Risks and benefits of percutaneous vertebroplasty or kyphoplasty in the management of osteoporotic vertebral fractures.

Vertebral fracture (VF) is the most common osteoporotic fracture and is associated with high morbidity and mortality. Conservative treatment combining antalgic agents and rest is usually recommended for symptomatic VFs. The aim of this paper is to review the randomized controlled trials comparing the efficacy and safety of percutaneous vertebroplasty (VP) and percutaneous balloon kyphoplasty (KP) versus conservative treatment. VP and KP procedures are associated with an acceptable general safety. Although the case series investigating VP/KP have all shown an outstanding analgesic benefit, randomized controlled studies are rare and have yielded contradictory results. In several of these studies, a short-term analgesic benefit was observed, except in the prospective randomized sham-controlled studies. A long-term analgesic and functional benefit has rarely been noted. Several recent studies have shown that both VP and KP are associated with an increased risk of new VFs. These fractures are mostly VFs adjacent to the procedure, and they occur within a shorter time period than VFs in other locations. The main risk factors include the number of preexisting VFs, the number of VPs/KPs performed, age, decreased bone mineral density, and intradiscal cement leakage. It is therefore important to involve the patients to whom VP/KP is being proposed in the decision-making process. It is also essential to rapidly initiate a specific osteoporosis therapy when a VF occurs (ideally a bone anabolic treatment) so as to reduce the risk of fracture. Randomized controlled studies are necessary in order to better define the profile of patients who likely benefit the most from VP/KP.

Influence des génériques sur le marché des médicaments

Ce rapport décrit le marché des médicaments remboursés par l'assurance obligatoire des soins (AOS) avec une intention particulière des génériques. En premier lieu, l'évolution des coûts et des quantités de médicaments entre 2006 et 2011; et présente la part de marché des génériques dans le marché des médicaments. Ensuite les économies résiduelles des génériques sont estimées dans l'hypothèse d'une utilisation plus étendue de ces derniers. Enfin le rapport montre l'influence des mesures des autorités fédérales dans le domaine des médicaments et de l'incidence de la commercialisation de génériques sur le prix des médicaments.

Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression.

Treg are the main mediators of dominant tolerance. Their mechanisms of action and applications are subjects of considerable debate currently. However, a human microRNA (miR) Treg signature has not been described yet. We investigated human natural Treg and identified a signature composed of five miR (21, 31, 125a, 181c and 374). Among those, two were considerably under-expressed (miR-31 and miR-125a). We identified a functional target sequence for miR-31 in the 3' untranslated region (3' UTR) of FOXP3 mRNA. Using lentiviral transduction of fresh cord blood T cells, we demonstrated that miR-31 and miR-21 had an effect on FOXP3 expression levels. We showed that miR-31 negatively regulates FOXP3 expression by binding directly to its potential target site in the 3' UTR of FOXP3 mRNA. We next demonstrated that miR-21 acted as a positive, though indirect, regulator of FOXP3 expression. Transduction of the remaining three miR had no direct effect on FOXP3 expression or on the phenotype and will remain the subject of future investigations. In conclusion, not only have we identified and validated a miR signature for human natural Treg, but also unveiled some of the mechanisms by which this signature was related to the control of FOXP3 expression in these cells.

Erste Resultate der HOT-Studie in der Schweiz. [Initial results of the HOT-study in Switzerland (hypertension optimal treatment)]

The HOT study (hypertension-optimal treatment) is an international clinical study on primary prevention of cardiovascular events in 19,193 hypertensive patients worldwide. It aims at the recognition of the optimal diastolic blood pressure value (< 90, < 85 or < 80 mmHg?) in order to maximize the possible benefit of an antihypertensive therapy. In addition, the HOT study investigates whether low doses of aspirin (75 mg/day) are able to reduce the occurrence of severe cardiovascular events. In Switzerland a total of 797 patients have been enrolled in the study. Antihypertensive therapy was initiated with felodipine = Plendil (5 mg/day). This vasoelective calcium antagonist could reduce diastolic blood pressure values to < 90 or < 80 mg/Hg, respectively, in one of two or one of three patients within the first three months. In nine or six patients, respectively out of ten a reduction of diastolic blood pressure values to < 90 or < 80 mmHg was reached within one year by combination of felodipine with other antihypertensive drugs (ACE inhibitors, beta blockers and diuretics).

