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Abstract The geriatric vision of palliative care is based on a multidisciplinary, patient‐centered approach, looking for a balance between human dignity and medical treatments with a particular focus on the social and ethical aspects. In order to develop the best care models, there is a rising need for a tighter collaboration of all the involved players (i.e., doctors, nurses, social workers). Indeed, the idea of a fragmented system without considering the patient or his/her family is not at all applicable to older patients with chronic disease. The causes of death, the phase of death changes, and the extend of last period of life could be a long phase characterized by complicated treatment decisions, difficult management of symptoms, multiple psychosocial problems, and complex spiritual distress. Recently, Italian guidelines on Comprehensive Geriatric Assessment (CGA) have been published. However, none of the identified studies on patients in hospice and other palliative care facilities met the criteria for inclusion. These findings underscore the need for further research to determine the potential benefits of a multidimensional approach for patients in hospice and other palliative care settings. Our reflections and suggestions on the CGA use for older persons in palliative care may be a starting point for an open and continuous dialogue with all the operators concerned.

Objective: To determine the seroreactivity profile for sexually transmitted infections (STIs) in a sample of community-dwelling older adults. Methods: Epidemiological survey using serological screening tests for reactivity to Treponema pallidum, HIV 1/2, and hepatitis B and C viruses in 495 older individuals (59.9% women) investigated regardless of signs or symptoms of STIs. Results: Reactivity rates for the etiological agents of AIDS and viral hepatitis B and C were compatible with the usual prevalence of these STIs in the Brazilian population. However, there was a very high prevalence of reactivity to syphilis (symptomatic or asymptomatic) in the group, equivalent to approximately 1290 cases per 10 000 older population, which suggests a proportionally greater exposure of older adults to infection with T. pallidum and to the risk of morbidity and mortality associated with STIs. Conclusions: This scenario indicates that adjustments are needed in geriatric centers to consider screening for STIs as an integral part of the routine clinical care of older people.

Serum carbohydrate antigen 19-9 (Ca19-9) is the only approved biomarker approved for the screening and diagnosis of pancreatic cancer (PC), but its value remains controversial. The aim of our study is to evaluate the role of CA 19-9 in the management of PC patients in jaundiced patients staged by both Computed Tomography (CT) and Endoscopic Ultrasound (EUS). Additionally, we evaluated traditional cholestasis marker behavior. Medical records of 73 patients have been retrospectively reviewed. We considered tumor size, tumor stage, CA 19-9, cytolysis, and cholestasis biomarkers. All patients underwent CT scan for staging. EUS +/− fine-needle biopsy (FNB) was performed in doubtful cases. Median alkaline phosphatase (ALP) and y-glutamyltransferase (GGT) levels were significantly lower compared to baseline after the biliary drainage (204 vs. 465 U/L, p < 0.0001, 204. U/L vs. 608.5, p < 0.0001, respectively), whilst no differences were observed for CA 19-9 levels. CA 19-9 showed significant association with the tumor stage in the pre-drainage setting. CT and EUS showed a low agreement in estimating tumor size (mean difference 4.8 mm 95% LoA −10.82–20.38). We did not find any significant correlation between CA 19-9 and bilirubin levels (r = −0.05, p = 0.7). In our cohort, survival rate was lower in patients with higher CA 19-9 levels (log rank p = 0.007). CA 19-9 has some limitations as a biomarker in the PC setting, thus it cannot address the treatment strategy alone. Nonetheless, it provides valuable information, and is not replaceable for the time being.

Abstract The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone. Collectively, these results demonstrate that LSD1 modulation improves antitumoral responses generated by ACT and anti-PDL1 therapy, providing the foundation for their clinical evaluation.

Abstract Background In non-small cell lung cancer (NSCLC) the efficacy of chemo-immunotherapy is affected by the high expression of drug efflux transporters as ABCC1 and by the low expression of ABCA1, mediating the isopentenyl pyrophosphate (IPP)-dependent anti-tumor activation of Vγ9Vδ2 T-lymphocytes. In endothelial cells ABCA1 is a predicted target of the transcription factor EB (TFEB), but no data exists on the correlation between TFEB and ABC transporters involved in the chemo-immuno-resistance in NSCLC. Methods The impact of TFEB/ABCC1/ABCA1 expression on NSCLC patients’ survival was analyzed in the TCGA-LUAD cohort and in a retrospective cohort of our institution. Human NSCLC cells silenced for TFEB (shTFEB) were analyzed for ABC transporter expression, chemosensitivity and immuno-killing. The chemo-immuno-sensitizing effects of nanoparticles encapsulating zoledronic acid (NZ) on shTFEB tumors and on tumor immune-microenvironment were evaluated in Hu-CD34+ mice by single-cell RNA-sequencing. Results TFEBlowABCA1lowABCC1high and TFEBhighABCA1highABCC1low NSCLC patients had the worst and the best prognosis, respectively, in the TCGA-LUAD cohort and in a retrospective cohort of patients receiving platinum-based chemotherapy or immunotherapy as first-line treatment. By silencing shTFEB in NSCLC cells, we demonstrated that TFEB was a transcriptional inducer of ABCA1 and a repressor of ABCC1. shTFEB cells had also a decreased activity of ERK1/2/SREBP2 axis, implying reduced synthesis and efflux via ABCA1 of cholesterol and its intermediate IPP. Moreover, TFEB silencing reduced cholesterol incorporation in mitochondria: this event increased the efficiency of OXPHOS and the fueling of ABCC1 by mitochondrial ATP. Accordingly, shTFEB cells were less immuno-killed by the Vγ9Vδ2 T-lymphocytes activated by IPP and more resistant to cisplatin. NZ, which increased IPP efflux but not OXPHOS and ATP production, sensitized shTFEB immuno-xenografts, by reducing intratumor proliferation and increasing apoptosis in response to cisplatin, and by increasing the variety of anti-tumor infiltrating cells (Vγ9Vδ2 T-lymphocytes, CD8+T-lymphocytes, NK cells). Conclusions This work suggests that TFEB is a gatekeeper of the sensitivity to chemotherapy and immuno-killing in NSCLC, and that the TFEBlowABCA1lowABCC1high phenotype can be predictive of poor response to chemotherapy and immunotherapy. By reshaping both cancer metabolism and tumor immune-microenvironment, zoledronic acid can re-sensitize TFEBlow NSCLCs, highly resistant to chemo- and immunotherapy.

