Comparison of Two Doses of Antithymocyte Globulin in Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation.

The appropriate dose of antithymocyte globulin (ATG) to be used in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is yet to be determined. We retrospectively analyzed the outcomes of patients who underwent unrelated or mismatch related RIC allo-HSCT for hematologic malignancies and received r-ATG (4.5 mg/kg, 141 patients) versus R-ATG (6 mg/kg, 216 patients). There was a higher incidence of cytomegalovirus (P < .001) and Epstein-Barr virus viremia (P =.03) in the R-ATG group than in the r-ATG group. The cumulative incidences of acute graft-versus-host disease (aGVHD) grades II to IV at day 180 in the r-ATG and R-ATG groups were 59% and 44% (P = .006) and grades III to IV 20% and 12% (P = .029), respectively. In multivariable models adjusting for disease diagnosis, the risk of aGVHD grades III to IV did not reach statistical significance (P = .087). The respective cumulative incidences of chronic GVHD in the r-ATG and R-ATG groups were 26% and 15% (P = .10), respectively. There were no significant differences in relapse rate (P = .24), nonrelapse mortality (P = .96), progression-free survival (P = .24), overall survival (P = .70), and GVHD-free relapse-free survival (P = .24). In this retrospective analysis, aGVHD incidence was higher in those treated with r-ATG compared with R-ATG, but this did not translate into significant differences of clinical outcome. Given the increasing use of RIC allo-HSCT for treating malignant hematologic conditions, the correct dose and schedule of ATG administration should be defined by prospective randomized controlled trials.

Lower limb preservation in pediatric trauma: a case study of Gustilo grade IIIC fracture in a 7-year-old.

This case report describes the intricate aspects of managing pediatric lower limb trauma. A 7-year-old patient had a severe compound fracture and significant soft tissue damage in the left lower limb, classified as Gustilo Grade IIIC. This necessitated the use of scoring systems such as the Mangled Extremity Severity Score and limb salvage index to assess the likelihood of limb preservation. Despite these high amputation risk indicators, a multidisciplinary approach has led to limb salvage surgery with internal fixation. Detailed postoperative monitoring revealed progressive recovery culminating in restored sensation, bone healing, and functional recovery. The discussion emphasizes the difficulties in deciding between limb salvage and amputation, stressing the importance of tailored care and cautious scoring system interpretation in pediatric cases. This conclusion advocates the prioritization of limb salvage in children owing to their unique healing capabilities while highlighting the need for further research to refine treatment protocols for pediatric lower limb trauma.

Age-dependent effects of high fat-diet on murine left ventricles: role of palmitate.

Obesity-associated heart disease results in myocardial lipid accumulation leading to lipotoxicity. However, recent studies are suggestive of protective effects of high-fat diets (HFD). To determine whether age results in differential changes in diet-induced obesity, we fed young and old (3 and 18 months) male C57Bl/6 mice control diet, low-fat diet (both 10 kcal% fat) or HFD (45 kcal% fat) for 16 weeks, after which we analyzed LV function, mitochondrial changes, and potential modifiers of myocardial structure. HFD or age did not change LV systolic function, although a mildly increased BNP was observed in all old mice. This was associated with increased myocardial collagen, triglyceride, diacylglycerol, and ceramide content as well as higher caspase 3 activation in old mice with highest levels in old HFD mice. Pyruvate-dependent respiration and mitochondrial biogenesis were reduced in all old mice and in young HFD mice. Activation of AMPK, a strong inducer of mitochondrial biogenesis, was reduced in both HFD groups and in old control or LFD mice. Cardiomyocytes from old rats demonstrated significantly reduced AMPK activation, impaired mitochondrial biogenesis, higher ceramide content, and reduced viability after palmitate (C16:0) in vitro, while no major deleterious effects were observed in young cardiomyocytes. Aged but not young cardiomyocytes were unable to respond to higher palmitate with increased fatty acid oxidation. Thus, HFD results in cardiac structural alterations and accumulation of lipid intermediates predominantly in old mice, possibly due to the inability of old cardiomyocytes to adapt to high-fatty acid load.

AMPK Activation Is Indispensable for the Protective Effects of Caloric Restriction on Left Ventricular Function in Postinfarct Myocardium.

BACKGROUND: Caloric restriction (CR) extends lifespan in many species, including mammals. CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation. Furthermore, it confers cardioprotection against acute ischemia-reperfusion injury. Here, we investigated the role of AMP-activated protein kinase (AMPK) in mediating the cardioprotective CR effects in failing, postinfarct myocardium. METHODS: Ligation of the left coronary artery or sham operation was performed in rats and mice. Four weeks after surgery, left ventricular (LV) function was analyzed by echocardiography, and animals were assigned to different feeding groups (control diet or 40% CR, 8 weeks) as matched pairs. The role of AMPK was investigated with an AMPK inhibitor in rats or the use of alpha 2 AMPK knock-out mice. RESULTS: CR resulted in a significant improvement in LV function, compared to postinfarct animals receiving control diet in both species. The improvement in LV function was accompanied by a reduction in serum BNP, decrease in LV proapoptotic activation, and increase in mitochondrial biogenesis in the LV. Inhibition or loss of AMPK prevented most of these changes. CONCLUSIONS: The failing, postischemic heart is protected from progressive loss of LV systolic function by CR. AMPK activation is indispensable for these protective effects.

