La ciencia desde la asistencia médica / Science from medical care

La formación académica sustenta las bases para el desempeño investigativo del egresado. No obstante, en el camino entre la proyección del pregrado y el rediseño del posgrado de los planes de estudio, persisten dificultades en el proceso investigativo. Se propone considerar la utilidad del vínculo asistencia-docencia-investigación, sustentado en la presencia de esta última en cada momento y espacio de la vida del profesional, en función de transformar su entorno y con ello, su desarrollo intelectual, según criterios y experiencia de los autores. Es reconocida, la importante y decisiva integración docente-asistencial-investigativa, elemento característico de las formas organizativas de la educación médica cubana. No es posible llevar a cabo una investigación de calidad, sin una práctica médica de excelencia La investigación clínica mejora la calidad de los médicos y debe fomentarse como actividad esencial. Se deben identificar las necesidades de aprendizaje, y entre ellas estar contenidos los problemas investigativos, en torno a los cuales se erigen las investigaciones científicas. Para un profesional, no es posible que se separen las 3 vertientes interrelacionadas: la asistencia, la docencia y la investigación. Por lo tanto, de su trabajo diario, justamente emerge la ciencia. La formación de recursos humanos en Cuba, en el contexto actual, es transformadora, revolucionaria y a favor del bienestar de la sociedad. El vínculo asistencia-docencia-investigación debe concebirse como un sistema articulado e integral presente en cada momento de actuación del sistema de salud que debe ser aprovechado por los profesionales, los directivos, en función de transformar su entorno, calidad y pertinencia(AU)

Academic training supports the bases for the graduate's research performance. However, on the path between the undergraduate projection and the postgraduate redesign of the study plans, difficulties persist in the research process. It is proposed to consider the usefulness of the assistance-teaching-research link, supported by the presence of the latter in every moment and space of the professional's life, in terms of transforming their environment and with it, their intellectual development, according to criteria and experience of the authors. The important and decisive integration of teaching-care-research is recognized, a characteristic element of the organizational forms of Cuban medical education. It is not possible to carry out quality research without excellent medical practice. Clinical research improves the quality of doctors and should be promoted as an essential activity. Learning needs must be identified, and among them the research problems, around which scientific research is built, must be contained. For a professional, it is not possible to separate the 3 interrelated aspects: assistance, teaching and research. Therefore, science emerges from daily work. The training of human resources in Cuba, in the current context, is transformative, revolutionary and in favor of the well-being of society. The care-teaching-research link must be conceived as an articulated and integral system present at every moment of action of the health system that must be taken advantage of by professionals, managers, in order to transform its environment, quality and relevance(AU)

Respuesta al tratamiento inmunosupresor de pacientes con hepatitis autoinmune

Introducción: La respuesta al tratamiento inmunosupresor en la hepatitis autoinmune influye en el curso clínico de la enfermedad y se asocia a mayor sobrevida. Objetivo: Describir la respuesta al tratamiento inmunosupresor en pacientes con hepatitis autoinmune. Método: Se realizó un estudio descriptivo, longitudinal, ambispectivo, en 32 enfermos con hepatitis autoinmune, los cuales recibieron tratamiento inmunosupresor con evaluación de la respuesta a los 6 meses. Las variables incluidas fueron: tipo de hepatitis autoinmune, forma de presentación, forma de debut y respuesta al tratamiento. Se utilizaron medidas descriptivas de resumen: media y desviación estándar para variables cuantitativas y porcentaje para las variables cualitativas. Para estimar la función de supervivencia se utilizó la curva de Kaplan-Meier y Log-rank para la comparación de medias. Resultados: El 71,9 % de los enfermos estaban con cirrosis en el momento del diagnóstico. Los 13 pacientes con remisión bioquímica permanecieron sin progresión en la evaluación actual. La supervivencia en los pacientes respondedores fue del 100 % y en los no respondedores de 47,5 % a los 10 años de seguimiento. Conclusiones: La respuesta al tratamiento inmunosupresor tiene un impacto positivo en la no progresión de la hepatitis autoinmune y se asoció a mayor supervivencia.

Introduction: The response to immunosuppressive treatment in autoimmune hepatitis influences the clinical course of the disease and is associated with a longer survival. Objective: Describe the response to immunosuppressive treatment in patients with autoimmune hepatitis. Method: A descriptive, longitudinal, ambispective study was carried out in 32 patients with autoimmune hepatitis, who received immunosuppressive treatment with response evaluation at 6 months. The variables included were: type of autoimmune hepatitis, form of presentation, form of onset, and response to treatment. Descriptive summary measures were used: mean and standard deviation for quantitative variables and percentage for qualitative variables. To estimate the survival function, the Kaplan-Meier curve and Log-rank were used to compare means. Results: 71.9 % of the patients were already cirrhotic at the time of diagnosis. The 13 patients with biochemical remission, remained without progression in the current evaluation. Survival in responding patients was 100 %, while in non-responders it was 47.5% at 10-year follow-up. Conclusions: The response to immunosuppressive treatment has a positive impact on the non-progression of autoimmune hepatitis and was associated with greater survival.

Folate Receptor Alpha-A Novel Approach to Cancer Therapy.