PurposePatients diagnosed with High Grade Gliomas (HGG) generally tend to have a relatively negative prognosis with a high risk of early tumor recurrence (TR) after post-operative radio-chemotherapy. The assessment of the pre-operative risk of early versus delayed TR can be crucial to develop a personalized surgical approach. The purpose of this article is to predict TR using MRI radiomic analysis.MethodsData were retrospectively collected from a database. A total of 248 patients were included based on the availability of 6-month TR results: 188 were used to train the model, the others to externally validate it. After manual segmentation of the tumor, Radiomic features were extracted and different machine learning models were implemented considering a combination of T1 and T2 weighted MR sequences. Receiver Operating Characteristic (ROC) curve was calculated with relative model performance metrics (accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)) at the best threshold based on the Youden Index.ResultsModels performance were evaluated based on test set results. The best model resulted to be the XGBoost, with an area under ROC curve of 0.72 (95% CI: 0.56 - 0.87). At the best threshold, the model exhibits 0.75 (95% CI: 0.63 - 0.75) as accuracy, 0.62 (95% CI: 0.38 - 0.83) as sensitivity 0.80 (95% CI: 0.66 - 0.89 as specificity, 0.53 (95% CI: 0.31 - 0.73) as PPV, 0.88 (95% CI: 0.72 - 0.94) as NPV.ConclusionMRI radiomic analysis represents a powerful tool to predict late HGG recurrence, which can be useful to plan personalized surgical treatments and to offer pertinent patient pre-operative counseling.

Este texto presenta los resultados de un proyecto de investigación que explora la fundamentación epistemológica de la Educación Religiosa Escolar (ERE) en Colombia a partir de la pregunta por el λόγος de los “estudios de la religión”. El problema central radica en cómo armonizar la ERE con la formación integral, evitando el proselitismo religioso en las instituciones educativas del país. Para abordar este desafío, se ha adoptado un enfoque cualitativo, utilizando un método de arqueología transmedia con una perspectiva epistemológica hermenéutica. Este enfoque permite analizar críticamente cómo los principios racionales de los estudios de la religión pueden contribuir a la construcción de una ERE que fomente el cultivo del sentido de la vida, la apertura a la trascendencia, una conciencia profunda de las convicciones y el desarrollo de un horizonte pluralista e intercultural. Como resultado, se espera evidenciar criterios pedagógicos que apoyen una ERE que esté alineada con los principios del respeto a la diversidad, proporcionando así un marco más holístico para su implementación en Colombia. En conclusión, se busca proponer una reflexión crítica y situada sobre la racionalidad de los estudios de la religión como un aporte significativo a los procesos educativos del país.

Abstract The demand for automated systems monitoring and supporting patients in their home-based recovery programs is substantial. While emerging technologies have been proposed as potential solutions to enhance at-home patient care, limited systems are in place due to their challenges in offering real-time monitoring and corrective feedback. Most proposed methodologies provide an overall measure or score for the executed movement. The proposed work involves the adaptation of an existing published dataset to cater to the needs of a system capable of remotely assisting patients, effectively acting as a virtual physical therapist able to provide corrective feedback. A dataset containing a set of three simple exercises for shoulder rehabilitation was processed. Each movement was meticulously annotated for temporal and categorical motion domains to monitor exercise execution in terms of the range of motion completeness and to evaluate compensatory movement patterns. This work carries substantial significance by offering a standardized and easily accessible model for human movement data, thus fostering the advancement of digital assistive systems designed to support home-based rehabilitation programs.

Abstract Predictive modelling of cancer outcomes using radiomics faces dimensionality problems and data limitations, as radiomics features often number in the hundreds, and multi-institutional data sharing is ()often unfeasible. Federated learning (FL) and feature selection (FS) techniques combined can help overcome these issues, as one provides the means of training models without exchanging sensitive data, while the other identifies the most informative features, reduces overfitting, and improves model interpretability. Our proposed FS pipeline based on FL principles targets data-driven radiomics FS in a multivariate survival study of non-small cell lung cancer patients. The pipeline was run across datasets from three institutions without patient-level data exchange. It includes two FS techniques, Correlation-based Feature Selection and LASSO regularization, and Cox Proportional-Hazard regression with Overall Survival as endpoint. Trained and validated on 828 patients overall, our pipeline yielded a radiomic signature comprising "intensity-based energy" and "mean discretised intensity". Validation resulted in a mean Harrell C-index of 0.59, showcasing fair efficacy in risk stratification. In conclusion, we suggest a distributed radiomics approach that incorporates preliminary feature selection to systematically decrease the feature set based on data-driven considerations. This aims to address dimensionality challenges beyond those associated with data constraints and interpretability concerns.

Summary: Replication origin assembly is a pivotal step in chromosomal DNA replication. In this process, the ORC complex binds DNA and, together with the CDC6 and CDT1, promotes the loading of the MCM helicase. Chemicals targeting origin assembly might be useful to sensitize highly proliferative cancer cells. However, identifying such compounds is challenging due to the multistage nature of this process. Here, using Xenopus laevis egg extract we set up a high-throughput screening to isolate MCM chromatin loading inhibitors, which led to the identification of NSC-95397 as a powerful inhibitor of replication origin assembly that targets CDC6 protein and promotes its degradation. Using systems developed to test selective drug-induced lethality we show that NSC-95397 triggers cell death both in human cells and Xenopus embryos that have higher proliferative ability. These findings demonstrate the effectiveness of molecules disrupting DNA replication processes in targeting hyperproliferating cells, highlighting their potential as anti-cancer molecules.

