A randomized,double‐blind,placebo‐controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis

Introduction: Complement activation at the neuromuscular junction is a primary cause of acetylcholine receptor loss and failure of neuromuscular transmission in myasthenia gravis (MG). Eculizumab, a humanized monoclonal antibody, blocks the formation of terminal complement complex by specifically preventing the enzymatic cleavage of complement 5 (C5). Methods: This study was a randomized, double‐blind, placebo‐controlled, crossover trial involving 14 patients with severe, refractory generalized MG (gMG). Results: Six of 7 patients treated with eculizumab for 16 weeks (86%) achieved the primary endpoint of a 3‐point reduction in the quantitative myasthenia gravis (QMG) score. Examining both treatment periods, the overall change in mean QMG total score was significantly different between eculizumab and placebo (P = 0.0144). After assessing data obtained from all visits, the overall change in mean QMG total score from baseline was found to be significantly different between eculizumab and placebo (P < 0.0001). Eculizumab was well tolerated. Conclusion: The data suggest that eculizumab may have a role in treating severe, refractory MG. Muscle Nerve, 2013     

PET-CT enteroclysis: a new technique for evaluation of inflammatory diseases of the intestine

Purpose While CT/MR enteroclysis provides excellent anatomical details, it fails to provide information on metabolic activity of the inflammatory lesions of the intestine. We conceptualized a fusion of metabolic imaging techniques such as PET and an anatomical imaging modality such as CT enteroclysis to derive information both on morphological details and functional activity of lesions at the same time. Patients and methods In a prospective study, we included 17 adult patients with newly diagnosed inflammatory diseases of the intestine. Low dose whole body PET-CT scan was obtained first, which began at approximately 60 min after injection of 10 mCi of ¹⁸fluoro-deoxyglucose (FDG). Subsequently, PET-CT enteroclysis of the abdomen was performed after infusion of 2 l of 0.5% methylcellulose through a naso-jejunal catheter. Results Fourteen patients had abnormal and three had normal PET-CT enteroclysis studies. Twenty-three segments of small intestine and 27 segments of large intestine showed increased FDG uptake. The detection rate of PET-CT enteroclysis was significantly higher (total =50 segments, 23 segments of small intestine and 27 segments of large intestine) as compared with barium studies (16 segments of small intestine) and colonoscopy (17 segments of large intestine) combined together (total =33 segments). In addition PET-CT enteroclysis showed extra-luminal FDG uptake (lymph nodes in two, sacroilitis in two, and mesenteric fat proliferation in five). Conclusions As a single investigation, PET-CT enteroclysis detects a significantly higher number of lesions both in the small and large intestine in comparison to that detected by conventional barium and colonoscopy combined together. This technique is non-invasive, feasible and very promising. Financial disclosure: All the authors of this study declare no conflict of interest and financial obligation.     

Dual ectopic thyroid: case series and review of the literature

Ectopic thyroid tissue is an uncommon congenital aberration. It is further unusual for ectopic thyroid to be present at 2 different sites simultaneously. Only 19 cases of dual ectopic thyroid have been reported in the English literature. Most of the patients were adolescents and presented with anterior neck swelling with or without altered metabolic status. Lingual/sublingual thyroid was the most common ectopic location. Subhyoid was the most common site of a second ectopic thyroid in these patients. The thyroid scan has been used successfully to diagnose ectopic thyroid tissue. We report 4 such cases in which ectopic thyroid tissue was simultaneously present at 2 different locations using thyroid scanning. The literature of already reported cases is reviewed in detail.     

Trabecular metal acetabular revision system (cup-cage construct) to address the massive acetabular defects in revision arthroplasty

The increasing number of total hip replacements in the younger clique has added to the demand for revision procedures. Revision situations are often encountered with infection, loss of bone stock and bone defects. There are various methods of reconstruction of acetabular defects. The management options of type 3B Paprosky acetabular defects are limited with allograft and conventional cages. Trabecular metal technology has evolved to address these bone defects. Trabecular metal acetabular revision system (TMARS) cup-cage construct is a new technique to address massive acetabular defects. We describe a case of failed hip reconstruction done for a Giant cell tumour of proximal femur managed by a two stage procedure, initial debridement and second stage reconstruction of acetabulum with TMARS cup-cage construct and femur with allograft prosthesis composite.     

