Associations between the Nutrient Profiling System Underlying the Nutri-Score Nutrition Label and Biomarkers of Chronic Low-Grade Inflammation: A Cross-Sectional Analysis of a Middle- to Older-Aged Population

Low-grade systemic inflammation is associated with a range of conditions. Diet may modulate inflammation and public health strategies are needed to guide consumers’ dietary choices and help prevent diet-related disease. The Food Standards Agency nutrient profiling system (FSAm-NPS) constitutes the basis of the five-colour front-of-pack Nutri-Score labelling system. No study to date has examined FSAm-NPS dietary index associations with biomarkers of inflammation. Therefore, our objective was to test relationships between the FSAm-NPS and a range of inflammatory biomarkers in a cross-sectional sample of 2006 men and women aged 46–73 years. Individual participant FSAm-NPS scores were derived from food frequency questionnaires. Pro-inflammatory cytokine, adipocytokine, acute-phase response protein, coagulation factor and white blood cell count concentrations were determined. Correlation and linear regression analyses were used to examine FSAm-NPS relationships with biomarker levels. In crude and adjusted analyses, higher FSAm-NPS scores, reflecting poorer nutritional quality, were consistently and positively associated with biomarkers. In fully adjusted models, significant associations with concentrations of complement component 3, c-reactive protein, interleukin 6, tumour necrosis factor alpha, resistin, white blood cell count, neutrophils, eosinophils and the neutrophil-to-lymphocyte ratio persisted. These results suggest that dietary quality, determined by Nutri-Score rating, is associated with inflammatory biomarkers related to health.     

Crohn’s disease,autoimmune thyroiditis,and beta-thalassemia trait in an adolescent: an unusual combination of diseases

An adolescent with complaints of fatigue, tachycardia, abdominal discomfort, and blood-stained diarrhea is presented. Clinical and laboratory evaluation revealed a microcytemic anemia with iron deficiency, beta thalassemia, and thyrotoxicosis with thyroid antibodies. Crohn’s disease was confirmed on endoscopy. A rapid normalization of clinical and laboratory parameters was observed following the initiation of therapy and further exacerbation of her illness was prevented. Although the simultaneous occurrence of Crohn’s disease, autoimmune thyroiditis, and a beta-thalassemia trait is likely to be coincidental, the combination of an autoimmune thyroid disease and Crohn’s disease is rare in pediatrics. Several issues of importance in the treatment of these conditions are discussed. Rectal blood loss associated with Crohn’s disease may lead to severe iron deficiency, especially in patients with preexistent beta-thalassemia trait, and those with thyroiditis are prone to developing hypothyroidism following treatment, requiring that they be monitored closely.     

HPV circulating tumor DNA to monitor the efficacy of anti‐PD‐1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report

Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV‐associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD‐1 immune checkpoint inhibitor, demonstrated significant efficacy as single‐agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single‐agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof‐of‐concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents.     

Two BRM promoter polymorphisms predict poor survival in patients with hepatocellular carcinoma

Polymorphisms in the promoter of the BRM gene, a critical subunit of the chromatin remodeling SWI/SNF complex, have previously been implicated in risk and prognosis in Caucasian‐predominant lung, head and neck, esophageal, and pancreatic cancers, and in hepatocellular cancers in Asians. We investigated the role of these polymorphisms in hepatocellular carcinoma (HCC) risk and prognosis. HCC cases were recruited in a comprehensive cancer center while the matched controls were recruited from family practice units from the same catchment area. For risk analyses, unconditional logistic regression analyses were performed in HCC patients and matched healthy controls. Overall survival analyses were performed using Cox proportional hazard models, Kaplan‐Meier curves, and log‐rank tests. In 266 HCC cases and 536 controls, no association between either BRM promoter polymorphism (BRM‐741 or BRM‐1321) and risk of HCC was identified (P > 0.10 for all comparisons). There was significant worsening of overall survival as the number of variant alleles increased: BRM‐741 per variant allele adjusted hazards ratio (aHR) 5.77, 95% confidence interval (CI) 2.89‐11.54 and BRM‐1321 per variant allele aHR 4.09, 95%CI 2.22‐7.51. The effects of these two polymorphisms were at least additive, where individuals who were double homozygotes for the variant alleles had a 45‐fold increase in risk of death when compared to those who were double wild‐type for the two polymorphisms. Two BRM promoter polymorphisms were strongly associated with HCC prognosis but were not associated with increased HCC susceptibility. The association was strongest in double homozygotes for the allele variants.     

