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)

A case of intestinal schwannoma initially suspected by transvaginal ultrasound.

Schwannomas are peripheral nerve sheath tumors. Due to their low incidence, few cases of colorectal schwannomas have been published, which increases the diagnostic challenge. The aim of this case report is to discuss the role of transvaginal ultrasound in different areas than the gynecological disorders, when on hands of properly trained professionals that perform systematized procedures. A 56-year-old woman consulted for postmenopausal genital bleeding. During transvaginal ultrasound, a colonic solid, hypervascularized mass of 23 × 26 mm was visualized. As a result of this incidental finding, the patient underwent a sigmoidectomy, with a final diagnosis of intestinal schwannoma. Transvaginal ultrasound is today one of the most useful and accurate diagnostic tools in the assessment of gynecological disorders. However, the proximity of other pelvic structures makes it possible to evaluate the presence of nongynecological conditions. This fact should encourage gynecologists to systematize the transvaginal ultrasound procedure.

Feasibility of targeted axillary dissection for de-escalation of surgical treatment after neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Targeted axillary dissection, which combines sentinel lymph node biopsy with removal of the proven involved node noted during the staging process, has been shown to improve axillary staging and decrease false negative rates after neoadjuvant chemotherapy in patients with breast cancer. OBJECTIVE(S): The main goal of this study was to assess the ability to identify and remove the clipped node and the false negative rate of targeted axillary dissection. METHODS: We performed a prospective study among patients with biopsy-confirmed nodal metastases who received neoadjuvant chemotherapy. A clip was placed on the sample node prior systemic therapy. After neoadjuvant chemotherapy, all patients underwent sentinel lymph node biopsy (dual tracer), localization and excision of the clipped node and axillary lymph node dissection. The clipped node was preoperatively localized in all cases placing an iodine-125 seed guided by ultrasound. The pathology of the sentinel nodes and clipped node was compared with other nodes. RESULTS: A total of 455 patients with invasive breast cancer were studied. Of the 148 patients with NAC, 32 met the eligibility criteria and were enrolled in the study. Mean age at diagnosis was 52.3 years. Systematic lymphadenectomy was performed in all patients, with an average of 14.3 lymph nodes removed. Detection rate of the clipped node alone was 96.9%, and 100% for targeted axillary dissection. Ability of clipped node alone to predict nodal status showed a FNR of 10,5% while SLNB alone performed by dual tracer and targeted axillary dissection, showed FNRs of 5.3% and 5.0%, respectively. Sentinel lymph nodes matched clipped node in 23 patients (74.2%). CONCLUSION (S): In node positive breast cancer patients, targeted axillary dissection is a reliably approach for axillary staging after neoadjuvant chemotherapy. The preoperative location of the clipped node is mandatory to increase the detection rate and optimize the results of the technique.

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.

Treatment with low-dose prednisone in refractory obstetric antiphospholipid syndrome: A retrospective cohort study and meta-analysis.

BACKGROUND: Glucocorticoids have been suggested as a potential therapy in refractory obstetric antiphospholipid syndrome (oAPS). Our aims were to describe a cohort of patients with oAPS treated with low-dose glucocorticoids and to perform a systematic review and meta-analysis evaluating the effects of additional glucocorticoids on the pregnancy outcomes in oAPS patients. METHODS: Retrospective study that included 11 women diagnosed with primary antiphospholipid syndrome. The meta-analysis was conducted by fitting random effects models and was checked for heterogeneity. RESULTS: All women had suffered from early pregnancy losses and two also had a history of fetal deaths. We studied 47 pregnancies that resulted in 32 abortions (68.1%) and 3 fetal deaths (6.4%). Twenty-six pregnancies were under treatment, mainly LDA and LMWH. Low-dose glucocorticoids were indicated in 13 pregnancies (always in association with LDA and LMWH). There was a decrease in pregnancy loss in those patients treated with LDA and LMWH. Treatment with glucocorticoids significantly increased the rate of successful pregnancy (38.5% abortions in treated vs 85.3% abortions in non-treated pregnancies; p=0.003). After multivariate GEE analysis, only glucocorticoids remained inversely associated with pregnancy loss (OR=0.157, (CI 0.025-0.968, p=0.046)). The meta-analysis showed that glucocorticoids tended to improve the frequency of successful pregnancy (OR= 0.509 (0.252-1.028), p=0.06). Three cases of gestational diabetes and one of preeclampsia were observed in our cohort. The meta-analysis, which mostly included studies using high-dose steroids, showed that glucocorticoids increased not only the frequency of preeclampsia and gestational diabetes, but also the rate of pre-term birth. CONCLUSIONS: The efficacy of low-dose glucocorticoids in addition to the standard therapy in patients with refractory oAPS should be confirmed in well-designed clinical trials. However, high doses of steroids significantly increase the frequency of maternal and fetal morbidities, making their use strongly inadvisable.

Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats.

Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats' full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor's vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these "vascular disease drivers" may pave novel research avenues for atherosclerosis pathobiology.

Thrombotic Microangiopathy in Patients Recovering from COVID-19.

INTRODUCTION: During the pandemic caused by the SARS-CoV-2 virus, some patients who develop severe forms of COVID-19 present thrombotic microangiopathy in the course of the disease's clinical progression. METHODS: Data came from direct patient observation and clinical records. We performed a kidney biopsy and used optical microscopy and immunofluorescence techniques. RESULTS: We present the case of a 78-year-old male patient, mestizo, overweight with a history of high blood pressure, ischemic cardiopathy and chronic obstructive pulmonary disease who was first admitted to the hospital due to respiratory symptoms and diarrhea related to COVID-19, from which he recovered. He was subsequently readmitted with symptoms of acute renal dysfunction accompanied by mild anemia and thrombocytopenia; at the same time, he resulted negative for COVID-19 via a real-time polymerase chain reaction test. A kidney biopsy revealed thrombi in glomerular capillaries, acute tubular necrosis, thickening of extraglomerular blood vessel walls, and C3 deposits in the glomerular tufts. CONCLUSIONS: We describe a case of thrombotic microangiopathy with kidney biopsy in a patient recovering from COVID-19. Acute renal dysfunction is a form of thrombotic microangiopathy that has been observed in patients recovering from COVID-19.

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.

Hallazgos ultraestructurales renales de pacientes con nefritis intersticial crónica de las comunidades agrícolas en El Salvador / Renal ultrastructural findings of patients with chronic interstitial nephritis from farming communities in El Salvador

Introducción: Desde hace 20 años se presenta en Centroamérica una enfermedad renal crónica que fundamentalmente afecta a hombres agricultores y no asociada a las causas tradicionales. Se caracteriza por presentar una nefritis intersticial crónica, en tanto las características ultraestructurales no se conocen con exactitud. En su origen se invoca el uso de agroquímicos y otros agentes nefrotóxicos, la deshidratación crónica, el consumo de medicamentos, entre otros factores. Objetivo: Describir las características ultraestructurales de la nefritis intersticial crónica en comunidades agrícolas. Método: Se realizó un estudio descriptivo de corte transversal. Se estudiaron muestras de biopsias renales de ocho pacientes con diagnóstico de nefritis intersticial crónica de las comunidades agrícolas. Resultados: De los ocho pacientes estudiados, dos (25 por ciento) trabajaban en labores agrícolas y cinco eran del sexo femenino (62,5 por ciento). Dos de los pacientes (25 por ciento) presentaban una enfermedad renal crónica estadio 2, y seis (75 por ciento) estadio 3. En cinco pacientes se hallaron fagolisosomas con presencia de componente lipídico entremezclado con material electrodenso en células del túbulo distal. En igual cantidad de pacientes se observaron cuerpos mieloides con zonas laminadas y núcleo central en células de túbulo proximal y de los vasos sanguíneos. Conclusiones: En pacientes de comunidades agrícolas que padecen nefritis intersticial crónica se evidencian fagolisosomas y estructuras mieloides en túbulos y vasos renales, cuyo contenido y origen se desconocen(AU)

