Radiological evaluation of colorectal anastomoses

Background and aims: The purpose of this study was to determine the accuracy, interobserver variability, timing and discordance with relaparotomy of postoperative radiological examination of colorectal anastomoses. Patient/methods: From 2000 to 2005, 429 patients underwent an

Metastases from renal cell carcinoma presenting as gastrointestinal bleeding: two case reports and a review of the literature

BACKGROUND: Bleeding from small bowel neoplasms account for 1–4% of cases of upper gastrointestinal haemorrhage. Renal cell carcinoma constitutes 3% of all adult malignancies and often presents insidiously. Consequently 25–30% of patients have metastases at the time of diagnosis. Gastrointestinal bleeding from renal cell carcinoma metastases is an uncommon and under-recognised manifestation of this disease. CASE REPORT: In this report we describe two cases of gastrointestinal bleeding from renal cell carcinoma metastases – in one patient bleeding heralded the primary manifestation of disease and in the other signified recurrence of disease following nephrectomy. CONCLUSION: These cases highlight the importance endoscopic vigilance in cases of undiagnosed upper gastrointestinal haemorrhage, especially in patients with a past history of renal cell carcinoma

The Amsterdam Studies of Acute Psychiatry I (ASAP-I); A prospective cohort study of determinants and outcome of coercive versus voluntary treatment interventions in a metropolitan area

Background The overall number of involuntary admissions is increasing in many European countries. Patients with severe mental illnesses more often progress to stages in which acute, coercive treatment is warranted. The number of studies that have examined this development and possible consequences in terms of optimizing health care delivery in emergency psychiatry is small and have a number of methodological shortcomings. The current study seeks to examine factors associated with compulsory admissions in the Amsterdam region, taking into account a comprehensive model with four groups of predictors: patient vulnerability, social support, responsiveness of the health care system and treatment adherence. Methods/Design This paper describes the design of the Amsterdam Study of Acute Psychiatry-I (ASAP-I). The study is a prospective cohort study, with one and two-year follow-up, comparing patients with and without forced admission by means of a selected nested case-control design. An estimated total number of 4,600 patients, aged 18 years and over, consecutively coming into contact with the Psychiatric Emergency Service Amsterdam (PESA) are included in the study. From this cohort, a randomly selected group of 125 involuntary admitted subjects and 125 subjects receiving non-coercive treatment are selected for further evaluation and comparison. First, socio-demographic, psychopathological and network characteristics, and prior use of health services will be described for all patients who come into contact with PESA. Second, the in-depth study of compulsory versus voluntary patients will examine which patient characteristics are associated with acute compulsory admission, also taking into account social network and healthcare variables. The third focus of the study is on the associations between patient vulnerability, social support, healthcare characteristics and treatment adherence in a two-year follow-up for patients with or without involuntarily admittance at the index consultation. Discussion The current study seeks to establish a picture of the determinants of acute compulsory admissions in the Netherlands and tries to gain a better understanding of the association with the course of illness and patient's perception of services and treatment adherence. The final aim is to find specific patient and health care factors that can be influenced by adjusting treatment programs in order to reduce the number of involuntary admissions

Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection

In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants

COMPASS identifies T-cell subsets correlated with clinical outcomes.

Advances in flow cytometry and other single-cell technologies have enabled high-dimensional, high-throughput measurements of individual cells as well as the interrogation of cell population heterogeneity. However, in many instances, computational tools to analyze the wealth of data generated by these technologies are lacking. Here, we present a computational framework for unbiased combinatorial polyfunctionality analysis of antigen-specific T-cell subsets (COMPASS). COMPASS uses a Bayesian hierarchical framework to model all observed cell subsets and select those most likely to have antigen-specific responses. Cell-subset responses are quantified by posterior probabilities, and human subject-level responses are quantified by two summary statistics that describe the quality of an individual's polyfunctional response and can be correlated directly with clinical outcome. Using three clinical data sets of cytokine production, we demonstrate how COMPASS improves characterization of antigen-specific T cells and reveals cellular 'correlates of protection/immunity' in the RV144 HIV vaccine efficacy trial that are missed by other methods. COMPASS is available as open-source software