Macropinocytosis is a cellular process that enables cells to engulf extracellular material, such as nutrients, growth factors, and even whole cells. It is involved in several physiological functions as well as pathological conditions. In cancer cells, macropinocytosis plays a crucial role in promoting tumor growth and survival under nutrient-limited conditions. In particular KRAS mutations have been identified as main drivers of macropinocytosis in pancreatic, breast, and non-small cell lung cancers. We performed a high-content screening to identify inhibitors of macropinocytosis in pancreatic ductal adenocarcinoma (PDAC)-derived cells, aiming to prevent nutrient scavenging of PDAC tumors. The screening campaign was conducted in a well-known pancreatic KRAS-mutated cell line (MIAPaCa-2) cultured under nutrient deprivation and using FITC-dextran to precisely quantify macropinocytosis. We assembled a collection of 3584 small molecules, including drugs approved by the Food and Drug Administration (FDA), drug-like molecules against molecular targets, kinase-targeted compounds, and molecules designed to hamper protein-protein interactions. We identified 28 molecules that inhibited macropinocytosis, with potency ranging from 0.4 to 29.9 μM (EC50). A few of them interfered with other endocytic pathways, while 11 compounds did not and were therefore considered specific “bona fide” macropinocytosis inhibitors and further characterized. Four compounds (Ivermectin, Tyrphostin A9, LY2090314, and Pyrvinium Pamoate) selectively hampered nutrient scavenging in KRAS-mutated cancer cells. Their ability to impair albumin-dependent proliferation was replicated both in different 2D cell culture systems and 3D organotypic models.These findings provide a new set of compounds specifically targeting macropinocytosis, which could have therapeutic applications in cancer and infectious diseases.

This article presents two cases that join user-driven innovation and additive manufacturing (AM) to examine latent business opportunities for AM in the medical sector. The first case arose as a response to shortages during the early stages of the covid 19 pandemic. The second case, explored in more depth, came from maker-medical collaboration during preparation for a life-threatening operation. Surgeons, confronted with a patient with a delicate heart condition, collaborated with a prototyping facility to print a realistic 3D model of the patient’s aortic aneurysm. The model allowed the surgeons to first study and then experiment to determine the most effective operation procedure before the actual operation, which shortened the surgery time by approximately 70%. Reducing surgery time creates two forms of value: improving patient outcomes and reducing costs. Shorter times under anesthetic and on cardiopulmonary bypass correlate with better surgical results. Reducing healthcare costs brings broad societal benefits in both publicly and privately funded healthcare systems. We outline a case for makerspaces to capture value by joining their expertise and manufacturing equipment with the needs of nearby healthcare systems for novel business development.

El Estado de Derecho implica la sujeción del poder estatal al Derecho y a una Constitución con fuerza normativa y primacía, incluyendo la separación, limitación y legitimación democrática de los poderes estatales, la distribución territorial del poder, la seguridad jurídica y el reconocimiento de los derechos fundamentales. Para ello, se requieren sistemas de justicia basados en las garantías de un “proceso justo”. Entre estas destaca el derecho a la independencia judicial en aspectos como la designación del tribunal, la duración del mandato y la separación de influencias políticas externas. Este estudio aborda estas cuestiones, centrándose en el caso español y en la crisis sistémica del Consejo General del Poder Judicial. Recibido: 09.02.2024 Aceptado: 04.03.2024

Abstract Background Few studies explored the effect of the combination of glucose sodium-cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on the incidence of cardiovascular events in patients with type 2 diabetes (T2D) and acute myocardial infarction (AMI). Methods We recruited patients with T2D and AMI undergoing percutaneous coronary intervention, treated with either SGLT-2i or GLP-1RA for at least 3 months before hospitalization. Subjects with HbA1c 50% was higher in the SGLT-2i/GLP-1RA group compared with both SGLT-2i and GLP-1RA groups. Interpretation The combination of SGLT-2i and GLP-1RA is associated with a reduced incidence of cardiovascular events in patients with T2D and AMI compared with either drug used alone, with a significant effect also on peri-infarcted myocardial rescue in patients without a second event. Trial registraition ClinicalTrials.gov ID: NCT06017544.

Spinal muscular atrophy linked to chromosome 5 (SMA-5q) is an autosomal recessive genetic disease caused by mutations in the SMN1. SMA-5q is characterized by progressive degeneration of the spinal cord and bulbar motor neurons, causing severe motor and respiratory impairment with reduced survival, especially in its more severe clinical forms. In recent years, highly effective disease-modifying therapies have emerged, either acting by regulating the splicing of exon 7 of the SMN2 gene or adding a copy of the SMN1 gene through gene therapy, providing a drastic change in the natural history of the disease. In this way, developing therapeutic guides and expert consensus becomes essential to direct the use of these therapies in clinical practice. This consensus, prepared by Brazilian experts, aimed to review the main available disease-modifying therapies, critically analyze the results of clinical studies, and provide recommendations for their use in clinical practice for patients with SMA-5q. This consensus also addresses aspects related to diagnosis, genetic counseling, and follow-up of patients under drug treatment. Thus, this consensus provides valuable information regarding the current management of SMA-5q, helping therapeutic decisions in clinical practice and promoting additional gains in outcomes.

El objetivo de este estudio fue analizar la relación entre estilo de vida y resiliencia en pobladores de una zona rural de Cajamarca. La investigación fue de diseño no experimental y de alcance descriptivo-correlacional. La muestra estuvo compuesta por 309 pobladores. Los instrumentos utilizados fueron el Cuestionario de Estilo de Vida Saludable (Santiago-Bazán & Carcausto, 2019) y la Escala de Resiliencia de Wagnild y Young y adaptado al Perú por Gómez (2019). Los resultados evidencian que el estilo de vida presenta diferencias significativas según el sexo (W = 27272.00; p < .01) y grupo etario (K = 11.175; p < .01). En cuanto a la relación entre las variables se encontró que relación estadísticamente significativa entre el estilo de vida saludable y la resiliencia (rho = .393; p < .01), a excepción de la dimensión físico/mental del estilo de vida que solo presentó relación con algunas dimensiones de la resiliencia. En conclusión, esta investigación pone en evidencia que la resiliencia cumple un rol fundamental en el estilo de vida de las personas de la zona rural de Cajamarca, quienes a pesar de no contar con las condiciones básicas y carencias de comodidades muestran adecuados indicadores de un estilo de vida saludable.

