Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis

Background  

Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis (RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients.     

Differential Effects of Wine Consumption on Colorectal Cancer Outcomes Based on Family History of the Disease

Potentially favorable effects of wine consumption on colorectal cancer (CRC) incidence have been reported, but effects on clinical outcomes are unknown. This case-only analysis was designed to investigate outcomes among familial (n = 141) and sporadic (n = 358) CRC patients enrolled in the University of California Irvine CRC gene-environment study during 1994–1996 based on their reported frequency of wine consumption in the year prior to diagnosis. Cases were categorized as either regular or infrequent wine consumers. Univariate survival rate analyses were estimated using the Kaplan and Meier method and log-rank test. Multivariate survival analyses were performed using Cox proportionalhazards ratios (HRs). Earlier stage at presentation (P = 0.034) was noted for familial (but not sporadic) CRC cases reporting regular wine consumption. An overall survival (OS) benefit was observed for familial (but not sporadic) CRC cases that were regular (10-yr OS = 75%) versus infrequent wine consumers (10-yr OS = 47%; P = 0.002). This survival improvement for familial CRC cases remained after adjustment for age, stage, treatment, and other clinically relevant factors (HR = 0.50, 95% confidence interval = 0.25–0.99). Our findings implicate favorable effects of wine consumption on stage at presentation and survival in CRC, selectively among familial CRC cases.     

Inhibition of Lupus by Genetic Alteration of the Interferon-α/β Receptor

Type I interferons (IFN-αβ) are immunoregulatory cytokines that promote both innate and adaptive immune responses. Although they have been implicated in human SLE, recent studies in mice have helped solidify this connection. By using lupus-prone mice with knockout of the IFN-αβ receptor, we and others have documented that lack of IFN-αβ leads to a marked reduction in disease manifestations, including autoantibody production, target organ damage and mortality. Furthermore, IFN-αβ was found to potentially contribute to several levels of disease pathogenesis. These included the differentiation and activation of dendritic cells, the activation and proliferation of T cells, T cell survival and the activation and survival of autoantibody-producing B cells. These findings strongly support the targeting of IFN-αβ in SLE and suggest that definition of the specific pathways critical for disease induction will be important for optimal intervention.     

Unusual localization of an adenoid cystic carcinoma subsequent to superficial parotidectomy for a benign lesion

Adenoid cystic carcinoma of the parotid gland is relatively rare. According to a retrospective study of the medical records and histopathology files of 514 cases of parotid tumors operated at our hospital over a period of 18 years, adenoid cystic carcinoma represented only 2.3% of all parotid gland neoplasms, a total of 12 cases. In our records we retrieved only one documented case of adenoid cystic carcinoma that originated in the parotid gland subsequent to superficial parotidectomy for a benign lesion (pleomorphic adenoma).An even more exceptional presentation of adenoid cystic carcinoma is as a bilobed tumor extending from the post auricular to the temporal and zygomatic region. The management of this case is presented along with a brief review of the literature concerning the evaluation and management of this rare entity.     

Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women

Background: Glyphosate is the most commonly used herbicide in the world and is purported to have a variety of health effects, including endocrine disruption and an elevated risk of several types of cancer. Blood DNA methylation has been shown to be associated with many other environmental exposures, but to our knowledge, no studies to date have examined the association between blood DNA methylation and glyphosate exposure.Objective: We conducted an epigenome-wide association study to identify DNA methylation loci associated with urinary glyphosate and its metabolite aminomethylphosphonic acid (AMPA) levels. Secondary goals were to determine the association of epigenetic age acceleration with glyphosate and AMPA and develop blood DNA methylation indices to predict urinary glyphosate and AMPA levels.Methods: For 392 postmenopausal women, white blood cell DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip array. Glyphosate and AMPA were measured in two urine samples per participant using liquid chromatography–tandem mass spectrometry. Methylation differences at the probe and regional level associated with glyphosate and AMPA levels were assessed using a resampling-based approach. Probes and regions that had an false discovery rate q<0.1 in ≥90% of 1,000 subsamples of the study population were considered differentially methylated. Differentially methylated sites from the probe-specific analysis were combined into a methylation index. Epigenetic age acceleration from three epigenetic clocks and an epigenetic measure of pace of aging were examined for associations with glyphosate and AMPA.Results: We identified 24 CpG sites whose methylation level was associated with urinary glyphosate concentration and two associated with AMPA. Four regions, within the promoters of the MSH4, KCNA6, ABAT, and NDUFAF2/ERCC8 genes, were associated with glyphosate levels, along with an association between ESR1 promoter hypomethylation and AMPA. The methylation index accurately predicted glyphosate levels in an internal validation cohort. AMPA, but not glyphosate, was associated with greater epigenetic age acceleration.Discussion: Glyphosate and AMPA exposure were associated with DNA methylation differences that could promote the development of cancer and other diseases. Further studies are warranted to replicate our results, determine the functional impact of glyphosate- and AMPA-associated differential DNA methylation, and further explore whether DNA methylation could serve as a biomarker of glyphosate exposure. https://doi.org/10.1289/EHP10174     

Pediatric surgery during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has had a major impact on pediatric surgery. The infection is often asymptomatic and atypical in children, while overlapping presentations with other infectious diseases generate additional diagnostic challenges. The high probability of missed pediatric cases and the invasive nature of surgery generate great concern for widespread transmission in this setting. Current guidelines suggest that triage of cases should be made on a case-by-case basis by a multidisciplinary team of experts. Decision-making can be assisted by classifying cases as elective, urgent, or an emergency according to the risks of delaying their surgical management. A workflow diagram should ideally guide the management of all cases from admission to discharge. When surgery is necessary, all staff should use appropriate personal protective equipment, and high-risk practices, such as aerosol-generating tools or procedures, should be avoided if possible. Furthermore, carefully designed organizational protocols should be established to minimize transmission while ensuring the uninterrupted operation of pediatric surgery units. For example, surgical teams can be divided into small weekly rotating groups, and healthcare workers should be continuously monitored for COVID-19 symptoms. Additionally, team protocols in the operating room can optimize communication and improve adherence to personal protective equipment use. Isolated operating rooms, pediatric intensive care units, and surgical wards should be specifically designed for suspected or confirmed COVID-19 cases. Finally, transportation of patients should be minimal and follow designated short routes. All these measures can help mitigate the effects of the COVID-19 pandemic on pediatric surgery units.