Hypovitaminosis D as a risk factor of subsequent vertebral fractures after kyphoplasty

Background contextOver the past 20 years, methods of minimally invasive surgery have been developed for the treatment of vertebral compression fractures. Balloon kyphoplasty and vertebroplasty are associated with a recurrent fracture risk in the adjacent levels after the surgical procedure. In certain patient categories with impaired bone metabolism, the risk of subsequent fractures after kyphoplasty is increased.PurposeTo determine the incidence of recurrent fractures after kyphoplasty and explore whether the status of bone metabolism and 25-hydroxyvitamin D (25(OH)D) levels affect the occurrence of these fractures.Study designProspective longitudinal clinical study.Patient sampleForty female postmenopausal women with primary osteoporosis and acute symptomatic vertebral compression fractures.Outcome measuresIdentification of new vertebral fractures and documentation of indicators of bone metabolism.MethodsA total of ninety-eight kyphoplasties were performed in 40 female patients. Balloon kyphoplasty was performed on all symptomatic acute vertebral compression fractures. Age, body mass index, history of tobacco use, number of initial vertebral fractures, intradiscal cement leakage, history of nonspinal fractures, use of antiosteoporotic medications, bone mineral density, bone turnover markers, and 25(OH)D levels were assessed. All participants were evaluated clinically and/or radiographically. Follow-up period was 18 months.ResultsThe mean population age was 70.6 years (range, 40–83 years). After initial kyphoplasty procedure, nine patients (11 levels) (22.5% of patients; 11.2% of levels) developed a postkyphoplasty vertebral compression fracture. Cement leakage was identified in seven patients (17.5%). The patients without recurrent fractures after kyphoplasty demonstrated higher levels of 25(OH)D (22.6±5.51 vs. 14.39±7.47; p=.001) and lower N-terminal cross-linked telopeptide values (17.11±10.20 vs. 12.90±4.05; p=.067) compared with the patients with recurrent fractures.ConclusionsBone metabolism and 25(OH)D levels seem to play a role in the occurrence of postkyphoplasty recurrent vertebral compression fractures.     

Accelerated renal fibrosis in cardiorenal syndrome is associated with long-term increase in urine neutrophil gelatinase-associated lipocalin levels

Background: Cardiac events are the main cause of death among patients with end-stage renal failure. Even a mild renal disease is currently considered a major risk factor for cardiovascular complications following myocardial infarction (MI). The aim of the present study was to detect histological, sera and urine characteristics of kidney injury in cardiorenal syndrome (CRS) compared to chronic kidney disease (CKD) with an intact cardiac function. Methods: We employed a rat model for CRS, in which an acute MI (AMI) was induced 4 weeks after establishment of subtotal nephrectomy. Four weeks later, left ventricular function was assessed by echocardiography and changes in renal performance were examined using histological and biochemical parameters. Results: Increased interstitial fibrosis as well as renal inflammation were observed in renal sections derived from CRS rats, compared to subtotal nephrectomy (CKD)-only animals. Moreover, we found that even though AMI on the background of CKD was not associated with a further decrease in creatinine clearance or a further increase in sera BUN levels compared to CKD only, a significant long-term elevation in urine neutrophil gelatinase-associated lipocalin (Ngal) levels was detectable post-MI induction. Conclusions: AMI in the CKD setting is associated with accelerated renal fibrosis and long-term elevated urine Ngal values, suggesting that cardiac dysfunction contributes to accelerated intrinsic kidney injury in CKD. The data indicate that elevated urine Ngal may potentially serve as an early non-invasive laboratory parameter for a left ventricular dysfunction-related renal injury.     

Valsalva prosthesis in aortic valve-sparing operations

Aortic valve-sparing operations have provided very good clinical outcomes. However, the absence of the sinuses of Valsalva might limit valve durability. The Gelweave Valsalva prosthesis, which presents pre-fashioned neo-sinuses, has been designed in order to avoid early leaflets deterioration. We report our results in 63 patients who underwent valve-sparing operations (reimplantation technique) using the Gelweave Valsalva graft. The main indication was ascending aorta aneurysm or annuloaortic ectasia, with or without aortic insufficiency. The operation was performed also in cases of Marfan syndrome, Bicuspid Aortic Valve (BAV), and acute Type A dissection. In-hospital mortality was of 4.7%, and two thirds were acute Type A dissection patients (P=0.01). There were no late deaths. Three years freedom from grade 3-4 AI and freedom from late aortic valve replacement were 91.7+/-4.3% and 93.8+/-5.1%, respectively. Aortic valve-sparing operations show good results in patients electively operated for aortic root ectasia. Aortic cusps repair may lead to late failure. Even if the Gelweave Valsalva prosthesis is easy to implant and it also reproduces pseudosinuses, a long-term follow up is necessary to determine if this graft may reduce leaflets deterioration.     