Introduction In some patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) is subclinical as under-lying inflammation of large vessels (LV) is present without evidence of related clinical manifestations. Different factors have been proposed as predictive of subclinical GCA in PMR patients. To date, the literature reports scant data about the association between subclinical GCA and long-lasting morning stiffness (MS) in patients at the time of diagnosis of PMR. Given this background, the aim of this study was to assess the association between subclinical GCA and MS < 45 min in patients with newly diagnosed PMR. Material and methods We performed an observational, retrospective, single-centre cohort study of patients consecutively referred to our public out-of-hospital rheumatologic clinic between January 2015 and December 2020, who could be classified as having PMR according to the 2012 EULAR/ACR criteria. Subclinical GCA was investigated through ultrasound examination of a core set of arteries (temporal, axillary, common carotid, and subclavian arteries), in accordance with the EULAR recommendations for the use of imaging in LV vasculitis. Patients who did not have GCA symptoms but showed halo sign in at least one of these arteries were described as having subclinical GCA. Results We included a total of 143 patients (35 men and 108 women). Their median age was of 71.5 years. Thirty-five had MS duration < 45 min at the time of PMR diagnosis. Subclinical GCA was found in 23 PMR patients (16.1%); 18 had a cranial and 5 an extracranial GCA. A univariate analysis highlighted that MS < 45 min was associated with a lower prevalence of GCA (OR = 0.11, 95% CI: 0.04–0.29; p < 0.0001). This association was retained in a multivariable analysis that accounted for 6 different potential covariates (OR = 0.06, 95% CI: 0.01–0.26; p < 0.0001. Conclusions In our study MS < 45 min at the time of PMR diagnosis was associated with a significantly lower risk of subclinical GCA, when patients were screened by ultrasound, of approximately 90%. Identification of a more accurate MS cut-off value could improve the accuracy for subclinical GCA in patients with newly diagnosed PMR.

The aim of this informative review was to investigate the application of radiomics in cancer imaging and to summarize the results of recent studies to support oncological imaging with particular attention to breast cancer, rectal cancer and primitive and secondary liver cancer. This review also aims to provide the main findings, challenges and limitations of the current methodologies. Clinical studies published in the last four years (2019–2022) were included in this review. Among the 19 studies analyzed, none assessed the differences between scanners and vendor-dependent characteristics, collected images of individuals at additional points in time, performed calibration statistics, represented a prospective study performed and registered in a study database, conducted a cost-effectiveness analysis, reported on the cost-effectiveness of the clinical application, or performed multivariable analysis with also non-radiomics features. Seven studies reached a high radiomic quality score (RQS), and seventeen earned additional points by using validation steps considering two datasets from two distinct institutes and open science and data domains (radiomics features calculated on a set of representative ROIs are open source). The potential of radiomics is increasingly establishing itself, even if there are still several aspects to be evaluated before the passage of radiomics into routine clinical practice. There are several challenges, including the need for standardization across all stages of the workflow and the potential for cross-site validation using real-world heterogeneous datasets. Moreover, multiple centers and prospective radiomics studies with more samples that add inter-scanner differences and vendor-dependent characteristics will be needed in the future, as well as the collecting of images of individuals at additional time points, the reporting of calibration statistics and the performing of prospective studies registered in a study database.

Abstract Background: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. Objective: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. Methods: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and inter-leukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. Results: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01–1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29–3.08; p = 0.002) were associated with treatment interruption. Study limitations: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. Conclusions: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

Anterior myocardial infarction is a critical condition with significant implications for cardiac function and patient prognosis. Despite advancements in reperfusion therapies, optimizing recovery during the early phases of myocardial infarction remains challenging. Anterior myocardial infarction can lead to substantial long-term effects on a patient’s health due to extensive damage to the heart muscle, particularly the left ventricle, impacting both quality of life and overall prognosis. Vericiguat, a soluble guanylate cyclase stimulator, has shown promise in heart failure, but its role in early anterior myocardial infarction has not yet been fully explored. By enhancing soluble guanylate cyclase activity, vericiguat may increase cyclic guanosine monophosphate production, leading to vasodilation, inhibition of platelet aggregation, and potential cardioprotective effects. Currently, treatment options for anterior myocardial infarction primarily focus on reperfusion strategies and managing complications. However, there is a critical need for adjunctive therapies that specifically target the pathophysiological changes occurring in the early phases of myocardial infarction. Vericiguat’s mechanism of action offers a novel approach to improving vascular function and myocardial health, potentially contributing to innovative treatment strategies that could transform the care and prognosis of patients with anterior myocardial infarction.

Objetivo: evaluar la presencia de complicaciones obstétricas en mujeres gestantes nativas con bartonelosis aguda por Bartonella bacilliformis en la zona endémica, de Caraz - Ancash a (2 237 m.s.n.m.). Materiales y métodos: estudio descriptivo en 50 mujeres gestantes que acudieron consecutivamente al Hospital ´´San Juan de Dios´´ de Caraz, durante el período comprendido entre los años 1999 - 2003. Todos los casos tuvieron diagnóstico definido mediante el frotis de sangre periférica positivo para Bartonella. Resultados: todas las gestantes fueron nativas y residían en la zona endémica, 64% procedían de las áreas rurales,adyacentes, 12% tenian antecedentes de haber padecido verruga peruana y el 10 % reportó tratamiento previo. La presentación inicial fué con palidez en el 80%, cefalea 76 %, dolores articulares 64%, fiebre 34 %, dolor abdominal 24 % y sangrado vaginal 18%. La edad promedio fué 25,5 años. La edad gestacional promedio fué 22,9 semanas. La hemoglobina promedio fue 9,8 g /dl . El índice parasitario promedio fue 23,2% (1 a 100); sólo el 22 % tuvo índice mayor del 50 % en el frotis .El 48% hizo alguna complicación obstétrica; abortos en el 26%, parto prematuro 8 %, óbito fetal 4 %, retención placentaria 4 % y sepsis 2%. Las complicaciones obstétricas fueron más frecuentes durante el primer trimestre de embarazo con el 71,4 %. No hubo muertes maternas en esta serie. Conclusión: las mujeres gestantes de zonas endemicas aquejadas por la enfermedad de Carrión o bartonelosis aguda por Bartonella baciliformis tienen una elevada frecuencia de complicaciones obstétricas, por lo que deben considerarse como gestantes de alto riesgo.