Aromatase inhibitors for infertility in polycystic ovary syndrome. The beginning or the end of a new era?

A meta-analysis of four trials showed significant advantage in pregnancy and delivery rates with aromatase inhibitors compared with CC in women with PCOS. A recent randomized trial demonstrated no clear benefit.     

Treatment of unexplained infertility with aromatase inhibitors or clomiphene citrate: a systematic review and meta-analysis

Treatment of unexplained infertility is empiric and different regimens or protocols have been used so far. Clomiphene can be used alone or combined with gonadotrophins. Aromatase inhibitors may offer an alternative for first-line treatment. To compare the efficacy of aromatase inhibitors versus climiphene, we conducted a systematic review and meta-analysis for randomized controlled trials comparing the above regimens to estimate live pregnancy rates in women with unexplained infertility. Trials were located through PubMed and Cochrane Library searches. Methodological quality of included trials has been assessed. Then, 2 x 2 tables were constructed, and pooled odds ratios (ORs) were calculated. Ten arms (273 patients) were included in the meta-analysis. ORs were homogeneous between studies (heterogeneity chi2 = 2.33, P = 0.676). No difference was observed for live pregnancies (pooled OR 0.87, 95% CI, 0.46-1.65, P = 0.666) for aromatase inhibitors versus clomiphene citrate; however, the definition of live pregnancy by the authors was clear only in one trial. Data regarding secondary outcomes were omitted, and methodogical quality of eligible trials did not reach high scores. Evidence from randomized data regarding the use of aromatase inhibitors is fragmented and weak. Aromatase inhibitors may have a role in the treatment of women with unexplained infertility desiring pregnancy. However, meticulous reporting and study design should be a priority in this field and large, registered, and properly designed randomized trials are essential to test whether aromatase inhibitors can be introduced as a first-line treatment in carefully selected subgroups of women with unexplained infertility.     

The effect of extracts of Searsia species on epileptiform activity in slices of the mouse cerebral cortex

ETHNOPHARMACOLOGICAL RELEVANCE: Searsia dentata and Searsia pyroides are used in traditional South African medicine to treat convulsions and epilepsy. Previous studies have demonstrated that extracts of these plants comprise compounds that bind to the flumazenil-sensitive site on the GABA(A) receptor. However, their use as anticonvulsant medicinal plants cannot be adequately explained by these findings. AIMS: The aim of this study was to examine the possible involvement of the glutamatergic system of extracts from the plants. MATERIALS AND METHODS: The mouse cortical wedge preparation was used for functional characterization of the extracts. The affinity towards the NMDA and the AMPA receptor was investigated using classical [(3)H]-GP39653 and [(3)H]-AMPA binding assays, respectively. RESULTS: The extracts of Searsia dentata and Searsia pyroides inhibited the spontaneous epileptiform discharges in mouse cerebral cortical slices with ED(50) of 0.62 and 1.67mg dry extract/mL, respectively. Both extracts displaced [(3)H]-GP39653 binding and significantly inhibited the NMDA-induced response during co-administration in cortical slices. CONCLUSION: In this study, the NMDA receptor antagonistic effect of the crude ethanolic extracts of these two South African medicinal plants was demonstrated.     

The role of interferon-gamma release assay in tuberculosis control

Tuberculosis is still one of the major global public health threats. Countries with low incidence must focus on exhausting the reservoir of future cases by preventing reactivation. Therefore, it is important to identify and effectively treat those individuals who have latent tuberculosis infection and who may develop active disease. The tuberculin skin test has been the standard for detection of immune response against M. tuberculosis since the beginning of the 20th century. The new millennium has brought advancement in the diagnosis of latent tuberculosis infection. The name of the new blood test is interferon-gamma release assay (IGRA). Croatia is a middle-incidence country with a long decreasing trend and developed tuberculosis control. To reach low incidence and finally eliminate tuberculosis, its tuberculosis programme needs a more aggressive approach that would include intensive contact investigation and treatment of persons with latent tuberculosis infection. This article discusses the current uses of IGRA and its role in tuberculosis control.