Clinical significance of intraoperative cultures of aneurysm walls and contents in elective abdominal aortic aneurysmectomy

To investigate the clinical significance of intraoperative cultures in elective abdominal aortic aneurysmectomy, we cultured the aneuryrymml wall and contents in 90 patients undergoing vascular graft surgery. Prosthetic graft infection was documented in 1 out of 62 patients with negative cultures and in none of 28 patients with positive cultures (x² = 0.4, p > 0.1). Bacterial growth was seen in neither of 2 inflammatory aneurysms, 3 of 14 atherosclerotic aneurysms and 2 of 5 aneurysms without specific features. A retrospective analysis of patients' charts aimed at finding possible risk factors failed to identify any correlation between results of cultures and length of hospitalization before surgery, time interval between angiography and surgery, route of angiography procedure or minutes of surgery before sample collection. We conclude that positive cultures may not imply clinical infection at the time of surgery and that prolonged post-operative organism-specific antibiotic therapy does not appear necessary to prevent graft contamination in patients undergoing elective abdominal aortic aneurysmectomy.     

Early ovarian cancer: Is there a role for systematic pelvic and para-aortic lymphadenectomy?

Baiocchi G, Raspagliesi F, Grosso G, Fontanelli R, Cobellis L, di Re E, di Re F. Early ovarian cancer: Is there a role for systematic pelvis and para-aortic lymphadenectomy? Int J Gynecol Cancer 1998; 8 : 103–108.
In order to focus on the incidence and the clinical significance of lymphatic spread in patients with cancer apparently confined to the ovaries, we present our 20 year experience in a large series of patients with early ovarian cancer who had systematic pelvic and para-aortic lymphadenectomy. A retrospective study of 280 consecutive patients is presented. Systematic pelvic and para-aortic lymphadenectomy was performed in 205 cases (73.2%). Selective sampling and node biopsy were performed in 30 (10.7%) and 7 (2.5%), respectively. Node metastases were found in 32/242 patients (13.2%). The incidence of metastatic nodes was significantly higher in patients with serous adenocarcinomas and/or poorly-differentiated tumors. When few nodes were involved (1–3) lymphatic spread was most ipsilateral to the tumor. Even though the retrospective nature of the study has to be considered, univariate analysis revealed statistically significant differences in 5-year survival based on FIGO stage, histology, grade of differentiation, and node status. By contrast, using multivariate analysis, none of these risk factors was an independent variable for predicting long-term survival. However, node status closely approached the statistically significant level ( P = 0.06). Only prospective and randomized studies can clarify the role of lymphadenectomy in early ovarian cancer. However, while awaiting these results, this surgical procedure should be a part of a research protocol.     

Nitrate in Drinking Water during Pregnancy and Spontaneous Preterm Birth: A Retrospective Within-Mother Analysis in California

Background: Nitrate is a widespread groundwater contaminant and a leading cause of drinking water quality violations in California. Associations between nitrate exposure and select adverse birth outcomes have been suggested, but few studies have examined gestational exposures to nitrate and risk of preterm birth (before 37 wk gestation).Objective: We investigated the association between elevated nitrate in drinking water and spontaneous preterm birth through a within-mother retrospective cohort study of births in California.Methods: We acquired over 6 million birth certificate records linked with Office of Statewide Health Planning and Development hospital discharge data for California births from 2000–2011. We used public water system monitoring records to estimate nitrate concentrations in drinking water for each woman’s residence during gestation. After exclusions, we constructed a sample of 1,443,318 consecutive sibling births in order to conduct a within-mother analysis. We used separate conditional logistic regression models to estimate the odds of preterm birth at 20–31 and 32–36 wk, respectively, among women whose nitrate exposure changed between consecutive pregnancies.Results: Spontaneous preterm birth at 20–31 wk was increased in association with tap water nitrate concentrations during pregnancy of 5 to <10mg/L [odds ratio (OR)=1.47; 95% confidence interval (CI): 1.29, 1.67] and ≥10mg/L (OR=2.52; 95% CI: 1.49, 4.26) compared with <5mg/L (as nitrogen). Corresponding estimates for spontaneous preterm birth at 32–36 wk were positive but close to the null for 5 to <10mg/L nitrate (OR=1.08; 95% CI: 1.02, 1.15) and for ≥10mg/L nitrate (OR=1.05; 95% CI: 0.85, 1.31) vs. <5mg/L nitrate. Our findings were similar in several secondary and sensitivity analyses, including in a conventional individual-level design.Discussion: The results suggest that nitrate in drinking water is associated with increased odds of spontaneous preterm birth. Notably, we estimated modestly increased odds associated with tap water nitrate concentrations of 5 to <10mg/L (below the federal drinking water standard of 10mg/L) relative to <5mg/L. https://doi.org/10.1289/EHP8205     

Chronic rejection after liver transplantation: Opening the Pandora’s box

Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the “early” phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.     

Rotavirus Seasonal Distribution and Prevalence Before and After the Introduction of Rotavirus Vaccine in a Peri-Urban Community of Lima,Peru

We evaluated the monthly distribution of rotavirus diarrhea in a cohort of children 12–24 months of age followed as part of a diarrhea clinical trial in a peri-urban community of Lima. We observed a peak of rotavirus diarrhea in the winter months and a decrease in rotavirus prevalence after the introduction of the rotavirus vaccine in Peru.     

Case Report of Small Cell Carcinoma of the Ovary,Hypercalcemic Type (Ovarian Rhabdoid Tumor) with SMARCB1 Mutation: A Literature Review of a Rare and Aggressive Condition

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive condition that is associated with the SMARCA4 mutation and has a dismal prognosis. It is generally diagnosed in young women. Here, we report a case of a young woman with SCCOHT harboring a rare molecular finding with a highly aggressive biological behavior. The patient had a somatic SMARCB1 mutation instead of an expected SMARCA4 alteration. Even though the patient was treated with high-dose chemotherapy followed by stem cell transplantation, she evolved with disease progression and died 11 months after her first symptoms appeared. We present a literature review of this rare disease and discuss the findings in the present patient in comparison to expected molecular alterations and options for SCCOHT treatment.     

PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival

Human T-cell leukemia virus type-1 (HTLV-1) is a tumorigenic retrovirus responsible for development of adult T-cell leukemia/lymphoma (ATLL). This disease manifests after a long clinical latency period of up to 2–3 decades. Two viral gene products, Tax and HBZ, have transforming properties and play a role in the pathogenic process. Genetic and epigenetic cellular changes also occur in HTLV-1-infected cells, which contribute to transformation and disease development. However, the role of cellular factors in transformation is not completely understood. Herein, we examined the role of protein arginine methyltransferase 5 (PRMT5) on HTLV-1-mediated cellular transformation and viral gene expression. We found PRMT5 expression was upregulated during HTLV-1-mediated T-cell transformation, as well as in established lymphocytic leukemia/lymphoma cell lines and ATLL patient PBMCs. shRNA-mediated reduction in PRMT5 protein levels or its inhibition by a small molecule inhibitor (PRMT5i) in HTLV-1-infected lymphocytes resulted in increased viral gene expression and decreased cellular proliferation. PRMT5i also had selective toxicity in HTLV-1-transformed T-cells. Finally, we demonstrated that PRMT5 and the HTLV-1 p30 protein had an additive inhibitory effect on HTLV-1 gene expression. Our study provides evidence for PRMT5 as a host cell factor important in HTLV-1-mediated T-cell transformation, and a potential target for ATLL treatment.