Folate receptor α (FR) was discovered many decades ago, along with drugs that target intracellular folate metabolism, such as pemetrexed and methotrexate. Folate is taken up by the cell via this receptor, which also targeted by many cancer agents due to the over-expression of the receptor by cancer cells. FR is a membrane-bound glycosyl-phosphatidylinositol (GPI) anchor glycoprotein encoded by the folate receptor 1 (FOLR1) gene. FR plays a significant role in DNA synthesis, cell proliferation, DNA repair, and intracellular signaling, all of which are essential for tumorigenesis. FR is more prevalent in cancer cells compared to normal tissues, which makes it an excellent target for oncologic therapeutics. FRα is found in many cancer types, including ovarian cancer, non-small-cell lung cancer (NSCLC), and colon cancer. FR is widely used in antibody drug conjugates, small-molecule-drug conjugates, and chimeric antigen-receptor T cells. Current oncolytic therapeutics include mirvetuximab soravtansine, and ongoing clinical trials are underway to investigate chimeric antigen receptor T cells (CAR-T cells) and vaccines. Additionally, FRα has been used in a myriad of other applications, including as a tool in the identification of tumor types, and as a prognostic marker, as a surrogate of chemotherapy resistance. As such, FRα identification has become an essential part of precision medicine.

The Role of CD4/6 Inhibitors in Breast Cancer Treatment.

Over the last decade, treatment paradigms for breast cancer have undergone a renaissance, particularly in hormone-receptor-positive/HER2-negative breast cancer. These revolutionary therapies are based on the selective targeting of aberrancies within the cell cycle. This shift towards targeted therapies has also changed the landscape of disease monitoring. In this article, we will review the fundamentals of cell cycle progression in the context of the new cyclin-dependent kinase inhibitors. In addition to discussing the currently approved cyclin-dependent kinase inhibitors for breast cancer, we will explore the ongoing development and search for predictive biomarkers and modalities to monitor treatment.

Íleon terminal: aspecto a tener en cuenta en la COVID-19 ¿causa o efecto?

Introducción: la comprensión histomorfológica y biomolecular del íleon terminal; sitio clave en el control de la absorción nutricional, del metabolismo, sistema inmunitario, microbiota intestinal, y función de órganos extradigestivos; justifica su participación en los procesos inflamatorios intestinales, como pudiera ser en la infección por el SARS-CoV2. Objetivos: describir las evidencias biomoleculares de los componentes tisulares del íleon que justifican su función en el eje hepático-intestinal, y citar hallazgos histomorfológicos del íleon en fallecidos de la COVID-19. Adquisición de información: se realizó una revisión sistemática, crítica de los estudios biomoleculares sobre los enterocitos, la barrera epitelial intestinal, microbiota y permeabilidad intestinal del íleon que fundamentan su función de barrera epitelial, reportados en sitios Web (PubMed, Scielos, Lilacs, y Elservier), entre 2000 a 2021, y se citan hallazgos preliminares de cortes histomorfológicos del íleon en fallecidos de la COVID-19. Desarrollo se describen las evidencias biomoleculares del íleon normal, y la repercusión de su pérdida, disbiosis e hiperpermeabilidad en los procesos inflamatorios intestinales; también se citan hallazgos histomorfológicos preliminares de ileítis en fallecidos de la COVID-19, que pudiera fundamentar la importancia de la intuición biomolecular del íleon en el equilibrio salud-enfermedad, cuya pérdida justificaría el progreso clínico de la COVID-19. Conclusiones: la revisión integral del íleon y la cita de los hallazgos histomorfológicos preliminares de ileítis en fallecidos de la COVID-19, motiva realizar estudios amplios, que infieran su papel en el progreso clínico de la COVID-19 y justifique el futuro de nuevas intervenciones terapéuticas para su integridad.

Introduction terminal ileum, key site of control of nutritional absorption, metabolism, immune system, intestinal microbiota and extradigestive organ function. Histomorphological and biomolecular understanding of the ileum justifies its participation in intestinal inflammatory processes, such as SARS-CoV2 infection. Objective to describe the biomolecular evidence of the tissue components of the ileum that justifies its function in the hepatic-intestinal axis, and to cite histomorphological findings of the ileum in deaths from COVID-19. Information acquisition a systematic review was carried out, critical of reports between 2000 and 2021, on websites (PubMed, Scielos, Lilacs, and Elservier), of the biomolecular studies of the ileum (enterocytes, intestinal epithelial barrier, microbiota and intestinal permeability), which support its epithelial barrier function, and preliminary findings of histomorphological sections of the ileum in deaths from COVID-19 are cited. Development: biomolecular evidence of the normal ileum is described, and the repercussion of its loss, dysbiosis and hyperpermeability in intestinal inflammatory processes, and preliminary histomorphological findings of ileitis in deaths from COVID-19 are cited, which could substantiate the importance of the biomolecular intuition of the ileum in the health-disease balance, that its loss would justify the clinical progress of COVID-19. Conclusions: the comprehensive review of the ileum and the citation of the preliminary histomorphological findings of ileitis in deaths from COVID-19 motivates conducting extensive studies that infer its role in the clinical progress of COVID-19 and justify the future of new interventions. therapeutic for its integrity.

