Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Influence of profilin on sensitisation profiles determined by cutaneous tests and IgE to major allergens in polysensitised patients

Background: Profilin sensitisation is considered a diagnostic confounding factor in areas where patients are exposed to multiple pollens. The aim of this study is to assess pollen sensitisation profiles in adults and children and to evaluate, by means of component-resolved diagnosis (CRD) and skin prick testing (SPT), which pollens may be considered as risk factors of profilin sensitisation in order to establish the best diagnostic approach in polysensitised patients. Methods: A total of 231 pollen-allergic patients (adults and children) were included, out of the pollen season, from an area with similar levels of pollen exposure. Allergological diagnosis was performed by SPT and determination of specific IgE (sIgE) to major allergen components (ADVIA-Centaur™). Patients had not received immunotherapy in the last 5 years and had to reside in the area for 5 consecutive years before entering the study. Results: The relation between sensitisation measured by SPT and by sIgE was studied using a model of cases (patients with +sIgE to a specific allergen) and controls (patients with -sIgE to the same allergen). The outcome, in terms of odds-ratios (OR), was statistically significant for Olea (Ole e 1) (p = 0.0005), Salsola (Sal k 1) (p = 0.0118) and Platanus (Pla a 1+ 2) (p = 0.0372). While positivity of SPT to most pollens was statistically associated with a risk of profilin sensitisation, by CRD the association was statistically significant only for Ole e 1 (OR 3.5, CI 95 %, 1.6-7.6, p = 0.0014), and Phl p 5 (OR 11.9, CI 95 %, 4.1-35.2, p < 0.001). When analysing this association using a logistic regression model, Phl p 5 was the only allergen associated with the risk of being sensitised to profilin (p = 0.0023). Conclusions: In patients sensitised to profilin, the concordance between SPT and CRD is much lower than in those not sensitised to profilin. CRD is able to provide refined information about which pollens increase the risk of sensitisation to profilin

Mesoporous Silicon Microparticles Enhance MHC Class I Cross-Antigen Presentation by Human Dendritic Cells

The mesoporous silicon microparticles (MSMPs) are excellent vehicles for releasing molecules inside the cell. The aim of this work was to use MSMPs to deliver viral specific MHC class I restricted epitopes into human antigen presenting cells (monocyte derived dendritic cells, MDDCs) to facilitate their capture, processing, and presentation to CD8+ (cytotoxic) T lymphocytes. We show for the first time that MSMPs vehiculation of antigenic peptides enhances their MHC class I presentation by human MDDCs to CD8 T lymphocytes

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012–May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Abstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Postoperative complications after pancreatoduodenectomy for malignancy: results from the Recurrence After Whipple’s (RAW) study

Background Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. Method Data were extracted from the Recurrence After Whipple’s (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012–2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien–Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. Results Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). Conclusion In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens

The Pyloric Caeca Area Is a Major Site for IgM+ and IgT+ B Cell Recruitment in Response to Oral Vaccination in Rainbow Trout

Although previous studies have characterized some aspects of the immune response of the teleost gut in response to diverse pathogens or stimuli, most studies have focused on the posterior segments exclusively. However, there are still many details of how teleost intestinal immunity is regulated that remain unsolved, including the location of IgM+ and IgT+ B cells along the digestive tract and their role during the course of a local stimulus. Thus, in the current work, we have studied the B cell response in five different segments of the rainbow trout (Oncorhynchus mykiss) digestive tract in both naïve fish and fish orally vaccinated with an alginate-encapsulated DNA vaccine against infectious pancreatic necrosis virus (IPNV). IgM+ and IgT+ cells were identified all along the tract with the exception of the stomach in naïve fish. While IgM+ cells were mostly located in the lamina propria (LP), IgT+ cells were primarily localized as intraepithelial lymphocytes (IELs). Scattered IgM+ IELs were only detected in the pyloric caeca. In response to oral vaccination, the pyloric caeca region was the area of the digestive tract in which a major recruitment of B cells was demonstrated through both real time PCR and immunohistochemistry, observing a significant increase in the number of both IgM+ and IgT+ IELs. Our findings demonstrate that both IgM+ and IgT+ respond to oral stimulation and challenge the paradigm that teleost IELs are exclusively T cells. Unexpectedly, we have also detected B cells in the fat tissue associated to the digestive tract that respond to vaccination, suggesting that these cells surrounded by adipocytes also play a role in mucosal defense. © 2013 Ballesteros et al.This work was supported by the Starting grant TEBLYM from the European Research Council and by the project AGL2010-18454 from the Spanish Ministerio de Economía y Competitividad.Peer Reviewe

Molecular characterization of three novel chemokine receptors in rainbow trout (Oncorhynchus mykiss)

Chemokines signal through a family of seven-transmembrane domain G-coupled receptors in order to regulate both leukocyte mobilization and activate the recruited cells. Although many chemokines have been identified in rainbow trout (Oncorhynchus mykiss), only a few chemokine receptors have been reported to date. In this work, we have cloned three novel chemokine receptors in rainbow trout. One of these receptors seems to be a clear orthologue of CCR6, while the second one constitutes a novel CCR9 gene different from the previous CCR9 reported in this species. This gene, which we have designated as CCR9B, represents another lineage of fish CCR9 genes, not previously identified. Finally, a deeper phylogenetic analysis of the third novel chemokine receptor gene, which had been identified on the basis of sequence similarity to CCR3, constitutes a novel lineage of CCR receptors which has no equivalent in humans and that may be teleost-specific. We have designated this novel gene as CCR13, to avoid any possible ascription to mammalian genes. Further transcriptional studies revealed that CCR6 was constitutively transcribed in thymus, gills, hindgut and peripheral blood leukocytes (PBLs), while CCR9B was strongly transcribed in thymus and PBLs but also in spleen, gills, hindgut and brain at lower levels. CCR13, on the other hand, was strongly detected in spleen, head kidney and PBLs and faintly in thymus, gills, brain and gonad. The data provided constitutes a step forward the identification of novel chemokine receptors that may contribute to a future understanding of chemokine signalling in fish. © 2012 Elsevier Ltd