The management of autoimmunity in patients with cholestatic liver diseases

Cholestatic liver diseases are rare diseases that often lead to cirrhosis and its consequent complications. In addition to liver-related morbidity, patients with cholestatic liver diseases often suffer from autoimmune diseases that affect several organs and tissues. The robust and efficient data collection and collaboration between hepatologists and rheumatologists have led to significant advancements in understanding the relationship between the cholestatic liver diseases and associated autoimmune diseases. In this paper, we discuss the cholestatic liver diseases (primary biliary cirrhosis, primary sclerosing cholangitis and immunoglobulin G4 associated cholangitis) and associated autoimmune diseases.     

Oral health referral trigger tools for people living with HIV

This study validated and compared two different Oral Health Referral Trigger Tools in the form of brief (3‐item and 5‐item) questionnaires designed to identify people living with HIV (PLHIV) with symptoms of oral disease requiring a dental referral from other health professionals. It was composed of a self‐completed questionnaire and oral screen by a dentist of a convenience sample selected from PLHIV attending two outpatient clinics for routine nondental care for HIV infection. The dental exam was completed by a single dentist at a third location. The one hundred participants were HIV positive, predominantly male and of Caucasian origin with a mean age of 45.6 years. Both referral tools were found to be valid and had adequate sensitivity to identify HIV positive subjects at risk of oral disease and facilitate appropriate referral by nondental health professionals to dental health service. When both tools were compared the 3‐item tool proved to be a more valid and sensitive indicator which could be easily applied by nondental staff to facilitate a dental referral.     

The Benefit of the Smartphone in Oral and Maxillofacial Surgery: Smartphone Use Among Maxillofacial Surgery Trainees and iPhone Apps for the Maxillofacial Surgeon

The use of smartphones has soared among healthcare professionals in recent years, with estimated figures reporting that the majority of clinicians own and use smartphones in the workplace. Smartphones allow the clinician to carry textbooks in their pocket, write documents on the move and use email and internet to enhance productivity and clinical decision making. These advances in smartphone technology have enabled access to healthcare information for the clinician and transfer of data between team members, giving rise to the phenomenon of telemedicine. With the ability to instantly transfer clinical data to the off-site surgeon, combined with purpose-built medical apps, the smartphone is rapidly becoming an invaluable tool for the modern surgeon. Many studies have linked the benefits of smartphones and apps in other surgical specialities, but no article to date has highlighted the merits and full scope of this technology to the Oral and Maxillofacial Surgeon. We report that 94 % of British maxillofacial surgery trainees own a smartphone, with 61 % owning an iPhone. 89 % of trainees questioned had downloaded medical apps and used them regularly during clinical activities. We discuss the clinical application of the smartphone in the field of oral and maxillofacial surgery and review a list of useful and relevant apps for the modern maxillofacial surgeon using the iPhone as an example platform.     

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer

Purpose

Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit.

Methods

We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection.

Results

Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise.

Conclusions

HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of ‘immune cold’ TNBCs.

     

Abdominal Adiposity and Coronary Heart Disease in Women

Context.— Obesity is a well-established risk factor for coronary heart disease (CHD), but whether regional fat distribution contributes independently to risk remains unclear. Objective.— To compare waist-hip ratio (WHR) and waist circumference in determining risk of CHD in women. Design and Setting.— Prospective cohort study among US female registered nurses participating in the Nurses' Health Study conducted between 1986, when the nurses completed a questionnaire, and follow-up in June 1994. Participants.— A total of 44,702 women aged 40 to 65 years who provided waist and hip circumferences and were free of prior CHD, stroke, or cancer in 1986. Main Outcome Measures.— Incidence of CHD (nonfatal myocardial infarction or CHD death). Results.— During 8 years of follow-up 320 CHD events (251 myocardial infarctions and 69 CHD deaths) were documented. Higher WHR and greater waist circumference were independently associated with a significantly increased age-adjusted risk of CHD. After adjusting for body mass index (BMI) (defined as weight in kilograms divided by the square of height in meters) and other cardiac risk factors, women with a WHR of 0.88 or higher had a relative risk (RR) of 3.25 (95% confidence interval [CI], 1.78-5.95) for CHD compared with women with a WHR of less than 0.72. A waist circumference of 96.5 cm (38 in) or more was associated with an RR of 3.06 (95% CI, 1.54-6.10). The WHR and waist circumference were independently strongly associated with increased risk of CHD also among women with a BMI of 25 kg/m² or less. After adjustment for reported hypertension, diabetes, and high cholesterol level, a WHR of 0.76 or higher or waist circumference of 76.2 cm (30 in) or more was associated with more than a 2-fold higher risk of CHD. Conclusions.— The WHR and waist circumference are independently associated with risk of CHD in women.      

Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach

AIMS: Whether immunohistochemical markers increase accuracy in predicting prognosis for gastrointestinal stromal tumours (GISTs) remains uncertain. However, past studies have used only small, heterogeneous patient groups. Our aim was to test previously studied and more novel morphological features as well as four immunohistochemical markers as prognostic indicators amongst a large cohort of surgically resected, gastric GISTs. METHODS AND RESULTS: Tissues from 127 gastric mesenchymal tumours were collected retrospectively and subjected to repeat histological assessment and immunophenotyping. Further immunohistochemistry was performed for Ki67, p53, Bcl-2 and cyclin D1. Complete follow-up data were collected for 108 patients with immunophenotyped diagnoses of GIST (i.e. c-kit+ tumours). At the census point, 52 patients were alive, 24 had died from their GISTs and the remainder of other causes. Univariate analysis showed the following predicted for shorter disease-specific survival: size > or =50 mm; necrosis, no intratumoral lymphocytes; mitotic count > or =5/50 high power fields; Ki67 labelling index > or =5%; p53 immunopositivity. Of these variables, multivariate analyses showed only mitotic count and, to a lesser extent, Ki67 labelling to be independent prognostic indicators. CONCLUSIONS: Mitotic count remains the best predictor of outcome following surgical resection of gastric GISTs. Ki67 immunohistochemistry does not provide better prognostication and p53, Bcl-2 and cyclin D1 immunohistochemistry provide no additional prognostication.