Key Points• The effect of donor age on survival is negated by the effect of patient age.• Survival did not differ between sibling and offspring donor transplantation.We studied the association between non-HLA donor characteristics (age, sex, donor- Two-year survival adjusted for CMV seropositivity, disease, and disease risk index was lower in patients aged 55 to 78 years after transplantation of grafts from donors younger than 30 years (53%) or aged at least 30 years (46%) compared with younger patients who received grafts from donors younger than 30 years (61%) and at least 30 years (60%; P , .0001).Similarly, 2-year survival in patients aged 55 to 78 years was lower after transplantation of grafts from siblings (45%) or offspring (48%) compared with patients aged 18 to 54 years after transplantation of grafts from siblings (62%), offspring (58%), and parents (61%; P , .0001). Graft failure was higher after transplantation of grafts from parents (14%) compared with siblings (6%) or offspring (7%; P 5 .02). Other non-HLA donor characteristics were not associated with survival or graft failure. The current analyses suggest patient and disease, rather than non-HLA donor characteristics, predominantly influence survival in adults.

Increasing attention has been given to secreted extracellular vesicles (EVs) in the past decades, especially in the portrayal of their molecular cargo and role as messengers in both homeostasis and pathophysiological conditions. This review presents the state-of-the-art proteomic technologies to identify and quantify EVs proteins along with their PTMs, interacting partners and structural details. The rapid growth of mass spectrometry-based analytical strategies for protein sequencing, PTMs and structural characterization has improved the level of molecular details that can be achieved from limited amount of EVs isolated from different biological sources. Here we will provide a perspective view on the achievements and challenges on EVs proteome characterization using mass spectrometry. A detailed bioinformatics approach will help us to picture the molecular fingerprint of EVs and understand better their pathophysiological function.

Pneumonia is one of the leading causes of death and mortality worldwide. The inflammatory responses that follow respiratory infections are protective leading to pathogen clearance but can also be deleterious if unregulated. The microbiota is known to be an important protective barrier against infections, mediating both direct inhibitory effects against the potential pathogen and also regulating the immune responses contributing to a proper clearance of the pathogen and return to homeostasis. GPR43 is one receptor for acetate, a microbiota metabolite shown to induce and to regulate important immune functions. Here, we addressed the role of GPR43 signaling during pulmonary bacterial infections. We have shown for the first time that the absence of GPR43 leads to increased susceptibility to Klebsiella pneumoniae infection, which was associated to both uncontrolled proliferation of bacteria and to increased inflammatory response. Mechanistically, we showed that GPR43 expression especially in neutrophils and alveolar macrophages is important for bacterial phagocytosis and killing. In addition, treatment with the GPR43 ligand, acetate, is protective during bacterial lung infection. This was associated to reduction in the number of bacteria in the airways and to the control of the inflammatory responses. Altogether, GPR43 plays an important role in the “gut–lung axis” as a sensor of the host gut microbiota activity through acetate binding promoting a proper immune response in the lungs.

Introduction Cardiac surgery is an aggressive procedure, inducing a great level of stress and disturbance to the homeostasis of the organism and underlying several postoperative complications. Surgical prehabilitation comprises pre-operative physical conditioning designed to improve the physiological and functional capacities of the individual, prepare the organism for surgical stress and reduce the risk of postoperative morbidity. Aim This systematic review and meta-analysis is aimed at evaluating the ability of prehabilitation to prevent post-surgical complications in cardiac patients. Methods We selected studies conducted among patients who were waiting for non-urgent cardiac surgical procedures, where a comparison between prehabilitation and standard treatment was made. A total of 3650 possible studies were researched, of which eight were selected for inclusion. Results A reduction in the number of complications in the groups submitted to prehabilitation (odds ratio = 0.41; 95% confidence interval (CI): 0.28-0.62; p < 0.001; I= 0%) was observed, as well as a significant increase in maximal inspiratory pressure (standard mean difference (SMD) = 0.66; 95% CI: 0.35-0.96; p < 0.001; I= 58%), a non-significant decrease in the length of stay (SMD = -0.56; 95% CI: -1.13, 0.01; p = 0.05; I= 93%), a non-significant increase in the distance walked by the intervention group in the six-minute walk test (SMD = 0.89; 95% CI -0.06, 1.84; p = 0.07) and a lack of effect on mechanical ventilation time (SMD = -0.03; 95% CI: -0.22, 0.16; p = 0.75; I= 0%). Conclusion Prehabilitation reduces the number of post-surgical complications and increases maximal inspiratory pressure; a reduction in the length of stay and an improvement of functional capacities are also probable.