Quiero comenzar esta carta señalando que entre las múltiples funciones del Colegio Médico del Perú se encuentra una muy importante, la cual es la de apoyar la educación médica continua, es por ello nuestra convicción y perseverancia en el trabajo realizado en la Revista Acta Médica Peruana en la seguridad de contribuir a esta importante función.

Introducción: la parasitosis zoonótica causada por Toxocara canis ha sido sugerida como posible agente etiológico del asma. Objetivo: evaluar la asociación entre la infección por Toxocara canis y el asma en niños del Hospital Nacional Cayetano Heredia (HNCH), Lima, Perú. Asimismo evaluar los factores asociados a la infección por T. canis en la población de estudio. Material y métodos: estudio caso-control, que incluyó a 75 niños asmáticos y 75 niños no asmáticos, de 2 a 13 años, atendidos en el HNCH en el año 2002. Se aplicó un cuestionario para evaluar los factores asociados a toxocariosis y a asma respectivamente. La seroprevalencia de T. canis fue determinada mediante la prueba ELISA IgG para T. canis. Resultados: la seroprevalencia de toxocariosis fue de 16%, no se encontró una asociación significativa entre la seropositividad para Toxocara canis y el asma. Sin embargo se observó una relación estadísticamente significativa entre una mayor frecuencia de crisis de sibilancia nocturna y una serología positiva para Toxocara canis. Los factores asociados a la toxocariosis fueron el contacto intenso con perros, particularmente con cachorros y una ausencia de grado de instrucción universitario de los padres. Los factores asociados al asma fueron: el poco contacto con perros y el grado de instrucción universitario de los padres. Conclusiones: no hubo asociación entre la presencia de serología positiva para T. canis y asma, pero sí con una mayor frecuencia de sibilancia nocturna. Son necesarios estudios posteriores que evalúen esta última observación.

Toxocariosis es una infección causada por larvas de nemátodos del género Toxocara siendo T. canis o Toxocara cati, nemátodos del perro y gato respectivamente, los más importantes para el ser humano. Las especies del Género Toxocara pertenecen a la orden Ascaridida, superfamilia Ascaridiodea, familia Toxocaridae2. La enfermedad es ocasionada principalmente por T. canis. La toxocariosis humana fue descrita por primera vez por Wilder en 1950, quien identificó un nemátodo de especie desconocida en un granuloma de retina de un niño. En 1952, Beaver reportó casos de una enfermedad multisistémica, crónica y severa, asociada a hipereosinofilia . En el Perú, en 1991, Maguiña y col reportaron los primeros casos de Larva migrans visceral y en 1999, Miranda y col, reportaron los primeros casos de Larva migrans ocular.

Até o momento, órgãos públicos, instituições de controle, agentes sociais não sabem como lidar com a questão das notícias falsas e cobram soluções dos estudiosos. A complexidade se torna ainda maior pelo fato de envolver não apenas agentes internacionais, governos do exterior, mas escritórios, equipamentos e máquinas de produção e bombardeamento de informações, assentados sobre doações e verbas milionárias, que transcendem em muito a capacidade de governos apresentarem medidas efetivas contra esse mal-uso da democracia. Mas isso não nos impede de aceitar o desafio. Possivelmente, após anos de debates, investigações, confronto de ideias possamos chegar a proposições que tenham condição de reverter o processo e garantir a todos a recuperação da confiança na democracia e nos processos de tomada de decisão.

Abstract Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10–15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells. Inhibition of C-rich (teloC) dilncRNAs with antisense oligonucleotides leads to DNA replication stress responses, increased genomic instability, and apoptosis induction selectively in ALT cells. Cell death is dependent on DNA replication and is increased by DNA replication stress. Mechanistically, teloC dilncRNA inhibition reduces RAD51 and 53BP1 recruitment to telomeres, boosts the engagement of BIR machinery, and increases C-circles and telomeric sister chromatid exchanges, without increasing telomeric non-S phase synthesis. These results indicate that teloC dilncRNA is necessary for a coordinated recruitment of DDR factors to ALT telomeres and it is essential for ALT cancer cells survival.

Abstract Purpose One of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus. Methods and materials Pre-treatment MR images from patients who underwent WBRT between 2010 and January 2020—and post-radiotherapy images in cases of relapse—were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences. Results We analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it. Conclusion These data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus.

Over the past decade, there has been a notable surge in AI-driven research, specifically geared toward enhancing crucial clinical processes and outcomes. The potential of AI-powered decision support systems to streamline clinical workflows, assist in diagnostics, and enable personalized treatment is increasingly evident. Nevertheless, the introduction of these cutting-edge solutions poses substantial challenges in clinical and care environments, necessitating a thorough exploration of ethical, legal, and regulatory considerations.A robust governance framework is imperative to foster the acceptance and successful implementation of AI in healthcare. This article delves deep into the critical ethical and regulatory concerns entangled with the deployment of AI systems in clinical practice. It not only provides a comprehensive overview of the role of AI technologies but also offers an insightful perspective on the ethical and regulatory challenges, making a pioneering contribution to the field.This research aims to address the current challenges in digital healthcare by presenting valuable recommendations for all stakeholders eager to advance the development and implementation of innovative AI systems.

