Paraprosthetic Complications After Endoprosthesis Replacement of Pelvis Joint with Implants

Purpose

The purpose of the paper is shaping of ideas about possible ways of decreasing complications of the analyzed types of operations and identification of opportunities of the impact on the socio-economic environment among the Afro-American population of USA. The paper demonstrates that the issue of coxofemoral prosthesis is not only a purely medical but also a social problem. In particular, availability of timely aid, as well as insurance in the form of surgery, refer to relevance of the range of problems.

Collagen nerve protector in rat sciatic nerve repair: A morphometric and histological analysis

Peripheral nerve repair is often complicated by fibroblastic scar formation, nerve dysfunction, and traumatic neuroma formation. Use of bio‐absorbable protective wraps may improve outcomes of these repairs. This study histologically compared the incidence of neuroma formation, connective tissue proliferation, and axonal regrowth in transected rat sciatic nerves repaired with and without tubular collagen nerve sleeves. Twenty Sprague‐Dawley rats underwent unilateral sharp sciatic nerve transection and microscopic nerve repair with four epineural sutures and were randomly treated with or without an encircling collagen nerve sleeve. Normal nerves from the contralateral sciatic nerve were also examined. At sacrifice three months later, the nerves were evaluated for traumatic neuroma formation, perineural scar formation, and morphometric analysis. Histological examination of normal and repaired nerves by a neuropathologist demonstrated healing, minimal Wallerian degeneration and no traumatic neuroma formation. Distal section analysis (nine nonwrapped, 10 wrapped), revealed no significant differences in total fascicular area, myelinated fibers per nerve, fiber density, myelin area per nerve, myelinated fiber diameter, axon diameter, myelin thickness, or G‐ratio. Significantly greater (P = 0.005) inner epineural connective tissue formation was observed in nonwrapped nerves (0.62 mm² ± 0.2) versus wrapped nerves (0.35 mm² ± 0.16). The ratio of connective tissue to fascicular area was larger in nonwrapped (1.08 ± 0.26) versus wrapped nerves (0.63 ± 0.22) (P < 0.001). This study demonstrated decreased inner epineural connective tissue formation with use of a collagen nerve wrap during primary repair of peripheral nerve transection in a rat sciatic nerve model. © 2010 Wiley‐Liss, Inc. Microsurgery 30:392–396, 2010.     

Renal Transplantation in Familial Dysautonomia: Report of Two Cases and Review of the Literature

Background and objectives: Chronic kidney disease (CKD) is an increasingly recognized complication of familial dysautonomia (FD), a neurodevelopmental disorder with protean systemic manifestations that are the result of sensory and autonomic dysfunction. Progressive renal dysfunction occurs due to chronic volume depletion and cardiovascular lability with supine hypertension and orthostatic hypotension. By age 25, nearly one-half of all patients with FD will have reached stage 3 CKD. Furthermore, dialysis for ESRD in FD patients is associated with multiple complications and poor outcomes.Design, settings, participants, & measurements: We report two patients with FD who developed ESRD at ages 27 and 16, respectively, and underwent renal transplantation. Transplant was performed after 3 months on intermittent hemodialysis (HD) in the first case and after 1 month on twice-weekly continuous veno-venous hemodialysis (CVVHD) in the second case.Results: Both patients tolerated surgery well and have maintained good graft function at 20 and 24 months posttransplantation, respectively. Symptomatic and functional improvements have included lower supine BP and increased sensitivity to antihypertensive agents.Conclusions: As general supportive care improves the lifespan of FD patients, issues related to the management of ESRD will become more important. Renal transplantation provides a viable alternative to dialysis for FD patients with ESRD.Familial dysautonomia (FD), a rare neurologic disorder with autosomal recessive inheritance, affects the development and survival of sensory and autonomic neurons. FD belongs to a group of disorders known as hereditary sensory and autonomic neuropathies (HSAN) and is termed HSAN type III (1). It almost exclusively affects individuals of Ashkenazi Jewish descent. The carrier frequency in this population is approximately 1 in 27 for the most common FD mutation, with 99.5% of all cases homozygous for this mutation (2–4). The clinical spectrum of neurologic sequelae associated with FD includes oropharyngeal incoordination and gastrointestinal dysmotility leading to feeding difficulties and recurrent aspiration, chemoreceptor insensitivity leading to respiratory dysfunction, and the “dysautonomic crisis” manifested by protracted vomiting or retching with cardiovascular and personality changes (5). A prominent manifestation is marked cardiovascular lability that includes postural hypotension without compensatory tachycardia as well as severe supine hypertension.Kidney disease is a common complication of FD. A recent study of chronic kidney disease (CKD) in the FD population found that nearly 40% of those studied reached at least stage 3 CKD by age 20, and greater than 75% progressed to stage 3 CKD or beyond by age 35 (6). Moreover, 3.5% of patients in the database of 596 patients had reached end-stage renal disease (ESRD) requiring dialysis. Global ischemic-type glomerulosclerosis (GS) has been described as the primary histopathology in patients with FD (7). An interplay between chronic volume depletion, BP lability, and the inability to regulate renal hemodynamics due to sympathethic dysfunction likely underlies the development and progression of kidney disease in these patients. These factors also greatly increase the risk of complications with dialysis, which is associated with increased mortality in the FD population (6).As survival improves and a greater proportion of FD patients are living into their 20s, measures aimed at the treatment of ESRD and at quality of life during ESRD are becoming more important. To our knowledge, there has been only one previously reported case of successful renal transplantation in a patient with FD. We present our experience with two additional patients, the first U.S. cases, who have undergone successful renal transplantation at our center and have continued to do well since transplantation.     

