Timing of antiretroviral therapy in Cambodian hospital after diagnosis of tuberculosis: impact of revised WHO guidelines

OBJECTIVE: To determine if implementation of 2010 World Health Organization (WHO) guidelines on antiretroviral therapy (ART) initiation reduced delay from tuberculosis diagnosis to initiation of ART in a Cambodian urban hospital. METHODS: A retrospective cohort study was conducted in a nongovernmental hospital in Phnom Penh that followed new WHO guidelines in patients with human immunodeficiency virus (HIV) and tuberculosis. All ART-naïve, HIV-positive patients initiated on antituberculosis treatment over the 18 months before and after guideline implementation were included. A competing risk regression model was used. FINDINGS: After implementation of the 2010 WHO guidelines, 190 HIV-positive patients with tuberculosis were identified: 53% males; median age, 38 years; median baseline CD4+ T-lymphocyte (CD4+ cell) count, 43 cells/µL. Before implementation, 262 patients were identified; 56% males; median age, 36 years; median baseline CD4+ cell count, 59 cells/µL. With baseline CD4+ cell counts ≤ 50 cells/µL, median delay to ART declined from 5.8 weeks (interquartile range, IQR: 3.7–9.0) before to 3.0 weeks (IQR: 2.1–4.4) after implementation (P < 0.001); with baseline CD4+ cell counts > 50 cells/µL, delay dropped from 7.0 (IQR: 5.3–11.3) to 3.6 (IQR: 2.9–5.3) weeks (P < 0.001). The probability of ART initiation within 4 and 8 weeks after tuberculosis diagnosis rose from 23% and 65%, respectively, before implementation, to 62% and 90% after implementation. A non-significant increase in 6-month retention and antiretroviral substitution was seen after implementation. CONCLUSION: Implementation of 2010 WHO recommendations in a routine clinical setting shortens delay to ART. Larger studies with longer follow-up are needed to assess impact on patient outcomes

Morphometric and mechanical characterization, insulin loading and in-vivo biocompatibility of chitosan particles aggregated scaffolds for tissue engineering

In tissue engineering, scaffolds development presents, among others, 3 key requirements: adequate morphological characteristics, mechanical performance and in-vivo biocompatibility. The aim of the present study was to evaluate chitosan-based scaffolds produced by particle aggregation in these key issues. Furthermore, chitosan scaffolds were loaded with insulin to promote chondrogenic differentiation. Micro-Computed Tomography (m-CT) was carried out for accurate morphometric characterization quantifying porosity, interconnectivity, particles and pores size that shown to be adequate. Dynamical Mechanical Analysis (DMA) showed that scaffolds are mechanically stable in wet state with a storage modulus of 4.21 1.04 MPa at 1Hz frequency. Insulin-loaded scaffolds were characterized and studied with a pre-chondrogenic cell line (ATDC-5). The in-vitro release was carried out mimicking cell culture conditions quantified by micro-BCA. [...]info:eu-repo/semantics/publishedVersio

Liposomal amphotericin B for visceral leishmaniasis in human immunodeficiency virus-coinfected patients: 2-year treatment outcomes in Bihar, India

Reports on treatment outcomes of visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection in India are lacking. To our knowledge, none have studied the efficacy of liposomal amphotericin B in VL-HIV coinfection. We report the 2-year treatment outcomes of VL-HIV-coinfected patients treated with liposomal amphotericin B followed by combination antiretroviral treatment (cART) in Bihar, India

Bacterial sepsis in patients with visceral leishmaniasis in Northwest Ethiopia

Background and Objectives. Visceral leishmaniasis (VL) is one of the neglected diseases affecting the poorest segment of world populations. Sepsis is one of the predictors for death of patients with VL. This study aimed to assess the prevalence and factors associated with bacterial sepsis, causative agents, and their antimicrobial susceptibility patterns among patients with VL. Methods. A cross-sectional study was conducted among parasitologically confirmed VL patients suspected of sepsis admitted to the University of Gondar Hospital, Northwest Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical samples were collected and cultured following the standard procedures. Results. Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%; 11/16), including two methicillin-resistant isolates (MRSA). Patients with focal bacterial infection were more likely to have bacterial sepsis (P<0.001). Conclusions. The prevalence of culture confirmed bacterial sepsis was high, predominantly due to S. aureus. Concurrent focal bacterial infection was associated with bacterial sepsis, suggesting that focal infections could serve as sources for bacterial sepsis among VL patients. Careful clinical evaluation for focal infections and prompt initiation of empiric antibiotic treatment appears warranted in VL patients