Abstract: Brazil has the second largest number of leprosy cases (a disease with a significant burden) in the world. Despite global and local efforts to eliminate this public health problem, inadequate or late diagnosis contribute to perpetuate its transmission, especially among household contacts. Tests such as the rapid IgM antibody detection (RT) and real-time polymerase chain reaction (RT-PCR) were developed to overcome the challenges of early diagnosis of leprosy. This study aimed to analyze the cost-effectiveness of a new diagnostic algorithm recommended by the Brazilian government to diagnose leprosy in household contacts of confirmed leprosy cases, which includes the RT and RT-PCR tests. A decision tree model was constructed and the perspective of the Brazilian Unified National Health System (SUS) and a 1-year time horizon were adopted. Only direct medical costs related to diagnostic tests were included. Effectiveness was measured as the number of avoided undiagnosed leprosy cases. Different scenarios were analyzed. The sequential use of RT, slit-skin smear (SSS) microscopy, and RT-PCR as recommended by the Brazilian Ministry of Health was compared to a base case (isolated SSS microscopy), yielding an incremental cost-effectiveness ratio of USD 616.46 per avoided undiagnosed leprosy case. Univariate sensitivity analysis showed that the prevalence of leprosy among household contacts was the variable that influenced the model the most. This is the first economic model to analyze a diagnostic algorithm of leprosy. Results may aid managers to define policies and strategies to eradicate leprosy in Brazil.

IntroductionThe use of contemporary drug-eluting stents (DES) has significantly improved outcomes of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, concerns exist regarding the long-term proinflammatory effects of durable polymer coatings used in most DES, potentially leading to long-term adverse events. First-generation polymer-free stent technologies, such as sirolimus- and probucol-eluting stents (PF-SES), have shown an excellent safety and efficacy profile. The aim of this study was to evaluate the safety and efficacy of the new ultrathin Coroflex ISAR NEO PF-SES, in a more-comers PCI population.MethodsThe CAESAR (a more-Comers populAtion trEated with an ultrathin struts polimer-free Sirolimus stent: An Italian post-maRketing study) registry is a multicenter, prospective study conducted in Italy, enrolling more-comers CAD patients undergoing PCI with the Coroflex ISAR NEO stent. Patients with left main (LM) disease, cardiogenic shock (CS), or severely reduced left-ventricular ejection fraction (LVEF) were excluded. The primary endpoint was target-lesion revascularization (TLR) at 1 year.ResultsA total of 425 patients were enrolled at 13 centers (mean age 66.9 ± 11.6 years, Diabetes mellitus 29%, acute coronary syndrome 67%, chronic total occlusion 9%). Of these, 40.9% had multivessel disease (MVD) and in 3.3% cases, the target lesion was in-stent restenosis (ISR). Clinical device success was reached in 422 (99.6%) cases. At 1 year, only two (0.5%) subjects presented ischemia-driven TLR. The 1-year rates of target vessel revascularization and MACE were 0.5% and 5.1%, respectively. Major bleeding was observed in four (1.0%) patients.ConclusionIn this multicenter, prospective registry, the use of a new ultrathin Coroflex ISAR NEO PF-SES in a more-comers PCI population showed good safety and efficacy at 1 year.

Introduction: The transorbital route has been proposed for addressing orbital and paramedian skull base lesions. It can be complemented by further marginotomies, as per “extended-transorbital approach” and combined with others ventro-basal approaches featuring the concept of “multiportal surgery”. Nevertheless, it cannot address some anatomical regions like the clinoid, carotid bifurcation and the Sylvian fissure. Therefore, we propose a combined transorbital and a supraorbital approach, attainable by a single infra-brow incision, and we called it “Uniportal multicorridor” approach. Research question: The aim of our study is to verify its feasibility and deep anatomical targets through a cadaveric study. Materials and methods: Anatomic dissections were performed at the Laboratory of ICLO Teaching and Research Center (Verona, Italy) on four formalin-fixed cadaveric heads injected with colored neoprene latex (8 sides). A stepwise dissection of the supraorbital and transorbital approaches (with an infra-brow skin incision) to the anterior tentorial incisura, clinoid area, lateral wall of the cavernous sinus, middle temporal fossa, posterior fossa, and Sylvian fissure is described. Results: We analyzed the anatomic areas reached by the transorbital corridor dividing them as follow: lateral wall of the cavernous sinus, middle temporal fossa, posterior fossa, and Sylvian fissure; while the anatomic areas addressed by the supraorbital craniotomy were the clinoid area and the anterior tentorial incisura. Conclusions: The described uniportal multi-corridor approach combines a transorbital corridor and a supraorbital craniotomy, providing a unique intra and extradural control over the anterior, middle, and posterior fossa, tentorial incisura and the Sylvian fissure, via an infra-brow skin incision.

Introdução: Os sintomas neuropsiquiátricos devidos a doenças autoimunes cerebrais são cada vez mais reconhecidos e relatados. Objetivos: Nós objetivamos fornecer uma revisão da encefalopatia autoimune, como um modelo de sintomas neuropsiquiátricos diretamente relacionados a um processo autoimune, que seja útil para a prática psiquiátrica. Métodos: Trata-se de uma revisão narrativa, adequada para retratar o estado de arte e atualização do conhecimento sobre as manifestações psiquiátricas da encefalite autoimune. Resultados e Discussão: As apresentações clínicas das encefalites autoimunes tendem a ser uma mistura de sintomas neuropsiquiátricos e somáticos. Declínio cognitivo rápido e inexplicável, psicose, catatonia, e delirium estão entre os sintomas mais comuns. A catatonia ocorre em aproximadamente 1/3 dos casos, com predominância de sintomas hipocinéticos. As anormalidades eletroencefalográficas e liquóricas são usualmente inespecíficas, complicando mais o diagnóstico diferencial. Apenas em 30% dos casos ocorrem anormalidades na ressonância magnética. Conclusão: Os psiquiatras são cruciais na identificação, diagnóstico e cuidado de indivíduos com doenças como a encefalite autoimune e no tratamento de sequelas neurocomportamentais de longo prazo.

