Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial.

BACKGROUND: Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. METHODS: In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda. RESULTS: We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1-2) vs 3 (2-3), P < 0.001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms. CONCLUSION: In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed. TRIAL REGISTRATION: The study was registered with the Pan African Clinical Trial Registry ( PACTR201110000321348 )

Effect of a Participatory Multisectoral Maternal and Newborn Intervention on Maternal Health Service Utilization and Newborn Care Practices: A Quasi-Experimental Study in Three Rural Ugandan Districts

Background: The MANIFEST study in eastern Uganda employed a participatory multisectoral approach to reduce barriers to access to maternal and newborn care services. Objectives: This study analyses the effect of the intervention on the utilization of maternal and newborn services and care practices. Methods: The quasi-experimental pre- and post-comparison design had two main components: community mobilization and empowerment, and health provider capacity building. The primary outcomes were utilization of antenatal care (ANC), delivery and postnatal care, and newborn care practices. Baseline (n = 2237) and endline (n = 1946) data were collected from women of reproductive age. The data was analysed using difference in differences (DiD) analysis and logistic regression. Results: The DiD results revealed an 8% difference in early ANC attendance (p < 0.01) and facility delivery (p < 0.01). Facility delivery increased from 66% to 73% in the intervention area, but remained unchanged in the comparison area (64% vs 63%, p < 0.01). The DiD results also demonstrated a 20% difference in clean cord care (p < 0.001) and an 8% difference in delayed bathing (p < 0.001). The intervention elements that predicted facility delivery were attending ANC four times [adjusted odds ratio (aOR) 1.42, 95% confidence interval (CI) 1.17–1.74] and saving for maternal health (aOR 2.11, 95% CI 1.39–3.21). Facility delivery and village health team (VHT) home visits were key predictors for clean cord care and skin-to-skin care. Conclusions: The multisectoral approach had positive effects on early ANC attendance, facility deliveries and newborn care practices. Community resources such as VHTs and savings are crucial to maternal and newborn outcomes and should be supported. VHT-led health education should incorporate practical measures that enable families to save and access transport services to enhance adequate preparation for birth.DFI

Tissue conservation for transplantation

Pathophysiological changes that occur during ischemia and subsequent reperfusion cause damage to tissues procured for transplantation and also affect long-term allograft function and survival. The proper preservation of organs before transplantation is a must to limit these injuries as much as possible. For decades, static cold storage has been the gold standard for organ preservation, with mechanical perfusion developing as a promising alternative only recently. The current literature points to the need of developing dedicated preservation protocols for every organ, which in combination with other interventions such as ischemic preconditioning and therapeutic additives offer the possibility of improving organ preservation and extending it to multiple times its current duration. This review strives to present an overview of the current body of knowledge with regard to the preservation of organs and tissues destined for transplantation

Factors associated with mortality.

Factors associated with mortality.</p

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Baseline patient characteristics.

Baseline patient characteristics.</p

Kaplan-Meier survival estimate of transfused patients.

Kaplan-Meier survival estimate of transfused patients.</p

Macrophage Subpopulation Dynamics Shift following Intravenous Infusion of Mesenchymal Stromal Cells

Intravenous infusion of mesenchymal stromal cells (MSCs) is thought to be a viable treatment for numerous disorders. Although the intrinsic immunosuppressive ability of MSCs has been credited for this therapeutic effect, their exact impact on endogenous tissue-resident cells following delivery has not been clearly characterized. Moreover, multiple studies have reported pulmonary sequestration of MSCs upon intravenous delivery. Despite substantial efforts to improve MSC homing, it remains unclear whether MSC migration to the site of injury is necessary to achieve a therapeutic effect. Using a murine excisional wound healing model, we offer an explanation of how sequestered MSCs improve healing through their systemic impact on macrophage subpopulations. We demonstrate that infusion of MSCs leads to pulmonary entrapment followed by rapid clearance, but also significantly accelerates wound closure. Using single-cell RNA sequencing of the wound, we show that following MSC delivery, innate immune cells, particularly macrophages, exhibit distinctive transcriptional changes. We identify the appearance of a pro-angiogenic CD9(+) macrophage subpopulation, whose induction is mediated by several proteins secreted by MSCs, including COL6A1, PRG4, and TGFB3. Our findings suggest that MSCs do not need to act locally to induce broad changes in the immune system and ultimately treat disease

Kidney Dysfunction After Vascularized Composite Allotransplantation

Background. Kidney dysfunction is a major complication after nonrenal solid organ transplants. Transplantation of vascularized composite allografts (VCA) has yielded successful midterm outcomes despite high rates of acute rejection and greater requirements of immunosuppression. Whether this translates in higher risks of kidney complications is unknown. Methods. Ninety-nine recipients of facial or extremity transplants from the Brigham and Women’s Hospital (BWH) and the International Registry on Hand and Composite Tissue Transplantation (IR) were reviewed. We assessed immunosuppression, markers of renal function over time, as well as pretransplant and posttransplant renal risk factors. Results. Data were obtained from 10 patients from BWH (age at transplant, 42.5 ± 13.8 years) and 89 patients (37.8 ± 11.5 years) from IR. A significant rise in creatinine levels (BWH, P = 0.0195; IR, P < 0.0001) and drop in estimated glomerular filtration rate (GFR) within the first year posttransplant was observed. The BWH and IR patients lost a mean of 22 mL/min GFR and 60 mL/min estimated GFR in the first year, respectively. This decrease occurred mostly in the first 6 months posttransplant (BWH). Pretransplant creatinine levels were not restored in either cohort. A mixed linear model identified multiple variables correlating with renal dysfunction, particularly tacrolimus trough levels. Conclusions. Kidney dysfunction represents a major complication posttransplantation in VCA recipients early on. Strategies to mitigate this complication, such as reducing calcineurin inhibitor trough levels or using alternative immunosuppressive agents, may improve long-term patient outcomes. Standardizing laboratory and data collection of kidney parameters and risk factors in VCA patients will be critical for better understanding of this complication