Systemic Inflammatory Effects of Traumatic Brain Injury, Femur Fracture, and Shock: An Experimental Murine Polytrauma Model

Objective. Despite broad research in neurotrauma and shock, little is known on systemic inflammatory effects of the clinically most relevant combined polytrauma. Experimental investigation in an animal model may provide relevant insight for therapeutic strategies. We describe the effects of a combined injury with respect to lymphocyte population and cytokine activation. Methods. 45 male C57BL/6J mice (mean weight 27 g) were anesthetized with ketamine/xylazine. Animals were subjected to a weight drop closed traumatic brain injury (WD-TBI), a femoral fracture and hemorrhagic shock (FX-SH). Animals were subdivided into WD-TBI, FX-SH and combined trauma (CO-TX) groups. Subjects were sacrificed at 96 h. Blood was analysed for cytokines and by flow cytometry for lymphocyte populations. Results. Mortality was 8%, 13% and 47% for FX-SH, WD-TBI and CO-TX groups (P < 0.05). TNFα (11/13/139 for FX-SH/WD-TBI/CO-TX; P < 0.05), CCL2 (78/96/227; P < 0.05) and IL-6 (16/48/281; P = 0.05) showed significant increases in the CO-TX group. Lymphocyte populations results for FX-SH, WD-TBI and CO-TX were: CD-4 (31/21/22; P = n.s.), CD-8 (7/28/34, P < 0.05), CD-4-CD-8 (11/12/18; P = n.s.), CD-56 (36/7/8; P < 0.05). Conclusion. This study shows that a combination of closed TBI and femur-fracture/ shock results in an increase of the humoral inflammation. More attention to combined injury models in inflammation research is indicated

Outbreak of Burkholderia cepacia bloodstream infections traced to the use of Ringer lactate solution as multiple-dose vial for catheter flushing, Phnom Penh, Cambodia

AbstractThe Burkholderia cepacia complex is a group of Gram-negative bacteria known as respiratory pathogens in cystic fibrosis patients, but also increasingly reported as a cause of healthcare associated infections. We describe an outbreak of B. cepacia bloodstream infections in a referral hospital in Phnom Penh, Cambodia. Over a 1.5-month period, blood cultures from eight adult patients grew B. cepacia. Bloodstream infection occurred after a median of 2.5 days of hospitalisation. Three patients died: 7, 10 and 17 days after blood cultures were sampled. As part of the outbreak investigation, patient files were reviewed and environmental sampling was performed. All patients had peripheral venous catheters that were flushed with Ringer lactate drawn from a 1 L bag, used as multiple-dose vial at the ward. Cultures of unopened Ringer lactate and disinfectants remained sterile but an in-use bag of Ringer lactate solution and the dispensing pin grew B. cepacia. The isolates from patients and flushing solution were identified as B. cepacia by recA gene sequence analysis, and random amplified polymorphic DNA typing confirmed clonal relatedness. The onset of the outbreak had coincided with the introduction of a dispensing pin with a screw fit that did not allow proper disinfection. Re-enforcement of aseptic procedures with sterile syringe and needle has ended the outbreak. Growth of B. cepacia should alert the possibility of healthcare associated infection also in tropical resource-limited settings. The use of multiple-dose vials should be avoided and newly introduced procedures should be assessed for infection control risks

Vascular endothelial growth factor and fibroblast growth Factor-2 incorporation in starch-based bone tissue-engineered constructs promote the In vivo expression of neovascularization mediators

