Duration of delayed graft function and outcomes after kidney transplantation from controlled donation after circulatory death donors: a retrospective study

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2–11.75) days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1 year, and a higher rate of acute rejection. On Kaplan–Meier analysis, the presence of DGF was associated with lower graft survival (log‐rank test P = 0.034), though duration of DGF was not (P = 0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617–11.450); P = 0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor.     

Pancreatic resection for locally advanced primary and metastatic nonpancreatic neoplasms

We conducted a retrospective review of our single-institution experience with pancreas resection for locally advanced primary malignancy or metastases from other organs. From January 1989 through April 2001 35 patients underwent pancreatic resection for locally advanced primary (17) and recurrent nonpancreatic (18) tumors. Patient records were examined for recurrence and survival. Seventeen patients with locally advanced primary tumors presented with pancreatic extension either into the head/body (six) or tail (11). Pancreatic resections were completed as en bloc procedures with the primary disease of stomach (five), colon (four), sarcoma (five), adrenal gland (one), or spleen (one). Procedures performed included pancreaticoduodenectomy for proximal lesions and distal pancreatectomy for disease limited to the pancreatic tail. Median overall survival was 56 months. Fourteen of 17 patients remain alive: three with disease and 11 without evidence of recurrence. Eighteen patients presented with recurrent tumor from a previously resected right upper quadrant tumor (nine) or metastases from an intra-abdominal source (nine). The primary source was colon (eight), biliary (three), sarcoma (three), melanoma (two), ovary (one), and unknown primary (one). Patients underwent pancreaticoduodenectomy, distal pancreatectomy, or resection of residual pancreas. Overall median survival was 46 months. In this group of 18 patients there was no increased survival in those patients with a time to recurrence from their primary tumor resection greater than 2 years. We conclude that pancreatic resection for locally advanced nonpancreatic or recurrent intra-abdominal malignancies is possible in properly selected patients. The ability to obtain disease-free margins through en bloc resection is a key component of therapy.     

Hyperphosphatemia,Phosphoprotein Phosphatases,and Microparticle Release in Vascular Endothelial Cells

Hyperphosphatemia in patients with advanced CKD is thought to be an important contributor to cardiovascular risk, in part because of endothelial cell (EC) dysfunction induced by inorganic phosphate (Pi). Such patients also have an elevated circulating concentration of procoagulant endothelial microparticles (MPs), leading to a prothrombotic state, which may contribute to acute occlusive events. We hypothesized that hyperphosphatemia leads to MP formation from ECs through an elevation of intracellular Pi concentration, which directly inhibits phosphoprotein phosphatases, triggering a global increase in phosphorylation and cytoskeletal changes. In cultured human ECs (EAhy926), incubation with elevated extracellular Pi (2.5 mM) led to a rise in intracellular Pi concentration within 90 minutes. This was mediated by PiT1/slc20a1 Pi transporters and led to global accumulation of tyrosine- and serine/threonine-phosphorylated proteins, a marked increase in cellular Tropomyosin-3, plasma membrane blebbing, and release of 0.1- to 1-μm-diameter MPs. The effect of Pi was independent of oxidative stress or apoptosis. Similarly, global inhibition of phosphoprotein phosphatases with orthovanadate or fluoride yielded a global protein phosphorylation response and rapid release of MPs. The Pi-induced MPs expressed VE-cadherin and superficial phosphatidylserine, and in a thrombin generation assay, they displayed significantly more procoagulant activity than particles derived from cells incubated in medium with a physiologic level of Pi (1 mM). These data show a mechanism of Pi-induced cellular stress and signaling, which may be widely applicable in mammalian cells, and in ECs, it provides a novel pathologic link between hyperphosphatemia, generation of MPs, and thrombotic risk.     

Patient profiling can identify patients with adult spinal deformity (ASD) at risk for conversion from nonoperative to surgical treatment: initial steps to reduce ineffective ASD management

Background Context

Non-operative management is a common initial treatment for patients with adult spinal deformity (ASD) despite reported superiority of surgery with regard to outcomes. Ineffective medical care is a large source of resource drain on the health system. Characterization of patients with ASD likely to elect for operative treatment from non-operative management may allow for more efficient patient counseling and cost savings.

