Actionable mutational profiling in solid tumors using hybrid-capture-based next-generation sequencing in a real-world setting in Spain.

OBJECTIVE: This study aimed to describe the performance of a next-generation sequencing (NGS) panel for the detection of precise genomic alterations in cancer in Spanish clinical practice. The impact of tumor characteristics was evaluated on informative NGS and actionable mutation rates. MATERIALS AND METHODS: A cross-sectional study was conducted at the Fundación Jiménez Díaz University Hospital (May 2021-March 2022) where molecular diagnostic of 537 Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples of diverse solid tumors (lung, colorectal, melanoma, gastrointestinal stromal, among others) was performed using AVENIO Tumor Tissue Targeted Kit. A descriptive analysis of the features of all samples was carried out. Multivariable logistic analysis was conducted to assess the impact of sample characteristics on NGS performance defined by informative results rate (for all tumors and for lung tumors), and on actionable mutations rate (for lung tumors only). RESULTS: AVENIO performance rate was 75.2% in all tumor samples and 75.3% in lung cancer samples, and the multivariable analysis showed that surgical specimens are most likely to provide informative results than diagnostic biopsies. Regarding the mutational findings, 727 pathogenic, likely pathogenic, or variant of unknown significance mutations were found in all tumor samples. Single nucleotide variant was the most common genomic alteration, both for all tumor samples (85.3% and 81.9% for all solid tumors and lung samples, respectively). In lung tumors, multivariable analysis showed that it is more likely to find actionable mutations from non-smokers and patients with adenocarcinoma, large cell, or undifferentiated histologies. CONCLUSION: This is the largest cohort-level study in Spain to profile the analyses of biopsy samples of different tumors using NGS in routine clinical practice. Our findings showed that the use of NGS routinely provides good rates of informative results and can improve tumor characterization and identify a greater number of actionable mutations.

D-index as a Risk Factor for Invasive Fungal Infections in Patients With Acute Lymphoblastic Leukemia From a Reference Hematology Center in Bogota.

Introduction Patients with hematologic malignancies are susceptible hosts for the development of invasive fungal infection (IFI), one of the main life-threatening infectious complications faced by these patients. Currently, we have antifungal prophylaxis strategies and antifungal treatment schemes and we recognize that the main risk factor involved is profound and prolonged neutropenia. D-index and cumulative D-index are quantitative parameters, which determine the magnitude of neutropenia, as a function of duration and depth and their value correlates with the occurrence of IFI. Material and methods A case-control study in patients older than 18 years with acute lymphoblastic leukemia (ALL) was admitted between 2009 and 2019 at the National Cancer Institute for induction, consolidation and salvage chemotherapy. Results A total of 167 patients were included, who received 288 cycles of chemotherapy, the latter were considered the unit of analysis. A generalized estimating equations (GEE) model was designed to analyze correlated data; three quantitative and continuous variables of interest were included in this model: age (years), D-index and deep neutropenia (days). For the population D-index, an odds ratio (OR) = 1.000227 (95% CI 1.0002-1.0004); p < 0.001 was obtained. Conclusion D-index is associated with the development of IFI in patients with ALL, with an exponential increase in OR as the absolute value of the D-index increases.

A cornichon protein controls polar localization of the PINA auxin transporter in Physcomitrium patens.

Newly synthesized membrane proteins pass through the secretory pathway, starting at the endoplasmic reticulum and packaged into COPII vesicles, to continue to the Golgi apparatus before reaching their membrane of residence. It is known that cargo receptor proteins form part of the COPII complex and play a role in the recruitment of cargo proteins for their subsequent transport through the secretory pathway. The role of cornichon proteins is conserved from yeast to vertebrates, but it is poorly characterized in plants. Here, we studied the role of the two cornichon homologs in the secretory pathway of the moss Physcomitrium patens. Mutant analyses revealed that cornichon genes regulate different growth processes during the moss life cycle by controlling auxin transport, with CNIH2 functioning as a specific cargo receptor for the auxin efflux carrier PINA, with the C terminus of the receptor regulating the interaction, trafficking and membrane localization of PINA.

The C-terminus of the cargo receptor Erv14 affects COPII vesicle formation and cargo delivery.