Introdução: O conhecimento sobre a neurobiologia dos transtornos psiquiátricos tem aumentado nas últimas décadas, da mesma forma que a psicofarmacologia tem gerado novos insights sobre o mecanismo de ação e aplicação de antipsicóticos modernos. Objetivo: A quetiapina se destaca como uma das principais e mais difundidas moléculas do grupo, razão pela qual merece ser mais bem compreendida nos seus vários aspectos, motivo dessa atualização. Método: Conduzimos uma breve revisão e atualização sobre vários aspectos da quetiapina, desde componentes de sua ação farmacológica, efeitos colaterais recentemente descritos, até novas indicações na psiquiatria moderna. Resultados: A molécula quetiapina é muito versátil, tendo amplo espectro de ações e indicações, não se restringindo à sua classe de antipsicótico e extrapolando para situações clínicas como insônia, depressão unipolar e bipolar, transtornos de ansiedade, transtorno de personalidade limítrofe, delirium, abuso de substâncias comórbidas, e outras. A quetiapina tem efeitos hipnóticos em doses baixas, efeitos sobre o humor em doses intermediárias e efeitos antipsicóticos em doses mais altas. Sua segurança na gravidez e amamentação, bem como na infância e em idosos, amplia ainda mais seu conjunto de indicações. Cuidados devem ser tomados com a síndrome de descontinuação e com seus efeitos metabólicos, mas a sedação e o ganho de peso são seus principais efeitos colaterais. Conclusões: A quetiapina se revela uma molécula altamente útil para várias condições psiquiátricas que representam problemas de saúde pública, dada sua prevalência global. Sua segurança e boa tolerabilidade, além de amplo espectro de indicações, a tornam uma molécula promissora para uso desde a atenção básica até cenários clínicos de transtornos psiquiátricos graves e resistentes aos tratamentos convencionais.

Abstract Background The COVID-19 pandemic put healthcare professionals, including residents (postgraduate trainees of health professions), under intense physical and psychological stress, hence at risk for mental disorders. We evaluated the prevalence of mental disorders among healthcare residents during the pandemic. Methods From July to September 2020, residents in medicine and other healthcare specialties in Brazil were recruited. The participants completed electronic forms with validated questionnaires (DASS-21, PHQ-9, BRCS) to screen for depression, anxiety, and stress, and to evaluate resilience. Data on potential predisposing factors for mental disorders were also collected. Descriptive statistics, chi-squared, students t, correlation and logistic regression models were applied. The study received ethical approval, and all participants provided informed consent. Results We included 1313 participants (51.3% medical; 48.7% nonmedical) from 135 Brazilian hospitals; mean (SD) age: 27.8 (4.4) years; 78.2% females; 59.3% white race. Of all participants, 51.3%, 53.4% and 52.6% presented symptoms consistent with depression, anxiety, and stress, respectively; 61.9% showed low resilience. Nonmedical residents exhibited higher anxiety compared to medical residents (DASS-21 anxiety score, mean difference: 2.26; 95% CI: 1.15–3.37; p

Abstract Background Sodium–glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids’ plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up. Methods In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis. Results At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p

Despite cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) being the current gold standard for non-invasive myocardial characterization and fibrosis quantification, its accessibility is limited, particularly in acute settings and in certain patient populations with contraindications to magnetic resonance imaging. Late iodine enhancement (LIE) in computed tomography (CT) imaging has emerged as a potential alternative, capitalizing on the similarities in the contrast kinetics between gadolinium and iodinated contrast agents. Studies have investigated LIE-CT’s effectiveness in myocardial infarction (MI) detection, revealing promising outcomes alongside some disparities compared to LGE-CMR. LIE-CT also proves beneficial in diagnosing non-ischemic heart diseases such as myocarditis, hypertrophic cardiomyopathy, and sarcoidosis. While LIE-CT demonstrates good accuracy in detecting certain myocardial pathologies, including acute MI and chronic fibrotic changes, it has limitations, such as the inability to detect diffuse myocardial enhancement. Nonetheless, thanks to the availability of optimized protocols with minimal radiation doses and contrast medium administration, integrating LIE-CT into cardiac CT protocols could enhance its clinical utility, particularly in acute settings, providing valuable prognostic and management insights across a spectrum of cardiac ischemic and non-ischemic conditions.

Leprosy is an infectious and contagious disease of slow evolution, triggered by Mycobacterium leprae. Arthritis is its third most common manifestation, after cutaneous and peripheral nerve involvement. Since musculoskeletal symptoms may be the initial presentation of the disease, it is important for health professionals to recognize its rheumatic manifestations for early diagnosis and appropriate treatment, especially in endemic areas. In addition, cases of leprosy have increased globally, notably in patients undergoing treatment with TNF-α blockers and due to the increase in migration and travel of people from developing countries to developed countries. This review proposes to discuss the main scenarios of mimicry of different rheumatic diseases by leprosy, as well as the role of immunosuppressive drugs used in rheumatology practice in the treatment of reactional states and in the risk of developing the infection.

Sleep-disordered breathing (SDB) represents an important cardiovascular risk factor that is still often underestimated and not always optimally treated. Such breathing disorders can induce several harmful effects on the heart, also favoring the development of arrhythmias, ischemic heart disease, and left ventricular remodeling. Obstructive sleep apnea syndrome (OSA) is more frequent in heart failure patients than in the general population, promoting the worsening of left ventricular dysfunction. Both sleep apnea and heart failure have common clinical manifestations but also similar neurohormonal characteristics, both contributing to the development and progression of heart failure and resulting in increased mortality. The pathophysiological mechanisms underlying left ventricular dysfunction associated with SDB will be analyzed, and the potential therapeutic effects of gliflozins on OSA in heart failure patients will be discussed.

Abstract Background No study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Methods We recruited 377 patients with T2DM and AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 T2DM were treated with SGLT2 inhibitors before PCI. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiac death, re-infarction, and heart failure related to ISR. In patients without ISR, minimal lumen area and minimal lumen diameter were assessed by coronary CT-angiography at 1-year follow-up. Results Glycemic control was similar in SGLT2i-treated patients and never SGLT2i-users. The incidence of ISR-related MACE was higher in never SGLT2i-users compared with SGLT2i-treated patients, an effect independent of glycemic status (HR = 0.418, 95% CI = 0.241–0.725, P = 0.002) and observed also in the subgroup of patients with HbA1c < 7% (HR = 0.393, 95% CI = 0.157–0.984, P = 0.027). In patients without the event, the stent patency was greater in SGLT2i-treated patients compared with never SGLT2i-users at 1-year follow-up. Conclusions SGLT2i treatment in T2DM is associated with a reduced incidence of ISR-related events, independently of glycemic control.

