MRI quantification of fatty infiltration and muscle atrophy in a mouse model of rotator cuff tears

Rotator cuff pathology is the most common shoulder problem seen by orthopedic surgeons. Rotator cuff muscle fatty infiltration and muscle atrophy are common in larger tears and are considered predicting factors for the prognosis of cuff repair. Clinically, MRI is the gold standard in determining fatty infiltration and muscle atrophy; however, analysis for MRI imaging is primarily qualitative in nature with the results lacking further validation. We have recently developed a mouse model of rotator cuff tears. The goal of this study is to quantify and verify rotator cuff muscle atrophy and fatty infiltration using high‐resolution MRI in our mouse model. The rotator cuff muscles were analyzed for fat using a triglyceride quantification assay (TQA), muscle volume was measured through water displacement (WD), and histology. The study revealed that MRI had a high correlation with fat as measured with histology and TQA (R² = 098). MRI also correlated well with atrophy measured with WD and wet weight. This suggests that MRI is a reliable modality in evaluating the progression of fatty infiltration and muscle atrophy following rotator cuff tears in a small animal model. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 421–426, 2013     

Metabolic syndrome and its association with fatty liver disease after orthotopic liver transplantation

The metabolic syndrome (MetS) might contribute to morbidity after orthotopic liver transplantation (OLT). For this reason, we searched for MetS‐associated risk factors and analyzed the link with nonalcoholic fatty liver disease (NAFLD) in OLT recipients. De novo MetS affected 32.9% of our cohort (n = 170) within 2 years after OLT. Multivariate analysis identified glycosylated hemoglobin (HbA1c) levels ≥5% [odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.56–8.13, P = 0.003], diabetes mellitus (OR = 4.31, CI = 1.69–10.99, P = 0.002), and arterial hypertension (OR = 4.59, CI = 1.46–14.49, P = 0.009) as independent risk factors for de novo MetS. MetS incidence correlated with steroid dosage after OLT (5.2 ± 2.4 mg/day vs. 7.1 ± 4.7 mg/day, P = 0.014), and was linked to NAFLD (P = 0.001) via obesity (OR = 4.67, CI = 1.55–14.1, P = 0.006) and dyslipidemia (OR = 4.23, CI = 1.35–13.3, P = 0.013) post‐OLT. In conclusion, we were able to identify low threshold HbA1c as a novel risk factor for MetS after OLT and described a link of MetS with NAFLD in transplant organs. This study also indicated that steroid treatment is associated with MetS rates after OLT.     

The predictive value of heart-type fatty acid-binding protein is independent from symptom duration in normotensive patients with pulmonary embolism

Background

Heart-type fatty acid-binding protein (H-FABP) is a useful biomarker for risk stratification of patients with pulmonary embolism (PE). In patients with acute myocardial infarction, H-FABP plasma concentrations rise after 30 minutes and return to normal within 20-24 hours. We tested whether the predictive value of H-FABP is affected by the duration of symptoms prior to diagnosis in patients with PE.

Material and Methods

We prospectively studied 257 consecutive normotensive patients with confirmed symptomatic PE.

Results

Patients with acute (< 24 hours; n = 150) symptom onset presented more often with syncope (28.7% vs. 6.5%; p < 0.001) compared to patients with symptoms ≥ 24 hours (n = 107); other baseline characteristics, comorbidities, and risk factors were distributed equally. Patients with an adverse 30-day outcome (6.6%) had higher H-FABP levels (11.84 [3.57-19.62] ng/ml) compared to patients with a favorable course (3.42 [1.92-5.42] ng/ml; p < 0.001). However, the proportion of patients with H-FABP levels ≥ 6 ng/ml did not differ among patients with acute symptom onset and late presentation (p = 0.104). Only tachycardia and elevation of H-FABP were associated with an increased risk of an adverse 30-day outcome both in patients with acute symptom onset (H-FABP: OR, 5.8; 95% CI, 1.4-24.5; p = 0.016; tachycardia: 7.0 [1.4-36.0]; p = 0.018) and late presentation (H-FABP: 9.3 [2.0-43.2]; p = 0.004 and tachycardia: 12.3 [1.5-103.6]; p = 0.021). The prognostic value could further be improved by the use of a simple H-FABP-based clinical prediction score.

Conclusions

Our findings indicate that H-FABP is a useful biomarker for risk stratification of normotensive patients with PE regardless of symptom duration prior to diagnosis.     