The effects of weight bearing on the distal tibiofibular syndesmosis: A study comparing weight bearing-CT with conventional CT

BackgroundSyndesmotic injures are common and weight bearing imaging studies are often advocated to assess disruption. Although studies have examined the anatomical relationship between the fibula and incisura, the effect of weight-bearing on the syndesmosis has not been well reported. We characterise the changes which occur at the syndesmosis during weight-bearing.MethodsIn this retrospective review we analysed the position of the fibula at the syndesmosis in a cohort of patients who underwent both non-weight-bearing and weight-bearing CT scans. The relative position of the fibula to the incisura was analysed to determine translation and rotation in the axial plane.Results26 patients were included. Comparison of measurements revealed statistically significant differences between groups which indicated that on weight-bearing the fibula translated laterally and posteriorly, and rotated externally with respect to the incisura.ConclusionsThis is the first study to measure the differences in position of the syndesmosis during weight-bearing in a population of patients that have undergone both weight bearing and non weight bearing CT. Our study confirms that weight-bearing results in lateral and posterior translation, and external rotation of the fibula in relation to the incisura and our findings should help in future studies looking at the effect of weight bearing on syndesmotic pathology.     

High value care education in general surgery residency programs: A multi-institutional needs assessment

BackgroundThe ACGME mandates that residency programs provide training related to high value care (HVC). The purpose of this study was to explore HVC education in general surgery residency programs.MethodsAn electronic survey was distributed to general surgery residents in geographically diverse programs.ResultsThe response rate was 29% (181/619). Residents reported various HVC components in their curricula. Less than half felt HVC is very important for their future practice (44%) and only 15% felt confident they could lead a QI initiative in practice. Only 20% of residents reported participating in a root cause analysis and less than one-third of residents (30%) were frequently exposed to cost considerations.ConclusionFew residents feel prepared to lead quality improvement initiatives, have participated in patient safety processes, or are aware of patients’ costs of care. This underscores the need for improved scope and quality of HVC education and establishment of formal curricula.     

Cerebral perfusion pressure directed therapy following traumatic brain injury and hypotension in swine

There is a paucity of studies, clinical and experimental, attesting to the benefit of cerebral perfusion pressure (CPP) directed pressor therapy following traumatic brain injury (TBI). The current study evaluates this therapy in a swine model of TBI and hypotension. Forty-five anesthetized and ventilated swine received TBI followed by a 45% blood volume bleed. After 1 h, all animals were resuscitated with 0.9% sodium chloride equal to three times the shed blood volume. The experimental group (PHE) received phenylephrine to maintain CPP > 80 mm Hg; the control group (SAL) did not. Outcomes in the first phase (n = 33) of the study were as follows: cerebro-venous oxygen saturation (S(cv)O(2)), cerebro-vascular carbon dioxide reactivity (DeltaS(cv)O(2)), and brain structural damage (beta-amyloid precursor protein [betaAPP] immunoreactivity). In the second phase (n = 12) of the study, extravascular blood free water (EVBFW) was measured in the brain and lung. After resuscitation, intracranial and mean arterial pressures were >15 and >80 mm Hg, respectively, in both groups. CPP declined to 64 +/- 5 mm Hg in the SAL group, despite fluid supplements. CPP was maintained at >80 mm Hg with pressors in the PHE group. PHE animals maintained better S(cv)O(2) (p < 0.05 at 180, 210, 240, 270, and 300 min post-TBI). At baseline, 5% CO(2) evoked a 16 +/- 4% increase in S(cv)O(2), indicating cerebral vasodilatation and luxury perfusion. By 240 min, this response was absent in SAL animals and preserved in PHE animals (p < 0.05). Brain EVBFW was higher in SAL animals; however, lung EVBFW was higher in PHE animals. There was no difference in betaAPP immunoreactivity between the SAL and PHE groups (p > 0.05). In this swine model of TBI and hypotension, CPP directed pressor therapy improved brain oxygenation and maintained cerebro-vascular CO(2) reactivity. Brain edema was lower, but lung edema was greater, suggesting a higher propensity for pulmonary complications.     