Correction to: Mothers screening for malnutrition by mid-upper arm circumference is non-inferior to community health workers: results from a large-scale pragmatic trial in rural Niger.

[This corrects the article DOI: 10.1186/s13690-016-0149-5.].

Mothers screening for malnutrition by mid-upper arm circumference is non-inferior to community health workers: results from a large-scale pragmatic trial in rural Niger.

BACKGROUND: Community health workers (CHWs) are recommended to screen for acute malnutrition in the community by assessing mid-upper arm circumference (MUAC) on children between 6 and 59 months of age. MUAC is a simple screening tool that has been shown to be a better predictor of mortality in acutely malnourished children than other practicable anthropometric indicators. This study compared, under program conditions, mothers and CHWs in screening for severe acute malnutrition (SAM) by color-banded MUAC tapes. METHODS: This pragmatic interventional, non-randomized efficacy study took place in two health zones of Niger's Mirriah District from May 2013 to April 2014. Mothers in Dogo (Mothers Zone) and CHWs in Takieta (CHWs Zone) were trained to screen for malnutrition by MUAC color-coded class and check for edema. Exhaustive coverage surveys were conducted quarterly, and relevant data collected routinely in the health and nutrition program. An efficacy and cost analysis of each screening strategy was performed. RESULTS: A total of 12,893 mothers and caretakers were trained in the Mothers Zone and 36 CHWs in the CHWs Zone, and point coverage was similar in both zones at the end of the study (35.14 % Mothers Zone vs 32.35 % CHWs Zone, p = 0.9484). In the Mothers Zone, there was a higher rate of MUAC agreement (75.4 % vs 40.1 %, p <0.0001) and earlier detection of cases, with median MUAC at admission for those enrolled by MUAC <115 mm estimated to be 1.6 mm higher using a smoothed bootstrap procedure. Children in the Mothers Zone were much less likely to require inpatient care, both at admission and during treatment, with the most pronounced difference at admission for those enrolled by MUAC < 115 mm (risk ratio = 0.09 [95 % CI 0.03; 0.25], p < 0.0001). Training mothers required higher up-front costs, but overall costs for the year were much lower ($8,600 USD vs $21,980 USD.). CONCLUSIONS: Mothers were not inferior to CHWs in screening for malnutrition at a substantially lower cost. Children in the Mothers Zone were admitted at an earlier stage of SAM and required fewer hospitalizations. Making mothers the focal point of screening strategies should be included in malnutrition treatment programs. TRIAL REGISTRATION: The trial is registered with clinicaltrials.gov (Trial number NCT01863394).

Caloric restriction delays cardiac ageing in rats: role of mitochondria.

AIMS: We tested whether long-term caloric restriction (CR) corrects pre-existing manifestations of cardiac ageing in rats. METHODS AND RESULTS: The age-specific effects of CR (-40%, 6 months) on mortality, left ventricular (LV) function, mitochondrial function, oxidative damage, and apoptosis were analysed in young (6 + 6 months) and senescent rats (24 + 6 months). CR in senescent rats significantly reduced mortality. LV and cardiomyocyte hypertrophy were reduced together with the mRNA expression and plasma concentrations of overload indicators BNP/ANP. Mitochondrial function was improved, resulting in lower oxidative damage and apoptotic activation. In particular, the pro-apoptotic Bcl-xS/Bcl-xL isoform pattern, mitochondrial translocation of Bax, release of cytochrome C into cytosol, and caspase-9 activation were reduced in comparison to age-matched rats on the control diet. However, CR resulted only in minor changes in young rats. Serum obtained from old control or CR rats was used for in vitro experiments. H9C2 cardiomyoblasts and adult rat ventricular cardiomyocytes preconditioned with CR serum demonstrated a low Bcl-xS/Bcl-xL ratio. H9C2 cells were resistant against H(2)O(2)-mediated loss of mitochondrial membrane potential, apoptosis activation, and reduced cell viability. Thus, beneficial effects of CR are mediated through circulating factors and can be mimicked with CR serum. However, this protection critically depended on a high Bcl-xL protein expression as seen after siRNA-mediated Bcl-xL knockdown. CONCLUSION: CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation and by preventing deterioration in LV function. Therefore, interventions that mimic these effects of CR may represent an additional therapeutic option for the aged or failing heart.