluyendo la selección de radionúclidos, la conjugación con biomoléculas mediante agentes quelantes como Ácido dodecano tetraacético (DOTA), Ácido Dietilen Triamino Penta Acético (DTPA) y Ácido hidracinonicotínico (HYNIC), y los procesos de purificación y caracterización. Resultados: se presentan ejemplos específicos, como la marcación de Bevacizumab y Tocilizumab con 99mTc y 177Lu, destacando sus aplicaciones en la imagenología y terapia del cáncer. Además, se exploran las aplicaciones clínicas y futuras investigaciones en el campo, enfatizando el potencial de la medicina personalizada y las terapias combinadas. Discusión: la tecnología de marcación con radionúclidos continúa avanzando, prometiendo mejoras significativas en el diagnóstico y tratamiento de enfermedades complejas, ofreciendo herramientas precisas y eficientes para la gestión de la salud. Presentamos una visión exhaustiva de las técnicas, estudios de caso y el impacto de esta metodología en la práctica clínica.

Introduction: The labeling of biomolecules with radionuclides is a fundamental technique in nuclear medicine that allows the visualization and treatment of various diseases, especially cancer. Materials and methods: This work discusses in detail the methods and applications of this technology, including radionuclide selection, conjugation to biomolecules using chelating agents such as dodecane tetraacetic acid (DOTA), Diethylene Triamino Penta Acetic Acid (DTPA), Hydrazinonicotinic acid (HYNIC), and purification and characterization processes. Results: Specific examples are presented, such as the labeling of Bevacizumab and Tocilizumab with 99mTc and 177Lu, highlighting their applications in cancer imaging and therapy. In addition, clinical applications and future research in the field are explored, emphasizing the potential for personalized medicine and combination therapies. Discussion: Radionuclide tagging technology continues to advance, promising significant improvements in the diagnosis and treatment of complex diseases, offering accurate and efficient tools for healthcare management. This chapter provides a comprehensive overview of the techniques, case studies and the impact of this methodology in clinical practice.

Introdução: A marcação de biomoléculas com radionuclídeos é uma técnica fundamental na medicina nuclear que permite a visualização e o tratamento de várias doenças, especialmente o câncer. Materiais e métodos: este artigo discute em detalhes os métodos e as aplicações dessa tecnologia, incluindo a seleção de radionuclídeos, a conjugação com biomoléculas usando agentes quelantes, como Ácido dodecano tetra-acético (DOTA), Ácido dietileno triamino pentaacético (DTPA) e Ácido hidrazinônico-tínico (HYNIC), e os processos de purificação e caracterização. Resultados: são apresentados exemplos específicos, como a marcação de Bevacizumab e Tocilizumab com 99mTc e 177Lu, destacando suas aplicações em imagens e terapia de câncer. Além disso, são exploradas as aplicações clínicas e as pesquisas futuras no campo, enfatizando o potencial da medicina personalizada e das terapias combinadas. Discussão: A tecnologia de marcação com radionuclídeos continua avançando, prometendo melhorias significativas no diagnóstico e no tratamento de doenças complexas, oferecendo ferramentas precisas e eficientes para o gerenciamento da saúde. Apresentamos uma visão geral abrangente das técnicas, estudos de caso e o impacto dessa metodologia na prática clínica.

Association Between Vedolizumab Treatment and Arthritis/Arthralgia in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Vedolizumab is a humanized gut selective drug that targets α4ß7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related. METHODS: Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). RESULTS: The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately. CONCLUSIONS: The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.

Alzheimer's Disease Immunotherapy and Mimetic Peptide Design for Drug Development: Mutation Screening, Molecular Dynamics, and a Quantum Biochemistry Approach Focusing on Aducanumab::Aß2-7 Binding Affinity.

Seven treatments are approved for Alzheimer's disease, but five of them only relieve symptoms and do not alter the course of the disease. Aducanumab (Adu) and lecanemab are novel disease-modifying antiamyloid-ß (Aß) human monoclonal antibodies that specifically target the pathophysiology of Alzheimer's disease (AD) and were recently approved for its treatment. However, their administration is associated with serious side effects, and their use is limited to early stages of the disease. Therefore, drug discovery remains of great importance in AD research. To gain new insights into the development of novel drugs for Alzheimer's disease, a combination of techniques was employed, including mutation screening, molecular dynamics, and quantum biochemistry. These were used to outline the interfacial interactions of the Aducanumab::Aß2-7 complex. Our analysis identified critical stabilizing contacts, revealing up to 40% variation in the affinity of the Adu chains for Aß2-7 depending on the conformation outlined. Remarkably, two complementarity determining regions (CDRs) of the Adu heavy chain (HCDR3 and HCDR2) and one CDR of the Adu light chain (LCDR3) accounted for approximately 77% of the affinity of Adu for Aß2-7, confirming their critical role in epitope recognition. A single mutation, originally reported to have the potential to increase the affinity of Adu for Aß2-7, was shown to decrease its structural stability without increasing the overall binding affinity. Mimetic peptides that have the potential to inhibit Aß aggregation were designed by using computational outcomes. Our results support the use of these peptides as promising drugs with great potential as inhibitors of Aß aggregation.