Artificial intelligence technologies are considered crucial in supporting a decentralized model of care in which therapeutic interventions are provided from a distance. In the last years, various approaches have been proposed to support remote monitoring and smart assistance in rehabilitation services. Comprehensive state-of-the-art of machine learning methods and applications is presented in this review. Following PRISMA guidelines, a systematic literature search strategy was led in PubMed, Scopus, and IEEE Xplore databases. The search yielded 519 records, resulting in 35 articles included in this study. Supervised and unsupervised machine learning algorithms were identified. Unobtrusive capture motion technologies have been identified as strategic applications to support remote and smart monitoring. The main tasks addressed by algorithms were activity recognition, movement classification, and clinical status prediction. Some authors evidenced drawbacks concerning the low generalizability of the results retrieved. Artificial intelligence-based applications are likely to impact the delivery of decentralized rehabilitation services by providing broad access to sustained and high-quality therapy. Future efforts are needed to validate artificial intelligence technologies in specific clinical populations and evaluate results reliability in remote conditions and home-based settings.

Isotretinoin is a retinoid derivative drug used in acne vulgaris treatment. Sacroiliitis has been reported as an uncommon adverse effect following isotretinoin treatment. We report a 30-year-old male patient who developed sacroiliitis after isotretinoin use. Stopping treatment with isotretinoin resulted in a complete disappearance of inflammatory back pain. A literature search was performed to assess the relevance of this association in everyday clinical practice, and to discuss whether the link between isotretinoin and sacroiliitis is causal or coincidental.

Abstract Big Data, and the derived analysis techniques, such as artificial intelligence and machine learning, have been considered a revolution in the modern practice of medicine. Big Data comes from multiple sources, encompassing electronic health records, clinical studies, imaging data, registries, administrative databases, patient-reported outcomes and OMICS profiles. The main objective of such analyses is to unveil hidden associations and patterns. In cardiac surgery, the main targets for the use of Big Data are the construction of predictive models to recognize patterns or associations better representing the individual risk or prognosis compared to classical surgical risk scores. The results of these studies contributed to kindle the interest for personalized medicine and contributed to recognize the limitations of randomized controlled trials in representing the real world. However, the main sources of evidence for guidelines and recommendations remain RCTs and meta-analysis. The extent of the revolution of Big Data and new analytical models in cardiac surgery is yet to be determined.

Abstract Predictive factors for response to regorafenib in recurrent glioblastoma, IDH-wildtype, are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform. We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH-wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a clinically available platform. Moreover, MGMT methylation and EGFRvIII expression analyses were performed. Six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months, in line with literature data. NGS analysis revealed a mutation in the EGFR pathway in 18% of cases and a mutation in the mitogen-activated protein-kinase (MAPK) pathway in 18% of cases. In the remaining cases, no mutations were detected. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p = 0.0061; for OS, 7 vs 9 months, p = 0.1076). Multivariate analysis confirmed that MAPK pathway mutations independently predicted a shorter PFS after regorafenib treatment (p = 0.0188). The negative prognostic role of MAPK pathway alteration was reinforced when we combined EGFR-mutated with EGFRvIII-positive cases. Recurrent glioblastoma tumors with an alteration in MAPK pathway could belong to the mesenchymal subtype and respond poorly to regorafenib treatment, while EGFR-altered cases have a better response to regorafenib. We thus provide a molecular selection criterion easy to implement in the clinical practice.

IntroductionMiller Fisher syndrome (MFS) is considered a rare variant of Guillain-Barré syndrome (GBS), a group of acute-onset immune-mediated neuropathies characterized by the classic triad of ataxia, areflexia, and ophthalmoparesis. The present review aimed to provide a detailed and updated profile of all aspects of the syndrome through a collection of published articles on the subject, ranging from the initial description to recent developments related to COVID-19.MethodsWe searched PubMed, Scopus, EMBASE, and Web of Science databases and gray literature, including references from the identified studies, review studies, and conference abstracts on this topic. We used all MeSH terms pertaining to “Miller Fisher syndrome,” “Miller Fisher,” “Fisher syndrome,” and “anti-GQ1b antibody.”ResultsAn extensive bibliography was researched and summarized in the review from an initial profile of MFS since its description to the recent accounts of diagnosis in COVID-19 patients. MFS is an immune-mediated disease with onset most frequently following infection. Anti-ganglioside GQ1b antibodies, detected in ~85% of patients, play a role in the pathogenesis of the syndrome. There are usually no abnormalities in MFS through routine neuroimaging. In rare cases, neuroimaging shows nerve root enhancement and signs of the involvement of the central nervous system. The most consistent electrophysiological findings in MFS are reduced sensory nerve action potentials and absent H reflexes. Although MFS is generally self-limited and has excellent prognosis, rare recurrent forms have been documented.ConclusionThis article gives an updated narrative review of MFS with special emphasis on clinical characteristics, neurophysiology, treatment, and prognosis of MFS patients.

Background: In patients with recent ACS, the latest ESC/EAS guidelines for management of dyslipidaemia recommend intensification of LDL-C-lowering therapy. Objective: Report a real-world picture of lipid-lowering therapy prescribed and cholesterol targets achieved in post-ACS patients before and after a specific educational program. Methods: Retrospective data collection prior to the educational course and prospective data collection after the course of consecutive very high-risk patients with ACS admitted in 2020 in 13 Italian cardiology departments, and with a non-target LDL-C level at discharge. Results: Data from 336 patients were included, 229 in the retrospective phase and 107 in the post-course prospective phase. At discharge, statins were prescribed in 98.1% of patients, alone in 62.3% of patients (65% of which at high doses) and in combination with ezetimibe in 35.8% of cases (52% at high doses). A significant reduction was obtained in total and LDL cholesterol (LDL-C) from discharge to the first control visit. Thirty-five percent of patients achieved a target LDL-C