Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America.The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations.The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3–T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001).To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations.

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Familial nonmedullary thyroid cancer (NMTC) has not been clearly linked to causal germline variants, despite the large role that genetic factors play in risk. Recently, HABP2 G534E (rs7080536A) has been implicated as a causal variant in NMTC. We have previously shown that the HABP2 G534E variant is not associated with TC risk in patients from the British Isles. Hispanics are the largest and the youngest minority in the United States and NMTC is now the second most common malignancy in women from this population. In order to determine if the HABP2 G534E variant played a role in NMTC risk among Hispanic populations, we analyzed 281 cases and 1105 population-matched controls from a multicenter study in Colombia, evaluating the association through logistic regression. We found that the HABP2 G534E variant was not significantly associated with NMTC risk (P=0.843) in this Hispanic group. We also stratified available clinical data by multiple available clinicopathological variables and further analyzed the effect of HABP2 on NMTC presentation. However, we failed to detect associations between HABP2 G534E and NMTC risk, regardless of disease presentation (P≥0.273 for all cases). Therefore, without any significant associations between the HABP2 G534E variant and NMTC risk, we conclude that the variant is not causal of NMTC in this Hispanic population.

Background and study aims: In the Western world, gastric cancer (GC) usually presents at an advanced stage, carrying a high mortality rate. Studies have reported that 14 % to 26 % of GCs are missed at endoscopy up to 3 years before diagnosis. Systematic Alphanumeric Coded Endoscopy (SACE) has been proposed to improve quality of esophagogastroduodenoscopy (EGD) by facilitating a complete examination of the upper gastrointestinal tract. This prospective cross-sectional study was designed to determine the frequency of gastric intraepithelial neoplasia (GIN) by using the SACE approach in cohort of patients from low socioeconomic level. It also used non-targeted biopsies to evaluate the frequency of premalignant conditions. Patients and methods: A total of 601 consecutive asymptomatic or dyspeptic patients were enrolled between January 2013 and November 2014 at the Huacho regional hospital in Peru. The SACE method proposed by Emura et al, which divides the stomach into 5 regions and 21 areas, was routinely used for diagnosis. Biopsy samples were obtained from any endoscopically detected focal lesion. To evaluate gastric premalignant conditions, 4 non-targeted biopsies were taken. Results: A total of 573 patients were analyzed. The mean age was 57 years, and the female:male ratio was 1.9 : 1. In all cases, complete photo-documentation of the 21 gastric areas was achieved. The overall rate of detection of GIN was 2.8 %. Low-grade displasia, high-grade dysplasia, and adenocarcinoma were found in 13 (2.3 %), 2 (0.3 %), and 1 (0.2 %) of the patients, respectively. The prevalence of at least 1 premalignant condition was 31 %, and helicobacter pylori infection was found in 57 % of patients. Conclusions: Using the SACE approach and with proper training, we have reported herein a high frequency of GIN in patients from a low socioeconomic status. Gastric cancer detection can be improved in a Western endoscopy setting when SACE, as a screening method, is performed by a trained endoscopist.

Abdominal angiostrongyliasis is a parasitic zoonosis, endemic in the American continent. Its etiological agent is Angiostrongylus costaricensis, a nematode whose definitive hosts are rats and other rodents and the intermediate hosts, slugs. Mammals acquire the infection by consuming vegetables contaminated with L3 larvae. The disease shows a heterogeneous clinical spectrum and given its low incidence its diagnosis is a great challenge.In Colombia, the first case was reported in 1979 and until 1998, only five additional cases have been reported. However, in the last two decades, no new cases were reported. Here we discuss two cases of children from Huila and Caquetá departments who developed the disease. Both cases required long in-patient care and multiple surgical interventions. The diagnosis was achieved by histopathological observation of parasitic elements inside the mesenteric arteries. One of the children died while the other fully recovered.We discuss the epidemiology, pathogenic cycle, clinical presentation, diagnosis, and prevention strategies of this disease paying particular attention to our patients’ features and the Colombian context.

Background: Cutaneous leishmaniasis (CL) may present with an inflammatory phenotype, characterized by pain, erythema, and purulent exudate, which is typically treated with antibiotics prior to anti-Leishmania treatment. Although the inflammatory phenotype suggests secondary bacterial infection, bacterial contribution to the pathogenesis of inflammatory CL has yet to be elucidated. The objective of this study was to document the spectrum of bacteria present in inflammatory and non-inflammatory ulcers of CL in order to understand the relationship between disease phenotype and bacterial pathogens.Methods & Materials: Filter paper lesion impressions (FPLIs) from 34 patients with CL (18 inflammatory and 16 noninflammatory CL) were evaluated via real-time PCR (qPCR) and end-point PCR targeting organisms implicated in skin-and softtissue infections, including: Staphylococcus aureus, Enterobacter cloacae, Streptococcus pyogenes, Enterococcus spp., Citrobacter freundii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia, as well as 16S rDNA. Positive specimens were Sanger sequenced for species confirmation.Results: Of 34 specimens, 26 (76%) (14 inflammatory and 12 non-inflammatory) had at least one bacterial species detected, and this did not differ by phenotype. Represented species detected include: Staphylococcus aureus (n = 14, 41%), Pseudomonas aeruginosa (n = 9, 26%), Enterobacter cloacae (n = 8, 24%), Citrobacter freundii (n = 8, 24%), Enterococcus spp. (n = 6, 18%), Streptococcus pyogenes (n = 4, 12%), Klebsiella pneumonia (n = 1, 3%) and Proteus mirabilis (n = 1, 3%). No ulcers were found to harbour Escherichia coli. Prevalence of individual bacterial species did not differ by CL phenotype (p > 0.15). In particular, S. aureus was detected in 6 (37.5%) non-inflammatory ulcers and 8 (44.4%) inflammatory ulcers (p = 1.00). Conclusion:Our findings do not support that bacterial prevalence or individual species composition differs by phenotype of CL ulcers. Further prospective analysis, including WGS of CL ulcers, is warranted to determine the role of empiric antibiotic therapy for those with an inflammatory phenotype of CL.