Efficient use of mepolizumab in children: An analysis of the economically justifiable price in Colombia.

INTRODUCTION: Asthma imposes a crucial economic burden on health systems, especially with the incorporation of new drugs. Recently, mepolizumab has been approved to prevent exacerbations in patients with eosinophilic asthma. This study explores the economically justifiable price of mepolizumab for preventing exacerbations in children with severe asthma. MATERIALS AND METHODS: A model was developed using the microsimulation to estimate the quality-adjusted costs and life years of two interventions: mepolizumab versus not applying standard treatment without mepolizumab. This analysis was made during a time horizon of 50 years and from a third-payer perspective. RESULTS: Mepolizumab was cost-effective using a WTP of U$ 19,992 per QALY, but not at a WTP of U$ 4828, U$ 5128 per QALY. The economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of U$ 4828, and U$ 5128 respectively. At the current price of Mepolizumab, U$ 780 per dose, only using a WTP higher than U$ 10,300 per QALY mepolizumab will be the best alternative to no mepolizumab. CONCLUSION: Our study shows that the economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of 4828 and 5180 respectively. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

Hypergammaglobulinemia D and Periodic Fever Syndrome (HIDS) in a 3-year-old Patient from Puerto Rico.

Mevalonate kinase deficiency is a rare autosomal recessive disease caused by mutations in the mevalonate kinase gene (MVK). Depending on the mutations, a patient with this deficiency can exhibit any one of a spectrum of rare autoinflammatory diseases, such as hypergammaglobulinemia D (hyper-IgD) with periodic fever syndrome and mevalonic aciduria. To date, approximately 300 cases with mutations in the MVK gene have been reported worldwide. Herein, we present a 3-year-old female from Puerto Rico with a history of fever, arthralgia, and skin lesions since her first month of age and who, upon genetic workup, was confirmed to have compound heterozygous mutations in the MVK gene. Given her medical history and the results of her genetic testing, she was diagnosed with hyper-IgD with periodic fever syndrome. She will be treated with canakinumab, an interleukin-1ß antagonist, after receiving the varicella and measles-mumps-rubella (MMR) vaccines.

In-Depth Analysis of the Peripheral Immune Profile of HER2+ Breast Cancer Patients on Neoadjuvant Treatment with Chemotherapy Plus Trastuzumab Plus Pertuzumab.

Currently, therapy for early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is based on the combination of trastuzumab and pertuzumab plus chemotherapy in a neoadjuvant regimen. The INMUNOHER study aimed to detect immunological markers in peripheral blood and their association with treatment response. Sixty-two HER2+ BC patients were recruited. Pre-treatment samples were obtained before the start of treatment, while post-treatment samples were obtained after completing therapy and before surgery and were analyzed by flow cytometry. The pathologic complete response (pCR) rate achieved was 82.3%. The expression of the NKp30, PD-1, and TIM-3 receptors was reduced in the Natural Killer (NK)-CD56dim subset of patients who did not achieve pCR. Following therapy, many changes were found in leukocytes, including alterations in T cell lymphocyte proportions. Also, the percentage of NK cells decreased, and several phenotypic changes were observed in this population. After treatment, IFN-γ production by NK cells against HER2+-cells with or without trastuzumab was significantly reduced. HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.

Efectividad de Plasma Rico en Fibrina en Lesiones de Osteonecrosis de los Maxilares Asociada a Medicamentos: Resumen Estructurado de Evidencia (FRISBEE) / Efficacy of fibrin-rich plasma in drug-associated osteonecrosis lesions of the jaws

Introducción: Este trabajo de investigación tiene como objetivo evaluar y determinar la efectividad del uso de plasma rico en fibrina (PRF) como tratamiento para las lesiones de osteonecrosis de los maxilares asociadas a medicamentos (MRONJ). Métodos: Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Se identificaron siete revisiones sistemáticas que en conjunto incluyeron 14 estudios primarios, de los cuales, solamente uno corresponde a un ensayo clínico aleatorizado, y el resto a estudios observacionales. No es seguro establecer con claridad si el uso de PRF mejora o contribuye a la resolución de lesiones de osteonecrosis de los maxilares asociados a medicamentos, debido a que el nivel de certeza de la evidencia es muy bajo.

Introduction: This research aims to evaluate and determine the effectiveness of using platelet-rich fibrin (PRF) as a treatment for medication-related osteonecrosis of the jaws (MRONJ). Methods: A search was conducted in Epistemonikos, the largest database of systematic reviews in health, maintained through the screening of multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. Data were extracted from the identified reviews, analyzed from the primary studies, and a summary of findings table was prepared using the GRADE method Results and conclusions: Seven systematic reviews were identified, which together included 14 primary studies, of which only one was a randomized clinical trial, and the rest were observational studies. It is unclear whether the use of PRF improves or contributes to the resolution of medication-related osteonecrosis of the jaws due to the very low certainty of the evidence.

[Severe atopic dermatitis in childhood in the era of personalized medicine]. / Dermatitis atópica severa en la infancia en la era de la medicina personalizada.

Atopic dermatitis (AD) is a chronic, non-infectious inflammatory dermatosis, with increasing prevalence in recent decades. Due to its chronic and recurrent nature, it diminishes the quality of life of patients and their families. In recent years, advances in the understanding of AD's pathophysiology have driven the development of targeted therapies such as monoclonal antibodies (mAbs) and Janus kinase inhibitors (JAKis) which modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. Four targeted therapies have been approved in the USA for the treatment of severe/refractory cases: dupilumab, tralokinumab, abrocitinib, and upadacitinib. This manuscript aims to present an update on the pathophysiology of AD, describe the new treatments available, and provide an analysis of the initial results of the use of these treatments in the pediatric population. We concluded that the high cost of these treatments often limits their prescription to situations where cases of atopic dermatitis are resistant to other conventional therapeutic options or when the disease reaches a severe degree. This underscores the importance of careful and accurate decision-making in the medical management of AD to ensure the efficient use of these therapeutic resources.

Selective inhibition of interleukin 6 receptor decreased inflammatory cytokines and increased proteases in an experimental model of critical calvarial defect.

Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.

[Cardiotoxicity from anti-HER-2 therapies in patients with HER-2 positive breast cancer]. / Cardiotoxicidad por terapias anti-HER-2 en pacientes con cáncer de mama HER-2 positivo.

Background: HER-2 positive (+) breast cancer (BC) accounts for 20-25% of BC, it is more aggressive, and it has a lower survival rate. Since the approval of trastuzumab in 1998, other HER-2-targeted therapies such as pertuzumab and trastuzumab emtansine (TDM1) have been introduced, improving patient survival. However, cardiotoxicity is an adverse effect of these treatments. Objective: To estimate the incidence of cardiotoxicity with trastuzumab, trastuzumab/pertuzumab, and TDM1 in women with HER-2 + BC treated over a 6-year period at the Hospital de Clínicas and the Hospital Departamental de Soriano. Material and methods: Observational, descriptive, and retrospective study which included patients with HER-2 + BC treated with trastuzumab, trastuzumab/pertuzumab, or TDM1. Results: 81 patients were included, with a cardiotoxicity incidence of 23.4%. Cardiotoxicity was determined by a > 10% decrease in left ventricular ejection fraction (LVEF) (57.9%) and a LVEF < 50% evident during treatment (42.1%). Only 1 patient presented symptomatic heart failure. 63.1% of those who discontinued treatment due to cardiotoxicity managed to resume it. No relationship was evident between cardiovascular history or the administration regimen and the development of cardiotoxicity. Conclusion: The study showed a cardiotoxicity incidence similar to the international one. Most did not present cardiac toxicity, and if they did, it was asymptomatic and reversible.