Meeting KDOQI Guideline Goals at Hemodialysis Initiation and Survival during the First Year

Background and objectives: To determine, in a national cohort of incident hemodialysis patients, whether meeting a greater number of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guideline goals at dialysis initiation was independently associated, in a graded manner, with lower first-year mortality rates.Design, setting, participants, & measurements: Patients who initiated hemodialysis between June 1, 2005, and May 31, 2007, in the US were included in this retrospective cohort analysis. Guidelines examined were (1) use of arteriovenous fistula or graft at initiation; (2) hemoglobin ≥11 g/dl; and (3) albumin at goal. The primary predictor variable was number of guideline goals (zero, one, two, or three) met at dialysis initiation. Cox regression analysis was used to compare time to death, adjusting for baseline characteristics.Results: At dialysis initiation, 59%, 31%, 9%, and 1.6% of patients met zero, one, two, or three guideline goals, respectively (total n = 192,307). After multivariate adjustment, mortality hazard ratios (95% confidence intervals) were 0.81 (0.80 to 0.83) for patients who met one, 0.53 (0.51 to 0.56) for patients who met two, and 0.34 (0.30 to 0.39) for patients who met three guideline goals, compared with patients who met none. Meeting each individual goal was also associated with lower mortality.Conclusions: These findings suggest a graded association between meeting a greater number of evidence-based guideline goals at dialysis initiation and lower risk of death during the first year on dialysis.The number of patients with end-stage renal disease (ESRD) requiring dialysis is increasing (1,2). Patients with ESRD have exceedingly high morbidity and mortality rates, particularly in the first year after dialysis initiation, when mortality exceeds 25% (1). To improve outcomes of patients with ESRD, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) developed evidence-based guidelines for the care of kidney disease patients. For patients with chronic kidney disease (CKD) approaching ESRD, the KDOQI guidelines recommend timely nephrology referral, nutritional consultation, fistula placement for dialysis access, and control of anemia, acidosis, and mineral and bone metabolism parameters (3). Evidence from prevalent dialysis patients (4) and from dialysis patients who survived on dialysis for at least 4 to 6 months (5,6) suggests that greater adherence to the KDOQI guidelines is associated with improved patient outcomes. Survival bias in these studies limits their generalizability to patients receiving renal replacement therapy who have survived beyond the initiation period. Whether guideline adherence at the time of dialysis initiation is associated with improved outcomes, particularly during the first year on dialysis, has not been examined.We aimed to determine, in a large nationally representative cohort of incident hemodialysis patients, whether meeting a greater number of KDOQI guideline goals, specifically goals related to vascular access, anemia management, and serum albumin, at dialysis initiation is independently associated, in a graded manner, with survival during the first dialysis year.     

Exaggerated responses to stress in the BTBR T+tf/J mouse: an unusual behavioral phenotype

This study shows that the BTBR T+tf/J mouse, a model for autism spectrum disorder (ASD), has increased levels of the stress hormone corticosterone, when compared to C57BL/6J mice. In addition, we have shown that tail suspension of the BTBR produces a heightened anxiety response in the elevated plus maze. These results suggest that the BTBR mouse is stressor-reactive exhibiting hormone responses that might predispose it to ASD.     

GDNF‐enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons

We previously demonstrated that coadministration of glial cell line‐derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC‐DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF‐enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord. © 2009 Wiley‐Liss, Inc.     

An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions

Background.

BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported.

Methods.

Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center.

Results.

Fifteen patients, five male, with a BRCA1 (n = 4) or BRCA2 (n = 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response.

Conclusion.

BRCA mutation–associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC.