Does arthroscopic assistance improve reduction in distal articular radius fracture? A retrospective comparative study using a blind CT assessment.

INTRODUCTION: The objective of this study was to compare the articular reduction in two groups of patients with a distal articular radius fracture who underwent surgery with versus without arthroscopic assistance. The initial hypothesis of this study is that arthroscopic assistance does not improve reduction in distal articular radius fractures. METHODS: The study was retrospective (1/04/2014-01/04/2017) and included 41 patients: 23 had arthroscopically assisted osteosynthesis, and 18 had not. All patients included had CT before and 3 months after surgery. All radiographic and CT measurements were retrospectively taken by an independent radiologist who did not know which operative technique was performed. Secondary judgement criteria were clinical analysis at 1-year follow-up and tourniquet time. We also reported all soft tissue injuries diagnosed and repaired and postoperative complications. RESULTS: At the third month, articular step was 0.91 ± 1.25 mm (arthroscopy) and 1.41 ± 1.68 mm (no arthroscopy), without statistical difference (p = 0.3756). No difference was found for articular gap between the two groups [arthroscopy (0.55 ± 1.04 mm), (no arthroscopy (0.82 ± 1.54 mm)] (p = 0.8574). Except for the tourniquet time, clinical results at 1-year follow-up were not different. One patient of each group had a scapholunate pinning, and 6 patients of the arthroscopy group had a TFCC 1B injury, which was repaired. CONCLUSION: This study did not demonstrate that arthroscopic assistance improves step and gap reduction of articular distal radius fracture, confirming initial hypothesis and recent literature data. LEVEL OF EVIDENCE: Retrospective, III.

Claudin-1, miR-122 and apolipoprotein E transductions improve the permissivity of SNU-182, SNU-398 and SNU-449 hepatoma cells to hepatitis C virus.

Hepatitis C virus (HCV) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU-182, SNU-398 and SNU-449 hepatoma cell lines were nonpermissive to HCV. To understand the nonpermissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin-1 (CLDN1) expression limited the viral entry process in SNU-182 and SNU-398 cells, respectively. Our results also showed that supplementation of the three cell lines with miR-122 partly restored the replication of a JFH1 HCV replicon. Finally, we observed that expression of apolipoprotein E (ApoE) was very low or undetectable in the three cell lines and that its ectopic expression permits the production of infectious viral particles in SNU-182 and SNU-398 cells but not in SNU-449 cells. Nevertheless, the supplementation of SNU-182, SNU-398 and SNU-449 cells with CLDN1, miR-122 and ApoE was not sufficient to render these cells as permissive as HuH-7 cells. Thus, these cell lines could serve as cell culture models for functional studies on the role of CLDN1, miR-122 and ApoE in HCV life cycle but also for the identification of new restriction and/or dependency host factors essential for HCV infection.

Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

Genetic recombination of the hepatitis C virus: clinical implications.

Genetic recombination is a well-known feature of RNA viruses that plays a significant role in their evolution. Although recombination is well documented for Flaviviridae family viruses, the first natural recombinant strain of hepatitis C virus (HCV) was identified as recently as 2002. Since then, a few other natural inter-genotypic, intra-genotypic and intra-subtype recombinant HCV strains have been described. However, the frequency of recombination may have been underestimated because not all known HCV recombinants are screened for in routine practice. Furthermore, the choice of treatment regimen and its predictive outcome remain problematic as the therapeutic strategy for HCV infection is genotype dependent. HCV recombination also raises many questions concerning its mechanisms and effects on the epidemiological and physiopathological features of the virus. This review provides an update on recombinant HCV strains, the process that gives rise to recombinants and clinical implications of recombination.

Genetic features of polioviruses isolated in Tunisia, 1991-2006.

