Homologous growth hormone accelerates healing of segmental bone defects

The effect of homologous recombinant porcine growth hormone (r-pGH) on secondary fracture healing was investigated in a diaphyseal defect of the tibia in Yucatan micropigs. A 1 cm defect of the tibia was created surgically and stabilized with an AO 3.5 mm DCP plate. The treatment group (12 animals) received 100 microg of r-pGH per kilogram of body weight subcutaneously once per day, whereas the control pigs (12 animals) received 1 mL of sodium chloride as placebo. For evaluation of the GH-axis, serum levels of insulin-like growth factor-I (IGF-I) were sampled every fourth day. The animals were killed 6 weeks after surgery. Quantitative computed tomography (qCT) was performed to determine bone mineral density (BMD) and bone mineral content (BMC) of the defect zone. The torsional stiffness and the torsional failure load were measured by destructive torsional testing of the defect and contralateral tibiae. qCT measurements revealed a significant increase in the BMC of the defect zone in the treatment group compared with controls (GH BMC = 2833 +/- 679 mg, placebo BMC = 2215 +/- 636 mg; p < 0.05), whereas the BMD values were similar in both groups (GH BMD = 668 +/- 60 mg/mm(2), placebo BMD = 629 +/- 52 mg/mm(2), p = 0.12). Torsional failure load was 70% higher and torsional stiffness 83% higher in the treatment group than in the control group (p < 0.05). The mean serum level of IGF-I in the treatment group increased to 382% of the preoperative basal level and decreased to 69% in the control group, and this difference was highly significant (p < 0.001). Our data indicate that daily administration of recombinant GH leads to an increase of serum IGF-I levels and stimulates secondary fracture healing, resulting in increased mechanical strength and stiffness of the callus.     

Surgical management of vertebral column metastatic disease

The spine is the most frequent site of skeletal metastases. Among all spinal malignancies metastatic disease is most frequent and indicative of disseminating tumor disease. Depending on primary tumor entity, estimated survival time, general health status of the patient, presence of spinal instability and neurological deficits an oncological useful and patient-specific therapeutic intervention should be performed. New anterior approaches, resections and reconstruction techniques are making surgery a preferred method over radiation therapy. For differential indication of the multiple surgical treatment modalities prognostic scores are available to assist individual decision making. Indications for surgery include survival prognosis of minimum 3 months, intractable pain, progress of myelon compression and/or neurological deficits under radiochemotherapy, spinal instability and necessity for histological diagnosis. Resulting quality of life depends on efficient decompression of the spinal cord and restoration of spinal stability. To achieve these ultimate goals there are different anterior and posterior approaches, instrumentations and vertebral body replacement implants available. Preoperative embolization should be performed in hypervascular tumors, e.g., renal cell cancer. Vertebro-/Kyphoplasty as a percutaneous intervention should be considered for painful multisegmental disease and symptomatic osteolysis without epidural tumor compression to reach analgesia and stability. A multidisciplinary approach in patient selection, decision making and management is an essential precondition for complication avoidance and acceptable quality of life.     

Heparininduzierte Thrombozytopenie

Heparin-induced thrombocytopenia (HIT) represents a serious side effect caused by an atypical immune response to platelet factor 4 leading to platelet activation and thrombin formation. These patients are at high risk of thromboembolism, with a rapid drop in platelet count between days 5 and 14 after the initiation of heparin treatment. In single cases, especially after major surgery, platelet count reduction might be absent or hidden by preceding thrombocytosis. Different clinical manifestations of HIT include unspecific skin reactions with potential necrosis at the site of heparin injection, mostly after the application of unfractionated heparin but also with low molecular weight heparin. In heparin-induced skin necrosis, administration of unfractionated or low molecular weight heparin is contraindicated and heparin therapy should be stopped immediately. Instead, an alternative anticoagulant in the form of a direct thrombin inhibitor such as argatroban, and respectively lepirudin, or danaparoid sodium must be administered. Due to frequent misinterpretations of heparin-induced unspecific skin reactions, especially in the absence of thrombocytopenia, we present two case reports which should increase the awareness of HIT’s various clinical pictures.     

