A randomized control trial to compare mortality in recipients of leucoreduced and non-leucoreduced whole blood transfusion in patients with cancer in Uganda.

BACKGROUND: Mortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting. METHODS: An open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality. RESULTS: There were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1-3) unit and 2 (IQR, 1-3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1-10) and was 6.2% (95% CI, 3.2-12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86-0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00-0.31, p < 0.01) were associated with reduced 30-day mortality. CONCLUSIONS: The study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed. TRIAL REGISTRATION: Pan African Clinical Trial Registry, https://pactr.samrc.ac.za/ (PACTR202302787440132). Registered on 06/02/2023.

An Adolescent Boy With Hypoxia, Microscopic Hematuria, and Hypertension.

A 13-year-old boy presented with hypoxia, microscopic hematuria, and elevated blood pressures. Persistent microscopic hematuria and hypertension led to investigation of glomerular and non-glomerular causes of hematuria. After reviewing his clinical course, family history, and laboratory testing, an additional test was sent, revealing the diagnosis.

Hip joint and muscle loading for persons with bilateral transfemoral/through-knee amputations: biomechanical differences between full-length articulated and foreshortened non-articulated prostheses.

BACKGROUND: Currently, there is little available in-depth analysis of the biomechanical effect of different prostheses on the musculoskeletal system function and residual limb internal loading for persons with bilateral transfemoral/through-knee amputations (BTF). Commercially available prostheses for BTF include full-length articulated prostheses (microprocessor-controlled prosthetic knees with dynamic response prosthetic feet) and foreshortened non-articulated stubby prostheses. This study aims to assess and compare the BTF musculoskeletal function and loading during gait with these two types of prostheses. METHODS: Gait data were collected from four male traumatic military BTF and four able-bodied (AB) matched controls using a 10-camera motion capture system with two force plates. BTF completed level-ground walking trials with full-length articulated and foreshortened non-articulated stubby prostheses. Inverse kinematics, inverse dynamics and musculoskeletal modelling simulations were conducted. RESULTS: Full-length articulated prostheses introduced larger stride length (by 0.5 m) and walking speed (by 0.3 m/s) than stubbies. BTF with articulated prostheses showed larger peak hip extension angles (by 10.1°), flexion moment (by 1.0 Nm/kg) and second peak hip contact force (by 3.8 bodyweight) than stubbies. There was no difference in the hip joint loading profile between BTF with stubbies and AB for one gait cycle. Full-length articulated prostheses introduced higher hip flexor muscle force impulse than stubbies. CONCLUSIONS: Compared to stubbies, BTF with full-length articulated prostheses can achieve similar activity levels to persons without limb loss, but this may introduce detrimental muscle and hip joint loading, which may lead to reduced muscular endurance and joint degeneration. This study provides beneficial guidance in making informed decisions for prosthesis choice.

Erratum: Momentum-Resolved Observation of Thermal and Quantum Depletion in a Bose Gas [Phys. Rev. Lett. 117, 235303 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.235303.

Evaluation of phosphorus runoff from sandy soils under conservation tillage with surface broadcasted recovered phosphates.

Potential new sources of phosphorus (P) fertilizer are the recovered P from livestock wastewater through chemical precipitation and the ash from combusting animal manures. Although most of the research on P losses from conservation tillage include high water-soluble P compounds from commercial fertilizer sources, information on the use of non-conventional, low water-soluble, recycled P sources is scarce. Particularly for sandy soils of the United States (US) Southeastern Coastal Plain region, research driven information on P loss into the environment is needed to determine recommendations for a direct use of new recycled P sources as crop P fertilizers. The objective of this study is to investigate the potential P runoff from sandy soils under conservation tillage, fertilized with recovered P from liquid swine manure and turkey litter ash in comparison with commercial P fertilizer triple superphosphate (TSP). The field study included two typical sandy soils of the US Southeastern Coastal Plain region, the Noboco and Norfolk. Simulated rain corresponding to the annual 30-min rainfall in the study site (Florence County, South Carolina) was applied to plots treated with recovered P from liquid swine manure, turkey litter ash, and TSP, including a control with no P added. The runoff was monitored and sampled every 5 min during the test and composite soil samples were collected from the top (0-15 cm) and subsurface (15-30 cm) soil layers in each plot. Laboratory analyses were conducted to quantify both total P (TP) and soluble reactive P (SRP) in runoff samples, and the soil test P in the soil layers. Two-way analyses of variances show significant treatment effects on both TP and SRP runoff. The quantities of SRP runoff from plots treated with the recovered P from swine manure and turkey litter ash represent respectively 1% and 7-8% of SRP runoff from plots treated with TSP. Hence, the use of the recovered P materials as crop P fertilizers through surface broadcast application present less environmental risks compared to commercial TSP.