Introduction: Chronic kidney disease mainly affecting male farmers and not associated to traditional causes has been present in Central America for twenty years. The condition is characterized by the presence of chronic interstitial nephritis, but its ultrastructural features are not fully known. Factors suggested as responsible for its occurrence include the use of agrochemicals and other nephrotoxic agents, chronic dehydration and medicine consumption. Objective: Describe the ultrastructural characteristics of chronic interstitial nephritis in farming communities. Method: A cross-sectional descriptive study was conducted of renal biopsy samples from eight patients diagnosed with chronic interstitial nephritis in farming communities. Results: Of the eight patients studied, two (25 percent) were farm workers and five (62.5percent) were female. Two of the patients (25 percent) had stage 2 and six (75 percent) stage 3 chronic kidney disease. In five patients evidence was found of phagolysosomes with lipid component mixed with electrodense material in distal tubule cells. An equal number of patients had myeloid bodies with laminated areas and central nucleus in proximal tubule and blood vessel cells. Conclusions: Evidence of phagolysosomes and myeloid structures of unknown content and origin was found in renal tubules and vessels of patients from farming communities diagnosed with chronic interstitial nephritis(AU)

COVID-19 and the Kidneys: Risk, Damage and Sequelae.

At fi rst, COVID-19 was thought to be primarily a respiratory disease, progressing in some patients to serious respiratory symptoms, pneumonia, severe respiratory distress syndrome and even death. Later analysis revealed entire systems were compromised, affecting other vital organs, including the kidneys, and a correlation was observed between chronic kidney disease (CKD) and COVID-19 severity COVID-19 severity.

Esclerosis peritoneal encapsulante en paciente en diálisis peritoneal domiciliaria / Encapsulating peritoneal sclerosis in a patient on home peritoneal dialysis

La esclerosis peritoneal encapsulante es una complicación poco común, pero muy grave, de la diálisis peritoneal. Esta complicación está asociada con altas tasas de morbilidad y mortalidad. El diagnóstico clínico requiere la presencia de obstrucción intestinal o función gastrointestinal alterada con signos patológicos y radiológicos de encapsulamiento intestinal. El diagnóstico patognomónico es solo con la realización de una biopsia peritoneal. El mecanismo patogénico exacto de esta entidad sigue siendo desconocido, aunque se asocia firmemente con el tiempo de duración del paciente en el tratamiento con diálisis peritoneal. Se presenta un caso clínico de esclerosis peritoneal encapsulante y se analizan las manifestaciones clínicas, diagnóstico, tratamiento, pronóstico y prevención(AU)

Encapsulating peritoneal sclerosis is a rare but very serious complication of peritoneal dialysis. This complication is associated with high morbidity and mortality rates. Clinical diagnosis is based on the presence of intestinal obstruction or altered gastrointestinal function with pathological and radiological signs of intestinal encapsulation. The pathognomonic diagnosis is achieved only by performing peritoneal biopsy. The exact pathogenic mechanism of this entity remains unknown, although it is strongly associated with the duration of the patient with peritoneal dialysis. We report a clinical case of encapsulating peritoneal sclerosis and the clinical manifestations, diagnosis, treatment, prognosis and prevention are analyzed(AU)

Marcadores morfológicos de hipoxia en el riñón fetal con insuficiencia placentaria tratado con neuro-EPO: estudio en ratas / Morphological markers of hypoxia in the fetal kidney with placental insufficiency treated with neuro-EPO: study in rats

RESUMEN Fundamento: la restricción del crecimiento intrauterino constituye una complicación del embarazo. Los recién nacidos con esta condición están expuestos a un mayor riesgo de morbimortalidad perinatal y postnatal. Objetivo: evaluar marcadores morfológicos de hipoxia en el desarrollo fetal y en el riñón, utilizando un modelo de insuficiencia placentaria tratado con eritropoyetina humana con bajo contenido de ácido siálico (neuro-Epo) en ratas. Métodos: se utilizaron tres grupos de ratas gestadas de la línea Wistar. Un grupo control (grupo I) y dos grupos experimentales (grupos II y III) con seis ratas cada uno. A las ratas de los grupos II y III se les realizó ligaduras de arterias uterinas en el día 16 de la gestación (E 16). Al grupo III desde E16 hasta E19 se le administró una dosis de 0,5 mg/kg/día de neuro-Epo por vía subcutánea y al grupo II se les administró placebo. En el día 20 de la gestación se pesaron los fetos y sus placentas. En el feto se midió la talla y los diámetros cefálicos. Las características morfométricas e histológicas en el riñón fetal se estudiaron con tinción de hematoxilina-eosina y PAS. Se realizó un análisis cualitativo histopatológico de sus tipos celulares. Resultados: los fetos con restricción del crecimiento intrauterino no mejoraron los marcadores de crecimiento. Se encontraron lesiones por hipoxia en el riñón fetal del grupo RCIU no tratado que mejoraron al administrar neuro-Epo. Conclusiones: la administración de neuro-Epo solo mostró efectos reparadores y protectores sobre alteraciones histológicas provocadas por la hipoxia en el riñón fetal.