Obesity and outcomes after blunt trauma

BACKGROUND: Obesity has proven to be an independent risk factor of mortality in the intensive care unit (ICU) in both nontrauma and trauma patients. The purpose of this study was to determine whether the detrimental effect of obesity extend to morbidity as well as mortality in the intensive and nonintensive care blunt trauma patients. METHODS: A retrospective comparison of obese (body mass index [BMI] > 30 kg/m2) to nonobese (BMI < 30 kg/m2) blunt trauma patients was performed between January 2004 and December 2005. Patient demographics, morbidity, mortality and ventilator, ICU, and hospital length of stays were analyzed. Continuous variables were evaluated using the Wilcoxon Rank test and the nominal variables were evaluated using the Fisher's exact test. RESULTS: A cohort of 338 nonobese patients was compared with 115 obese patients during the study. These groups were similar in age (p = 0.19), gender (p = 0.37), and mechanism (p = 0.13). Their severity of injury were similar, demonstrated by nonsignificant differences in Injury Severity Score (p = 0.45), New Injury Severity Score (p = 0.51), Abdomen Abbreviated Injury Score (AIS; p = 0.49), and head AIS (p = 0.64). The subset of obese patients who never went to the ICU had a slightly longer hospital stay with a p value of 0.055. Overall the mortality rates were not different between the groups (3.5% obese versus 7.1% nonobese, p = 0.26). CONCLUSIONS: This group of obese blunt trauma patients had similar mortality rates to their leaner counterparts possibly because their complications were minimized. Despite this finding, a subset of obese patients had longer hospital stays which increases the financial burden to the patient and hospital. Effort should be made to facilitate their discharge to avoid complications and minimize cost.     

Multiplicity of solid organ injury: influence on management and outcomes after blunt abdominal trauma

OBJECTIVE: The current study was undertaken to examine how concomitant injury to liver and spleen after blunt abdominal trauma affects management and outcomes. METHODS: This study was a retrospective chart review of all blunt abdominal trauma patients admitted with a diagnosis of liver or spleen injury at two Level I trauma centers over a 4-year period. Presentation, injury grade, management, and outcomes were analyzed. Patients with single-organ injury (liver or spleen) were compared with patients having injury to both organs (liver and spleen). Significance was set at 95% confidence intervals. RESULTS: Of 1,288 patients who met entry criteria, 1,125 had single (spleen, 573; liver, 552) organ injury (group S) and 163 had injury to both organs (group B). Group B patients had significantly higher Injury Severity Score, higher admission lactate, and lower admission systolic blood pressure and base excess. Eighty-one percent (915 of 1,125) of group S and 69% (112 of 163) of group B patients were managed nonoperatively (p < 0.05). Of the nonoperatively managed patients, 5.8% (53 of 915) in group S and 11.6% (13 of 112) in group B failed this form of therapy (p < 0.05). Higher failure rate in group B was because of bleeding from injured solid organ(s), and not non-solid organ related failures. Mortality, intensive care unit and hospital lengths of stay, and transfusion requirements were all significantly higher in group B. CONCLUSION: Blunt trauma patients with concomitant injury to liver and spleen have higher Injury Severity Score, mortality, lengths of stay, and transfusion requirements. There is a higher failure rate with nonoperative management, and therefore extra vigilance is warranted when choosing this form of therapy in the presence of injury to both organs.     

Optimal Approach to Circumferential Decompression and Reconstruction for Thoracic Spine Metastatic Disease

Background

Circumferential decompression has been demonstrated to be the first-line therapy for patients with metastatic tumors in the thoracic spine requiring surgical intervention. However, there is significant debate regarding whether these tumors are best accessed anteriorly utilizing a thoracotomy or posteriorly. We used decision analysis to determine which approach yields greater health-related quality of life (QOL).

Methods

We searched Medline, Embase, and the Cochrane Library for relevant articles published between 1990 and 2011 on anterior and posterior approaches to metastatic disease in the thoracic spine. QOL values for major treatment outcomes were determined using the existing literature. Separate models were created for ambulatory and nonambulatory patients. A Monte Carlo simulation and sensitivity analyses were used to determine which treatment strategy resulted in the highest QOL.

Results

For ambulatory patients, an anterior approach resulted in a slightly higher QOL, and for nonambulatory patients, a posterior approach was favored, but these differences were not statistically significant.

Conclusions

Using a decision-analytic model, we found no significant difference in QOL resulting from anterior versus posterior approaches to metastatic lesions in the thoracic spine. Decisions should instead be based on surgeon comfort, tumor characteristics, anatomy of the lesion, patient-related factors, and goals of the operation.