Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia:a Multinational Point Prevalence Study of Hospitalised Patients

Pseudornonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding

Endocrine cells in atresic chick embryo intestine: histochemical and immunohistochemical study

Intestinal motility disorders are an important problem in the postoperative management of patients with intestinal atresia. Intestinal motility could be initiated by luminal factors that activate intrinsic and extrinsic primary afferent nerves involved in the peristaltic reflex. Endocrine cells act as a key point, because they transfer information regarding the intestinal contents and intraluminal pressure to nerve fibers lying in close proximity to the basolateral surface of the epithelium. In chick embryo, experimental intestinal atresia is associated with disorders in the development of the enteric nervous system, related to the severity of intestinal dilation. Our aim was to investigate the distribution pattern of endocrine cells in the developing endocrine system of chick embryo small intestine with experimentally-induced atresia on day 12 and on day 16. Changes in enteroendocrine population were examined in gut specimens (excised proximal and distal to the atresia) from experimental embryos 19 days old and in control sham-operated chick embryos at the same age. Sections from proximal and distal bowel and control bowel were stained with Grimelius silver stain, a valuable histochemical method for detecting the argyrophil and argentophilic cells, and with an immunohistochemical procedure for detecting serotonin and neurotensin immunoreactive cells. In chick embryo proximal bowel, intestinal dilation differed in the various embryos. We found significantly higher enteroendocrine cell counts in proximal bowel than in distal and control bowel. The differences depended on the precociousness of surgery and the severity of dilation. Considering the major contribution of enteroendocrine cells to the peristaltic reflex, our data may help to explain the pathogenesis of motility disorders related to intestinal atresia

Supplementary Material for: Ocular metastasis as first presentation of large-cell neuroendocrine carcinoma

We report a rare case of an aggressive large-cell neuroendocrine lung tumour which presented with ocular metastasis. A 70-year-old lady presented with a four-week history of left eye pain and photophobia. Ocular examination revealed left-sided episcleritis and she was treated with topical lubricants and steroids. However, she re-presented six months later with recurrent left eye symptoms, and was found to have an iris stroma amelanotic lesion, posterior synechiae, 360-degrees rubeosis iridis, raised intraocular pressure and trace vitreous inflammation. Ultrasound biomicroscopy revealed a left thickened iris with an associated ciliary body lesion. Sarcoid-related ocular inflammation was suspected, but a computed tomography (CT) scan of the lung revealed an incidental right upper lobe lesion. Histology from a trans-corneal iris biopsy showed a high-grade neuroendocrine carcinoma, and the diagnosis of metastatic lung large-cell neuroendocrine carcinoma was confirmed via high-resolution CT-scan, positron emission tomography scan and CT-guided lung biopsy. She was given multiple courses of different chemotherapy regimens along with palliative radiotherapy. However, the tumour and its metastases continued to progress and she passed away four years after her initial presentation. Ocular metastatic large-cell neuroendocrine carcinoma is rare, and first presentation with ocular metastasis is even rarer. This case highlights the importance of early detection of ocular metastases in order to hasten oncological treatment. A low threshold for systemic investigations and ophthalmology referral in cases of unexplained, refractory ocular symptomatology is essential given the heterogenous presentation, rarity and poor prognosis of these tumours, even with maximal treatment