Reduced number of CD169+ macrophages in pre‐metastatic regional lymph nodes is associated with subsequent metastatic disease in an animal model and with poor outcome in prostate cancer patients

Background

Tumor‐derived antigens are captured by CD169⁺ (SIGLEC1⁺) sinus macrophages in regional lymph nodes (LNs), and are presented to effector cells inducing an anti‐tumor immune response. Reduced CD169 expression in pre‐metastatic regional LNs is associated with subsequent metastatic disease and a poor outcome in several tumor types, but if this is the case in prostate cancer has not been explored.

Methods

CD169 expression was measured with immunohistochemistry in metastasis‐free regional LNs from 109 prostate cancer patients treated with prostatectomy (January 1996 to April 2002). Possible associations of CD169 expression with PSA‐relapse, prostate cancer death, Gleason score, and other clinical data were assessed using Kaplan‐Meier survival‐ and Cox regression analysis. In addition, the Dunning rat prostate tumor model was used to examine CD169 expression in pre‐metastatic LNs draining either highly metastatic MatLyLu‐ or poorly metastatic AT1‐tumors.

Results

In patients with low CD169 immunostaining in metastasis‐free regional LNs, 8 of the 27 patients died from prostate cancer compared with only three of the 82 patients with high immunostaining (P < 0.001). CD169 expression in regional LNs was not associated with PSA‐relapse. Rats with highly metastatic tumors had decreased CD169 immunoreactivity in pre‐metastatic regional LNs compared with rats with poorly metastatic tumors.

Conclusion

Low expression of CD169 in metastasis‐free regional LNs indicates a reduced anti‐tumor immune response. If verified in other studies, CD169 expression in regional LNs could, in combination with other factors, potentially be used as a marker of prostate cancer aggressiveness.     

Operative differences for posterior spinal fusion after vertebral body tethering: Are we fusing more levels in the end?

Purpose

Little is known about the perioperative characteristics associated with a posterior spinal fusion (PSF) in adolescent idiopathic scoliosis patients previously treated with vertebral body tethering (VBT). We aimed to determine if operative time, estimated blood loss, postoperative length of stay, instrumentation type, and implant density differed in patients that received a PSF (i.e., PSF-Only) or a PSF following a failed VBT (i.e., PSF–VBT).

Methods

We retrospectively assessed matched cohort data (PSF–VBT = 22; PSF-Only = 22) from two multi-center registries. We obtained: (1) operative time, (2) estimated blood loss, (3) postoperative length of stay, (4) instrumentation type, and (5) implant density. Theoretical fusion levels prior to the index procedure were obtained for PSF–VBT and compared to the actual levels fused.

Results

We observed no difference in operative time, estimated blood loss, or postoperative length of stay. Instrumentation type was all-screw in PSF-Only and varied in PSF–VBT with nearly 25% of patients exhibiting a hybrid construct. There was no added benefit to removing anterior instrumentation prior to fusion; however, implant density was higher in PSF-Only (1.9 ± 0.2) than when compared to PSF–VBT (1.7 ± 0.3). An additional two levels were fused in 50% of PSF–VBT patients, most of which were added to the distal end of the construct.

Conclusions

We found that operative time, estimated blood loss, and postoperative length of stay were similar in both cohorts; however, the length of the fusion construct in PSF–VBT is likely to be two levels longer when a failed VBT is converted to a PSF.

