Comparative Study of Modified Posterior Operation to Treat Kümmell's Disease

The present study aimed at examining the curative effect of modified posterior operation on treatment of Kümmell''s disease.About 30 patients of Kümmell''s disease with complete image and clinical data treated during June 2004 to July 2013 were conducted with anterior and posterior approaches, respectively. Kyphotic Cobb angle, fractured vertebra wedge angle, and the anterior and posterior heights of fractured vertebra were all measured through x-ray before and after operation, and the pain visual analog scale (VAS) was determined for evaluating the effect of operations. The injury and restoration of neurological function were assessed using Frankel classification.Patients in group A were treated with anterior operation, whereas group B was posterior operation. Postoperatively, VAS score, kyphotic Cobb angle, anterior vertebra height, and pathologic vertebra wedge angle were all significantly improved in patients with Kümmell''s disease receiving modified posterior operation (group B). Similar results were also observed in patients with anterior operation. The improvement of VAS and correction rate of kyphotic Cobb angle indicated equivalent effects of posterior and anterior operations. Meanwhile, alleviated neurological function damage was observed in 2 groups. Relevant factor analysis illustrated that there was no significant correlation of the severity and improvement rate of pain symptoms with age, medical history, anterior and posterior vertebra heights, kyphotic Cobb angle, and pathological vertebra wedge angle.Compared with traditional anterior approach, modified posterior operation, adopting transpedicular vertebral body grafting combined with vertebral pedicle screw fixation, could produce equivalent effects on kyphosis correction, pain relief, and improvement of neurological function in patients with Kümmell''s disease.     

Evaluation of Degenerative Lumbar Scoliosis After Short Segment Decompression and Fusion

The objective of this study was to investigate short segment decompression of degenerative lumbar scoliosis (DLS) and the efficiency of fusion treatment.After DLS surgery, the patients were retrospectively reviewed using the VAS (visual analog scale) and ODI (Oswestry Disability Index) to assess clinical outcomes. All patients underwent posterior lumbar decompressive laminectomy, pedicle screw internal fixation, and posterolateral bone graft fusion surgery. Radiographic measurements included the scoliotic Cobb angle, the fused Cobb angle, the anterior intervertebral angle (AIA), the sagittal intervertebral angle (SIA), and lumbar lordosis angle. The relationships between these parameters were examined by bivariate Pearson analysis and linear regression analysis.Preoperatively, the Cobb angle at the scoliotic segment was 15.4°, which decreased to 10.2° immediately following surgery (P < 0.05). The AIA significantly increased by the last follow-up (4.4 ± 3.4) compared with pre- and postoperative values (2.5 ± 2.8 and 2.2 ± 2.4, respectively; P < 0.05). However, the scoliotic Cobb angle and the AIA did not correlate with the VAS or ODI scores. At the final follow-up, no patients had pseudoarthrosis or internal instrumentation-related complications.Short fusion surgical treatment results in limited DLS correction, with correction loss over time. The AIA between the upper adjacent segment and proximal fused vertebra continues to increase postoperatively, which does not exacerbate clinical symptoms, as reflected by the low reoperation rates for repairing degeneration at adjacent levels.     

A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer

Lessons Learned

• The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
• Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
• The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.

BackgroundThe RAS/RAF/MEK/ERK signaling pathway is associated with proliferation and progression of hepatocellular carcinoma (HCC). Preclinical data suggest that paradoxical activation of the MAPK pathway may be one of the resistance mechanisms of sorafenib; therefore, we evaluated trametinib plus sorafenib in HCC.MethodsThis was a phase I study with a 3+3 design in patients with treatment‐naïve advanced HCC. The primary objective was safety and tolerability. The secondary objective was clinical efficacy.ResultsA total of 17 patients were treated with three different doses of trametinib and sorafenib. Two patients experienced dose‐limiting toxicity, including grade 4 hypertension and grade 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin over 7 days. Maximum tolerated dose was trametinib 1.5 mg daily and sorafenib 200 mg twice a day. The most common grade 3/4 treatment‐related adverse events were elevated AST (37%) and hypertension (24%). Among 11 evaluable patients, 7 (63.6%) had stable disease with no objective response. The median progression‐free survival (PFS) and overall survival (OS) were 3.7 and 7.8 months, respectively. Phosphorylated‐ERK was evaluated as a pharmacodynamic marker, and sorafenib plus trametinib inhibited phosphorylated‐ERK up to 98.1% (median: 81.2%) in peripheral blood mononuclear cells.ConclusionTrametinib and sorafenib can be safely administered up to trametinib 1.5 mg daily and sorafenib 200 mg twice a day with limited anticancer activity in advanced HCC.     

Measured and predicted resting energy expenditure in wheelchair rugby athletes

Objective: Report measured resting energy expenditure (REE) in wheelchair rugby athletes and evaluate agreement between REE and the prediction models of Chun, Cunningham, Harris-Benedict, Mifflin, Nightingale and Gorgey, and Owen.

Design: Cohort-based validation study.

Setting. Paralympic team training camp.

Participants: Fourteen internationally competitive athletes who play wheelchair rugby, 13 of whom had cervical spinal cord injuries (SCI).

Outcome Measures: A portable metabolic analyzer was used to measure REE following an overnight fast and dual-energy X-ray absorptiometry (DXA) was used to assess lean body mass for the prediction equations.

Results: REE in the current sample was 1735?±?257?kcal?×?day^?1 ranging from 1324 to 2068?kcal?×?day^{?1 Bhambhani Y. Physiology of wheelchair racing in athletes with spinal cord injury. Sports Med 2002;32(1):23–51.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]}. Bland–Altman analyses revealed negative mean bias but similar limits of agreement between measured REE and scores predicted by Chun, Cunningham, Mifflin, Nightingale and Gorgey, and Owen models in elite athletes who play wheelchair rugby.

Conclusion: Prediction models regressed on persons with and without SCI under-predicted REE of competitive wheelchair rugby athletes. This outcome may be explained by the higher REE/fat-free mass (FFM) ratio of current athletes compared to less active samples. Findings from the current study will help practitioners to determine nutrient intake needs on training days of varied intensity.     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.