Usefulness of primary care electronic networks to assess the incidence of chlamydia, diagnosed by general practitioners

Background: Chlamydia is the most common curable sexually transmitted infection (STI) in the Netherlands. The majority of chlamydia diagnoses are made by general practitioners (GPs). Baseline data from primary care will facilitate the future evaluation of the ongoing large population-based screening in the Netherlands. The aim of this study was to assess the usefulness of electronic medical records for monitoring the incidence of chlamydia cases diagnosed in primary care in the Netherlands. Methods. In the electronic records of two regional and two national networks, we identified chlamydia diagnoses by means of ICPC codes (International Classification of Primary Care), laboratory results in free text and the prescription of antibiotics. The year of study was 2007 for the two regional networks and one national network, for the other national network the year of study was 2005. We calculated the incidence of diagnosed chlamydia cases per sex, age group and degree of urbanization. Results: A large diversity was observed in the way chlamydia episodes were coded in the four different GP networks and how easily information concerning chlamydia diagnoses could be extracted. The overall incidence ranged from 103.2/100,000 to 590.2/100,000. Differences were partly related to differences between patient populations. Nevertheless, we observed similar trends in the incidence of chlamydia diagnoses in all networks and findings were in line with earlier reports. Conclusions: Electronic patient records, originally intended for individual patient care in general practice, can be an additional source of data for monitoring chlamydia incidence in primary care and can be of use in assessing the future impact of population-based chlamydia screening programs. To increase the usefulness of data we recommend more efforts to standardize registration by (specific) ICPC code and laboratory results across the existing GP networks

Proposed model for the interaction between intestinal and lung impairment in cystic fibrosis (CF).

<p>Intestinal alterations due to CFTR dysfunction may result in malnutrition with consistent respiratory muscle weakness and comprised innate lung defences [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138062#pone.0138062.ref054" target="_blank">54</a>], an impaired barrier function with consequent bacterial translocation to the lungs, and release of inflammatory mediators (cytokines such as interleukin (IL)-8, IL-1 and tissue necrosis factor (TNF)-a, immunoglobulins, lactoferrin, neutrophil elastase, and calprotectin [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138062#pone.0138062.ref011" target="_blank">11</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138062#pone.0138062.ref017" target="_blank">17</a>]) into the systemic circulation, contributing to lung inflammation and impaired lung function. Inflammatory mediators in the lung (cytokines such as IL-8, IL-6, IL-1 and TNF-a, complement factor 5A, neutrophils, proteases (elastase), oxigen radicals, and leukotriene B4 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138062#pone.0138062.ref058" target="_blank">58</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138062#pone.0138062.ref059" target="_blank">59</a>]) are released into the systemic circulation and will reach the intestine or, alternatively, can be swallowed with sputum (together with lung bacteria) and enter the gastrointestinal tract. Further, impaired lung function may result in splanchic hypoperfusion and intestinal hypoxia affecting the intestine. Taken together, this may contribute to intestinal inflammation and impairment and explain the complex interrelationship between CF enteropathy and lung function.</p

Serum I-FABP levels were significantly elevated in cystic fibrosis patients as compared with control subjects.

<p>Boxplot of serum I-FABP concentrations in the study groups, showing the median, the 25^th percentile, the 75^th percentile and the range of values. * Significant difference, p<0.001.</p

Distribution of faecal calprotectin levels in patients with cystic fibrosis (CF).

<p>The upper normal limit for faecal calprotectin (50 ug/g) is indicated by the dashed line.</p

Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses

Although immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (PD-1), can deliver durable antitumor effects, most patients with cancer fail to respond. Recent studies suggest that ICI efficacy correlates with a higher load of tumor-specific neoantigens and development of vitiligo in patients with melanoma. Here, we report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes. Moreover, expansion of peripheral blood CD8+ T cell populations specific for melanocyte antigens was observed only in patients who responded to anti-PD-1 therapy, suggesting that ICI can promote breakdown of tolerance toward tumor-lineage self-antigens. In a mouse model of poorly immunogenic melanomas, spreading of epitope recognition toward wild-type melanocyte antigens was associated with markedly improved anti-PD-1 efficacy in two independent approaches: introduction of neoantigens by ultraviolet (UV) B radiation mutagenesis or the therapeutic combination of ablative fractional photothermolysis plus imiquimod. Complete responses against UV mutation-bearing tumors after anti-PD-1 resulted in protection from subsequent engraftment of melanomas lacking any shared neoantigens, as well as pancreatic adenocarcinomas forcibly overexpressing melanocyte-lineage antigens. Our data demonstrate that somatic mutations are sufficient to provoke strong antitumor responses after checkpoint blockade, but long-term responses are not restricted to these putative neoantigens. Epitope spreading toward T cell recognition of wild-type tumor-lineage self-antigens represents a common pathway for successful response to ICI, which can be evoked in neoantigen-deficient tumors by combination therapy with ablative fractional photothermolysis and imiquimod