Experiencias en la realización de autopsias a puérperas fallecidas por la COVID-19

Introducción: El SARS-CoV-2 causa graves neumonías. Las gestantes experimentan cambios inmunológicos y fisiológicos, que pueden hacerlas más susceptibles a las infecciones respiratorias virales, incluida la COVID-19. Objetivo: Exponer las características de una serie de casos de muertes maternas, confirmadas con la COVID-19. Métodos: Se realizó un estudio de serie de autopsias parciales, a las puérperas confirmadas al SARS-CoV-2, revisadas por el grupo especial de trabajo de anatomía patológica para la COVID-19, en el año 2021. Se analizaron las variables edad, historia obstétrica y causas de muerte, en el Hospital Militar Central "Dr. Luis Díaz Soto". Resultados: En el 2021 fueron atendidas 425 gestantes confirmadas al SARS-CoV-2, de ellas 16 fallecieron (3,8 %). A todas se les realizó cesárea, por beneficio materno-fetal e ingresaron en la unidad de cuidados intensivos, con comorbilidades entre las cuales la obesidad y la diabetes fueron más frecuentes. La media de fecha de inicio de los síntomas fue 5,18 días, todas contacto de casos positivos; en las causas de muerte la hipoxia sistémica afectó a un tercio de las fallecidas; el edema pulmonar de permeabilidad se presentó en el 100 % de las puérperas y en todas las muertes maternas hubo daño múltiple de órganos. Conclusiones: El edema pulmonar de permeabilidad afecta a todos los casos, con impacto importante como causa de muerte, así como en la expresión de la hipoxia y la respuesta inflamatoria sistémica. La COVID-19 es la causa básica de muerte en todos los casos.

Introduction: SARS-CoV-2 causes severe pneumonias. Pregnant women experience immunological and physiological changes, which may make them more susceptible to viral respiratory infections, including COVID-19. Objective: To present the characteristics of a case series of maternal deaths confirmed with COVID-19. Methods: A serial study of partial autopsies of postpartum women confirmed with SARS-CoV-2, reviewed by the special working group of pathological anatomy for COVID-19, in the year 2021, was carried out. The variables age, obstetric history and causes of death were analyzed at the Central Military Hospital "Dr. Luis Díaz Soto". Results: In 2021, 425 pregnant women with confirmed SARS-CoV-2 were attended, 16 of them died (3.8%). All of them underwent cesarean section for maternal-fetal benefit and were admitted to the intensive care unit, with comorbidities among which obesity and diabetes were more frequent. The mean date of symptom onset was 5.18 days, all contact positive cases; in the causes of death systemic hypoxia affected one third of the deceased; permeability pulmonary edema was present in 100 % of the puerperal women and in all maternal deaths there was multiple organ damage. Conclusions: Permeability pulmonary edema affects all cases, with important impact as a cause of death, as well as in the expression of hypoxia and systemic inflammatory response. COVID-19 is the basic cause of death in all cases.

Cirrhosis in intrahepatic cholangiocarcinoma: prognostic importance and impact on survival.

CONTEXT: Cholangiocarcinoma (CCA), a malignancy of the biliary tract epithelium is of increasing importance due to its rising incidence worldwide. There is a lack of data on cirrhosis in intrahepatic CCA (iCCA) and how it affects overall survival and prognosis. OBJECTIVES: The primary objective of this study was to examine if there were differences in survival outcomes between iCCA patients with concomitant cirrhosis and those without cirrhosis. METHODS: The National Cancer Database (NCDB) was used to identify and study patients with iCCA from 2004 to 2017. The presence of cirrhosis was defined using CS Site-Specific Factor 2 where 000 indicated no cirrhosis and 001 indicated the presence of cirrhosis. Descriptive statistics were utilized for patient demographics, disease staging, tumor, and treatment characteristics. Kaplan-Meier (KM) method with log-rank test and a multivariate logistic regression model was used to assess if the presence of cirrhosis in iCCA was associated with survival status and long-term survival (60 or more months after diagnosis). RESULTS: There were 33,160 patients with CCA in NCDB (2004-2017), of which 3644 patients were diagnosed with iCCA. One thousand fifty-two patients (28.9%) had cirrhosis as defined by Ishak Fibrosis score 5-6 on biopsy and 2592 patients (71.1%) did not meet the definition for cirrhosis. Although in univariate analyses using KM/log-rank tests showed a survival advantage for non-cirrhotic patients, there was no statistically significant association found between cirrhosis and survival status (OR = 0.82, p = 0.405) or long-term survival (OR = 0.98, p = 0.933) when multivariate analysis was used. iCCA patients with cirrhosis and Stage 1 tumor had the highest median OS (132 months) vs 73.7 months in the non-cirrhotic arm, while patients with stage IV disease who had cirrhosis had half the survival time of those without. Our data thus indicates that the presence of cirrhosis is not an independent prognostic factor for survival.