Introducción: el cáncer de mama (CM) HER-2 positivo (+) representa el 20-25% de los CM, es más agresivo y tiene menor sobrevida. Desde la aprobación del trastuzumab en 1998, se han introducido otras terapias dirigidas al HER-2 como pertuzumab y trastuzumab emtansina (TDM1), con lo cual ha mejorado la supervivencia de las pacientes. Sin embargo, la cardiotoxicidad representa un efecto adverso de estos tratamientos. Objetivo: estimar la incidencia de cardiotoxicidad con trastuzumab, trastuzumab/pertuzumab y TDM1 en mujeres con CM HER-2 +, tratadas en un periodo de 6 años en el Hospital de Clínicas y el Hospital Departamental de Soriano. Material y métodos: estudio observacional, descriptivo y retrospectivo que incluyó pacientes con CM HER-2 +, tratadas con trastuzumab, trastuzumab/pertuzumab o TDM1. Resultados: se incluyeron 81 pacientes. La incidencia de cardiotoxicidad fue del 23.4%. La cardiotoxicidad se determinó por una disminución > 10% de la fracción de ejección del venticulo izquierdo (FEVI) (57.9%) y por una FEVI < 50%, evidenciada durante el tratamiento (42.1%). Únicamente una paciente presentó insuficiencia cardiaca sintomática. El 63.1% de quienes suspendieron el tratamiento por cardiotoxicidad logró reanudarlo. No se evidenció una relación entre los antecedentes cardiovasculares ni con el esquema de administración y el desarrollo de cardiotoxicidad. Conclusión: el estudio mostró una incidencia de cardiotoxicidad similar a la internacional. La mayoría no tuvo toxicidad cardiaca y si la hubo fue asintomática y reversible.

Safety and efficacy of biologic drugs in children or adolescents with atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

Children and adolescents suffering from moderate-to-severe atopic dermatitis (AD) face a significant disease burden that greatly impacts their quality of life. Treatment options for AD are currently limited. To assess the safety and efficacy of biologic drugs, dupilumab, lebrikizumab, or tralokinumab, in improving outcomes in patients with moderate to severe inadequately controlled AD. We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing dupilumab, lebrikizumab or tralokinumab to placebo in patients with AD. We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs), random effects model was used and a p-value <0.05 was considered as statistically significant. We analysed data into Review Manager 5.4. A total of five RCTs and 973 patients were included, of whom 592 were prescribed a biologic drug. Compared with placebo, patients receiving a biologic drug had a greater improvement, achieved an Investigator Global Assessment (IGA) score of 0 or 1 (OR 5.05; 95% CI 3.08-8.29), Eczema Area and Severity Index (EASI) 75 (OR 6.87; 95% CI 4.71-10.02), EASI 50 (OR 8.89; 95% CI 6.18-12.78) and EASI 90 (8.30; 95% CI 4.81-14.31). The proportion of patients with 3 points or more (OR 6.56; 95% CI 4.34-9.90) or 4 points or more (OR 8.09; 95% CI 5.19-12.59) improvement from baseline in peak pruritus NRS was significantly higher with biologic drugs than placebo. There were no significant differences between groups regarding adverse events (OR 0.79; 95% CI 0.58-1.07), and conjunctivitis (OR 2.08; 95% CI 1.00-4.33). In this meta-analysis, dupilumab, lebrikizumab, and tralokinumab have shown significant improvements in signs, symptoms and quality of life in children or adolescents with moderate to severe AD. Larger studies may be needed to continue evaluating the safety and efficacy of these biologic drugs in this patient population.

Regimes de tratamento com cetuximabe ou pembrolizumabe para carcinoma espinocelular de cabeça e pescoço recidivado ou metastático / Cetuximab or pembrolizumab treatment regimens for recurrent or metastatic head and neck squamous cell carcinoma

INTRODUÇÃO: Os CECP desenvolvem-se a partir do epitélio da mucosa na cavidade oral, faringe e laringe e são as neoplasias malignas mais comuns que surgem na cabeça e pescoço. Aproximadamente 40% dos cânceres de cabeça e pescoço ocorrem na região de cavidade oral; 15% na faringe; 25% na laringe; e o restante em glândulas salivares e tireoide. Estudos clínicos em pacientes com CECP recidivado ou metastático indicam que os medicamentos mais ativos são o metotrexato, cisplatina, fluorouracila, bleomicina, paclitaxel e docetaxel. No entanto, esses medicamentos produziram taxas de resposta da ordem de 20%-30%, com curta duração (3-5 meses) e raramente respostas completas. Devido às evidências do regime EXTREME (cetuximabe, cisplatina e 5-fluorouracil) demonstrarem um aumento significativo no tempo de sobrevida global em comparação com o grupo controle com menos eventos adversos, o regime foi estabelecido como o tratamento padrão de primeira linha. Adicionalmente, devido ao pembrolizumabe ativar a resposta do sistema imunológico contra o câncer, a imunoterapia também tem sido uma opção de primeira linha para tratamento de pacientes com CECP recidivado ou metastático, especialmente em expressores de PD-1, aproximadamente 85% dos cas