Polished Trays Reduce Backside Wear Independent of Post Location in Posterior-stabilized TKAs

Background

Backside damage of the polyethylene in TKA is a potential source of debris. The location of the tibial post in posterior-stabilized implants may influence micromotion, and thus affect backside damage, as may surface roughness.

Questions

We used implant retrieval analysis to (1) examine if there were differences in backside damage among three modern posterior-stabilized implants attributable to variable surface roughness; (2) determine if the location of damage on the tibial post affected the pattern of backside damage; and (3) determine if demographics influenced backside damage.

Methods

We identified 403 posterior-stabilized tibial retrieved inserts (147 NexGen^®, 152 Optetrak^®, 104 Genesis^® II). The damage on the surfaces of the tibial posts was previously graded. The backside of the inserts (divided into quadrants) were scored for evidence of damage. The total quadrant damage was compared for each implant group, the relationship between post face damage and location of damage on the backside was determined for each implant group, and total backside damage was compared among the three implant groups.

Results

No correlation was found between the location of damage on the post and location of damage on the backside of the implant for any of the three groups. The Genesis^® II polyethylene implants, which articulate with a highly polished tibial tray, showed a significantly lower total backside damage score (p < 0.01) when compared with the other two implant groups. The Genesis^® II and Optetrak^® showed significantly more damage in the posterior quadrants of the implants (p < 0.01) when compared with the anterior quadrants. A linear regression analysis revealed that lower tibial tray surface roughness was correlated with decreased damage.

Conclusions

An implant design with a highly polished tibial tray was associated with decreased backside damage. However, tibial post design and location did not influence the location of backside damage.

Clinical Relevance

Our study showed that a highly polished tibial tray was associated with decreased damage to the backside of polyethylene inserts independent of post design and location. These findings should be taken into consideration when new generations of implants are designed.     

Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases

BACKGROUND: Necrotizing and crescentic glomerulonephritis related to antineutrophil cytoplasmic autoantibodies (ANCA) is typically referred to as "pauci-immune"; however, it is not unusual for renal biopsies in such cases to exhibit some immune complex deposition within glomeruli on immunofluorescence and/or electron microscopic study. The composition and intraglomerular localization of such deposits in ANCA-glomerulonephritis has not been widely studied, and their potential pathologic and clinical significance is not clear, although a possible synergistic effect between immune complexes and ANCA in producing more severe glomerulonephritis is suggested by some human and animal studies. METHODS: Electron micrographs from 126 renal biopsies showing necrotizing/crescentic glomerulonephritis characterized by positive ANCA serology [C-ANCA, anti-proteinase 3 (anti-PR3), or anti-myeloperoxidase (MPO)] or necrotizing arteritis in the absence of known ANCA results were examined for the presence, quantity, and location of electron-dense deposits. The presence or absence of such deposits was correlated with histologic findings (fraction of glomeruli with crescents and segmental necrotizing lesions, mesangial and endocapillary hypercellularity), immunofluorescence findings, and clinical data, including serum creatinine and 24-hour urine protein levels at the time of biopsy. RESULTS: Sixty-eight (54%) of these biopsies showed glomerular immune complex deposits on electron microscopy; 87% of the latter also showed positive immunofluorescence findings for at least one immunoglobulin or complement component, although staining was relatively mild in most instances (< or =2+ on a 0 to 4+ scale in all but eight cases). Nearly half of biopsies negative for deposits by electron microscopy also showed positive immunofluorescence findings, though even more so than in cases with deposits on electron microscopy the intensity of immunofluorescence staining in these biopsies was typically very weak (trace or trace to 1+ in most cases, none >2+). Hypercellularity within the glomerular tuft was seen in 50% of biopsies with deposits on electron microscopy but only 14% of those without deposits; in each group this was usually mild and mesangial. Notably, the presence of deposits on electron microscopy was associated with a higher median level of proteinuria (3.2 versus 1.3 g/24 hours, P < 0.0001) and a higher median percentage of glomeruli with crescents (62.5% versus 44.0%, P= 0.06). CONCLUSION: Immune complex deposits were found on electron microscopy in just over half of renal biopsies with crescentic glomerulonephritis associated with positive ANCA serology and/or necrotizing arteritis. Clinical correlations suggest that these immune complex deposits may somehow potentiate the effect of ANCA in producing glomerulonephritis.     