Quantitative ultrasonography of facial muscles

Introduction: There is no standardized method for examination of facial muscles with ultrasound. The purpose of this study was to identify those facial muscles accessible for reliable identification and to provide reference data. Methods: In healthy subjects all facial muscles were screened for visibility, separation from adjacent muscles, and reliability of landmarks. Bilateral scans of reliable muscles were performed in 40 adult volunteers. Results: Six facial muscles were clearly demarcated with ultrasound. These were: frontalis, orbicularis oculi, orbicularis oris, depressor anguli oris, depressor labii inferioris, and mentalis muscles. Cross-sectional area and muscle thickness showed gender differences and were independently related to age for some muscles. A significant left–right side difference was only seen for the orbicularis oculi muscle in women. Conclusions: These data demonstrate the usefulness of ultrasonography to assess facial muscles and provide reference values that can be applied in the clinical setting. Muscle Nerve 47: 878–883, 2013     

Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post‐transplant CDT monitoring for alcohol relapse assessment – a retrospective study

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post‐LT long‐term observation is challenging, and biomarkers as carbohydrate‐deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow‐up was 73 months (0–213). One‐ and five‐year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post‐transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single‐center analysis showed good post‐transplant long‐term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post‐LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.     

Reversible HLA multimers (Streptamers) for the isolation of human cytotoxic T lymphocytes functionally active against tumor- and virus-derived antigens

The development of MHC/peptide multimers has facilitated the visualization and purification of antigen-specific T cells. However, the persistence of multimers leads to prolonged T cell receptor signaling and subsequently to altered T-cell function. We have recently developed a new type of MHC/peptide multimers, which can be dissociated from the T cell. Herein, we have generated and tested for the first time reversible HLA/peptide multimers, termed Streptamers, for the isolation of human T cells. The Streptamer technique demonstrates the specificity and sensitivity of conventional HLA/peptide tetramers with regards to the sorting of human T lymphocytes. This is shown for T cells directed against immunogenic peptides derived from viral and tumor-associated antigens. We show that antigen-specific cytotoxic T cells remain functionally active following Streptamer dissociation, whereas lytic function and proliferation of the T cells is impaired in the presence of conventional tetramers. These novel HLA/peptide Streptamer reagents allow the isolation of antigen-specific T cells with preserved function and, therefore, facilitate the development of adoptive T cell transfer regimens for the treatment of patients with cancer or infectious diseases.     

Vaccinia virus double-stranded RNA-binding protein E3 does not interfere with siRNA-mediated gene silencing in mammalian cells

Vaccinia virus (VACV) evolved several strategies to evade antiviral cellular defence. The vaccinia virus E3 protein for example binds and sequesters double stranded RNA (dsRNA) and counteracts interferon action. We were interested to find out whether and to what extend E3 interferes with RNA silencing mediated by short interfering RNA (siRNA) in mammalian cells. We could show that the expression of a VACV-encoded marker gene can be efficiently inhibited by siRNA independently of the presence of the E3 protein. In addition, expression of E3 had no impact on RNA polymerase III promoter-derived shRNA-induced silencing of a cellular gene in human cells. Both VACV early and late gene expression could be inhibited by siRNA. Furthermore, downregulation of the expression of the E3L gene itself by siRNA in VACV infected cells produced the previously described phenotype of a knock-out virus, which illustrates the power of siRNA for vaccinia virus gene function analysis.     

Blood polymorphonuclear leukocyte migration as a predictive marker for infections in severe trauma: comparison with various inflammation parameters

Objective To assess in patients with multiple trauma the relevance of the following as predictive markers for infections: the inflammation parameters white blood count, body temperature, blood polymorphonuclear leukocyte (PMN) migration; blood levels of C-reactive protein, PMN elastase, procalcitonin, neopterin, interleukin 6, interleukin 8, malondialdehyde, total antioxidative status; the stress parameters cortisol and lactate.Design Prospective observational cohort study.Setting Intensive Care Unit of a university surgical department.Patients Twenty-six patients with multiple trauma of differing severity.Measurements and results Trauma severity was estimated by the ISS. PMN migration upon F-Met-Leu-Phe stimulation was determined in fresh whole blood in a ready-for-use, one-way membrane filter assay and evaluated by automated image analysis. The other parameters were measured with commercially available tests. During hospitalization, nine patients developed infections, and 17 patients were free of infection. PMN migration below a critical minimum preceded infections in eight of the infected, but occurred in only three of the non-infected patients (positive/negative predictive values 0.72/0.93; sensitivity/specificity 0.88/0.82; likelihood ratio 5.0). Fever (38.0 °C) had predictive values of 0.83/0.80 and a high likelihood ratio of 9.4, but a low sensitivity/specificity of 0.55/0.94. The other parameters were without significance. Procalcitonin, elastase, C-reactive protein, neopterin and lactate correlated positively with the injury severity score.Conclusion PMN migration proved to be a highly sensitive predictive marker for infections. The whole-blood PMN migration test may facilitate early aggressive antimicrobial therapy.Coauthors are listed in alphabetical order