Infección por SARS-CoV-2, endotelitis y ácidos biliares: una visión integradora / SARS-CoV-2 infection, endotheliitis and bile acids: an integrative view

Introducción: La endotelitis es causada por mecanismos complejos asociados a comorbilidades inmunitario-metabólicas como expresión del daño producido por diversos agentes, como el caso de las acciones proinflamatorias debidas a la interacción del virus SARS-CoV-2 con los ácidos biliares, que pueden estar implicadas en la mortalidad por la COVID-19. Objetivo: Describir las evidencias biomoleculares de la citotoxicidad de los ácidos biliares sobre el endotelio y la posible relación con la endotelitis de los cortes histológicos de tejidos de fallecidos por la COVID-19, asociada o no a las comorbilidades conocidas. Métodos: Se realizó una revisión sistemática y crítica de los artículos reportados sobre ácidos biliares y endotelitis desde 1963 hasta 2021 en los sitios web (PubMed, SciELO, Lilacs y Elservier). Se citó la histología del tejido pulmonar con daño endotelial en 34 fallecidos por COVID-19 en el Hospital Militar Central "Luis Díaz Soto", cuyos cortes histológicos fueron examinados en el Hospital Clínico Quirúrgico "Hermanos Ameijeiras". Asimismo, se describieron las acciones y las propiedades físico-químicas de los ácidos biliares que pudieran relacionarse con la endotelitis observada en dichos cortes histológicos. Conclusiones: Los ácidos biliares hidrofóbicos conjugados con glicinas, por sus propiedades e incrementos séricos hallados en las comorbilidades inmunitario-metabólicas y en las enfermedades hepato-intestinales, pudieran tener un papel en la endotelitis presente en pacientes de la COVID-19, con estadíos graves y críticos(AU)

Introduction: Endotheliitis is caused by complex mechanisms associated with immune-metabolic comorbidities as an expression of the damage produced by various agents, such as the case of proinflammatory actions due to the interaction of the SARS-CoV-2 virus with bile acids, which may be involved in mortality from COVID-19. Objective: To describe the biomolecular evidence of bile acid cytotoxicity on the endothelium and the possible relationship with endothelitis of histological sections of tissues from COVID-19 deaths, associated or not with known comorbidities. Methods: A systematic and critical review of the articles reported on bile acids and endothelitis from 1963 to 2021 was conducted on the websites (PubMed, SciELO, Lilacs and Elservier). It was cited the histology of lung tissue with endothelial damage in 34 deceased by COVID-19 at "Luis Díaz Soto" Central Military Hospital, whose histological sections were examined at "Hermanos Ameijeiras" Clinical Surgical Hospital. Likewise, the actions and physicochemical properties of bile acids that could be related to observed endothelitis in these histological sections were described. Conclusions: Hydrophobic bile acids conjugated with glycine, due to their properties and serum increases found in immune-metabolic comorbidities and hepato-intestinal diseases, could have a role in endothelitis present in COVID-19 patients, with severe and critical stages(AU)

Experiencias de autopsias a fallecidos por la COVID-19 / Autopsy experiences of deceased by COVID-19

RESUMEN Introducción: Se presenta un caso de paciente fallecido por la COVID-19, que los autores consideran prototipo de la mayor parte de los fallecidos por esta afección, que se le realizó a autopsia. Objetivo: Divulgar las experiencias en el estudio de la autopsia de este tipo de pacientes y contribuir a su aplicación en la práctica asistencial y científica. Caso clínico: Se presenta un paciente masculino de 78 años, con hipertensión arterial, diabetes mellitus y obesidad, que comenzó con tos, fiebre, secreción nasal, que ingresa con diagnóstico de la COVID-19, evoluciona hacia la gravedad y fallece 10 días después de su ingreso. Se presentan los elementos fundamentales de la historia clínica, los diagnósticos de causas de muerte pre mortem y post mortem. Se precisan los diagnósticos en la autopsia y los resultados de la evaluación de la calidad de los diagnósticos de causas de muerte clínicos. Conclusiones: Las experiencias del estudio de esta autopsia como prototipo, reafirman los daños ocasionados por el SARS-CoV-2 y aporta a los conocimientos de este campo.

ABSTRACT Introduction: A case of a patient who died from COVID-19 is presented, which the authors consider to be the prototype of most of those who died from this condition, which was performed at autopsy. Objective: Disseminate the experiences in the study of the autopsy of this type of patients and contribute to its application in clinical and scientific practice. Clinical case: A 78-year-old male patient is presented, with arterial hypertension, diabetes mellitus and obesity, who began with cough, fever, runny nose, who was admitted with a diagnosis of COVID-19, progressed to severity and died 10 days later. of his admittance. The fundamental elements of the clinical history, the diagnoses of causes of death pre-mortem and post-mortem are presented. Autopsy diagnoses and quality assessment results of clinical cause of death diagnoses are specified. Conclusions: The experiences of the study of this autopsy as a prototype, reaffirm the damage caused by SARS-CoV-2 and contribute to the knowledge of this field.