The endoplasmic reticulum (ER) is the start site of the secretory pathway, where newly synthesized secreted and membrane proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Little is known about how post-translational modification events regulate packaging of cargo into COPII vesicles. The Saccharomyces cerevisiae protein Erv14, also known as cornichon, belongs to a conserved family of cargo receptors required for the selection and ER export of transmembrane proteins. In this work, we show the importance of a phosphorylation consensus site (S134) at the C-terminus of Erv14. Mimicking phosphorylation of S134 (S134D) prevents the incorporation of Erv14 into COPII vesicles, delays cell growth, exacerbates growth of sec mutants, modifies ER structure and affects localization of several plasma membrane transporters. In contrast, the dephosphorylated mimic (S134A) had less deleterious effects, but still modifies ER structure and slows cell growth. Our results suggest that a possible cycle of phosphorylation and dephosphorylation is important for the correct functioning of Erv14.

Tumor-Infiltrating Lymphocytes and Immune Response in HER2-Positive Breast Cancer.

Human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer accounts for 15 to 25% of breast cancer cases. Although therapies based on the use of monoclonal anti-HER2 antibodies present clinical benefit for a subtype of patients with HER2-positive breast cancer, more than 50% of them are unresponsive to targeted therapies or they eventually relapse. In recent years, reactivation of the adaptive immune system in patients with solid tumors has emerged as a therapeutic option with great potential for clinical benefit. Since the approval of the first treatment directed against HER2 as a therapeutic target, the range of clinical options has expanded greatly, and, in this sense, cellular immunotherapy with T cells relies on the cytotoxicity generated by these cells, which ultimately leads to antitumor activity. Lymphocytic infiltration of tumors encompasses a heterogeneous population of immune cells within the tumor microenvironment that exhibits distinct patterns of immune activation and exhaustion. The prevalence and prognostic value of tumor-infiltrating lymphocyte (TIL) counts are associated with a favorable prognosis in HER2-positive breast cancers. This review discusses emerging findings that contribute to a better understanding of the role of immune infiltrates in HER2-positive breast cancer. In addition, it summarizes the most recent results in HER2-positive breast cancer immunotherapy and anticipates which therapeutic strategies could be applied in the immediate future.

Milk-Gelling Properties of Proteases Extracted from the Fruits of Solanum Elaeagnifolium Cavanilles.

There is little information on the milk coagulation process by plant proteases combined with chymosins. This work is aimed at studying the capability of protease enclosed in the ripe fruits of Solanum elaeagnifolium (commonly named trompillo) to form milk gels by itself and in combination with chymosin. For this purpose, proteases were partially purified from trompillo fruits. These proteases had a molecular weight of ~60 kDa, and results suggest cucumisin-like serine proteases, though further studies are needed to confirm this observation. Unlike chymosins, trompillo proteases had high proteolytic activity (PA = 50.23 UTyr mg protein-1) and low milk-clotting activity (MCA = 3658.86 SU mL-1). Consequently, the ratio of MCA/PA was lower in trompillo proteases (6.83) than in chymosins (187 to 223). Our result also showed that milk gels formed with trompillo proteases were softer (7.03 mPa s) and had a higher release of whey (31.08%) than the milk gels clotted with chymosin (~10 mPa s and ~4% of syneresis). However, the combination of trompillo proteases with chymosin sped up the gelling process (21 min), improved the firmness of milk gels (12 mPa s), and decreased the whey release from milk curds (3.41%). Therefore, trompillo proteases could be combined with chymosin to improve the cheese yield and change certain cheese features.

Falla autonómica asociada a hipoglucemia / Hypoglycemia associated autonomic failure

La hipoglucemia inadvertida (HI) es una complicación del tratamiento de la diabetes mellitus tipo 1 (DM1) y DM2 tratada con insulina o sulfonilureas, que se caracteriza por una capacidad reducida para percibir el inicio de los episodios de hipoglucemia. En general, coexiste con una insuficiente respuesta hormonal contrarreguladora a la hipoglucemia denominada falla autonómica asociada a la hipoglucemia (FAAH). El desarrollo de HI y de falla contrarreguladora a la hipoglucemia aumentan significativamente el riesgo de hipoglucemias severas. Se han desarrollado escalas de puntuación para identificar, en la consulta clínica, a este grupo de personas con elevado riesgo de hipoglucemias severas. La piedra angular del tratamiento consiste en evitar las hipoglucemias mediante una intervención multifactorial de cuidados clínicos y educación estructurada.

