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.     

Immunotherapy for advanced hepatocellular carcinoma: From clinical trials to real-world data and future advances

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers. Advanced HCC is managed with systemic therapies; the tyrosine kinase inhibitor (TKI) sorafenib has been used in 1^st-line setting since 2007. Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors (ICIs) are licensed in 1^st- and 2^nd-line treatment setting. The treatment field of advanced HCC is continuously evolving. Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents, such as other ICIs, TKIs, and anti-angiogenics. Novel immunotherapies including adoptive cell transfer, vaccine-based approaches, and virotherapy are also being brought to the fore. Yet, despite advances, several challenges persist. Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort. Consequently, issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications, comorbidities, or poor performance status; lack of response, efficacy, and safety data; and cost-effectiveness. Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making. This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC, with a focus on ICIs, as well as novel immunotherapy strategies underway.     

Evaluating the impact of using a wound‐specific oral nutritional supplement to support wound healing in a rehabilitation setting

Chronic wounds adversely affect patient quality of life, increase the risk of mortality, and impose high costs on healthcare systems. Since protein‐energy malnutrition or specific nutrient deficiencies can delay wound healing, nutritionally focused care is a key strategy to help prevent or treat the occurrence of non‐healing wounds. The objective of our study of inpatients in a rehabilitation hospital was to quantify the effect of daily wound‐specific oral nutritional supplementation (WS‐ONS) on healing chronic wounds. Using electronic medical records, we conducted a retrospective analysis of patients with chronic wounds. We identified records for (a) a treatment group who received standard wound care + usual hospital diet + daily WS‐ONS for ≥14 days, and (b) a control group who received standard wound care + a usual hospital diet. We collected data for demographics, nutritional status, and wound‐relevant health characteristics. We examined weekly measurements of wound number and sizes (surface area for superficial wounds or volume for non‐superficial wounds). There were 341 patients identified, 114 with 322 wounds in the treatment group and 227 patients with 420 wounds in the control group. We found that rehabilitation inpatients who were given nutritional support had larger wounds and lower functional independence on admission. At discharge, wound area reduction (percent) was nearly two‐fold better in patients who were given daily WS‐ONS + usual hospital diet compared to those who consumed usual diet only (61.1% vs 34.5%). Overall, weekly wound improvement (lowered wound area or wound volume) was more likely in the WS‐ONS group than in the Control group, particularly from the start of care to week 2. Inpatients with largest wounds and lowest functional independence on admission were most likely to be given WS‐ONS, an indication that caregivers recognised the need for supplementation. Week‐to‐week improvement in wound size was more likely in patients who received WS‐ONS than in those who did not. Specifically, wound areas and wound volumes were significantly lower at discharge among patients who were given specialised nutritional support. More research in this field is needed to improve care and reduce healthcare costs.     

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