Reduction of cyclosporine following the introduction of everolimus in maintenance heart transplant recipients: a pilot study

Data are scarce concerning the calcineurin inhibitor dose reduction required following introduction of everolimus in maintenance heart transplant recipients to maintain stable renal function. In a 48-week, multicenter, single-arm pilot study in heart transplant patients >12 months post-transplant, everolimus was started at 1.5 mg/day (subsequently adjusted to target C ₀ 5–10 ng/ml). Mycophenolate mofetil or azathioprine was discontinued on the same day and cyclosporine (CsA) dose was reduced by 25%, with a further 25% reduction each time calculated glomerular filtration rate (cGFR) decreased to <75% of baseline. Of 36 patients enrolled, 25 were receiving everolimus at week 48. From baseline to week 48, there was a mean decrease of 44.5%, 50.9% and 44.6% in CsA dose, C ₀ and C ₂, respectively. Mean cGFR was 68.9 ± 14.5 ml/min at baseline and 61.6 ± 11.5 ml/min at week 48 ( P  = 0.018). The prespecified criterion for stable renal function was met, i.e. a mean decrease ≤25% of cGFR from baseline. Two patients experienced biopsy-proven acute rejection Grade 3A (5.6%). Between baseline and week 48, there were significant increases in total cholesterol, LDL-cholesterol and triglycerides, and small but significant elevations in liver enzymes. This 1-year pilot study suggests that CsA dose reduction of ca. 40% after initiation of everolimus was associated with a decrease in cGFR, however, based on the prespecified criteria stable renal function was attained.     

Transverse plane pelvic rotation in adolescent idiopathic scoliosis: primary or compensatory?

Several studies have suggested that the pelvis is involved in the etiology or pathogenesis of adolescent idiopathic scoliosis (AIS). The purpose of this retrospective, cross-sectional radiographic study is to identify any correlation between the transverse plane rotational position of the pelvis in stance and operative-size idiopathic or congenital scoliosis deformities, using Scheuermann’s kyphosis and isthmic spondylolisthesis patients for comparison. The hypothesis tested was that the direction of transverse pelvic rotation is the same as that for a thoracic scoliosis. As a group, AIS patients had a significant transverse plane pelvic rotation in the same direction as the thoracic curve. When subdivided into the six Lenke curve patterns, this was true for the groups with a major thoracic curve: thoracic (1), double thoracic (2) and double curve patterns (3). It was not true for patterns with a major thoracolumbar/lumbar curve: single thoracolumbar/lumbar (5) and double thoracic-thoracolumbar/lumbar (6). Nor was it true for triple (4) curves. The Lenke 1 and 2 major thoracic curves without compensatory thoracolumbar/lumbar curves did not have the predicted pelvic rotation. All congenital scoliosis patients studied had main thoracic curves and significant transverse plane pelvic rotation in the same direction as the thoracic curve. There was no transverse plane pelvic rotation in the Scheuermann’s kyphosis or isthmic spondylolisthesis patients. We interpret these findings as consistent with a compensatory rotation of the pelvis in the same direction as the main thoracic curve in most patients with a compensatory thoracolumbar/lumbar curve as well as in patients with main thoracic congenital scoliosis.     

A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica

Purpose

Systematic review comparing biological agents, targeting tumour necrosis factor α, for sciatica with placebo and alternative interventions.

Methods

We searched 21 electronic databases and bibliographies of included studies. We included randomised controlled trials (RCTs), non-RCTs and controlled observational studies of adults who had sciatica treated by biological agents compared with placebo or alternative interventions.

Results

We pooled the results of six studies (five RCTs and one non-RCT) in meta-analyses. Compared with placebo biological agents had: better global effects in the short-term odds ratio (OR) 2.0 (95 % CI 0.7–6.0), medium-term OR 2.7 (95 % CI 1.0–7.1) and long-term OR 2.3 [95 % CI 0.5 to 9.7); improved leg pain intensity in the short-term weighted mean difference (WMD) −13.6 (95 % CI −26.8 to −0.4), medium-term WMD −7.0 (95 % CI −15.4 to 1.5), but not long-term WMD 0.2 (95 % CI −20.3 to 20.8); improved Oswestry Disability Index (ODI) in the short-term WMD −5.2 (95 % CI −14.1 to 3.7), medium-term WMD −8.2 (95 % CI −14.4 to −2.0), and long-term WMD −5.0 (95 % CI −11.8 to 1.8). There was heterogeneity in the leg pain intensity and ODI results and improvements were no longer statistically significant when studies were restricted to RCTs. There was a reduction in the need for discectomy, which was not statistically significant, and no difference in the number of adverse effects.

Conclusions

There was insufficient evidence to recommend these agents when treating sciatica, but sufficient evidence to suggest that larger RCTs are needed.

Electronic supplementary material

The online version of this article (doi:10.1007/s00586-013-2739-z) contains supplementary material, which is available to authorized users.