Hypoglycemia unawereness is a complication of type 1 diabetes treatment and of type 2 diabetes treatment treated with insulin or sulfonylureas, characterized by a reduced ability to perceive the onset of episodes of hypoglycemia. In general, it coexists with an insufficient counterregulatory hormonal response to hypoglycemia called: hypoglycemia associated autonomic failure (HAAF). The development of hypoglycemia unawereness and counterregulatory failure to hypoglycemia significantly increase the risk of severe hypoglycemia. Scoring scales have been developed to identify this group of people at high risk of severe hypoglycemia in the clinic. The cornerstone of treatment is to avoid hypoglycemia through a multifactorial intervention of clinical care and structured education.

Alternaria chartarum sclerokeratouveitis: A new fungus cause.

We report a case of Alternaria chartarum sclerokeratouveitis with an unfavorable response to treatment. To the best of our knowledge, there are no previous reports of this fungus invading the sclera. A 68-year-old diabetic farmer male patient presented with a 3-week history of pain and redness and a decrease in visual acuity occurring 5 days before admittance in the right eye. Examination revealed severe mixed hyperemia and a scleral calcified plaque with a surrounding area of ischemia and lysis. The cornea showed diffuse infiltrates, stromal edema, and hypopyon. Initial scrapings were negative, and empiric antibiotics were started. After a fungus was reported, topical and systemic antifungals were initiated, but there was no clinical response. The eye was enucleated. A slow-growing fungus A. chartarum, resistant to voriconazole, was isolated. Fungal etiology must be kept in mind when dealing with infectious scleritis. Despite treatment, the outcome of this case was unfavorable due to the slow-growing nature of the fungus and this strain's resistance to voriconazole.

Effects of a Rehabilitation Programme with a Nasal Inspiratory Restriction Device on Exercise Capacity and Quality of Life in COPD.

OBJECTIVE: The objective was to assess the effects of a nasal restriction device for inspiratory muscle training, called Feelbreathe®, added to a rehabilitation program (RP) on exercise capacity, quality of life, dyspnea and inspiratory muscle strength in patients with stable COPD. METHODS: Patients were randomized into three groups, one performed a supervised RP using the Feelbreathe® device (FB group), the second group developed the same RP with oronasal breathing without FB (ONB group) and the third was the control group (CG). We evaluated inspiratory muscle strength (PImax), dyspnea (mMRC), quality of life (CAT) and exercise capacity (6MWT) before and after 8-week of RP. RESULTS: A total of 16 patients completed the study, seven in FB group, five in ONB group and four in the CG. After the RP, the FB group showed a significant increase in PImax (93.3 ± 19.1 vs. 123.0 ± 15.8 mmHg) and in the 6MWT distance (462.9 ± 71.8m vs. 529.1 ± 50.1 m) and a decrease in the CAT score (9.7 ± 6.5 vs. 5.9 ± 6.0) and in the mMRC dyspnea score. FB provides greater improvement in PImax, dyspnea, quality of life and 6MWT than ONB. CONCLUSIONS: The Feelbreathe® device provides greater improvements in quality of life, dyspnea, exercise capacity and inspiratory muscle strength compared to patients that did not use it.

Trastornos neurocognitivos en pacientes VIH positivos: datos preliminares de una cohorte prospectiva uruguaya / Neurocognitive disorders in positive HIV patients: preliminary data of a Uruguayan prospective cohort

Introducción: la incidencia de formas leves y moderadas de trastornos neurocognitivos (TNC) en pacientes con VIH (virus de inmunodeficiencia humana) permanece en ascenso a pesar del uso de terapia antirretroviral (TARV). En la región existen escasos trabajos que estudiaron los TNC en VIH. Objetivos: describir características de pacientes con TNC, identificar posibles etiologías y si se realiza su búsqueda. Material y método: estudio transversal de recolección prospectiva. Se reclutaron en forma consecutiva pacientes de 18 a 60 años VIH positivos sin patología estructural del sistema nervioso central. Se aplicaron exámenes de laboratorio, preguntas para tamizaje de TNC, escala instrumental de actividades de la vida diaria (EIAVD) e internacional de demencia por VIH (EIDV), Adenbrooke's Cognitive Examination Revisado (ACE-R). ACE-R fue elegida como prueba de referencia de desempeño neurocognitivo. Se utilizó inventario de Beck para pesquisa de trastorno depresivo. Análisis estadístico con sistema SPSS. Resultados y discusión: se reclutaron 20 pacientes, se diagnosticó TNC en 9/20 (45%). Los médicos tratantes plantearon TNC en 2/9 pacientes. El análisis multivariado encontró asociación entre desempleo (p=0,012) y menor escolarización (p=0,035) en pacientes con TNC. Etiología de TNC en 9/9 fue multifactorial. Refirieron TNC en el tamizaje 8/9 pacientes. EIDV fue adecuada para detección de TNC severo, pero no para leve. EIAVD tampoco logró detectar algunos casos de TNC. Conclusiones: casi la mitad de pacientes presentaron TNC de causa multifactorial con asociación a desempleo y menor escolarización. Los médicos tratantes no plantearon este diagnóstico, lo que marca la importancia de la evaluación neuropsicológica sistemática en pacientes VIH.

