COVID-19 y embarazo: caso clínico de presentación crítica, inflamación placentaria y transmisión vertical fetal demostrada / COVID-19 and pregnancy: clinical case of critical presentation, placental inflammation and demonstrated fetal vertical transmission

ANTECEDENTES: La pandemia global de COVID-19 llega al continente americano en marzo del año 2020 y en menos de dos meses reúne a más de la mitad de los casos a nivel global. OBJETIVO: Caso clínico de una mujer embarazada con una presentación crítica de COVID-19 y embarazo a las 25 semanas de gestación, en el contexto del peak de la pandemia en Chile en el otoño del año 2020. CASO CLÍNICO: El 20 de junio de 2020, una mujer de 34 años, con 25 semanas de embarazo, es trasladada desde Hospital de San Bernardo a Clínica Las Condes en Santiago, Chile, con un cuadro de 10 días de evolución de COVID-19, que evoluciona a una situación crítica con insuficiencia respiratoria severa. Ingresa a unidad de cuidados intensivos para ventilación mecánica. Las imágenes de radiología simple y de tomografía axial computarizada de tórax demuestran una neumopatía bilateral con imágenes características opacidades en vidrio esmerilado, asociado a engrosamiento intersticial, imágenes descritas previamente como características para COVID-19. La paciente permanece en unidad de cuidados intensivos en ventilación mecánica por siete días, con evolución favorable posterior, mejoría del cuadro séptico y alta después de 22 días de hospitalización. El parto ocurre en forma espontánea a las 38 semanas, la madre y el recién nacido evolucionan en buen estado general. El examen histopatológico placentario demuestra compromiso inflamatorio vellositario y los exámenes de anticuerpos en sangre del recién nacido demuestran la presencia de anticuerpos del tipo IgG e IgM. Se trata de uno de los pocos casos demostrados reportados de transmisión transplacentaria vía sanguínea de SARS-CoV-2 de la madre al recién nacido.

BACKGROUND: The global COVID-19 pandemic reaches the American continent in March 2020 and in less than two months it brings together more than half of the cases globally.OBJECTIVE: The clinical case of a 25-week pregnant woman with a critical presentation of COVID-19 and pregnancy at 25 weeks of gestation, is presented in the context of the peak of the pandemic in Chile in the fall of 2020. CLINICAL CASE: On June 20, 2020, a 34-year-old woman, 25 weeks pregnant, is transferred from Hospital de San Bernardo to Clinica Las Condes in Santiago, Chile, with a ten-day evolution of a COVID-19 that evolves to critical with severe respiratory failure. She is admitted to the intensive care unit for mechanical ventilation. Chest computerized axial tomography images demonstrate bilateral pneumopathy with characteristic images of ground-glass opacities, associated with interstitial thickening, images previously described as characteristics for COVID-19. The patient remains in the intensive care unit on mechanical ventilation for seven days, with subsequent favorable evolution, improvement of the septic condition, and discharge after 22 days of hospitalization. Delivery occurs at 38 weeks, the mother and the newborn evolve in good general condition. The placental histopathological examination demonstrates villous inflammatory involvement, and the newborn's blood tests show the presence of IgG and IgM antibodies. It is one of the few reported cases of transplacental transmission of SARS-CoV-2 from the mother to the newborn.

Characterization of Chilean patients with sporadic colorectal cancer according to the three main carcinogenic pathways: Microsatellite instability, CpG island methylator phenotype and Chromosomal instability.

Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher's exact and/or chi-square test. Survival curves were estimated with Kaplan-Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.

Linfoma difuso de células grandes B rectal en un paciente con colitis ulcerosa / Rectal diffuse large B cell lymphoma appearing after immunosuppression for ulcerative colitis: report of one case

Primary colorectal lymphoma is a rare form of presentation of gastrointestinal tract lymphomas. Inflammatory bowel disease and its treatment are risk factors for its development. We report a 47-year-old male patient with Ulcerative Colitis of two years of evolution, treated initially with azathioprine and later on with infliximab. Due to a relapse in symptoms after the second dose of infliximab, a new coloncoscopy was performed showing a rectal ulcerative lesion, corresponding to a large cell Non-Hodgkin's Lymphoma. The patient was successfully treated with RCHOP chemotherapy (Rituximab cyclophosphamide doxorubicin vincristine prednisone). He is currently in disease remission.

[Characterization of patients with sporadic colorectal cancer following the new Consensus Molecular Subtypes (CMS)]. / Caracterización de pacientes con cáncer colorrectal esporádico basado en la nueva subclasificación molecular de consenso.

BACKGROUND: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. AIM: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways. MATERIAL AND METHODS: Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal. RESULTS: CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases. CONCLUSIONS: This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine.

Caracterización de pacientes con cáncer colorrectal esporádico basado en la nueva subclasificación molecular de consenso / Characterization of patients with sporadic colorectal cancer following the new Consensus Molecular Subtypes (CMS)

Background: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. Aim: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways. Material and Methods: Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal. Results: CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases. Conclusions: This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine.

[Rectal diffuse large B cell lymphoma appearing after immunosuppression for ulcerative colitis. Report of one case]. / Linfoma difuso de células grandes B rectal en un paciente con colitis ulcerosa.