Prospective randomized trial comparing flutamide as adjuvant treatment versus observation after radical prostatectomy for locally advanced, lymph node-negative prostate cancer

OBJECTIVE: To assess the efficacy and the tolerability of flutamide as adjuvant treatment after radical prostatectomy for locally advanced, lymph node-negative prostate cancer. METHODS: Men with locally advanced, lymph node-negative prostate cancer were randomized after radical prostatectomy to receive either flutamide 750mg daily or no adjuvant treatment. Recurrence-free and overall survival were the study end points. Recurrence was defined as a PSA value greater than 5ng/ml or two values greater than 2ng/ml more than three months apart with increasing tendency or three values greater than 1ng/ml more than three months apart with increasing tendency or any clinical recurrence. RESULTS: 309 patients (157 in the control arm and 152 in the flutamide arm) were eligible for efficacy analysis. The median follow-up was 6.1 years. Recurrence-free survival was better in the flutamide group ( P=0.0041), there was, however, no detectable difference in overall survival ( p=0.92 ). Moreover, there was a considerable toxicity reported in the flutamide group. CONCLUSION: Although having some effect on disease recurrence, adjuvant flutamide treatment does not improve median-term overall survival after radical prostatectomy for locally advanced, lymph node-negative prostate cancer.     

Predicting discharge location of hip fracture patients; the new discharge of hip fracture patients score

Purpose

This paper reports on the development and validity of a new instrument, called the discharge of hip fracture patients score (DHP), that predicts at admission the discharge location in patients living in their own home prior to hip fracture surgery.

Methods

A total of 310 patients aged 50 years and above were included. Risk factors for discharge to an alternative location (DAL) were analysed with a multivariable regression analysis taking the admission variables into account with different weights based on the estimates. The score ranged from 0–100 points. The cut-off point for DAL was calculated using a ROC analysis. Reliability of the DHP was evaluated.

Results

Risk factors for DAL were higher age, female gender, dementia, absence of a partner and a limited level of mobility. The cut-off point was set at 30 points, with a sensitivity of 83.8%, a specificity of 64.7% and positive predictive value of 79.2%.

Conclusion

The DHP is a valid, simple and short instrument to be used at admission to predict discharge location of hip fracture patients.     

A double-blind, randomized, active-controlled study for post-hemorrhoidectomy pain management with liposome bupivacaine, a novel local analgesic formulation

This randomized, active-controlled study evaluated the extent and duration of analgesia after administration of liposome bupivacaine (LB), a novel formulation of bupivacaine, compared with bupivacaine HCl given via local infiltration in excisional hemorrhoidectomy. One hundred patients were randomly assigned to receive a single dose of bupivacaine HCl 75 mg (0.25% with 1:200,000 epinephrine) or LB 66, 199, or 266 mg upon completion of hemorrhoidectomy. Postoperative pain intensity was assessed using a numeric rating scale at rest to calculate a cumulative pain score (area under the curve). Cumulative pain scores were significantly lower with LB at each study dose (P < 0.05) compared with bupivacaine HCl 72 hours after surgery. Post hoc analysis showed that mean total postoperative opioid consumption was statistically significantly lower for the LB 266-mg group compared with the bupivacaine HCl group during the 12- to 72-hour postoperative period (P = 0.019). Median time to first opioid use was 19 hours for LB 266 mg versus 8 hours for bupivacaine HCl (P = 0.005). Incidence of opioid-related adverse events was 4 per cent for LB 266 mg compared with 35 per cent for bupivacaine HCl (P = 0.007). Local infiltration with LB resulted in significantly reduced postsurgical pain compared with bupivacaine HCl in patients after hemorrhoidectomy surgery.