BACKGROUND: Genetic characterisation of polioviruses remains highly important even in countries where wild poliovirus circulation has been interrupted. Sequence data on representative wild strains from all geographical regions is required for surveillance purposes and surveillance for vaccine-related isolates with increased potential for transmissibility in humans should continue. OBJECTIVE: To report the genetic characteristics of wild and vaccine-related polioviruses isolated in Tunisia from 1991 to 2006. STUDY DESIGN: Wild isolates were sequenced in the VP1 genomic region and compared to each other. Vaccine-related isolates were assessed for genetic recombination by PCR/RFLP and sequence analysis of the 3D region. Recombinant viruses were assessed for genetic drift in the VP1 region. RESULTS: The VP1 sequences of the last wild isolates, all from serotype3, showed 97.7-98.7% nucleotide homology. Nineteen percent of vaccine-related isolates were vaccine/vaccine intertypic recombinants. No recombinant with non-poliovirus enteroviruses was identified. Mutational differences in the VP1 sequences of recombinant viruses ranged from 0.0% to 0.7% indicating a limited replication period. CONCLUSIONS: This study provides sequence data on wild polioviruses from Tunisia/North Africa and shows that in countries with continuous high vaccine coverage transmission of vaccine-related polioviruses is time-limited.

Successful treatment of disseminated Geotrichum capitatum infection with a combination of caspofungin and voriconazole in an immunocompromised patient.

Disseminated Geotrichum capitatum infection is uncommon, and has been reported exclusively in immunocompromised patients. The prognosis is poor with a mortality rate of approximately 50-75%. We report a case of disseminated G. capitatum infection in a severely neutropenic patient who was receiving chemotherapy for acute myeloblastic leukaemia. G. capitatum was isolated from blood cultures, skin lesions, bronchoalveolar lavage fluid, throat swabs and stools. The infection was successfully cured with a combination of voriconazole and caspofungin.

[Chronic urticaria]. / Urticaire chronique.

Chronic urticaria (CU) is a common disease of unknown origin. Its impact on the quality of life is significant. Antibodies to high affinity receptors expressed on mast cells and basophiles (FcepsilonRI) are found in 30% of cases and may be associated with more severe and prolonged symptoms. A wide variety of disorders can be associated with CU. However, in the absence of suggestive signs or symptoms, an extensive workup rarely permits the diagnosis of an underlying pathology. In this case, the work up should be minimal. The newer generation oral anti-histamines represent the first line treatment. In the refractory cases, other drugs may be considered but few controlled studies support their use.

Extremely premature infants: How does death in the delivery room influence mortality rates in two level 3 centers in France?

OBJECTIVES: Mortality rates of very preterm infants may vary considerably between healthcare facilities depending on the neonates' place of inclusion in the cohort study. The objective of this study was to compare the mortality rates of live-born extremely preterm neonates observed in two French tertiary referral hospitals, taking into account the occurrence of neonatal death both in the delivery room and in the neonatal intensive care unit (NICU). METHODS: Retrospective observational study including all pregnancy terminations, stillbirths and live-born infants within a 22- to 26-week 0/6 gestational age range was registered by two French level 3 university centers between 2009 and 2013. The mortality rates were compared between the two centers according to two places of inclusion: either the delivery room or the NICU. RESULTS: A total of 344 infants were born at center A and 160 infants were born at center B. Among the live-born neonates, the rates of neonatal death were similar in center A (54/125, 43.2%) and center B (33/69, 47.8%; P=0.54). However, neonatal death occurred significantly more often in the delivery room at center A (31/54, 57.4%) than at center B (6/33, 18.2%; P<0.001). Finally, the neonatal death rate of live-born very preterm neonates admitted to the NICU was significantly lower in center A (25/94, 26.6%) than in center B (27/63, 42.9%; P=0.03). CONCLUSIONS: This study points out how the inclusion of deaths in the delivery room when comparing neonatal death rates can lead to a substantial bias in benchmarking studies. Center A and center B each endorsed one of the two models of preferential place of neonatal death (delivery room or NICU) detailed in European studies. The reasons behind the two different models and their impact on how parents perceive supporting their neonate need further investigation.

Transcriptional repression by suppressor of hairless involves the binding of a hairless-dCtBP complex in Drosophila.

