Effects of ovariectomy on bone turnover,porosity, and biomechanical properties in ovine compact bone 12 months postsurgery

Compact bone makes up approximately 80% of the human skeleton by mass; but there are little data available on the effects of increased bone turnover on compact bone mechanical and material properties. This study addresses this question by measuring intracortical remodeling, resorption cavity number, and porosity in an ovariectomized (OVX) sheep model, and measures changes in biomechanical properties. Thirty‐eight sheep were divided into two groups. Group 1 were controls (n = 19), and Group 2 were ovariectomized (OVX; n = 19). Fluorochrome dyes were administered intravenously to both groups at five time points over 12 months post‐OVX to label sites of bone turnover. At 12 months post‐OVX all animals were euthanized. Samples were harvested from the left metatarsal and were analyzed for intracortical bone turnover at five time points, the number of resorption cavities, and the level of intracortical porosity. The effects of these parameters on bone biomechanical properties were then measured. Bone turnover was increased in the OVX group at 6, 9, and 12 months (p < 0.05). Resorption was also higher in the OVX group at 12 months (p < 0.05). Furthermore, porosity was significantly increased in the OVX group at 12 months (p < 0.05). Stiffness and yield strength were reduced in the OVX group compared to controls (p = 0.05). Ultimate compressive strength and work to fracture did not differ between groups. These findings provide new insights into the mechanisms and effects of increased bone turnover on bone material and microstructural properties. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:303–309, 2009     

Prognostic Factors for Survival in Patients With Locally Recurrent Extremity Soft Tissue Sarcomas

Background Factors prognostic for survival in patients with locally recurrent extremity soft tissue sarcomas (STS) are poorly defined, thus making it difficult to identify high-risk patients who may benefit from adjuvant therapy.Methods A total of 1421 patients underwent surgical treatment for primary extremity STS at a single institution between 1982 and 2002. Of these, 179 (13%) patients underwent complete surgical resection of an isolated local recurrence and were the subjects of this study. Clinicopathologic factors from both the primary tumor and the local recurrence were analyzed.Results The median interval to initial local recurrence was 16 months: 65% developed a local recurrence by 2 years and 90% by 4 years. Only four patients who presented with a low-grade primary tumor progressed to a high-grade local recurrence. Independent prognostic factors for disease-specific survival after local recurrence were a high histological grade (hazard ratio, 5.1; P = .0004), a large local recurrence tumor size (hazard ratio, 1.5; P = .0001), and a short local recurrence–free interval (hazard ratio, 1.6; P = .0001). Patients who developed a local recurrence >5 cm in 16 months (n = 44; 0 low grade) had a 4-year disease-specific survival of 18%, compared with 81% for patients who developed a local recurrence 5 cm in >16 months (n = 46; 11 low grade).Conclusions Histological grade, local recurrence size, and local recurrence–free interval are independently predictive of survival in patients with locally recurrent extremity STS. A large local recurrence that develops in a short interval indicates a biologically aggressive tumor with a high tumor-specific mortality. Patients who develop such recurrences are ideal subjects for systemic neoadjuvant therapy trials.     

Perioperative Complications After Living Kidney Donation: A National Study

We integrated the US transplant registry with administrative records from an academic hospital consortium (97 centers, 2008–2012) to identify predonation comorbidity and perioperative complications captured in diagnostic, procedure, and registry sources. Correlates (adjusted odds ratio, aOR) of perioperative complications were examined with multivariate logistic regression. Among 14 964 living kidney donors, 11.6% were African American. Nephrectomies were predominantly laparoscopic (93.8%); 2.4% were robotic and 3.7% were planned open procedures. Overall, 16.8% of donors experienced a perioperative complication, most commonly gastrointestinal (4.4%), bleeding (3.0%), respiratory (2.5%), surgical/anesthesia‐related injuries (2.4%), and “other” complications (6.6%). Major Clavien Classification of Surgical Complications grade IV or higher affected 2.5% of donors. After adjustment for demographic, clinical (including comorbidities), procedure, and center factors, African Americans had increased risk of any complication (aOR 1.26, p = 0.001) and of Clavien grade II or higher (aOR 1.39, p = 0.0002), grade III or higher (aOR 1.56, p < 0.0001), and grade IV or higher (aOR 1.56, p = 0.004) events. Other significant correlates of Clavien grade IV or higher events included obesity (aOR 1.55, p = 0.0005), predonation hematologic (aOR 2.78, p = 0.0002) and psychiatric (aOR 1.45, p = 0.04) conditions, and robotic nephrectomy (aOR 2.07, p = 0.002), while annual center volume >50 (aOR 0.55, p < 0.0001) was associated with lower risk. Complications after live donor nephrectomy vary with baseline demographic, clinical, procedure, and center factors, but the most serious complications are infrequent. Future work should examine underlying mechanisms and approaches to minimizing the risk of perioperative complications in all donors.     

