Adult vaccination for pneumococcal disease: a comparison of the national guidelines in Europe.

Pneumococcal disease constitutes a major global health problem. Adults aged over 50 years and younger adults with specific chronic health conditions are at risk for invasive pneumococcal disease, associated with substantial morbidity and mortality. In Europe, two vaccine types are used in adults for pneumococcal immunization: pneumococcal polysaccharide vaccine (PPV23) and pneumococcal conjugate vaccine (PCV13). To provide an overview and to compare the national guidelines for pneumococcal immunization for adults in Europe. In November 2016, national guidelines on pneumococcal vaccination for adults of 31 European countries were obtained by Google search, the website of European Centre for Disease Prevention and Control, and contacting public health officials. In our analysis, we distinguished between age-based and risk-based guidelines. In October 2017, we used the same method to retrieve guideline updates. We observed great variability regarding age, risk groups, vaccine type, and use of boosters. In age-based guidelines, vaccination is mostly recommended in adults aged over 65 years using PPV23. Boosters are generally not recommended. An upper age limit for vaccination is reported in three countries. In the immunocompromised population, vaccination with both vaccines and administration of a booster is mostly recommended. In the population with chronic health conditions, there is more heterogeneity according vaccine type, sequence, and administration of boosters. Asplenia is the only comorbidity for which all countries recommend vaccination. The great variability in European pneumococcal vaccination guidelines warrants European unification of the guidelines for better control of pneumococcal disease.

Defining the molecular basis of oncogenic cooperation between TAL1 expression and Pten deletion in T-ALL using a novel pro-T-cell model system.

T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple mutations combined with the ectopic expression of transcription factors in developing T cells. However, the molecular basis underlying cooperation between transcription factor expression and additional oncogenic mutations in driving T-ALL has been difficult to assess due to limited robust T-cell model systems. Here we utilize a new ex vivo pro-T-cell model to study oncogenic cooperation. Using a systems biological approach we first dissect the pro-T-cell signaling network driven by interleukin-7, stem cell factor and Notch1 and identify key downstream Akt, Stat, E2f and Myc genetic signaling networks. Next, this pro-T-cell system was used to demonstrate that ectopic expression of the TAL1 transcription factor and Pten deletion are bona-fide cooperating events resulting in an increased stem cell signature, upregulation of a specific E2f signaling network and metabolic reprogramming with higher influx of glucose carbons into the tricarboxylic acid cycle. This ex vivo pro-T-cell system thereby provides a powerful new model system to investigate how normal T-cell signaling networks are perturbed and/or hijacked by different oncogenic events found in T-ALL.

Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury.

Sepsis-induced acute kidney injury (AKI) is a frequent complication of critically ill patients and leads to high mortality rates. The specificity of currently available urinary biomarkers for AKI in the context of sepsis is questioned. This study aimed to discover urinary biomarkers for septic AKI by contemporary shotgun proteomics in a mouse model for sepsis and to validate these in individual urine samples of mice and human septic patients with and without AKI. At 48 h after uterine ligation and inoculation of Escherichia coli, aged mice (48 weeks) became septic. A subgroup developed AKI, defined by serum creatinine, blood urea nitrogen, and renal histology. Separate pools of urine from septic mice with and without AKI mice were collected during 12 h before and between 36-48 h after infection, and their proteome compositions were quantitatively compared. Candidate biomarkers were validated by Western blot analysis of urine, plasma, and renal tissue homogenates from individual mice, and a limited number of urine samples from human septic patients with and without AKI. Urinary neutrophil gelatinase-associated lipocalin, thioredoxin, gelsolin, chitinase 3-like protein 1 and -3 (CHI3L3) and acidic mammalian chitinase were the most distinctive candidate biomarkers selected for septic AKI. Both neutrophil gelatinase-associated lipocalin and thioredoxin were detected in urine of septic mice and increased with severity of AKI. Acidic mammalian chitinase was only present in urine of septic mice with AKI. Both urinary chitinase 3-like protein 1 and -3 were only detected in septic mice with severe AKI. The human homologue chitinase 3-like protein 1 was found to be more excreted in urine from septic patients with AKI than without. In summary, urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice. Further studies of human chitinase proteins are likely to lead to additional insights in septic AKI.

Upper and lower gastrointestinal evaluation of elderly inpatients who are iron deficient.

PURPOSE: Iron deficiency anemia is commonly caused by chronic gastrointestinal blood loss, and a thorough examination of the gastrointestinal tract has become standard practice. In contrast, iron deficiency without anemia has hardly been studied, and its causes are less certain. The aim of the present study was to determine the diagnostic value of upper and lower gastrointestinal evaluation in elderly hospitalized patients with iron deficiency, irrespective of the hemoglobin level. PATIENTS AND METHODS: In a prospective study, 151 consecutive elderly patients with iron deficiency (serum ferritin level < 50 microg/L at two separate occasions) were investigated using esophagogastroduodenoscopy with colonoscopy (n = 90) or barium enema (n = 61). RESULTS: A potential upper gastrointestinal tract lesion was found in 47 (49%) of the 96 anemic patients and in 31 (56%) of the 55 nonanemic patients (P = 0.38). Nonanemic patients had a greater prevalence of erosive gastritis or duodenitis. Anemic patients (72%) were more frequently investigated with a colonoscopy than nonanemic patients (38%, P = 0.001), and a lower gastrointestinal lesion was found in 32% of the anemic patients and 16% of the nonanemic patients (P = 0.03). Cancer was the most common lesion in the colon; 11 of the 18 patients were asymptomatic. Site-specific symptoms, fecal occult blood loss, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) were not associated with the detection of gastrointestinal lesions. In 9.5% of the patients with a benign upper gastrointestinal lesion, a synchronous colonic tumor was found. CONCLUSION: Elderly patients with iron deficiency should undergo endoscopic examination, irrespective of the hemoglobin level. The presence of gastrointestinal symptoms, a positive fecal occult blood test, and the use of NSAIDs are of limited value in guiding the diagnostic procedure.