The nutritional status of patients submitted to hematopoietic stem cell transplant is considered an independent risk factor, which may influence on quality of life and tolerance to the proposed treatment. The impairment of nutritional status during hematopoietic stem cell transplant occurs mainly due to the adverse effects resulting from conditioning to which the patient is subjected. Therefore, adequate nutritional evaluation and follow-up during hematopoietic stem cell transplant are essential. To emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to the nutritional assessment of the patient, the Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplant: Adults was prepared, aiming to standardize and update Nutritional Therapy in this area. Dietitians, nutrition physicians and hematologists from 15 Brazilian centers thar are references in hematopoietic stem cell transplant took part.

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Leukodystrophies (LD) are devastating inherited disorders leading to rapid neurological deterioration and premature death. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected LD. Cord blood is a common donor source for transplantation of these patients because it is rapidly available and can be used without full HLA matching. However, precise recommendations allowing care providers to identify patients who benefit from HSCT are lacking. In this study, we define risk factors and describe the early and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood transplantation (CBT) at an European Society for Blood and Marrow Transplantation center or at Duke University Medical Center from 1996 to 2013. Factors associated with higher overall survival (OS) included presymptomatic status (77% vs 49%; = .006), well-matched (≤1 HLA mismatch) CB units (71% vs 54%; = .009), and performance status (PS) of >80 vs <60 or 60 to 80 (69% vs 32% and 55%, respectively; = .003). For patients with PS≤60 (n = 20) or 60 to 80 (n = 24) pre-CBT, only 4 (9%) showed improvement. Of the survivors with PS>80 pre-CBT, 50% remained stable, 20% declined to 60 to 80, and 30% to <60. Overall, an encouraging OS was found for LD patients after CBT, especially for those who are presymptomatic before CBT and received adequately dosed grafts. Early identification and fast referral to a specialized center may lead to earlier treatment and, subsequently, to improved outcomes.

Umbilical cord blood (UCB) transplantation has a high early mortality rate primarily related to transplanted stem cell dose. To decrease early mortality and enhance engraftment, a portion of selected cord blood units (20% to 50%) was expanded with cytokines and the copper chelator tetraethylenepentamine (carlecortemcel-L) and transplanted with the unmanipulated fraction after myeloablative conditioning. The primary endpoint was 100-day survival, which was compared with a contemporaneous double-unit cord blood transplantation (DUCBT) group. We enrolled 101 patients at 25 sites; the DUCBT comparison (n = 295) was selected from international registries using study eligibility criteria. Baseline carlecortemcel-L study group unit nucleated cell (NC) and CD34 were 3.06 × 10 cell dose/kg and 1.64 × 10 cell dose/kg. Median NC and CD34 fold expansion were 400 and 77, with a mean total CD34 infused of 9.7 × 10/kg. The 100-day survival was 84.2% for the carlecortemcel-L study group versus 74.6% for the DUCBT group (odds ratio, .50; 95% CI, .26 to .95; P = .035). Survival at day 180 was similar for the 2 groups; the major cause of death after day 100 was opportunistic infections. Faster median neutrophil (21 days versus 28 days; P < .0001), and platelet (54 days versus 105 days; P = .008) engraftment was seen in the carlecortemcel-L study group; acute and chronic graft-versus-host disease rates were similar. In this multinational comparative study, transplanting expanded CD34 stem cells from a portion of a single UCB unit, with the remaining unmanipulated fraction improved 100-day survival compared with DUCBT control patients while facilitating myeloid and platelet engraftment. This trial was registered at www.clinicaltrials.gov as #NCT00469729.