Heparin in haemorrhagic infarction in cerebral venous sinus thrombosis

Morbidity and mortality in puerperal cerebral venous thrombosis (CVT) can be reduced by arresting the progression of thrombosis using heparin. However, conventional dose of heparin requires monitoring of coagulation parameters and carries a risk of haemorrhage. The present study involved 56 patients of puerperal CVT with CT evidence of haemorrhagic infarction. Twenty nine of these patients received low dose heparin till 30th post-partum day or symptomatic relief. Their clinical features and severity were similar to 27 patients who did not receive heparin. The mortality and morbidity at discharge was significantly less (P < 0.001) in heparin treated group. There were no haemorrhagic complications. Low dose heparin is safe and effective in cerebral venous thrombosis, even with haemorrhagic infarction.     

Forced swimming stress induced alterations in ingestive behavior in rats.

The effects of forced swimming stress (15 minutes per day) on body weight, food intake, blood sugar, water intake, and urine output were studied in adult male Wistar rats on the first, seventh, fourteenth and 21st days in different subgroups. There was a significant initial decrease in the body weight up to 14 days followed by a regain in the body weight, which was sustained until 21 days. Though there was no change in the food intake initially for 7 days, after 14 days a significant increase in the food intake was observed. A significant hypoglycemia was observed throughout the entire period of stress. More significant fall in the blood sugar level was observed in the initial period of exposure of stress (1-7 days). There was a significant reduction in the water intake in the stressed animals. Urine output decreased significantly up to 7 days of stress, though it got marginally increased later. Thus, repeated stress may produce a reduction in body weight only initially, which is accompanied with an initial decrease in food and water intake also. The peak response to stress was seen after 7 days of stress exposure. There was a gradual recovery back to normal in the body weight, food intake, and water intake and urine output when stress period was prolonged to 14-21 days. This is suggestive of the adaptation of the organism to repeated exposure of similar kind of stress.     

Clinical sequelae after rhBMP-2 use in a minimally invasive transforaminal lumbar interbody fusion

Background contextRecent reports of postoperative radiculitis, bone osteolysis, and symptomatic ectopic bone formation after recombinant human bone morphogenetic protein-2 (rhBMP-2) use in transforaminal lumbar interbody fusions (TLIFs) are a cause for concern.PurposeTo determine the clinical and radiographic complications associated with BMP utilization in a minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) environment.Study design/settingRetrospective clinical case series at a single institution.Patient sampleFive hundred seventy-three consecutive patients undergoing an MIS-TLIF.Outcome measuresReoperation rates and total costs associated with complications of rhBMP-2 use and pseudarthrosis.MethodsA retrospective review of 610 consecutive patients undergoing an MIS-TLIF (2007–2010) by a single surgeon at our institution was performed (mean age 48.7 years, range 26–82 years). All patients underwent an MIS laminectomy with bilateral facetectomy, single TLIF cage, unilateral pedicle screw fixation, and 12 mg (large kit) or 4.2 mg (small kit) of rhBMP-2. The BMP-2 collagen-soaked sponge was placed anteriorly in the disc space, followed by local bone graft, and then the cage was filled only with local bone and no BMP-2. Patients were evaluated at 6 months and 1 year with computed tomography (CT) scan. Those demonstrating neuroforaminal bone growth, osteolysis/cage migration, or pseudarthrosis were reviewed, and cost data including direct cost/procedure for both index and revision surgeries were collected.ResultsOf the 573 patients, 10 (1.7%) underwent 15 additional procedures based on recalcitrant radiculopathy and CT evidence of neuroforaminal bone growth, vertebral body osteolysis, and/or cage migration. Thirty-nine patients (6.8%) underwent reoperation for clinically symptomatic pseudarthrosis. Bone overgrowth was associated with nerve impingement and radiculopathy in all 10 patients (small kit, n=9; large kit, n=1). Osteolysis and cage migration occurred in 2 (20%) of these same 10 patients. Average total costs were calculated per procedure ($19,224), and the costs for reoperation equaled $14,785 per encounter for neuroforaminal bone growth and $20,267 for pseudarthrosis.ConclusionsSymptomatic ectopic bone formation, vertebral osteolysis, and pseudarthrosis are recognized complications with the use of rhBMP-2 in MIS-TLIFs. Potential causes include improper dosage and a closed space that prevents the egress of the postoperative BMP-2 fluid collection. Management of these complications has a substantial cost for the patient and the surgeon and needs to be considered with the off-label use of rhBMP-2.     