Notch is the receptor for a conserved signaling pathway that regulates numerous cell fate decisions during development [1]. Signal transduction involves the presenilin-dependent intracellular processing of Notch and the nuclear translocation of the intracellular domain of Notch, NICD [2-6]. NICD associates with Suppressor of Hairless [Su(H)], a DNA binding protein, and Mastermind (Mam), a transcriptional coactivator [7-9]. In the absence of Notch signaling, Su(H) acts as a transcriptional repressor [10, 11]. Repression by Su(H) is relieved by the activation of Notch [12-16]. In the Drosophila embryo, this transcriptional switch from repression to activation is important for patterning the expression of the single-minded (sim) gene along the dorsoventral axis [12]. Here, we investigate the mechanisms by which Su(H) inhibits the expression of Notch target genes in Drosophila. We show that Hairless, an antagonist of Notch signaling [17-19], is required to repress the transcription of the sim gene. Hairless forms a DNA-bound complex with Su(H). Furthermore, it directly binds the Drosophila C-terminal Binding Protein (dCtBP), which acts as a transcriptional corepressor. The dCtBP binding motif of Hairless is essential for the function of Hairless in vivo. We propose that Hairless mediates transcriptional repression by Su(H) via the recruitment of dCtBP.

Microstructural modeling of collagen network mechanics and interactions with the proteoglycan gel in articular cartilage.

Cartilage matrix mechanical function is largely determined by interactions between the collagen fibrillar network and the proteoglycan gel. Although the molecular physics of these matrix constituents have been characterized and modern imaging methods are capable of localized measurement of molecular densities and orientation distributions, theoretical tools for using this information for prediction of cartilage mechanical behavior are lacking. We introduce a means to model collagen network contributions to cartilage mechanics based upon accessible microstructural information (fibril density and orientation distributions) and which self-consistently follows changes in microstructural geometry with matrix deformations. The interplay between the molecular physics of the collagen network and the proteoglycan gel is scaled up to determine matrix material properties, with features such as collagen fibril pre-stress in free-swelling cartilage emerging naturally and without introduction of ad hoc parameters. Methods are developed for theoretical treatment of the collagen network as a continuum-like distribution of fibrils, such that mechanical analysis of the network may be simplified by consideration of the spherical harmonic components of functions of the fibril orientation, strain, and stress distributions. Expressions for the collagen network contributions to matrix stress and stiffness tensors are derived, illustrating that only spherical harmonic components of orders 0 and 2 contribute to the stress, while orders 0, 2, and 4 contribute to the stiffness. Depth- and compression-dependent equilibrium mechanical properties of cartilage matrix are modeled, and advantages of the approach are illustrated by exploration of orientation and strain distributions of collagen fibrils in compressed cartilage. Results highlight collagen-proteoglycan interactions, especially for very small physiological strains where experimental data are relatively sparse. These methods for determining matrix mechanical properties from measurable quantities at the microscale (composition, structure, and molecular physics) may be useful for investigating cartilage structure-function relationships relevant to load-bearing, injury, and repair.

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française (summary).

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.

Effects of damage in the articular surface on the cartilage response to injurious compression in vitro.

Macroscopic structural damage to the cartilage articular surface can occur due to slicing in surgery, cracking in mechanical trauma, or fibrillation in early stage osteoarthrosis. These alterations may render cartilage matrix and chondrocytes susceptible to subsequent mechanical injury and contribute to progression of degenerative disease. To examine this hypothesis, single 300 microm deep vertical slices were introduced across a diameter of the articular surface of osteochondral explant disks on day 6 after dissection. Then a single uniaxial unconfined ramp compression at 7 x 10(-5) or 7 x 10(-2) s(-1) strain rate to a peak stress of 3.5 or 14 MPa was applied on day 13 during which mechanical behavior was monitored. Effects of slices alone and together with compression were measured in terms of explant swelling and cell viability on days 10 and 17. Slicing alone induced tissue swelling without significant cell death, while compression alone induced cell death without significant tissue swelling. Under low strain rate loading, no differences in the response to injurious compression were found between sliced and unsliced explants. Under high strain rate loading, slicing rendered cartilage more easily compressible and appeared to slightly reduce compression-induced cell and matrix injury. Findings highlight microphysical factors important to cartilage mechanical injury, and suggest ways that macroscopic structural damage may accelerate or, in certain cases, possibly slow the progression of cartilage degeneration.