Visión de las causas de muerte por la COVID-19 con las experiencias de las autopsias / Vision of the causes of death by COVID-19 with the experiences of autopsies

RESUMEN El 30 de enero de 2020, la Organización Mundial de la Salud declaró a la infección por SARS-CoV-2 una emergencia internacional de salud pública. La autopsia, considerada el mejor método de estudio del enfermo y la enfermedad, corrobora que los pacientes pueden morir por la acción directa del virus (fallecidos por la COVID-19), mientras que otros positivos al SARS-CoV-2, no mostraron cambios morfológicos pulmonares atribuidos a la acción del virus. Se propone establecer los criterios diagnósticos morfológicos en el contexto de la epidemia por el SARS-CoV-2 y la COVID-19 en los fallecidos en Cuba, a partir del estudio sistemático de las autopsias. Se han identificado los patrones morfológicos que se establecen en los pulmones de los pacientes fallecidos bajo el efecto de la COVID-19. El edema pulmonar de permeabilidad con el ensanchamiento de tabique pulmonar, el depósito de la membrana hialina desorganizada en el interior de los alveolos, el desprendimiento de células epiteliales (neumocitos y células bronquiales y bronquiolares), seguida de la hiperplasia epitelial con presencia en ocasiones de cambios metaplásicos y atipias, y finalmente, la fibrosis. Cuando se realizan autopsias, es posible ubicar cada enfermedad en su lugar, en el cronopatograma, lo que permite realizar el reparo de los certificados de defunción, para evaluar el lugar que la COVID-19 ha ocupado como causa de muerte en la población estudiada. En criterio del colectivo, identificar en las alteraciones morfológicas, es imprescindible para elaborar el cronopatograma del fallecido y la adecuada evaluación clínico patológica del paciente.

ABSTRACT On January 30, 2020, the World Health Organization (WHO) declared SARS-CoV-2 infection an international public health emergency. The autopsy, considered the best method of studying the patient and the disease, corroborates that patients can die from the direct action of the virus (who died from COVID-19), while others positive for SARS-CoV-2 did not show morphological lung changes attributed to the action of the virus. It is proposed to establish the morphological diagnostic criteria in the context of the SARS-CoV-2 and COVID-19 epidemic in the deceased in Cuba based on the systematic study of autopsies. The morphological patterns that are established in the lungs of patients who died under the effect of COVID-19 have been identified. The pulmonary edema of permeability with the widening of the pulmonary septum, the deposit of the disorganized hyaline membrane inside the alveoli, the detachment of epithelial cells (pneumocytes and bronchial and bronchiolar cells), followed by epithelial hyperplasia with sometimes the presence of metaplastic changes and atypia, and finally, fibrosis. When autopsies are performed, it is possible to locate each disease in its place, in chronopathogram, which allows death certificates repair to be carried out to assess the place that COVID-19 has occupied as a cause of death in the population studied. In the opinion of the group, identifying morphological alterations is essential to prepare the chronopathogram of the deceased and the adequate clinical-pathological evaluation of the patient.

Mantle Cell Lymphoma: the Role of Risk-Adapted Therapy and Treatment of Relapsed Disease.

PURPOSE OF REVIEW: In this review, the current treatment strategies are recapped, evolving agents are discussed, and we provide guidance in treating R/R MCL. RECENT FINDINGS: There has been an advancement in treatment using targeted therapy, cellular therapies including chimeric antigen receptor (CAR) T cell therapy and hematopoietic stem cell transplantation (HSCT) and novel therapeutic agents including non-covalent BTKis, bispecific antibodies, and antibody-drug conjugates for treatment of refractory and relapsed mantle cell lymphoma. Mantle cell lymphoma (MCL) is a mature B-cell lymphoma that is associated with a poor prognosis. Current treatments include immunochemotherapy, chemotherapy and autologous stem cell transplantation (SCT) which place patients in remission but result in relapse. Chemoimmunotherapy uses chemotherapeutic agents paired with rituximab in patients who have chemo-sensitive disease with prolonged remission of at least > 2 years and/or have contraindications to chemotherapy that serve as bridges to more definitive treatment. Additional therapies including proteosome inhibitor-based therapies and immunomodulators, like bortezomib and lenalidomide, can be used as single agents or in combination with others. Bruton's tyrosine kinase (BTK) inhibitors including ibrutinib, acalaburtinib, and zanubrutinib have also been proven effective for the treatment of (R/R) disease. Another agent is Venetoclax, a robust drug that can be used in MCL after progression or intolerance to BTKi. Newer advances in the management of MCL have led to the utilization of cellular therapies including chimeric antigen receptor (CAR) T cell therapy and SCT that are options for healthy young (< 65 years old) who have progressed through several lines of therapies. With progression of disease, mutations are acquired that cause therapy resistance. Novel therapeutic agents such as non-covalent BTKis, bispecific antibodies, and antibody-drug conjugates are paving the way for advancements in treatment for R/R MCL. R/R MCL is a complex disease with many therapeutic options none of which has been proven superior in head-to-head comparison. In this review, the current treatment strategies are recapped, evolving agents are discussed, and we provide guidance in treating R/R MCL.

Blocking EGFR with nimotuzumab: a novel strategy for COVID-19 treatment.

Background: Lung injury and STAT1 deficit induce EGFR overexpression in SARS-CoV-2 infection. Patients & methods: A phase I/II trial was done to evaluate the safety and preliminary effect of nimotuzumab, an anti-EGFR antibody, in COVID-19 patients. Patients received from one to three infusions together with other drugs included in the national guideline. Results: 41 patients (31 severe and 10 moderate) received nimotuzumab. The median age was 62 years and the main comorbidities were hypertension, diabetes and cardiovascular disease. The antibody was very safe and the 14-day recovery rate was 82.9%. Inflammatory markers decreased over time. Patients did not show signs of fibrosis. Conclusion: Nimotuzumab is a safe antibody that might reduce inflammation and prevent fibrosis in severe and moderate COVID-19 patients. Clinical Trial Registration: RPCEC00000369 (rpcec.sld.cu).

