Bony impingement affects range of motion after total hip arthroplasty: A subject‐specific approach

Hip range of motion after total hip arthroplasty has been shown to be dependent on prosthetic design and component placement. We hypothesized that bony anatomy would significantly affect range of motion. Computer models of a current generation hip arthroplasty design were virtually implanted in a model of pelvis and femur in various orientations ranging from 35° to 55° cup abduction, 0° to 30° cup anteversion, and 0° to 30° femoral anteversion. Four head sizes ranging from 22.2 to 32 mm and two neck sizes ranging from 10‐mm and 12‐mm diameter were tested. Range of motion was recorded as maximum flexion–extension, abduction–adduction, and axial rotation of the femur before any contact between prosthetic components or bone was detected. Bony impingement preceded component impingement in about 44% of all conditions tested, ranging from 66% in adduction to 22% in extension. Range of motion increased as head size increased. However, increasing head size also increased the propensity for bony impingement, which tended to reduce the beneficial effect of increased head size on range of motion. Reducing neck diameter had a greater effect on prosthetic impingement (mean, 3.5° increase in range of motion) compared to bone impingement (mean, 1.9°). This model allowed for a clinically relevant assessment of range of motion after total hip arthroplasty and may also be used with patient‐specific geometry [such as that obtained from preoperative computed tomography (CT) scans] for more accurate preoperative planning. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:443–452, 2008     

Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia

Abstract: Polysomnographic sleep patterns and melatonin secretion were investigated in 10 patients (age: 41.3 ± 9.5 years) who suffered from chronic primary insomnia and complained predominantly about difficulties in maintaining sleep and in five healthy controls (age 27.2 ± 0.7 years). Nocturnal plasma melatonin concentrations were obtained hourly, measured by direct radioimmunoassay and statistically compared between insomniacs and controls with age as a covariate. Plasma melatonin levels in the patient group tended to begin increasing earlier in the evening and were significantly (P ± 0.01) lower during the middle of the night (peak value 82.5 ± 26.5 pg/ml) than in the healthy controls (peak value 116.8 ± 13.5 pg/ml). Among the patients, the most severely reduced nocturnal plasma melatonin levels were found in those patients with a history of sleep disturbance lasting for longer than five years (N = 6; age 41.8 ± 11.7 years; duration 15.3 ± 5.9 years; peak value 72.1 ± 25.0 pg/ml); whereas those chronic insomniacs affected for fewer than five years had relatively higher nocturnal levels (N = 4; age 40.6 ± 6.5 years; duration 3.8 ± 1.5 years; peak value 98.2 ± 23.9 pg/ml). These results show that the circadian rhythm of melatonin secretion is disturbed in patients with chronic primary insomnia, and that the nocturnal plasma melatonin secretion is increasingly more affected the longer the patients are unable to maintain a regular sleep pattern.     

Influence of interleukin 12B (IL12B) polymorphisms on spontaneous and treatment-induced recovery from hepatitis C virus infection

BACKGROUND/AIMS: Interleukin-12 (IL-12) governs the Th1-type immune response, affecting the spontaneous and treatment-induced recovery from HCV-infection. We investigated whether the IL12B polymorphisms within the promoter region (4 bp insertion/deletion) and the 3'-UTR (1188-A/C), which have been reported to influence IL-12 synthesis, are associated with the outcome of HCV infection. METHODS: We analyzed 186 individuals with spontaneous HCV clearance, 501 chronically HCV infected patients, and 217 healthy controls. IL12B 3'-UTR and promoter genotyping was performed by Taqman-based assays with allele-specific oligonucleotide probes and PCR-based allele-specific DNA-amplification, respectively. RESULTS: The proportion of IL12B promoter and 3'-UTR genotypes did not differ significantly between the different cohorts. However, HCV genotype 1-infected patients with high baseline viremia carrying the IL12B 3'-UTR 1188-C-allele showed significantly higher sustained virologic response (SVR) rates (25.3% vs. 46% vs. 54.5% for A/A, A/C and C/C) due to reduced relapse rates (24.2% vs. 12% vs. zero % for A/A, A/C and C/C). CONCLUSIONS: IL12B 3'-UTR 1188-C-allele carriers appear to be capable of responding more efficiently to antiviral combination therapy as a consequence of a reduced relapse rate. No association of IL12B polymorphisms and self-limited HCV infection could be demonstrated.     