The ideal bone tissue-engineered (TE) construct remains to be found, although daily discoveries significantly contribute to improvements in the field and certainly have valuable long-term outcomes. In this work, different TE elements, aiming at bone TE applications, were assembled and its effect on the expression of several vas- cularization/angiogenesis mediators analyzed. Starch/polycaprolactone (SPCL) scaffolds, obtained by two different methodologies, were combined with fibrin sealant (Baxter), human adipose-derived stem cells (hASCs), and growth factors (vascular endothelial growth factor [VEGF] or fibroblast growth factor-2 [FGF-2]), and implanted in vascular endothelial growth factor receptor-2 (VEGFR2)-luc transgenic mice. The expression of VEGFR2 along the implantation of the designed constructs was followed using a luminescence device (XenogenÒ) and after 2 weeks, the explants were retrieved to perform histological analysis and reverse transcriptase–polymerase chain reaction for vascularization (VEGF and VEGFR1) and inflammatory (tumor necrosis factor-alpha, interleukin-4, and interferon-gamma) markers. It was showed that SPCL scaffolds ob- tained by wet spinning and by fiber bonding constitute an adequate support for hASCs. The assembled TE constructs composed by fibrin sealant, hASCs, VEGF, and FGF-2 induce only a mild inflammatory reaction after 2 weeks of implantation. Additionally, the release of VEGF and FGF-2 from the constructs enhanced the ex- pression of VEGFR2 and other important mediators in neovascularization (VEGF and VEGFR1). These results indicate the potential of VEGF or FGF-2 within a bone TE construct composed by wet-spun SPCL, fibrin sealant, and hASCs in promoting the vascularization of newly formed tissue.The author Tircia C. Santos acknowledges the Marie Curie European Program for a short-term scholarship in the Alea Jacta EST project (MEST-CT-2004-008104). This work was developed under the scope of the European Network of Excellence EXPERTISSUES (NMP3-CT-2004-5000283)

Chitosan improves the biological performance of soy-based biomaterials

Soybean protein has been proposed for distinct applications within nutritional, pharmaceutical, and cosmetic industries among others. More recently, soy-based biomaterials have also demonstrated promising properties for biomedical applications.However, althoughmany reports within other fields exist, the inflammatory/immunogenic potential of those materials is still poorly understood and therefore can hardly be controlled. On the contrary, chitosan (Cht) has been well explored in the biomedical field, either by itself or combined with synthetic or other natural-based polymers. Therefore, the combination of chitosan with soybean protein is foreseen as a suitable approach to control the biological behavior of soy-based biomaterials. Under this context this work was designed to try to understand the influence of chitosan in the host response elicited by soy-based biomaterials. Soybean protein isolate powder (SI-P) and Cht powder (Cht-P) were injected as suspension into the intraperitoneal cavity of rats. SI-P induced the recruitment of higher numbers of leukocytes compared to the Cht-P during the entire observation period. In this sense, SI-P elicited a considerable reaction from the host comparing to the Cht-P, which elicited leukocyte recruitment similar to the negative control.After subcutaneous implantation of the soybean and denatured membranes, (SI-M and dSI-M) a severe host inflammatory reaction was observed. Conversely, Cht/soy-based membranes (Cht/soy-based membranes) showed the induction of a normal host response after subcutaneous implantation in rats, which allowed concluding that the addition of chitosan to the soy-based membranes improved their in vivo performance. Thus, the presented results assert the improvement of the host response, considering inflammatory cells recruitment, and overall inflammatory reaction,when chitosan is combined to soybean. Together with previous results that reported their promising physicochemical characteristics and their inability to activate human polymorphonuclear neutrophils in vitro, the herein presented conclusions reinforce the usefulness of theCht/ soy-based membranes and justify the pursue for a specific application within the biomedical field.The author Tircia C. Santos acknowledges the Marie Curie European Program for a short-term scholarship in the Alea Jacta EST project (MEST-CT-2004-008104). This work was developed under the scope of the European Network of Excellence EXPERTISSUES (NMP3-CT-2004-5000283)

Chitosan/soy-based membranes enhance wound reepithelialization in partial thickness skin wounds

[Excerpt] Chitosan-based biomaterials proved to have promising characteristics for wound dressing and skin regeneration. In the context of developing new natural-based biomaterials for these applications, chitosan and soybean-based biomaterials were proposed. These materials were shown to be non cytotoxic and to impair human leukocytes activation in vitro. Thus the goal of this study was to evaluate the in vivo performance of chitosan/soy-based membranes in the regeneration of partial thickness skin wounds. Excisional skin wounds were created on the backs of rats and the healing capacity of chitosan/soy-based membranes was assessed after 1 and 2 weeks. To promote impaired wound healing all rats were injected with a steroid. [...]This work was partially supported by the European Union funded STREP Project HIPPOCRATES (NMP3-CT-2003-505758) and was carried out under the scope of the European NoE EXPERTISSUES (NMP3-CT-2004-500283).info:eu-repo/semantics/publishedVersio