[Termination of pregnancy without feticide: A French national survey]. / L'interruption médicale de grossesse sans fœticide : une enquête nationale.

PURPOSE: Termination of pregnancy without feticide (TOPWF) is poorly known in France and far less practiced than palliative care after term birth of a child having a lethal pathology. Few teams consider it and its practice remains confidential. This survey tries to describe it. MATERIAL AND METHODS: A national survey was realized in 2014 using a questionnaire sent to 50 centers of prenatal diagnosis depending on a perinatal diagnosis center in France. RESULTS: Thirty-one centers answered the questionnaire. Seven teams shared their experience of TOPWF after 22-24 weeks gestation (WG). This practice concerned fetuses affected by "lethal" pathologies. The absence of feticide followed a parental request or a proposal of the medical team, after individual discussion in a multidisciplinary meeting. All the children born alive after TOPWF benefited of palliative care. The 24 other centers having answered our investigation performed systematically the feticide beyond 22-24 WG. They so wished "to protect" the fetus, the parents and the nursing team. A majority of these teams faced parental demands of abstention of feticide but few of them answered it favorably. CONCLUSION: A robust "palliative culture" seems essential to allow the nursing team to consider the development of TOPWF.

[Anaphylaxis: initial management]. / Anaphylaxie: prise en charge initiale.

Anaphylaxis is an immediate systemic reaction caused by an external agent. Its initial management depends on the severity of the reaction. In case of benign to moderate reaction, anti-histamine and steroid treatment are sufficient to control the process, and management is ambulatory. A severe reaction (hypotension, dyspnea) can be life threatening and adrenalin administration by the intramuscular route is indicated. In this case, it is advocated to observe the evolution for 24 hours in the hospital and the patient should be prescribed adrenaline auto-injectors. It is recommended that individuals who have experienced anaphylaxis should receive consultation from an allergist regarding diagnosis, prevention and treatment.

Ofatumumab in refractory chronic lymphocytic leukemia: experience through the French early access program.

BACKGROUND: The Autorisation Temporaire d'Utilisation (ATU) is an early access program available in France for drugs aimed at treating severe diseases not yet covered by a marketing authorization, for patients without any other therapeutic option and who cannot be included in a clinical trial. PATIENTS AND METHODS: This report presents the use of single-agent ofatumumab in 30 patients with advanced chronic lymphocytic leukemia (CLL) in the French ATU program. RESULTS: These very-high-risk patients had received multiple previous treatments (median = 6), and most had disease that was fludarabine-refractory or alemtuzumab-refractory (or both) or was unsuitable for alemtuzumab treatment. In the intent-to-treat analysis, the overall response rate was 47% (4 of 30, complete response; 10 of 30, partial response). Of 13 patients with 17p deletion, 6 displayed response to ofatumumab, including 2 complete responses. Treatment was well tolerated, with 17 grade 3 or 4 adverse events; 4 cases of grade 3 or 4 infusion reactions were reported, with favorable immediate outcome. Among nonhematologic complications, infections were the most frequent. CONCLUSION: The results confirm the efficacy and acceptable tolerability profile of ofatumumab as a single agent in severely ill patients with CLL. Attention should be paid to possible early infusion reactions to ofatumumab, as well as to the risk of infection.

Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families.

The aims of this study were to estimate the prevalence of major maturity-onset diabetes of the young (MODY) subtypes in Spanish MODY families and to analyze genotype-phenotype correlations. Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. In families carrying GCK mutations, the influence of genetic defects on fetal growth was investigated by comparing the birth weights of 32 offspring discordant for the mutations. Mutations in MODY genes were identified in 64% of the families. GCK/MODY2 mutations were the most frequently found, in 41%: seven novel (R369P, S411F, M298K, C252Y, Y108C, A188E, and S383L) and 2 already described mutations. Four pedigrees (18%) harbored mutations in the HNF-1alpha/MODY3 gene, including a previously unreported change (R271G). One family (4%) carried a novel mutation in the HNF-4alpha gene (IVS5-2delA), representing the first report of a MODY1 pedigree in the Spanish population. The age at diagnosis was prepubertal in MODY2 index patients and pubertal in MODY3 patients. Overt diabetes was rare in MODY2 and was invariably present in MODY3 index patients. Chronic complications of diabetes were absent in the MODY2 population and were present in more than 40% of all relatives of MODY3. Birth weight was lower in the presence of a GCK fetal mutation when the mutation was of paternal origin. The MODY1 patient was diagnosed at 15 yr of age. She developed intermittent microalbuminuria despite good metabolic control, and severe late-onset complications were common within her family. Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. The inheritance of GCK defects by the fetus results in a reduction of birth weight. Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications.