Ex Vivo Costimulatory Blockade to Generate Regulatory T Cells From Patients Awaiting Kidney Transplantation

Short‐term outcomes of kidney transplantation have improved dramatically, but chronic rejection and regimen‐related toxicity continue to compromise overall patient outcomes. Development of regulatory T cells (Tregs) as a means to decrease alloresponsiveness and limit the need for pharmacologic immunosuppression is an active area of preclinical and clinical investigation. Nevertheless, the immunomodulatory effects of end‐stage renal disease on the efficacy of various strategies to generate and expand recipient Tregs for kidney transplantation are incompletely characterized. In this study, we show that Tregs can be successfully generated from either freshly isolated or previously cryopreserved uremic recipient (responder) and healthy donor (stimulator) peripheral blood mononuclear cells using the strategy of ex vivo costimulatory blockade with belatacept during mixed lymphocyte culture. Moreover, these Tregs maintain a CD3⁺CD4⁺CD25⁺CD127^lo surface phenotype, high levels of intracellular FOXP3 and significant demethylation of the FOXP3 Treg‐specific demethylation region on allorestimulation with donor stimulator cells. These data support evaluation of this simple, brief Treg production strategy in clinical trials of mismatched kidney transplantation.     

Patient and Parent Perspectives of Adolescent Laparoscopic Adjustable Gastric Banding (LAGB)

Background

Adolescent obesity is a significant global health challenge and severely obese adolescents commonly experience serious medical and psychosocial challenges. Consequently, severe adolescent obesity is increasingly being treated surgically. The limited available research examining the effectiveness of adolescent bariatric surgery focuses primarily on bio-medical outcomes. There is a need for a more comprehensive understanding of the behavioural, emotional and social factors which affect adolescents’ and parents’ experience of weight loss surgery.

Methods

Patient and parents’ perspectives of adolescent LAGB were examined using a qualitative research methodology. Individual, semi-structured interviews were conducted with eight adolescent patients and five parents. Thematic analysis was used to identify key themes in the qualitative data.

Results

Patients and parents generally considered adolescent laparoscopic adjustable gastric banding (LAGB) to be a life-changing experience, resulting in physical and mental health benefits. Factors considered to facilitate weight loss following surgery included parental support and adherence to treatment guidelines. Many adolescents reported experiencing surgical weight loss stigma and challenging interpersonal outcomes after weight loss for which they felt unprepared.

Conclusions

Patients and parents perceived LAGB positively. There are opportunities to improve both the experience and outcomes of adolescent LAGB through parental education and enhancements to surgical aftercare programmes.

     

Quality of dying in head and neck cancer patients: a retrospective analysis of potential indicators of care.

OBJECTIVE: The objective of this study was to evaluate the quality of the dying experience in a cohort of head and neck cancer patients by a retrospective analysis of potential indicators of care. STUDY DESIGN: The study design included retrospective case note analysis of previously evaluated factors considered important in the care of terminally ill patients and validated indicators of care obtainable from administrative data. The documented factors were analyzed to indicate specific elements of the quality of death and dying experience. RESULTS: Pain was a common symptom (84%) and was managed successfully in all patients, with 93% receiving opioids. Management of other symptoms, except neuropsychological problems, were satisfactory. Sixty-three percent of patients died in hospital and only 22% had a relative present at the time of death. Resuscitation status was documented in only 65% of the notes, though none were admitted to the intensive care unit or underwent resuscitation. Fifty-three percent of patients were admitted as an emergency in the last month of life and bleeding was the most common cause of admission. CONCLUSION: Valuable information can be obtained from a focused retrospective analysis. The indicators evaluated suggest that biomedical aspects of care are being recognized and addressed, although there is room for improvement. Psychosocial and spiritual aspects of care were not documented and must be taken into account to assess the "complete quality of dying" experience.     

Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria >/= 9.5 log(10) copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed. Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss.     

Extent of lymph node dissection in melanoma of the trunk or lower extremity

The extent of lymph node dissection necessary to optimize survival and minimize local recurrence in patients with melanoma of the trunk or lower extremity is not well defined. We reviewed the records of 420 patients undergoing superficial or combined superficial and deep groin dissection for melanoma. Prognosis depended on the extent of lymph node involvement rather than the extent of surgery performed. Node-positive patients undergoing elective lymph node dissection had an improved survival over those undergoing therapeutic lymph node dissection. In no subgroup of patients was more extensive lymphadenectomy associated with significant improvement in survival or alteration in pattern of recurrence. Dissection of the deep pelvic nodes in patients with melanoma appears to be of more prognostic than therapeutic value.