Usefulness of programmed ventricular stimulation in predicting future arrhythmic events in patients with cardiac sarcoidosis

The utility of programmed ventricular stimulation to predict future arrhythmic events in patients with cardiac sarcoidosis is unknown. Similarly, the long-term benefit of implantable cardioverter-defibrillators (ICDs) in cardiac sarcoidosis has not been established. Thirty-two consecutive patients with cardiac sarcoidosis underwent programmed ventricular stimulation. Patients with spontaneous or inducible sustained ventricular arrhythmias (n = 12) underwent ICD insertion. All study patients were followed for the combined arrhythmic event end point of appropriate ICD therapies or sudden death. Mean length of follow-up to sustained ventricular arrhythmia or sudden death was 32 +/- 30 months. Five of 6 patients (83%) with spontaneous sustained ventricular arrhythmias and 4 of 6 patients (67%) without spontaneous but with inducible sustained ventricular arrhythmias received appropriate ICD therapy. Two of 20 patients (10%) with neither spontaneous nor inducible sustained ventricular arrhythmias experienced sustained ventricular arrhythmias or sudden death. Programmed ventricular stimulation predicted subsequent arrhythmic events in the entire population (relative hazard 4.47, 95% confidence interval [CI] 1.30 to 15.39) and in patients who presented without spontaneous sustained ventricular arrhythmias (relative hazard 6.97, 95% CI 1.27 to 38.27). No patient with an ICD died of a primary arrhythmic event. In patients with spontaneous or inducible sustained ventricular arrhythmias, mean survival from first appropriate ICD therapy to death or cardiac transplant was 60 +/- 46 months, with only 2 patients dying or reaching transplant at study end. In conclusion, programmed ventricular stimulation identifies patients with cardiac sarcoidosis at high risk for future arrhythmic events. ICDs effectively terminate life-threatening arrhythmias in high-risk patients, with significant survival after first appropriate therapy.     

Retention of Point-of-Care Ultrasound Skills Among Practicing Physicians: Findings of the VA National POCUS Training Program

BackgroundPoint-of-care ultrasound (POCUS) use continues to increase in many specialties, but lack of POCUS training is a known barrier among practicing physicians. Many physicians are obtaining POCUS training through postgraduate courses, but the impact of these courses on skill retention and frequency of POCUS use post-course is unknown. The purpose of this study was to assess the change in POCUS knowledge, skills, and frequency of use after 6-9 months of participating in a brief training course.MethodsCourse participants’ POCUS knowledge and hands-on technical skills were tested pre-course using an online, 30-question knowledge test and a directly observed skills test, respectively. The same knowledge and skills tests were repeated immediately post-course and after 6-9 months using remote tele-ultrasound software. Course participants completed a survey on their POCUS use pre-course and after 6-9 months post-course.ResultsThere were 127 providers who completed the POCUS training course from October 2016 to November 2017. Knowledge test scores increased from a median of 60% to 90% immediately post-course followed by a slight decrease to 87% after 8 months post-course. Median skills test scores for 4 common POCUS applications (heart, lung, abdomen, vascular access) increased 36-74 points from pre-course to immediately post-course with a 2–7-point decrease after 8 months. Providers reported more frequent POCUS use post-course, which suggests application of their POCUS knowledge and skills in clinical practice. More frequent use of cardiac POCUS applications was associated with significantly greater retention of cardiac skills at 8 months.ConclusionsPracticing physicians can retain POCUS knowledge and hands-on skills 8 months after participating in a 2.5-day POCUS training course, regardless of frequency of POCUS use post-course.     

Longitudinal study on circulating miRNAs in patients after lung cancer resection

There is an urgent need of comprehensive longitudinal analyses of circulating miRNA patterns to identify dynamic changes of miRNAs in cancer patients after surgery. Here we provide longitudinal analysis of 1,205 miRNAs in plasma samples of 26 patients after lung cancer resection at 8 time points over a period of 18 months and compare them to 12 control patients. First, we report longitudinal changes with respect to the number of detected miRNAs over time and identified a significantly increased number of miRNAs in patients developing metastases (p = 0.0096). A quantitative analysis with respect to the expression level of the detected miRNAs revealed more significant changes in the miRNA levels in samples from patients without metastases compared to the non-cancer control patients. This analysis provided further evidence of miRNA plasma levels that are changing over time after tumor resection and correlate to patient outcome. Especially hsa-miR-197 could be validated by qRT-PCR as prognostic marker. Also for this miRNA, patients developing metastases had levels close to that of controls while patients that did not develop metastases showed a significant up-regulation.In conclusion, our data indicate that the overall miRNome of a patient that later develops metastases is less affected by surgery than the miRNome of a patient who does not show metastases. The relationship between altered plasma levels of specific miRNAs with the development of metastases would partially have gone undetected by an analysis at a single time point only.     

Actions of Angiotensin II on Isolated Cardiac Fibroblasts

Angiotensin (Ang) II contributes to myocardial hypertrophy by modulating fibroblast function. In the nonhypertrophied adult rat, rabbit, monkey and human heart, both angiotensin receptor subtypes, AT1 and AT2, are expressed. AT1 seems to be present on almost all myocardial cells, whereas AT2 has so far been localized to coronary endothelial cells and to fibroblasts.AT1 signaling in fibroblasts resembles in many aspects growth factor and cytokine signaling. It includes Ca2+ influx, protein kinase C activation, tyrosine phosphorylation of a number of proteins, activation of the JAK–STAT pathway, and protooncogene induction. Effects of Ang II on the cellular level include proliferation, migration, activation of paracrine–autocrine loops via TGF-1 and other mediators, stimulation of cell–cell interaction, and synthesis of matrix proteins, i.e., collagens I and III and fibronectin. Ang II stimulation induces an increase in osteopontin, which then engages to the v3 integrin receptor on the cell surface of the fibroblasts. These events appear necessary for increased DNA synthesis and collagen gel contractions.Several modulators of fibroblast function interfere with the effects of Ang II, including prostaglandins, which interact with matrix synthesis; nitric oxide, which modulates proliferation at the level of cell cycle regulation; and endothelin, which transmits Ang II-induced proliferation signals. Mechanical loading of intact hearts also affects isolated fibroblast function, and therefore, isolated fibroblasts from pressure- and volume-loaded animals exhibit specific features that interfere with matrix synthesis and calcium handling.Fibroblasts from explanted human hearts respond to Ang II and to Ang (1–7) by DNA and protein synthesis. So far, binding assays to identify angiotensin receptor subtypes have been inconclusive. PCR has consistently revealed the presence of AT1. It is possible that AT2 receptors are also present on human cardiac fibroblasts in vivo, but their number is downregulated by growth factors in cell culture. The question concerning the conditions under which Ang II stimulates collagen formation in human cardiac fibroblasts cannot yet be conclusively answered.     

Non-invasive testing of acquired long QT syndrome: evidence for multiple arrhythmogenic substrates

BACKGROUND: Although well-defined clinically and electrocardiographically, Acquired Long QT Syndrome (LQTS) remains elusive from a pathophysiologic point of view. An increasingly accepted hypothesis is that it represents an attenuated form of Congenital Long QT Syndrome. To test this hypothesis further, we investigated patients with Acquired LQTS, using various investigations that are known to give information in patients with Congenital LQTS. METHODS: All the investigations were performed in patients with a history of Acquired Long QT Syndrome, defined by marked transient QT lengthening (QT>600 ms) and/or torsades de pointes. Measurement of the QT interval dispersion, the interlead difference for the QT interval on a 12-lead ECG, was performed in 18 patients and compared with 18 controls, matched for age and sex. To assess sympathetic myocardial innervation, I-123 Meta-iodobenzylguanidine (I-123-MIBG) scintigraphy was performed in 12 patients, together with Thallium scintigraphy, to rule out abnormal myocardial perfusion. Time-frequency analysis of a high-resolution ECG using a wavelet technique, was made for nine patients and compared with 38 healthy controls. Finally, genetic studies were performed prospectively in 16 consecutive patients, to look for HERG, KCNE1, KCNE2 and KCNQ1 mutations. The functional profile of a mutated HERG protein was performed using the patch-clamp technique. RESULTS: Compared with the control group, a significant increase in QT dispersion was observed in the patients with a history of Acquired LQTS (55+/-15 vs. 33+/-9 ms, P<0.001). In another group of patients with Acquired LQTS, 123 I-MIBG tomoscintigraphy demonstrated a decrease in the sympathetic myocardial innervation. Time--frequency analysis using wavelet transform, demonstrated an abnormal frequency content within the QRS complexes, in the patients with Acquired LQTS, similar to that found in Congenital LQTS patients. Molecular screening in 16 consecutive patients, identified one patient with a missense mutation on HERG, one of the LQTS genes. Expression of the mutated HERG protein led to altered K(+) channel function. CONCLUSION: Our results suggest that Acquired and Congenital Long QT Syndromes have some common features. They allow the mechanism of the clinical heterogeneity, found in both syndromes, to be understood. Further multi-facet approaches are needed to decipher the complex interplay between the main determinants of these arrhythmogenic diseases.     

Amino acid-modified calcitonin immunization induces tumor epitope-specific immunity in a transgenic mouse model for medullary thyroid carcinoma

Up to now, no relevant tumor antigen has been identified in medullary thyroid carcinoma (MTC). The aim of the present study was to prove the concept of an immunization with an amino acid-modified calcitonin (CT) for the treatment of MTC in a transgenic mouse model. Amino acid-modified (human) CT has been chosen for vaccination because of its higher binding affinity to the murine H2-Kb-MHC molecule. Mice were immunized over 6 months with monthly injections of amino acid-modified CT-pulsed dendritic cells. For enumeration of tumor epitope-specific CD8+ cytotoxic T cells, tetramer analyses were performed. CT peptide-treated mice revealed a mean 0.73 +/- 0.45 and 0.91 +/- 0.59% positive cells, depending on the two tetramers tested, whereas no increase was seen in control protein-immunized mice (0.08-0.12% tetramer-positive cells). Importantly, the subset of CT-specific CD8+ T cells also showed a high expression of interferon-gamma. In line with these results, CT-immunized mice also showed an intratumor infiltration with CD8+ T lymphocytes. Importantly, we also found a diminished tumor outgrowth of -57% and a decrease of the serum CT levels (2.0 +/- 0.1 pg/ml) compared with control protein-immunized Ret/Cal mice (3.0 +/- 0.4 pg/ml). In summary, we show that amino acid-modified CT is recognized from the immune system leading to a specific antitumor immune response and a diminished tumor outgrowth in transgenic MTC mice. The results are of potential importance because they might be applicable to patients with metastatic spread of a MTC.