Occurrence of an HIV-1 gp160 endoproteolytic activity in low-density vesicles and evidence for a distinct density distribution from endogenously expressed furin and PC7/LPC convertases.

Human immunodeficiency virus (HIV) glycoprotein (gp) 160 processing by host cell proteinases is an essential step for viral fusion and infectivity. We have identified a rat liver subcellular fraction which specifically processes gp160 into gp120 and gp41. Using equilibration of microsomes in sucrose gradients, the gp160 cleavage activity was associated with particles equilibrating at low densities, well-separated from the endoplasmic reticulum, cis-Golgi network, Golgi stacks, lysosomes and plasma membrane. Its density distribution was compatible with light secretory vesicles derived from the trans-Golgi network (TGN) or to endosomes, but association with endosomes was not supported by free flow electrophoresis. Although furin and pro-protein convertase (PC) 7/LPC have been proposed as the major gp160 processing convertases, the rat liver microsomal gp160 processing activity was essentially resolved from furin and only partially overlapped PC7/LPC. These data suggest that proteinase(s) other than furin and PC7/LPC, presumably located in TGN-derived vesicles, may participate in the gp160 processing into gp120 and gp41.

Static compression of articular cartilage can reduce solute diffusivity and partitioning: implications for the chondrocyte biological response.

Chondrocytes depend upon solute transport within the avascular extracellular matrix of adult articular cartilage for many of their biological activities. Alterations to bioactive solute transport may, therefore, represent a mechanism by which cartilage compression is transduced into cellular metabolic responses. We investigated the effects of cartilage static compression on diffusivity and partitioning of a range of model solutes including dextrans of molecular weights 3 and 40 kDa, and tetramethylrhodamine (a 430 Da fluorophore). New fluorescence methods were developed for real-time visualization and measurement of transport within compressed cartilage explants. Experimental design allowed for multiple measurements on individual explants at different compression levels in order to minimize confounding influences of compositional variations. Results demonstrate that physiological levels of static compression may significantly decrease solute diffusivity and partitioning in cartilage. Effects of compression were most dramatic for the relatively high molecular weight solutes. For 40 kDa dextran, diffusivity decreased significantly (p<0.01) between 8% and 23% compression, while partitioning of 3 and 40 kDa dextran decreased significantly (p<0.01) between free-swelling conditions and 8% compression. Since diffusivity and partitioning can influence pericellular concentrations of bioactive solutes, these observations support a role for perturbations to solute transport in mediating the cartilage biological response to compression.

Search for DNA sequence variations using a MutS-based technology.

The search for DNA sequence variations (DSV) is emphasized with genetic studies of a large number of multifactorial diseases. Saturation of regions of interest with diallelic polymorphisms will be an essential step to pinpoint, through association studies, predisposing genes. We have developed a solid-phase method based on the ability of mismatch binding protein MutS to recognize single nucleotide mismatches. This approach was applied to the study of 83 sequence-tagged sites (STSs) extracted from an eight centimorgans (cM) chromosome 21 region. One-third of tested STSs were found to be polymorphic leading to a frequency of one DSV every 822 base pairs (bp). Sequencing of analyzed STSs showed the high reliability of the MutS-based technology for mismatches up to 2 bp in DNA fragments ranging in size from 200 bp to 1 kilobase (kb). The entire assay which is performed in a solid-phase format without the need of electrophoresis or sequencing, will provide an efficient tool for new polymorphism detection.