Introduction: the incidence of mild and moderate neurocognitive disorders (NCDs) in HIV patients continues to increase in spite of antiretroviral therapy (ART). Only a few studies in the region focused on HIV associated NCDs. Objective: to describe the characteristics of NCDs patients, identify posible etiologies and decide whether to start the search. Method: transversal study with a prospective collection of data. HIV positive patients between 18 and 60 years old with no structural defects of the central nervous system (CNS) were consecutively recruited. Laboratory tests were applied as well as screening for CNS, the Instrumental activities of daily living (IADLs) scale, the International HIV Dementia Scale (IHDS), and the Adenbrooke's Cognitive Examination revised exam (ACE-R). The latter was chosen as the reference test for neurocognitive performance. The Beck Depression inventory (BDI) was used to identify drepression. Statistical analysis was conducted with the SPSS system. Results and discussion: 20 patients were recruited, NCD was diagnosed in 9 out of 20 patients (45%). Treating physicians spoke about NCD in 2 of the 9 patients. Multivariate analysis revealed an association between unemployment (p=0.012) and a lower schooling rate (p=0.035) in patients with NCDs. Etiology of NCD was multifactorial in all 9 patients. 8 out of 9 patients were referred as NCDs in the screening. IHDS was appropriate to identify severe NCDs, although it failed in mild cases. Also, IADLs failed to identify a few cases of NCDs. Conclusions: almost half of the patients presented multifactorial NCDs, associated to unemployment and a lower rate of schooling. Treating physicians did not consider this diagnosis, what reflects the importance of a systematic neuropsychological assessment in HIV patients.

Introdução: a incidência de formas leves e moderadas de transtornos neurocognitivos (TNC) em pacientes com VIH (vírus de imunodeficiência humana) continua crescendo apesar do uso da terapia antirretroviral (TARV). Poucos trabalhos estudaram TNC em pacientes VIH positivos na regiao. Objetivos: descrever as características dos pacientes com TNC, identificar possíveis etiologias e se são pesquisados no paciente. Método: estudo transversal com coleta de dados prospectiva. Foram incluídos de forma consecutiva pacientes com idades entre 18 e 60 anos VIH positivos sem patologia estrutural do sistema nervoso central (SNC). Foram realizados exames de laboratório, um questionário para triagem dos TNC, e foram aplicadas as escalas Instrumental de Atividades da Vida Diária (EIAVD), Internacional de Demência por VIH (EIDV) e Adenbrooke's Cognitive Examination Revisado (ACE-R). Esta última foi escolhida como prova de referencia de desempenho neurocognitivo. O inventário de Beck foi utilizado para pesquisa de transtorno depressivo. A análise estatística foi realizada com o pacote SPSS. Resultados e discussão: foram incluídos 20 pacientes sendo que os TNC foram diagnosticados em 9/20 (45%). Os médicos que atenderam esses pacientes diagnosticaram TNC em 2/9 pacientes. A análise multivariada mostrou uma associação entre desemprego (p=0,012) e menor escolarização (p=0,035) em pacientes com TNC. A etiologia dos TNC em 9/9 foi multifatorial. A triagem mostrou TNC em 8/9 pacientes. O teste EIDV foi adequado para a detecção dos TNC severos porém não para leves, e também não pode detectar alguns casos de TNC. Conclusões: quase a metade dos pacientes apresentou TNC de causa multifatorial associados a desemprego e menor escolarização. Os médicos que atenderam os pacientes não diagnosticaram esses transtornos o que mostra a importância da avaliação neuropsicológica sistemática em pacientes VIH.