ABSTRACT Foundation: intrauterine growth restriction constitutes a complication of pregnancy. Newborns with this condition are exposed to an increased risk of perinatal and postnatal morbidity and mortality. Objective: to evaluate morphological markers of hypoxia in fetal and kidney development, using a model of placental insufficiency treated with human erythropoietin with low sialic acid content (neuro-Epo) in rats. Methods: three groups of gestated rats from the Wistar line were used. A control group (group I) and two experimental groups (groups II and III) with six rats each. Rats of groups II and III had uterine artery ligation on day 16 of pregnancy (E 16). Group III from E16 to E19 was administered a dose of 0.5 mg / kg / day of neuro-Epo subcutaneously and group II was administered placebo. On the 20th day of gestation the fetuses and their placentas were weighed. The fetuses' size and cephalic diameters were measured. Morphometric and histological features in the fetal kidney were studied with hematoxylin-eosin staining and PAS. A qualitative histopathological analysis of their cell types was performed. Results: fetuses with intrauterine growth restriction did not improve growth markers. Hypoxia lesions were found in the fetal kidney of the untreated RCIU group that improved by administering neuro-Epo. Conclusions: the administration of neuro-Epo only showed reparative and protective effects on histological alterations caused by hypoxia in the fetal kidney.

Chronic interstitial nephritis of nontraditional causes in Salvadoran agricultural communities.

In El Salvador, a form of chronic kidney disease (CKD) of nontraditional causes (CKDnt) affecting farmers is being reported. Its behavior has been epidemic and is responsible for tens of thousands of deaths. This article summarizes the results obtained from a series of studies conducted to identify the epidemiology and clinical behavior of this disease, proposing a case definition and an etiopathogenic hypothesis. Methods included a survey of CKD in agricultural communities studying 2,388 people ≥ 18 years and 1,755 < 18, a descriptive clinical study followed by histopathological assessment conducted in 46 possible cases of CKDnt ≥ 18 years, and a national survey to study the prevalence of CKD and associated risk factors in 4,817 participants ≥ 20 years followed by a nested case-control study. In the agricultural communities, the prevalence of CKD in adults was 18% (men: 23.9%, women: 13.9%), 26.8% in agricultural workers (non-agricultural 13.8%), CKDnt accounted for 51.9% of cases. CKD in the population < 18 years was 3.9% (mean estimated glomerular filtration rate > 160 mL/1.73m2). The national CKD prevalence was 12.6% (urban: 11.3%; rural: 14.4%; males: 17.8%, females 8.5%), and CKDnt was only 3.8%; with associations between CKD and exposure to agrochemicals. The clinical study revealed the presence of markers of kidney damage (A3 albuminuria: 80.4%; ß2-microglobulin: 78.2%), urine electrolyte anomalies (100% hypermagnesuria, 45.7% hypernatriuria, 43.5% osmotic polyuria), abnormal osteotendinous reflexes (45.7%), sensorineural hearing loss (56.5%), and damage of the tibial arteries by Doppler imaging (66.7%). Biopsies revealed a chronic tubulointerstitial nephropathy. The etiopathogenesis of CKDnt is possibly multifactorial, including environmental contamination by agrochemicals, heat stress, and dehydration.

Tratamiento con corticoides en abortos espontáneos de repetición: revisión sistemática de la literatura / Corticosteroid treatment in recurrent pregnancy losses: systematic literature review