The Level of Protein in Milk Formula Modifies Ileal Sensitivity to LPS Later in Life in a Piglet Model

Background: Milk formulas have higher protein contents than human milk. This high protein level could modify the development of intestinal microbiota, epithelial barrier and immune functions and have long-term consequences. Methodology/Principal findings: We investigated the effect of a high protein formula on ileal microbiota and physiology during the neonatal period and later in life. Piglets were fed from 2 to 28 days of age either a normoprotein (NP, equivalent to sow milk) or a high protein formula (HP, +40% protein). Then, they received the same solid diet until 160 days. During the formula feeding period ileal microbiota implantation was accelerated in HP piglets with greater concentrations of ileal bacteria at d7 in HP than NP piglets. Epithelial barrier function was altered with a higher permeability to small and large probes in Ussing chambers in HP compared to NP piglets without difference in bacterial translocation. Infiltration of T cells was increased in HP piglets at d28. IL-1b and NF-kappa B sub-units mRNA levels were reduced in HP piglets at d7 and d28 respectively; plasma haptoglobin also tended to be reduced at d7. Later in life, pro-inflammatory cytokines secretion in response to high doses of LPS in explants culture was reduced in HP compared to NP piglets. Levels of mRNA coding the NF-kappa B pathway sub-units were increased by the challenge with LPS in NP piglets, but not HP ones. Conclusions/Significance: A high protein level in formula affects the postnatal development of ileal microbiota, epithelial barrier and immune function in piglets and alters ileal response to inflammatory mediators later in life

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

Background: The regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLE CS), it acts not as a proteinase, but as a receptor for a 1proteinase inhibitor (a 1PI, a 1antitrypsin, SerpinA1). Binding of a1PI to HLECS forms a motogenic complex. We previously demonstrated that a1PI deficiency attends HIV-1 disease and that a1PI augmentation produces increased numbers of immunocompetent circulating CD4 + lymphocytes. Herein we investigated the mechanism underlying the a 1PI deficiency that attends HIV-1 infection. Methods and Findings: Active a 1PI in HIV-1 subjects (median 17 mM, n = 35) was significantly below normal (median 36 mM, p,0.001, n = 30). In HIV-1 uninfected subjects, CD4 + lymphocytes were correlated with the combined factors a1PI, HLECS + lymphocytes, and CXCR4 + lymphocytes (r 2 = 0.91, p,0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with.220 CD4 cells/ml, CD4 + lymphocytes were correlated solely with active a 1PI (r 2 =0.93,p,0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human a 1PI. Chimpanzee a 1PI differs from human a1PI by a single amino acid within the 3F5-binding epitope. Unlike human a1PI, chimpanzee a1PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4 + lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-a 1PI immune complexes correlated with decreased CD4 + lymphocytes in HIV-1 subjects

Th1 Disabled Function in Response to TLR4 Stimulation of Monocyte-Derived DC from Patients Chronically-Infected by Hepatitis C Virus

Background: Lack of protective antibodies and inefficient cytotoxic responses are characteristics of chronic hepatitis C infection. A defect in dendritic cell (DC) function has thus been suspected, but this remains a controversial issue. Methods and Findings: Here we show that monocyte-derived DC (MoDC) from chronically-infected patients can mature in response to TLR1/2, TLR2/6 or TLR3 ligands. In contrast, when stimulated with the TLR4 ligand LPS, MoDC from patients show a profound defect in inducing IFNc secretion by allogeneic T cells. This defect is not due to defective phenotypic maturation or to the presence of HCV-RNA in DC or monocytes but is correlated to reduced IL-12 secretion by DC. Restoration of DC ability to stimulate IFNc secretion can be obtained by blocking MEK activation in DC, indicating that MEK/ ERK pathway is involved in the Th1 defect of MoDC. Monocytes from HCV patients present increased spontaneous secretion of cytokines and chemokines, especially MIP-1b. Addition of MIP-1b on healthy monocytes during differentiation results in DC that have Th1 defect characteristic of MoDC from HCV patients, suggesting that MIP-1b secretion by HCV monocytes participates in the Th1 defect of DC. Conclusions: Our data indicate that monocytes from HCV patients are activated in vivo. This interferes with their differentiation into DC, leading to deficient TLR4 signaling in these cells that are enable to induce a Th1 response. Thi

Variability in the use of pulse oximeters with children in Kenyan hospitals: A mixed-methods analysis.