Frequency of red blood cell allo-immunization in patients undergoing blood transfusion at the Uganda Cancer Institute.

Background: There is limited data on red blood cell (RBC) alloimmunization in patients with cancer in sub-Saharan Africa (SSA). We examined the frequency of RBC alloimmunization in transfused patients with cancers in Uganda. Methods: A randomized control trial was conducted on participants at the Uganda Cancer Institute. Eligible participants were age ≥15 years and required blood transfusion. Participants were randomized to receive either leucoreduced or non-leucoreduced blood transfusion. Participants' plasma samples were screened for RBC alloantibodies at enrolment and 3-4 weeks after blood transfusion using a 2-cell panel of reagent group O RBCs using the tube method. Antibody identification was performed using a 10-cell panels of reagent RBCs. Participants were considered alloimmunized if antibodies to RBC antigens were identified. Results: A total of 277 participants were randomized (leucoreduced blood, n=137; non-leucoreduced blood, n=140). Overall, the most represented diagnoses were gynaecological cancers (n=88, 31.8%), acute leukaemia (n=35, 12.6%), and gastrointestinal cancers (n=25, 9.0%). Concomitant HIV infection was present in 26 (9.4%) participants. Most participants received <5 units of blood during the study. No study participant developed allo-antibodies. Conclusion: There was no RBC alloimmunization in participants with cancers. Routine RBC allo-antibody screening in all patients with cancer in SSA requires further research.

Mortality and its associated factors in transfused patients at a tertiary hospital in Uganda.

Blood transfusion is life-saving but sometimes also associated with morbidity and mortality. There is limited data on mortality in patients transfused with whole blood in sub-Saharan Africa. We described the 30-day all-cause mortality and its associated factors in patients transfused with whole blood to inform appropriate clinical intervention and research priorities to mitigate potential risks. A retrospective study was performed on purposively sampled patients transfused with whole blood at the Uganda Cancer Institute (UCI) and Mulago hospital in the year 2018. Two thousand twelve patients with a median (IQR) age of 39 (28-54) years were enrolled over a four month period. There were 1,107 (55%) females. Isolated HIV related anaemia (228, 11.3%), gynaecological cancers (208, 10.3%), unexplained anaemia (186, 9.2%), gastrointestinal cancers (148, 7.4%), and kidney disease (141, 7.0%) were the commonest diagnoses. Most patients were transfused with only one unit of blood (n = 1232, 61.2%). The 30 day all-cause mortality rate was 25.2%. Factors associated with mortality were isolated HIV related anaemia (HR 3.2, 95% CI, 2.3-4.4), liver disease (HR 3.0, 95% CI, 2.0-4.5), kidney disease (HR 2.2, 95% CI, 1.5-3.3; p<0.01), cardiovascular disease (HR 2.9, 95% CI, 1.6-5.4; p<0.01), respiratory disease (HR 3.0, 95% CI 1.8-4.9; p<0.01), diabetes mellitus (HR 4.1, 95% CI, 2.3-7.4; p<0.01) and sepsis (HR 6.2, 95% CI 3.7-10.4; p<0.01). Transfusion with additional blood was associated with survival (HR 0.8, 95% CI 0.7-0.9, p<0.01). In conclusion, the 30-day all-cause mortality was higher than in the general inpatients. Factors associated with mortality were isolated HIV related anaemia, kidney disease, liver disease, respiratory disease, cardiovascular disease, diabetes mellitus and sepsis. Transfusion with additional blood was associated with survival. These findings require further prospective evaluation.

Integrated spatial multiomics reveals fibroblast fate during tissue repair.

In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to skin injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to reveal potential mechanisms controlling fibroblast fate during migration, proliferation, and differentiation following skin injury, and thereby reexamine the canonical phases of wound healing. These findings have broad implications for the study of tissue repair in complex organ systems.