Analysis of factors among 30-day and 1-year mortality rates in patients with borderline stable-unstable intertrochanteric hip fracture

ObjectiveThis study aimed to evaluate the possible effects of surgical procedures on mortality and to identify the possible risk factors for mortality in the management of geriatric hip fractures.MethodsA total of 191 patients (105 women and 86 men; mean age 82.26±9.681 [60–108] years) with AO/OTA 31A2.2 intertrochanteric fractures and treated with sliding hip screw, proximal femoral nail, or hemiarthroplasty were included in this retrospective cohort study. The treatment type was decided by the responsible surgeon according to the patients’ pre-injury activity level, bone quality, and features of the fracture. Age, sex, type of fracture, type of surgery performed, American society of anesthesiology (ASA) grade, type of anesthesia, time to surgery, type of physical therapy, length of hospital stay, and number of comorbidities were documented. We evaluated the 30-day and 1-year mortality of patients treated with sliding hip screw (SHS), proximal femoral nail antirotation (PFN-A), or hemiarthroplasty and identified the possible risk factors for mortality.ResultsA total of 49 patients underwent SHS, 58 underwent PFN-A, and 84 underwent hemiarthroplasty. Of these, 2 patients with SHS, 2 with PFN-A, and 11 with hemiarthroplasty died within 30 days after surgery, whereas 7 patients with SHS, 15 with PFN-A, and 23 with hemiarthroplasty died 1 year after surgery. The 30-day and 1-year overall mortality rates were 7.9% and 23.6%, respectively. Both the 30-day and 1-year mortality risks were higher in patients undergoing hemiarthroplasty than in patients undergoing SHS (p=0.068 versus 0.058). The 30-day mortality was higher in patients receiving general anesthesia than in those receiving combined spinal and epidural anesthesia (p=0.009). The 1-year mortality risk was higher in patients with ASA grade 4 than in those with grade 1 and 2 (p=0.045). Advanced age (p=0.022) and male sex (p=0.007) were also found to be the risk factors for 1-year mortality.ConclusionWe demonstrated that higher ASA grade, male sex, general anesthesia, and hemiarthroplasty procedures are associated with higher mortality rates in elderly patients with hip fractures. Thus, we highly recommend orthopedic surgeons to consider all these factors in the management of intertrochanteric hip fractures in the geriatric population.Level of EvidenceLevel IV, Prognostic Study     

Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: −7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m²). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.     

Platelet glycoprotein VI-dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets

Platelet activation and thrombus formation have been implicated to be detrimental for intraportal pancreatic islet transplants. The platelet-specific collagen receptor glycoprotein VI (GPVI) plays a key role in thrombosis through cellular activation and the subsequent release of secondary mediators. In aggregometry and in a microfluidic dynamic assay system modeling flow in the portal vein, pancreatic islets promoted platelet aggregation and triggered thrombus formation, respectively. While platelet GPVI deficiency did not affect the initiation of these events, it was found to destabilize platelet aggregates and thrombi in this process. Interestingly, while no major difference was detected in early thrombus formation after intraportal islet transplantation, genetic GPVI deficiency or acute anti-GPVI treatment led to an inferior graft survival and function in both syngeneic mouse islet transplantation and xenogeneic human islet transplantation models. These results demonstrate that platelet GPVI signaling is indispensable in stable thrombus formation induced by pancreatic islets. GPVI deficiency resulted in thrombus destabilization and inferior islet engraftment indicating that thrombus formation is necessary for a successful intraportal islet transplantation in which platelets are active modulators.     

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7–14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.     

Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection

The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.