Neonatal steroids induce a down-regulation of tenascin-C and elastin and cause a deceleration of the first phase and an acceleration of the second phase of lung alveolarization.

Pre- and postnatal corticosteroids are often used in perinatal medicine to improve pulmonary function in preterm infants. To mimic this clinical situation, newborn rats were treated systemically with dexamethasone (Dex), 0.1-0.01 mg/kg/day on days P1-P4. We hypothesized that postnatal Dex may have an impact on alveolarization by interfering with extracellular matrix proteins and cellular differentiation. Morphological alterations were observed on 3D images obtained by high-resolution synchrotron radiation X-ray tomographic microscopy. Alveolarization was quantified stereologically by estimating the formation of new septa between days P4 and P60. The parenchymal expression of tenascin-C (TNC), smooth muscle actin (SMA), and elastin was measured by immunofluorescence and gene expression for TNC by qRT-PCR. After Dex treatment, the first phase of alveolarization was significantly delayed between days P6 and P10, whereas the second phase was accelerated. Elastin and SMA expressions were delayed by Dex treatment, whereas TNC expression was delayed and prolonged. A short course of neonatal steroids impairs the first phase of alveolarization, most likely by altering the TNC and elastin expression. Due to an overshooting catch-up during the second phase of alveolarization, the differences disappear when the animals reach adulthood.

Importance of the subscapularis muscle after total shoulder arthroplasty.

BACKGROUND: The rotator cuff muscles are the main stabilizer of the glenohumeral joint. After total shoulder arthroplasty using anterior approaches, a dysfunction of the subscapularis muscle has been reported. In the present paper we tested the hypothesis that a deficient subscapularis following total shoulder arthroplasty can induce joint instability. METHODS: To test this hypothesis we have developed an EMG-driven musculoskeletal model of the glenohumeral joint. The model was based on an algorithm that minimizes the difference between measured and predicted muscular activities, while satisfying the mechanical equilibrium of the glenohumeral joint. A movement of abduction in the scapular plane was simulated. We compared a normal and deficient subscapularis. Muscle forces, joint force, contact pattern and humeral head translation were evaluated. FINDINGS: To satisfy the mechanical equilibrium, a deficient subscapularis induced a decrease of the force of the infraspinatus muscle. This force decrease was balanced by an increase of the supraspinatus and middle deltoid. As a consequence, the deficient subscapularis induced an upward migration of the humeral head, an eccentric contact pattern and higher stress within the cement. INTERPRETATION: These results confirm the importance of the suscapularis for the long-term stability of total shoulder arthroplasty.

Pédiatrie [Perinatal asphyxia and neonatal hydronephrosis]

Perinatal asphyxia. Perinatal asphyxia remains one of the most important causes for high mortality and morbidity in the neonatal population. Despite intensive animal and clinical research in this field, no pharmocological strategy has been shown neuroprotective in humans. Moderate hypothermia for severely and moderately asphyctic babies has been aknowledged since a few years as therapeutical approach to improve the outcome of these infants, specifically the long-term follow up (18 months). Neonatal hydronephrosis. Neonatal hydronephrosis is a pathology that requires regular and efficient follow up by a multidisciplinary team. One of the causes of neonatal hydronephrosis is obstructive pathologies which may endanger the kidney. We have developed a strategy that allows a rapid diagnosis of obstructive pathologies with minimal radiological exams. Moreover, this strategy assures the coordination between obstetricians, neonatologists, pediatric urologists, and pediatric nephrologists.

Virtual anthropology: A comparison between the performance of conventional X-ray and MDCT in investigating the trabecular structure of long bones.