     

Prevention of severe contractures might replace multilevel surgery in cerebral palsy: results of a population-based health care programme and new techniques to reduce spasticity

During the 1990s three new techniques to reduce spasticity and dystonia in children with cerebral palsy (CP) were introduced in southern Sweden: selective dorsal rhizotomy, continuous intrathecal baclofen infusion and botulinum toxin treatment. In 1994 a CP register and a health care programme, aimed to prevent hip dislocation and severe contractures, were initiated in the area. The total population of children with CP born 1990-1991, 1992-1993 and 1994-1995 was evaluated and compared at 8 years of age. In non-ambulant children the passive range of motion in hip, knee and ankle improved significantly from the first to the later age groups. Ambulant children had similar range of motion in the three age groups, with almost no severe contractures. The proportion of children treated with orthopaedic surgery for contracture or skeletal torsion deformity decreased from 40 to 15% (P = 0.0019). One-fifth of the children with spastic diplegia had been treated with selective dorsal rhizotomy. One-third of the children born 1994-1995 had been treated with botulinum toxin before 8 years of age. With early treatment of spasticity, early non-operative treatment of contracture and prevention of hip dislocation, the need for orthopaedic surgery for contracture or torsion deformity is reduced, and the need for multilevel procedures seems to be eliminated.     

Critical influence of natural regulatory CD25+ T cells on the fate of allografts in the absence of immunosuppression

BACKGROUND: Allografts are occasionally accepted in the absence of immunosuppression. Because naturally occurring CD4(+)CD25(+) regulatory T cells (natural CD25(+) Treg cells) have been shown to inhibit allograft rejection, we investigated their influence on the outcome of allografts in nonimmunosuppressed mouse recipients. METHODS: We compared survival times of male CBA/Ca skin grafts in female CBA/Ca recipients expressing a transgenic anti-HY T-cell receptor on a RAG-1(+/+) (A1[M]RAG+) or a RAG-1(-/-) (A1[M]RAG-) background. Depletion of natural CD25(+) Treg cells in A1[M]RAG+ mice was achieved by in vivo administration of the PC61 monoclonal antibody. The influence of natural CD25(+) Treg cells on the fate of major histocompatibility complex class II-mismatched (C57BL/6X bm12)F1 skin or bm12 heart transplants in C57BL/6 recipients was also assessed. Finally, we investigated the impact of natural CD25(+) Treg cells on the production of T-helper (Th)1 and Th2 cytokines in mixed lymphocyte cultures between C57BL/6 CD4(+) CD25(-) T cells as responders and bm12 or (C57BL/6X bm12)F1 antigen-presenting cells as stimulators. RESULTS: Male allografts were spontaneously accepted by female A1(M)RAG+ mice but readily rejected by female A1(M)RAG+ mice depleted of natural CD25(+) Treg cells by pretreatment with the PC61 monoclonal antibody. Depletion of CD25(+) Treg cells also enhanced eosinophil-determined rejection of (C57BL/6X bm12)F1 skin grafts or bm12 cardiac grafts in C57BL/6 recipients. Finally, natural CD25(+) Treg cells inhibited the production of interleukin (IL)-2, interferon-gamma, IL-5, and IL-13 in mixed lymphocyte culture in a dose-dependent manner. CONCLUSION: Natural CD25(+) Treg cells control Th1- and Th2-type allohelper T-cell responses and thereby influence the fate of allografts in nonimmunosuppressed recipients.     

Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases

Introduction: Mitochondrial-derived peptides (MDPs) are encoded within the mitochondrial genome. They signal within the cell or are released to act as autocrine/paracrine/endocrine cytoprotective factors playing a key role in the cellular stress response. The first reported and better characterized MDP is humanin (HN), which exerts robust protective effects against a myriad of cytotoxic stimuli in many cell types. These effects have led to the evaluation of HN and its analogs as therapeutic targets for several chronic diseases.

Areas covered: We describe the latest findings on the mechanism of action of HN and discuss the role of HN as therapeutic target for neurodegenerative and cardiovascular diseases, diabetes, male infertility, and cancer. Since HN can be detected in circulation, we also depict its value as a biomarker for these diseases.

Expert opinion: HN analogs and peptide mimetics have been developed over the last decade and show promising results in preclinical models of degenerative diseases. Local administration of gene therapy vectors that overexpress or silence endogenous HN could also hold therapeutic potential. Controversy on the role of HN in cancer progression and chemoresistance should be addressed before the translation of these therapeutic approaches.