Background: After SARS-CoV-2 infection, many cells in the lung express a new receptor called EGFR. Overexpression of EGFR can worsen the pulmonary disease and provoke fibrosis. Patients & methods: The initial impact of using a drug that blocks EGFR, nimotuzumab, was evaluated in COVID-19 patients. Results: 41 patients received nimotuzumab by the intravenous route together with other medications. The median age was 62 years, and patients had many chronic conditions including hypertension, diabetes and cardiac problems. Treatment was well tolerated and 82.9% of the patients were discharged by day 14. Serial laboratory tests, x-rays and CT scan evaluations showed the improvement of the patients. Conclusion: Nimotuzumab is a safe drug that can be useful to treat COVID-19 patients.

Primary Pulmonary Choriocarcinoma Treated With Neoadjuvant Chemotherapy and Lobectomy: A Case Report.

Primary pulmonary choriocarcinomas (PPC) are a rare form of extragonadal germ cell tumors (GCT). They present as lung nodules and secrete beta-human chorionic gonadotropin (ß-HCG). This is a rare case of PPC that presented insidiously in a postmenopausal woman. Clinical suspicion arose due to markedly elevated serum ß-HCG and lung tumor biopsy immunohistochemical staining negative for markers of small cell and non-small cell carcinomas of the lung. The diagnosis of PPC was made after staining positive for markers of GCTs including ß-HCG in the absence of a primary tumor in the reproductive organs. The patient was treated with neoadjuvant vincristine, ifosfamide, and cisplatin (VIP) chemotherapy, followed by video-assisted thoracoscopic surgery (VATS) with lobectomy and mediastinal lymph node dissection. This is the first reported case of PPC treated with VIP induction chemotherapy. The patient initially had complete pathologic response and remission; however, she presented with relapse at a nine-month follow-up with new pulmonary nodules and metastatic disease to the brain.

Endoscopic retrograde cholangiopancreatography and carbohydrate antigen 19-9 in the differential diagnosis of biliary strictures.

INTRODUCTION: bile-duct strictures include a wide spectrum of benign and malignant diseases. OBJECTIVE: to determine the usefulness of endoscopic retrograde cholangio-pancreatography (ERCP) and circulating carbohydrate antigen 19-9 (CA 19-9) for the differential diagnosis of biliary strictures. METHOD: an observational, prospective, cross-sectional study was performed in 75 patients with biliary stricture diagnosed by ERCP between October 2018 and January 2020. The variables included type of biliary stricture as diagnosed by ERCP, biliary cytology, and CA 19-9 levels. For the statistical analysis, descriptive statistics were used according to type of variable. The relationships between them was analyzed using Pearson's chi-square and Fisher's exact probability tests, assuming differences were significant when p < 0.05. The cut-off point for CA 19-9 was calculated using the ROC curve, and Cohen's kappa index was used to measure concordance between diagnostic methods. RESULTS: cytology was positive in 51 (68 %) patients with biliary stenosis. Mean age was 63 years. Acute cholangitis predominated in malignant strictures (93.7 %). There was agreement between cytology and the cut-off value calculated for CA 19-9 of 85.4 U/mL, with a kappa agreement index of 0.332 (p = 0.004), and between ERCP and cytology, with a kappa concordance index of 0.701 (p < 0.001). CONCLUSIONS: a serum CA 19-9 value higher than 85.4 U/mL is highly related to neoplastic biliary stenosis.

Autopsia y certificados médicos de defunción en fallecidos relacionados con la COVID-19

RESUMEN Introducción: La pandemia de la COVID-19 ha sido la mayor del siglo actual y motivo de numerosos trabajos científicos. En Cuba se ha constituido el Grupo Temporal de Anatomía Patológica para estudiar las autopsias de los fallecidos por la COVID-19 (más de 400). Los certificados médicos de defunción, documentos de inestimable valor, en Cuba se reparan de acuerdo a los resultados de las autopsias, para elevar su calidad. Objetivos: Evaluar los resultados de las autopsias con diagnósticos de COVID-19, comparadas con los certificados médicos de defunción. Métodos: Se evaluaron los diagnósticos de causas de muerte de 65 autopsias del año 2020 con sus certificados médicos de defunción. Los diagnósticos fueron procesados en el Sistema Automatizado de Registro y Control de Anatomía Patológica. Se analizaron las causas directas de muerte, causas básicas de muerte, causas de muerte intermedias y causas de muerte contribuyentes. Se definió la coincidencia total de ambos diagnósticos, coincidencia parcial, no coincidencia o discrepancia diagnóstica y datos insuficientes. Resultados: Las discrepancias diagnósticas de causa básica y directa de muerte son 46,2 % y 60,0 % del total de casos y 19,4 % y 64,5 % cuando la COVID-19 fue causa básica de muerte. Las elevadas cifras de discrepancias diagnósticas, se corresponden con las reportadas en estudios previos, tanto en diagnósticos clínicos como en los certificados médicos de defunción. Conclusiones: Existe elevadas cifras de discrepancias diagnósticas en los resultados de las autopsias con diagnósticos de COVID-19, comparadas con los certificados médicos de defunción.

ABSTRACT Introduction: The COVID-19 pandemic has been the largest in the current century and the reason for numerous scientific works. In Cuba, the Temporary Group of Pathological Anatomy has been established to study the autopsies of those who died from COVID-19 (more than 400). The medical death certificates, documents of inestimable value, in Cuba are repaired according to the results of the autopsies, to raise their quality. Objectives: To evaluate the results of autopsies with COVID-19 diagnoses, compared to medical death certificates. Methods: The diagnoses of causes of death of 65 autopsies of the year 2020 were evaluated with their medical death certificates. The diagnoses were processed in the Automated System for the Registration and Control of Pathology. Direct causes of death, basic causes of death, intermediate causes of death, and contributing causes of death were analyzed. The total agreement of both diagnoses was defined, partial agreement, diagnostic mismatch or discrepancy, and insufficient data. Results: Diagnostic discrepancies of basic and direct cause of death are 46.2 % and 60.0 % of all cases and 19.4 % and 64.5 % when COVID-19 was basic cause of death. The high figures for diagnostic discrepancies correspond to those reported in previous studies, both in clinical diagnoses and in medical death certificates. Conclusions: There are high numbers of diagnostic discrepancies compared with the results of autopsies with COVID-19 diagnoses, compared to medical death certificates.

Autopsias de pacientes con enfermedad respiratoria aguda / Autopsies of patients with acute respiratory disease

Introducción: La enfermedad respiratoria aguda es la entidad más frecuente en la vida del ser humano y las enfermedades respiratorias agudas se encuentran entre las causas de muerte. La autopsia es el mejor método del estudio del enfermo y su realización es una fortaleza del sistema de salud cubano. Objetivo: Determinar las características demográficas y morfológicas que se encontraron en las autopsias de fallecidos con enfermedad respiratoria aguda. Método: Se realizó un estudio descriptivo y de corte transversal, de los fallecidos a quienes se realizó autopsia, en el periodo de 1986 al 2019. Se estudiaron las variables edad, sexo, comorbilidades, causas de muerte y relación clínico - patológica. Resultados: La población quedó conformada por 390 autopsias que presentaban estas afecciones (2,5 por ciento). El grupo de edades entre 65 a 84 años fue el más afectado en ambos sexos. En las causas directas de muerte predominó la bronconeumonía bacteriana. Se destaca la elevada coincidencia en las causas directas de muerte y las discrepancias en las causas básicas. La línea de tendencia indica el incremento progresivo en el transcurso de los años estudiados. Conclusiones: Las características demográficas muestran que todos los grupos de edades están afectados, con predominio de 65 a 84 años, en ambos sexos. El pulmón fue el órgano más afectado en las causas directas de muerte, con predominio de la bronconeumonía, mientras que la mayoría presenta enfermedad respiratoria aguda como causa básica de muerte, con elevada discrepancia en su relación clínico patológica(AU)

Introduction: Acute respiratory disease is the most frequent entity in human life and acute respiratory diseases are among the causes of death. The autopsy is the best method of studying the patient and it is a strength of the Cuban health system. Objective: To determine the demographic and morphological characteristics found in the autopsies of the deceased with acute respiratory diseases. Method: A descriptive and cross-sectional study was carried out of the deceased who underwent autopsy, in the period from 1986 to 2019. The variables age, sex, comorbidities, causes of death and clinical-pathological relationship were studied. Results: The population was made up of 390 autopsies with these conditions (2.5 percent). The 65 to 84 age group was the most affected in both sexes. In direct causes of death, bacterial bronchopneumonia predominated. The high coincidence in the direct causes of death and the discrepancies in the basic causes stand out. The trend line indicates the progressive increase in the course of the years studied. Conclusions: The demographic characteristics show that all age groups are affected, with a predominance of 65 to 84 years, in both sexes. The lung was the most affected organ in direct causes of death, with a predominance of bronchopneumonia, while the majority had acute respiratory disease as the basic cause of death, with a high discrepancy in its clinical-pathological relationship(AU)

Diagnóstico de nefrosclerosis en fallecidos autopsiados / Diagnosis of nephrosclerosis in autopsied deceased

Introducción: La nefrosclerosis se produce debido al daño de la microvasculatura glomerular. El daño vascular a nivel glomerular, reduce su capacidad funcional y el daño se acelera debido a la hipertensión arterial, diabetes mellitus, obesidad y otros causantes de daño renal. Objetivo: Identificar el diagnóstico histopatológico de nefrosclerosis y describir características de fallecidos autopsiados con esta entidad. Métodos: Fueron analizados 135 449 fallecidos autopsiados en Cuba, de 15 o más años de edad, entre los años 1963 y 2015, se revisaron los diagnósticos histopatológicos de nefrosclerosis. Se precisaron además los diagnósticos de causa directa de muerte y de causa básica de muerte, así como su asociación con otras entidades. Se analizó además: edad, sexo, diagnóstico histopatológico de nefrosclerosis, diagnósticos de causa directa y básica de muerte, y asociación con otras entidades patológicas. Resultados: Hubo diagnóstico histopatológico de nefrosclerosis en 56 422 (40,2 por ciento), de ellos el 91,8 por ciento tenían 55 o más años de edad, el 52,9 por ciento fue del sexo masculino y el 47,0 por ciento femenino. La bronconeumonía (25,88 por ciento) fue la principal causa directa de muerte, los trastornos ateroscleróticos y la hipertensión arterial se identificaron como las principales causas básicas de muerte. Conclusiones: Hubo un elevado porcentaje de diagnósticos de nefrosclerosis en los fallecidos autopsiados en Cuba, en un período de 52 años. Predominaron los pacientes mayores de 55 años, del sexo masculino, así como la asociación con enfermedades básicas ateroscleróticas e hipertensión arterial(AU)

Introduction: Nephrosclerosis occurs due to damage to the glomerular microvasculature. Vascular damage at the glomerular level reduces its functional capacity and the damage is accelerated due to high blood pressure, diabetes mellitus, obesity and other causes of kidney damage. Objective: To identify the histopathological diagnosis of nephrosclerosis and describe characteristics of autopsied deceased with this entity. Methods: 135,449 autopsied deceased in Cuba, aged 15 or over, between 1963 and 2015 were analyzed, the histopathological diagnoses of nephrosclerosis were reviewed. The diagnoses of direct cause of death and basic cause of death were also specified, as well as their association with other entities. It was also analyzed: age, sex, histopathological diagnosis of nephrosclerosis, diagnoses of direct and basic cause of death, and association with other pathological entities. Results: There was a histopathological diagnosis of nephrosclerosis in 56,422 (40.2 percent), of them 91.8 percent were 55 years of age or older, 52.9 percent were male and 47.0 percent female. Bronchopneumonia (25.88 percent) was the main direct cause of death, atherosclerotic disorders and arterial hypertension were identified as the main basic causes of death. Conclusions: There was a high percentage of nephrosclerosis diagnoses in autopsied deceased in Cuba, in a period of 52 years. Male patients over 55 years of age predominated, as well as the association with basic atherosclerotic diseases and arterial hypertension(AU)

Relación de los genotipos CagA/VacA del Helicobacter pylori con lesiones precursoras de cáncer gástrico / Relationship of CagA/VacA genotypes of Helicobacter pylori with precursor lesions of gastric cancer

Introducción: El Helicobacter pylori predispone al cáncer gástrico. Los individuos con cepas CagA y VacA s1m1 desarrollan lesiones de la mucosa más graves. El sistema Operative Link on Gastritis Assessment permite determinar el riesgo de cáncer y define la atrofia como la lesión típica de progresión de la gastritis crónica. Objetivo: Relacionar los genotipos CagA y VacA del Helicobacter pylori con lesiones precursoras de cáncer gástrico. Métodos: Se realizó un estudio descriptivo en 62 pacientes. Las variables incluidas fueron los genotipos CagA y VacA del Helicobacter pylori y los estadios de OLGA (0, I, II, III, IV), las cuales se relacionaron. Se emplearon como medidas de resumen para variables cualitativas la frecuencia absoluta y el porcentaje. Para evaluar la asociación entre variables cualitativas se aplicó el test X2 (ji cuadrado). Se aceptó un nivel de significación estadística p ≤ 0,05. Para explorar la relación entre dos variables dicotómicas se utilizó el riesgo relativo. Se trabajó con un nivel de confiabilidad del 95 por ciento. Resultados: El 68 por ciento de los pacientes con atrofia presentaron genotipo CagA y el 55 por ciento genotipo VacA s1m1. El 6 por ciento de los pacientes con CagA se encontraban en estadio 0; 11 por ciento en estadio I; 40 por ciento en estadio II y 16 por ciento en estadio III. El 37 por ciento de los pacientes con VacA s1m1 estaban en estadio II. Conclusiones: Los genotipos CagA y VacA s1m1 fueron los más frecuentes y se relacionaron con la presencia de atrofia gástrica(AU)

Introduction: Helicobacter pylori predisposes to gastric cancer. Individuals with CagA and VacA s1m1 strains develop more severe mucosal lesions. The Operative Link on Gastritis Assessment system allows determining the risk of cancer and defines atrophy as the typical lesion in the progression of chronic gastritis. Objective: Relate the CagA and VacA genotypes of Helicobacter pylori with precursor lesions of gastric cancer. Methods: A descriptive study was carried out in 62 patients. The variables included were the CagA and VacA genotypes of Helicobacter pylori and the OLGA stages (0, I, II, III, IV), which were related. The absolute frequency and the percentage were used as summary measures for qualitative variables. To evaluate the association between qualitative variables, the X2 test (chi-square) was applied. A level of statistical significance p≤0.05 was accepted. To explore the relationship between two dichotomous variables, the relative risk was used. We worked with a confidence level of 95 percent. Development: 68 percent of the patients with atrophy had a CagA genotype and 55 percent had a VacA s1m1 genotype. 6 percent of the patients with CagA were in stage 0; 11 percent in stage I; 40 percent in stage II and 16 percent in stage III. 37 % of the patients with VacA s1m1 were stage II. Conclusions: The CagA and VacA s1m1 genotypes were the most frequent and were related to the presence of gastric atrophy(AU)