Antecedentes: el tratamiento de los abortos espontáneos de repetición es controvertido dada la escasez de evidencia disponible al respecto. El objetivo de este trabajo es hacer una revisión sistemática de la literatura acerca del uso de corticoides como terapia de los abortos espontáneos de repetición. Material y métodos: revisión sistemática de la literatura incluyendo 76 artículos clasificados en tres grupos: estudios realizados en pacientes con abortos espontáneos de repetición idiopáticos, abortos espontáneos de repetición asociados a síndrome antifosfolípido y pacientes con fallos de técnicas de fecundación in vitro. Resultados: la revisión de la literatura muestra resultados heterogéneos en cuanto a la contribución de los corticoides en la mejora del desenlace gestacional. Su administración ha demostrado ser beneficiosa en los casos de abortos espontáneos de repetición idiopáticos y posiblemente en aquellos asociados a síndrome antifosfolípido. Los resultados son contradictorios en el caso de las mujeres sometidas a fecundación in vitro, no existiendo metaanálisis concluyentes al respecto. En cuanto a la seguridad, los corticoides han demostrado no producir teratogenicidad. La administración de dosis altas durante largo tiempo se asocia con morbilidad materno-fetal, principalmente crecimiento intrauterino retardado, preeclampsia, diabetes gestacional, hipertensión gestacional, rotura prematura de membranas y parto pretérmino. Sin embargo, el empleo de dosis bajas durante periodos cortos no se ha asociado con efectos adversos maternos ni fetales. Conclusiones: la revisión de la literatura apoya el uso de los corticoides a dosis bajas durante las primeras semanas de embarazo en las pacientes con abortos espontáneos de repetición idiopáticos y posiblemente en los asociados a síndrome antifosfolípido, mientras que su utilidad en pacientes sometidas a técnicas de fecundación in vitro es controvertida

Background: Management of recurrent pregnancy losses is controversial due to the scarcity of literature available. Our aim is to perform a systematic review of the literature about the use of corticoids as therapy for recurrent pregnancy losses. Material and methods: Systematic literature review including 76 papers classified in three groups: idiopathic recurrent pregnancy losses, antiphospholipid syndrome related recurrent pregnancy losses, and patients with failure of in vitro fertilisation. Results: Literature review shows heterogeneous results regarding the effect of corticosteroids in pregnancy outcome. They have been proved to be beneficial in idiopathic recurrent pregnancy losses and possibly in antiphospholipid syndrome related recurrent pregnancy losses. Results are controversial in women undergoing in vitro fertilisation, and conclusive metaanalysis are lacking.Regarding safety, corticosteroids have been shown to be non teratogenic. Long term high dose treatment is associated with maternal and fetal morbitidies, particularly intrauterine growth restriction, preeclampsia, gestational diabetes, gestational hypertension, premature rupture of membranes and premature birth. However, low dose corticosteroids during short periods of time have not been associated with maternal or fetal complications. Conclusions: The literature review supports the use of low dose corticosteroids during the first weeks of pregnancy in patients with idiopathic recurrent pregnancy losses, and possibly in antiphospholipid syndrome related recurrent pregnancy losses. Their efficacy in patients undergoing in vitro fertilisation is controversial

Encefalitis por anticuerpos contra el receptor de NMDA con afectación hemisférica unilateral / Anti-NMDA receptor encephalitis with unilateral hemispheric affectation

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Mortalidad en pacientes con enfermedad renal. Instituto de Nefrología. 2016 y 2017 / Mortality in patients with kidney disease. Institute of Nephrology, 2016 and 2017

Introducción: La Enfermedad Renal Crónica es un problema de salud mundial. Objetivo: Determinar el comportamiento de la mortalidad en pacientes con enfermedad renal en el Instituto de Nefrología durante 2016 y 2017. Material y Métodos: Estudio observacional descriptivo transversal de pacientes fallecidos con necropsia realizada. Se registraron variables demográficas, de laboratorio, las relacionadas con la terapia de reemplazo de la función renal y con el diagnóstico anatomo-patológico. Para cada una de las variables se calcularon frecuencias absolutas y relativas. En el caso de la variable presencia de sepsis en las defunciones, fue empleada la prueba de chi-cuadrado para la bondad del ajuste, para probar la hipótesis nula H0: de igualdad de la distribución de las tres categorías de la variable. Resultados: Se estudiaron 48 fallecidos con necropsia, 48,9 por ciento del total de fallecidos en el periodo. La correspondencia clínico patológica fue 80,1 por ciento. Predominó el sexo masculino, el grupo de edad superior a 60 años y la hipertensión arterial como antecedente. El método de terapia de reemplazo renal más documentado fue la hemodiálisis, mediante catéter venoso central un 87,8 por ciento. El 61,8 por ciento de los fallecidos recibieron tratamiento hemodialítico por 3 meses o menos. La sepsis fue la segunda causa de muerte precedida por eventos cardio y cerebrovasculares; no obstante, en el análisis de la totalidad de necropsias, la infección asociada directa o indirecta a la muerte tuvo una frecuencia mayor. Conclusiones: La infección directa o indirectamente asociada a la muerte, la hipoalbuminemia y el acceso vascular mediante catéter se relacionan con la mortalidad en el periodo(AU)