Fumadora con múltiples recaídas / Smokers with multiple relapses

No disponible

Genomic Profiling of HER2-Positive Gastric Cancer: PI3K/Akt/mTOR Pathway as Predictor of Outcomes in HER2-Positive Advanced Gastric Cancer Treated with Trastuzumab.

BACKGROUND: HER2-positive gastric cancer (GC) affects 7%-34% of patients with GC. Trastuzumab-based first-line treatment has become the standard of care for HER2-positive advanced gastric cancer (AGC). However, there are no clinically validated biomarkers for resistance to HER2-targeted therapies. Upregulation of PI3K pathway and tyrosine kinase receptor (TKR) alterations have been noted as molecular mechanisms of resistance in breast cancer. Our study aimed to perform a molecular characterization of HER2-positive AGC and investigate the role of PI3K/Akt/mTOR signaling pathway activation and TKR gene copy number (GCN) gains as predictive biomarkers in HER2-positive AGC treated with trastuzumab. PATIENTS AND METHODS: Forty-two HER2-positive GC samples from patients treated with trastuzumab-based first-line chemotherapy were selected. DNA samples were sequenced. PTEN and MET immunohistochemistry were also performed. RESULTS: Concurrent genetic alterations were detected in 97.1% of HER2-positive AGC. We found activation of PI3K/Akt/mTOR pathway in 52.4% of patients and TKR GCN gains in 38.1%. TKR GCN gains did not correlate with overall survival (OS) or progression-free survival (PFS). Multivariate Cox models showed that PI3K/Akt/mTOR activation negatively affects the effectiveness of trastuzumab-based chemotherapy in terms of OS and PFS. CONCLUSION: Our results provide for the first time a detailed molecular profile of concurrent genetic alterations in HER2-positive AGC. PI3K pathway activation could be used as a predictive marker of worse outcome in this patient population. In addition, gains in copy number of other TKR genes in this subgroup may also influence the survival benefit obtained with trastuzumab. IMPLICATIONS FOR PRACTICE: This article reports, for the first time, a detailed molecular profile of genomic alterations in patients with HER2-positive advanced gastric cancer (AGC). PI3K/Akt/mTOR signaling pathway activation seems to have a differentially negative effect on overall survival and progression-free survival in AGC treated with trastuzumab-based chemotherapy. Combining different targeted agents could be a successful therapeutic strategy to improve the prognosis of HER2-positive AGC.

Evaluation of Expression of Human Epidermal Growth Factor Receptor 2 (HER2) in Gastric and Gastroesophageal Junction Adenocarcinoma Using IHC and Dual-ISH.

BACKGROUND/AIM: Trastuzumab® is used for human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma. Our aim was to compare HER2 expression by immunohistochemistry (IHC) and dual in situ hybridization (DISH) in early-stage vs. late-stage gastric and GEJ tumors. MATERIALS AND METHODS: Fifty early-stage and 50 late-stage gastric tumors and a similar number of early-stage and late-stage GEJ tumors were studied. HER2 was analyzed by IHC and dual-ISH using tissue microarray. RESULTS: Of 200 selected cases, 168 had satisfactory results. Among the 110 cases with both tests successfully performed, there were only five cases with discrepancy between assays (4.5%). Seven equivocal (2+) cases by IHC were all found to be amplified by dual-ISH. When compared with IHC, dual-ISH identified 12 additional HER2-positive cases (10.9%). CONCLUSION: The 12.5% overall overexpression/amplification in gastric and GEJ adenocarcinomas is in concordance with previous reports. No correlation was found between tumor stage and HER2 overexpression/amplification. Determination of HER2 in limited tissue samples benefits from combinational IHC and ISH testing.

Aligning digital CD8+ scoring and targeted next-generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early-stage squamous cell lung carcinoma.

AIMS: To study programmed death ligand 1 (PD-L1) expression, tumour-infiltrating T lymphocytes (TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas (SCCs). METHODS AND RESULTS: The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next-generation sequencing (NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD-L1 IHC expression in tumour cells (TCs). Furthermore, high SP142 PD-L1 expression in immune cells (ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD-L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD-L1-positive TCs with the three antibodies were found in samples with cyclin-dependent kinase 6 (CDK6) amplification, with high amplification of proto-oncogene C-Myc (CMYC) or with cyclin D1-PI3 kinase subunit alpha (CCND1-PIK3CA) co-amplification. High SP142 PD-L1 IHC expression in ICs showed a non-significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 (FGFR1) amplification were negative for all PD-L1 clones. CONCLUSIONS: Our preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD-L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors.