Prosthetic mitral valve thrombosis,malfunction, and paroxysmal mitral regurgitation

Intermittent dysfunction of mechanical mitral valve prosthesis is an uncommon condition. It carries serious clinical implications if unrecognized. Here, we present a case of a 28‐year‐old female with a history of rheumatic multivalvular disease, for which she had undergone double valve replacement and tricuspid annuloplasty. Six months later, she presented with heart failure. Clinical examination revealed intermittent loss of closing clicks followed by a pansystolic murmur at the apex, suggestive of mitral prosthetic valve dysfunction. We highlight the echocardiographic findings of paroxysmal mitral valvular regurgitation secondary to prosthetic valve malfunction secondary to prosthetic valve thrombosis.     

Role of insulin resistance indices in predicting new‐onset diabetes after kidney transplantation

New‐onset diabetes mellitus (NODAT) is a serious complication following renal transplantation. In this cohort study, we studied 118 nondiabetic renal transplant recipients to examine whether indices of insulin resistance and secretion calculated before transplantation and at 3 months post‐transplantation are associated with the development of NODAT within 1 year. We also analysed the long‐term impact of early diagnosed NODAT. Insulin indices were calculated using homeostasis model assessment (HOMA) and McAuley's Index. NODAT was diagnosed using fasting plasma glucose. Median follow‐up was 11 years. The cumulative incidence of NODAT at 1 year was 37%. By logistic regression, recipient age (per year) was the only significant pretransplant predictor of NODAT (OR 1.04, CI 1.009–1.072), while age (OR 1.04, CI 1.005–1.084) and impaired fasting glucose (OR 2.97, CI 1.009–8.733) were significant predictors at 3 months. Pretransplant and 3‐month insulin resistance and secretion indices did not predict NODAT. All‐cause mortality was significantly higher in recipients developing NODAT within 1 year compared with those remaining nondiabetic (44% vs. 22%, log‐rank P = 0.008). By Cox's regression analysis, age (HR 1.075, CI 1.042–1.110), 1‐year creatinine (HR 1.007, CI 1.004–1.010) and NODAT within 3 months (HR 2.4, CI 1.2–4.9) were independent predictors of death. In conclusion, NODAT developing early after renal transplantation was associated with poor long‐term patient survival. Insulin indices calculated pretransplantation using HOMA and McAuley's Index did not predict NODAT.     

Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor,masitinib

The host foreign body response (FBR) adversely effects the performance of numerous implanted biomaterials especially biosensors, including clinically popular glucose-monitoring sensors. Reactive formation of a fibrous capsule around implanted sensors hinders the transport of essential analytes to the sensor from the surrounding tissue, resulting in loss of glucose response sensitivity and eventual sensor failure. Several strategies have sought to mitigate the foreign body response's effects on CGM sensors through the use of local delivery of pharmaceuticals and biomolecules with limited success. This study describes release of a tyrosine kinase inhibitor – masitinib – from the sensor implant to target tissue resident mast cells as key mediators of the FBR. Model implants are coated with a composite polymer hydrophilic matrix that rapidly dissolves upon tissue implantation to deposit slower-degrading polymer microparticles containing masitinib. Matrix dissolution limits coating interference with sensor function while establishing a local controlled-release delivery depot formulation to alter implant tissue pharmacology and addressing the FBR. Drug efficacy was evaluated in a murine subcutaneous pocket implant model. Drug release extends to more than 30 days in vitro. The resulting FBR in vivo, evaluated by implant capsule thickness and inflammatory cell densities at 14, 21, and 28 days, displays statistically significant reduction in capsule thickness around masitinib-releasing implant sites compared to control implant sites.