Primary colorectal lymphoma is a rare form of presentation of gastrointestinal tract lymphomas. Inflammatory bowel disease and its treatment are risk factors for its development. We report a 47-year-old male patient with Ulcerative Colitis of two years of evolution, treated initially with azathioprine and later on with infliximab. Due to a relapse in symptoms after the second dose of infliximab, a new coloncoscopy was performed showing a rectal ulcerative lesion, corresponding to a large cell Non-Hodgkin's Lymphoma. The patient was successfully treated with RCHOP chemotherapy (Rituximab cyclophosphamide doxorubicin vincristine prednisone). He is currently in disease remission.

[Pancreatic metastasis from renal cell carcinoma: a case report]. / Metástasis pancreáticas tardías secundarias a cáncer de células renales: caso clínico.

We report the case of a 60-year-old woman with multiple pancreatic nodules found on abdominal computed tomography. Thirteen years earlier she had undergone a left nephrectomy for renal cell carcinoma. The patient underwent surgery with a preoperative diagnosis of multifocal metastatic or neuroendocrine tumor. At surgery, two metastatic nodules of renal cell carcinoma were found and excised. After four years of follow up there is no evidence of recurrence.

Peliosis hepática focal: Caso clínico radiológico / Peliosis hepatis: Report of one case

Peliosis hepatis is a rare vascular condition of the liver characterized by the presence of cystic blood-fi lled cavities distributed randomly throughout the liver parenchyma. We report a 46 year old female, with dyspepsia. An abdominal Doppler ultrasound showed a hyper vascularized solid liver nodule of 5 cm diameter. Magnetic resonance imaging and CT scan showed the same hyper vascularized nodule. With the possible diagnoses of primary hepatocellular carcinoma or focal nodular hyperplasia, the patient was subjected to an excision of hepatic segment VI, where the nodule was located. The pathological diagnosis of the surgical piece was a peliosis hepatis.

Metástasis pancreáticas tardías secundarias a cáncer de células renales: Caso clínico / Pancreatic metastasis from renal cell carcinoma: A case report

We report the case of a 60 year old woman with multiple pancreatic nodules found on abdominal computed tomography. Thirteen years earlier she had undergone a left nephrectomy for renal cell carcinoma. The patient underwent surgery with a preoperative diagnosis of multifocal metastatic or neuroendocrine tumor. At surgery, two metastatic nodules of renal cell carcinoma were found and excised. After four years of follow up there is no evidence of recurrence.

[Peliosis hepatis: report of one case]. / Peliosis hepática focal: Caso clínico radiológico.

Peliosis hepatis is a rare vascular condition of the liver characterized by the presence of cystic blood-fi lled cavities distributed randomly throughout the liver parenchyma. We report a 46 year old female, with dyspepsia. An abdominal Doppler ultrasound showed a hyper vascularized solid liver nodule of 5 cm diameter. Magnetic resonance imaging and CT scan showed the same hyper vascularized nodule. With the possible diagnoses of primary hepatocellular carcinoma or focal nodular hyperplasia, the patient was subjected to an excision of hepatic segment VI, where the nodule was located. The pathological diagnosis of the surgical piece was a peliosis hepatis.

Effects of chronic copper exposure during early life in rhesus monkeys.

BACKGROUND: Whether infants regulate copper absorption and the potential effects of excess copper in early life remain poorly defined. OBJECTIVE: The objective of the study was to assess copper retention, liver copper content, and liver function in infant rhesus monkeys fed infant formula containing 6.6 mg Cu/L. DESIGN: From birth to 5 mo of age, infant rhesus monkeys were fed formula that was supplemented with copper (0.6 mg Cu/L; n = 5) or not supplemented (n = 4). In all animals, weight and crown-rump length (by anthropometry), hemoglobin, hematocrit, plasma ceruloplasmin activity, and zinc and copper concentrations were measured monthly (birth to 6 mo) and at 8 and 12 mo. When the animals were 1, 5, and 8 mo old, liver copper and metallothionein concentrations, liver histology (by light and electron microscopy), and the number of Kupffer cells were assessed, and 67Cu retention was measured. Liver function was assessed by measurement of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activities and protein, albumin, bilirubin, and blood urea nitrogen concentrations. RESULTS: 67Cu retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with approximately 75% in controls at age 2 mo. At age 8 mo, 67Cu retention was 22.9% in copper-treated animals and 31.5% in controls. Liver histology remained normal by light microscopy, with mild ultrastructural signs of cell damage at 5 mo. Liver copper concentration was 4711, 1139, and 498 microg/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microg/g at 2 mo in controls. Measurements could not be completed in all animals. CONCLUSIONS: No clinical evidence of copper toxicity was observed. Copper absorption was down-regulated; increases in liver copper content at ages 1 and 5 mo did not result in histologic damage. Ultrastructural changes at age 5 mo could signal early cellular damage.

Hamartoma quístico: diagnóstico prenatal y seguimiento del recién nacido / Cystic hamartoma: prenatal diagnosis and newborn follow up

Se presenta un caso clínico con diagnóstico prenatal de tumoración hepática fetal, corroborándose en el recién nacido la existencia de hamartoma quístico cuyo tratamiento quirúrgico fue exitoso