Neuropatía autonómica diabética: manifestaciones clínicas poco conocidas / Diabetic autonomic neuropathy: little known clinical manifestations

La neuropatía crónica es la complicación más prevalente de la diabetes. De las distintas formas de neuropatía diabética, la polineuropatía distal y simétrica y la neuropatía autonómica, particularmente la neuropatía autonómica cardíaca, son las más estudiadas y en ocasiones son asintomáticas. Los pacientes con prediabetes también pueden desarrollar neuropatías similares a la neuropatía diabética. La prevención es un componente clave en la atención de estas complicaciones. La neuropatía autonómica diabética afecta varios órganos y sistemas de la economía. Nuestro objetivo es describir aquellas manifestaciones clínicas poco conocidas, y en consecuencia poco tenidas en cuenta, que afectan el sistema cardiovascular, el gastrointestinal y el compromiso vesical

Chronic neuropathy is the most prevalent of the diabetic complications. Distal and symmetric sensitive polyneuropathy, and autonomic compromise, particularly cardiac autonomic neuropathy,are the most studied; occasionally they are asymptomatic. Like diabetic patients, prediabetics can also develop neuropathy. Prevention is a key component in these complications. Autonomic neuropathy affects several body´s organs and systems. Our goal is to describe those less known clinical manifestations, and because of this, less considered complications that affect cardiovascular, gastrointestinal system and bladder functioning

Plant and yeast cornichon possess a conserved acidic motif required for correct targeting of plasma membrane cargos.

The export of membrane proteins along the secretory pathway is initiated at the endoplasmic reticulum after proteins are folded and packaged inside this organelle by their recruiting into the coat complex COPII vesicles. It is proposed that cargo receptors are required for the correct transport of proteins to its target membrane, however, little is known about ER export signals for cargo receptors. Erv14/Cornichon belong to a well conserved protein family in Eukaryotes, and have been proposed to function as cargo receptors for many transmembrane proteins. Amino acid sequence alignment showed the presence of a conserved acidic motif in the C-terminal in homologues from plants and yeast. Here, we demonstrate that mutation of the C-terminal acidic motif from ScErv14 or OsCNIH1, did not alter the localization of these cargo receptors, however it modified the proper targeting of the plasma membrane transporters Nha1p, Pdr12p and Qdr2p. Our results suggest that mistargeting of these plasma membrane proteins is a consequence of a weaker interaction between the cargo receptor and cargo proteins caused by the mutation of the C-terminal acidic motif.

Primary Cardiac Tumors in Infancy: A Case Report and Literature Review.

Sudden death in infants due to primary cardiac tumors is extremely rare. Herein we describe a case of an 8-month-old male infant, without any previous medical history, who died in a hospital in the city of Medellín-Antioquia, Colombia. The family stated that approximately 15 minutes after he received a bottle, the baby became cyanotic and subsequently lost consciousness. He was taken to the hospital immediately; however, he arrived lifeless. As this was a sudden death case, the child was referred to the Institute of Legal Medicine and Forensic Sciences in the city of Medellín to clarify the cause, manner, and mechanism of death. The forensic autopsy revealed a eutrophic infant with central and peripheral cyanosis, without signs of trauma, and the internal examination found a single cardiac tumor in the anterior wall of the left ventricle. The mass was white and whorled; histological evaluation diagnosed a fibroma. The manner of death was natural due to a cardiogenic shock caused by a primary tumor.

Actualización del tratamiento de la polineuropatía diabética periférica dolorosa 2015. Comité de Neuropatía Diabética. Sociedad Argentina de Diabetes / Treatment update of painful peripheral diabetic neuropathy. Diabetic Neuropathy Committee 2015. Argentine Society of Diabetes

La diabetes es una enfermedad crónica y progresiva que se asocia a complicaciones potencialmente discapacitantes, entre ellas, la neuropatía diabética es probablemente la afectación sintomática más frecuente con importante impacto social y económico. El tratamiento de la neuropatía somática dolorosa y del sistema nervioso autónomo ha sido un desafío durante años. Nuevas terapéuticas se encuentran disponibles, las cuales mejoran el dolor y brindan esperanza de lograr alivio a personas que padecen esta complicación