BACKGROUND: Pulse oximetry, a relatively inexpensive technology, has the potential to improve health outcomes by reducing incorrect diagnoses and supporting appropriate treatment decisions. There is evidence that in low- and middle-income countries, even when available, widespread uptake of pulse oximeters has not occurred, and little research has examined why. We sought to determine when and with which children pulse oximeters are used in Kenyan hospitals, how pulse oximeter use impacts treatment provision, and the barriers to pulse oximeter use. METHODS AND FINDINGS: We analyzed admissions data recorded through Kenya's Clinical Information Network (CIN) between September 2013 and February 2016. We carried out multiple imputation and generated multivariable regression models in R. We also conducted interviews with 30 healthcare workers and staff from 14 Kenyan hospitals to examine pulse oximetry adoption. We adapted the Integrative Model of Behavioural Prediction to link the results from the multivariable regression analyses to the qualitative findings. We included 27,906 child admissions from 7 hospitals in the quantitative analyses. The median age of the children was 1 year, and 55% were male. Three-quarters had a fever, over half had a cough; other symptoms/signs were difficulty breathing (34%), difficulty feeding (34%), and indrawing (32%). The most common diagnoses were pneumonia, diarrhea, and malaria: 45%, 35%, and 28% of children, respectively, had these diagnoses. Half of the children obtained a pulse oximeter reading, and of these, 10% had an oxygen saturation level below 90%. Children were more likely to receive a pulse oximeter reading if they were not alert (odds ratio [OR]: 1.30, 95% confidence interval (CI): 1.09, 1.55, p = 0.003), had chest indrawing (OR: 1.28, 95% CI: 1.17, 1.40, p < 0.001), or a very high respiratory rate (OR: 1.27, 95% CI: 1.13, 1.43, p < 0.001), as were children admitted to certain hospitals, at later time periods, and when a Paediatric Admission Record (PAR) was used (OR PAR used compared with PAR not present: 2.41, 95% CI: 1.98, 2.94, p < 0.001). Children were more likely to be prescribed oxygen if a pulse oximeter reading was obtained (OR: 1.42, 95% CI:1.25, 1.62, p < 0.001) and if this reading was below 90% (OR: 3.29, 95% CI: 2.82, 3.84, p < 0.001). The interviews indicated that the main barriers to pulse oximeter use are inadequate supply, broken pulse oximeters, and insufficient training on how, when, and why to use pulse oximeters and interpret their results. According to the interviews, variation in pulse oximeter use between hospitals is because of differences in pulse oximeter availability and the leadership of senior doctors in advocating for pulse oximeter use, whereas variation within hospitals over time is due to repair delays. Pulse oximeter use increased over time, likely because of the CIN's feedback to hospitals. When pulse oximeters are used, they are sometimes used incorrectly and some healthcare workers lack confidence in readings that contradict clinical signs. The main limitations of the study are that children with high levels of missing data were not excluded, interview participants might not have been representative, and the interviews did not enable a detailed exploration of differences between counties or across senior management groups. CONCLUSIONS: There remain major challenges to implementing pulse oximetry-a cheap, decades old technology-into routine care in Kenya. Implementation requires efficient and transparent procurement and repair systems to ensure adequate availability. Periodic training, structured clinical records that include prompts, the promotion of pulse oximetry by senior doctors, and monitoring and feedback might also support pulse oximeter use. Our findings can inform strategies to support the use of pulse oximeters to guide prompt and effective treatment, in line with the Sustainable Development Goals. Without effective implementation, the potential benefits of pulse oximeters and possible hospital cost-savings by targeting oxygen therapy might not be realized