Recently, modern cross-sectional imaging techniques such as multi-detector computed tomography (MDCT) have pioneered post mortem investigations, especially in forensic medicine. Such approaches can also be used to investigate bones non-invasively for anthropological purposes. Long bones are often examined in forensic cases because they are frequently discovered and transferred to medico-legal departments for investigation. To estimate their age, the trabecular structure must be examined. This study aimed to compare the performance of MDCT with conventional X-rays to investigate the trabecular structure of long bones. Fifty-two dry bones (24 humeri and 28 femora) from anthropological collections were first examined by conventional X-ray, and then by MDCT. Trabecular structure was evaluated by seven observers (two experienced and five inexperienced in anthropology) who analyzed images obtained by radiological methods. Analyses contained the measurement of one quantitative parameter (caput diameter of humerus and femur) and staging the trabecular structure of each bone. Preciseness of each technique was indicated by describing areas of trabecular destruction and particularities of the bones, such as pathological changes. Concerning quantitative parameters, the measurements demonstrate comparable results for the MDCT and conventional X-ray techniques. In contrast, the overall inter-observer reliability of the staging was low with MDCT and conventional X-ray. Reliability increased significantly when only the results of the staging performed by the two experienced observers were compared, particularly regarding the MDCT analysis. Our results also indicate that MDCT appears to be better suited to a detailed examination of the trabecular structure. In our opinion, MDCT is an adequate tool with which to examine the trabecular structure of long bones. However, adequate methods should be developed or existing methods should be adapted to MDCT.

Malaria haplotype frequency estimation.

We present a Bayesian approach for estimating the relative frequencies of multi-single nucleotide polymorphism (SNP) haplotypes in populations of the malaria parasite Plasmodium falciparum by using microarray SNP data from human blood samples. Each sample comes from a malaria patient and contains one or several parasite clones that may genetically differ. Samples containing multiple parasite clones with different genetic markers pose a special challenge. The situation is comparable with a polyploid organism. The data from each blood sample indicates whether the parasites in the blood carry a mutant or a wildtype allele at various selected genomic positions. If both mutant and wildtype alleles are detected at a given position in a multiply infected sample, the data indicates the presence of both alleles, but the ratio is unknown. Thus, the data only partially reveals which specific combinations of genetic markers (i.e. haplotypes across the examined SNPs) occur in distinct parasite clones. In addition, SNP data may contain errors at non-negligible rates. We use a multinomial mixture model with partially missing observations to represent this data and a Markov chain Monte Carlo method to estimate the haplotype frequencies in a population. Our approach addresses both challenges, multiple infections and data errors.

Is trauma in Switzerland any different? epidemiology and patterns of injury in major trauma - a 5-year review from a Swiss trauma centre.

Switzerland, the country with the highest health expenditure per capita, is lacking data on trauma care and system planning. Recently, 12 trauma centres were designated to be reassessed through a future national trauma registry by 2015. Lausanne University Hospital launched the first Swiss trauma registry in 2008, which contains the largest database on trauma activity nationwide. METHODS: Prospective analysis of data from consecutively admitted shock room patients from 1 January 2008 to 31 December 2012. Shock room admission is based on physiology and mechanism of injury, assessed by prehospital physicians. Management follows a surgeon-led multidisciplinary approach. Injuries are coded by Association for the Advancement of Automotive Medicine (AAAM) certified coders. RESULTS: Over the 5 years, 1,599 trauma patients were admitted, predominantly males with a median age of 41.4 years and median injury severity score (ISS) of 13. Rate of ISS >15 was 42%. Principal mechanisms of injury were road traffic (40.4%) and falls (34.4%), with 91.5% blunt trauma. Principal patterns were brain (64.4%), chest (59.8%) and extremity/pelvic girdle (52.9%) injuries. Severe (abbreviated injury scale [AIS] score ≥ 3) orthopaedic injuries, defined as extremity and spine injuries together, accounted for 67.1%. Overall, 29.1% underwent immediate intervention, mainly by orthopaedics (27.3%), neurosurgeons (26.3 %) and visceral surgeons (13.9%); 43.8% underwent a surgical intervention within the first 24 hours and 59.1% during their hospitalisation. In-hospital mortality for patients with ISS >15 was 26.2%. CONCLUSION: This is the first 5-year report on trauma in Switzerland. Trauma workload was similar to other European countries. Despite high levels of healthcare, mortality exceeds published rates by >50%. Regardless of the importance of a multidisciplinary approach, trauma remains a surgical disease and needs dedicated surgical resources.