Introduction: Chronic kidney disease is a health problem worldwide. Objective: To determine the behavior of mortality in patients with kidney damage in the Nephrology Institute during the years between 2016 and 2017. Material and Method: A cross-sectional descriptive observational study was conducted in 48 deceased patients who underwent necropsy. Demographic and laboratory variables were recorded, as well as those related to the type of renal function replacement therapy and the anatomopathological diagnosis. Absolute and relative frequencies were calculated for each of the variables. In the case of the variable presence of sepsis in deaths, the Chi-Square Goodness-of-Fit Test was used to test the Null Hypothesis HO: uniformity of the distribution of the three categories of the variable. Results: A total of 48 deceased were studied at necropsy, representing 48.9 percent of the total number of deaths within the period. The clinical- pathological correlation was 80.1percent. The male sex, the group over the age of 60 years, and arterial hypertension as antecedent of the disease predominated in the study. The most documented method of renal function replacement therapy was hemodialysis which was performed through central venous catheter, 87.8 percent. The 61.8 percent of deceased patients received hemodialysis treatment for 3 months or less. Sepsis represented the second cause of death preceded by cardiovascular and cerebrovascular events. However, during the analysis of all the necropsies, the direct or indirect infection associated with the death had a greater frequency. Conclusions: Direct or indirect infections associated with death, hypoalbuminemia, and the vascular access with venous catheter was related to mortality during the observed period(AU)

Dos nuevos casos de síndrome de Leigh por mutación m.13513G>A en el gen MTND5 / Two new cases of Leigh syndrome caused by mutation m.13513G> A in the MTND5 gene

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Epidemic of Chronic Kidney Disease of Nontraditional Etiology in El Salvador: Integrated Health Sector Action and South-South Cooperation.

In El Salvador, chronic kidney disease had reached epidemic propor-tions towards the end of this century's first decade. In 2011-2012, the Ministry of Health reported it was the leading cause of hospital deaths in men, the fifth in women, and the third overall in adult hospital fa-talities. Farming was the most common occupation among men in dialysis (50.7%). By 2017, chronic kidney disease admissions had overwhelmed hospital capacity.In 2009, El Salvador's Ministry of Health, Cuba's Ministry of Public Health and PAHO launched a cooperative effort to comprehensively tackle the epidemic. The joint investigations revealed a total prevalence of chronic kidney disease in the adult population of farming communities higher than that reported internationally (18% vs.11%-14.8%), higher in men than in women (23.9% vs 13.9%) and higher in men who were farmers/farmworkers than in men who were not (31.3% vs. 14.8%). The disease was also detected in children. An association was found between chronic kidney disease and exposure to agrochemicals (OR 1.4-2.5). In 51.9% of all chronic kidney disease cases, traditional causes (diabetes, hyperten-sion, glomerulopathies, obstructive nephropathies and cystic diseases) were ruled out and the existence of a particular form of chronic kidney disease of nontraditional etiology was confirmed (whose initial cases were reported as early as 2002). In the patients studied, functional altera-tions and histopathologic diagnosis confirmed a chronic tubulointerstitial nephritis; most presented with neurosensory hearing loss, altered tendon refiexes and tibial artery damage. The main results of this cooperation were the epidemiologic, physio-pathologic, clinical and histopathologic characterization of chronic kid-ney disease of nontraditional etiology. This characterization facilitated case definition for the epidemic and led to the hypothesis of systemic toxicity from agrochemicals (e.g., paraquat, glyphosate), which par-ticularly affect the kidneys and to which farmers/farmworkers (who may also become dehydrated in the fields) are most exposed. The research thus also laid the foundations for design of comprehensive intersectoral government actions to reduce cases and put an end to the epidemic. KEYWORDS Chronic kidney disease; chronic renal failure; tubuloint-erstitial nephritis; epidemiology; histopathology; international coopera-tion; agrochemicals; environmental pollutants, noxae, and pesticides; occupational health; PAHO; El Salvador; Cuba.