Keutel Syndrome, a review of 50 years of literature

Keutel syndrome (KS) is a rare autosomal recessive genetic disorder that was first identified in the beginning of the 1970s and nearly 30 years later attributed to loss-of-function mutations in the gene coding for the matrix Gla protein (MGP). Patients with KS are usually diagnosed during childhood (early onset of the disease), and the major traits include abnormal calcification of cartilaginous tissues resulting in or associated with malformations of skeletal tissues (e.g., midface hypoplasia and brachytelephalangism) and cardiovascular defects (e.g., congenital heart defect, peripheral pulmonary artery stenosis, and, in some cases, arterial calcification), and also hearing loss and mild developmental delay. While studies on Mgp-/- mouse, a faithful model of KS, show that pathologic mineral deposition (ectopic calcification) in cartilaginous and vascular tissues is the primary cause underlying many of these abnormalities, the mechanisms explaining how MGP prevents abnormal calcification remain poorly understood. This has negative implication for the development of a cure for KS. Indeed, at present, only symptomatic treatments are available to treat hypertension and respiratory complications occurring in the KS patients. In this review, we summarize the results published in the last 50 years on Keutel syndrome and present the current status of the knowledge on this rare pathology.CA-16115 - EJPRD2019-290 - UIDB/04326/2020info:eu-repo/semantics/publishedVersio

Biotyping of Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates from France and Algeria Using MALDI- TOF MS

Abstract Background: Klebsiella pneumoniae is one of the most important pathogens responsible for nosocomial outbreaks worldwide. Epidemiological analyses are useful in determining the extent of an outbreak and in elucidating the sources and the spread of infections. The aim of this study was to investigate the epidemiological spread of K. pneumoniae strains using a MALDI-TOF MS approach

Clinical and MRI outcomes 10 years after repair of massive posterosuperior rotator cuff tears

BACKGROUND: Massive rotator cuff tears are challenging to treat, with few or no studies on long-term outcomes of repair. The purpose of this study was to report 10-year outcomes following repair of massive posterosuperior rotator cuff tears, with and without extension into the subscapularis, and to determine prognostic factors that could influence clinical scores and retear rates. METHODS: The records of 234 patients who underwent repair of a massive posterosuperior rotator cuff tear at a total of 15 centers were retrieved. Patients were asked to return for evaluation at 10 years; 78 patients could not be contacted, 7 had died, and 19 had undergone a reoperation. A total of 130 patients (68% men) with a mean age (and standard deviation) of 56.1 ± 7.7 years (range, 26 to 79 years) were evaluated clinically, and 102 of them were also evaluated using magnetic resonance imaging (MRI). The tear was confined to the supraspinatus and infraspinatus tendons in 94 shoulders and also involved the superior portion of the subscapularis in 36 shoulders. Univariable and multivariable regressions were performed to determine whether 10-year total Constant-Murley scores and repair integrity were associated with patient characteristics, tear patterns, or repair techniques. RESULTS: In the study cohort, complications were noted in 14 shoulders (11%) (stiffness in 10 and infection in 4). For the 130 shoulders evaluated clinically, the mean total Constant-Murley score improved from 53.1 ± 15.9 (range, 14 to 83) preoperatively to 78.5 ± 11.3 (range, 36 to 98) at 10 years. Of the 102 shoulders evaluated using MRI, 32 had a retear (Sugaya type IV or V). Of the 19 shoulders that underwent a reoperation (excluded from the study cohort), 9 had a retear. The overall prevalence of retears was 34%. Multivariable regression analysis revealed a significant association between the 10-year Constant-Murley score and preoperative retraction of the infraspinatus tendon, but no association between retears and any of the variables. Involvement of the subscapularis had no significant effect on preoperative or postoperative Constant-Murley scores or retear rates. CONCLUSIONS: Patients who had repair of a massive posterosuperior rotator cuff tear maintained considerable improvements in clinical and radiographic outcomes at 10 years. Partial concomitant tears of the subscapularis did not affect the total postoperative Constant-Murley scores or retear rates

Real-Time Microbiology Laboratory Surveillance System to Detect Abnormal Events and Emerging Infections, Marseille, France

International audienceInfectious diseases are a major threat to humanity, and accurate surveillance is essential. We describe how to implement a laboratory data–based surveillance system in a clinical microbiology laboratory. Two historical Microsoft Excel databases were implemented. The data were then sorted and used to execute the following 2 surveillance systems in Excel: the Bacterial real-time Laboratory-based Surveillance System (BALYSES) for monitoring the number of patients infected with bacterial species isolated at least once in our laboratory during the study periodl and the Marseille Antibiotic Resistance Surveillance System (MARSS), which surveys the primary β-lactam resistance phenotypes for 15 selected bacterial species. The first historical database contained 174,853 identifications of bacteria, and the second contained 12,062 results of antibiotic susceptibility testing. From May 21, 2013, through June 4, 2014, BALYSES and MARSS enabled the detection of 52 abnormal events for 24 bacterial species, leading to 19 official reports. This system is currently being refined and improved

Clinical and structural outcome twenty years after repair of isolated supraspinatus tendon tears

BACKGROUND: This study evaluated the clinical and structural outcome 20 years after repair of isolated supraspinatus tendon tears. We hypothesized that the results would deteriorate over time. MATERIALS AND METHODS: For this retrospective multicenter study, 137 patients were recalled for a clinical and imaging assessment. Six patients (4.3%) had died from unrelated causes, 52 (38.0%) were lost to follow-up, and 13 (9.5%) had undergone reoperations. This left 66 patients for clinical evaluation. Radiographs and magnetic resonance imaging were additionally performed for 45 patients, allowing assessment of osteoarthritis, tendon healing, fatty infiltration (FI), and muscle atrophy. RESULTS: The Constant Score (CS) improved from 51.5 ± 14.1 points preoperatively to 71 points (P < .05) with a mean Subjective Shoulder Value (SSV) of 77.2% ± 22%. Tendon discontinuity (Sugaya IV-V) was present in 19 of 45 patients (42 %), and there was advanced FI (Goutallier III-IV) of the supraspinatus in 12 (27%) and of the infraspinatus muscle in 16 (35%). Supraspinatus atrophy was present in 12 patients (28%), advanced arthritis in 6, and cuff tear arthropathy in 12 (30%). The CS and SSV were significantly inferior for shoulders with FI of stages III to IV (P < .05). The CS was lower in cuff tear arthropathy and correlated with infraspinatus FI. CONCLUSIONS: At 20 years after surgical repair of isolated supraspinatus tears, the clinical outcome remains significantly above the preoperative state. FI of the infraspinatus is the most influential factor on long-term clinical outcome

Benefits of condensed tannins in forage legumes fed to ruminants:Importance of structure, concentration, and diet composition

Condensed tannins (CTs) account for up to 20% of the dry matter in forage legumes used as ruminant feeds. Beneficial animal responses to CTs have included improved growth, milk and wool production, fertility, and reduced methane emissions and ammonia volatilization from dung or urine. Most important is the ability of such forages to combat the effects of gastrointestinal parasitic nematodes. Inconsistent animal responses to CTs were initially attributed to concentration in the diet, but recent research has highlighted the importance of their molecular structures, as well as concentration, and also the composition of the diet containing the CTs. The importance of CT structural traits cannot be underestimated. Interdisciplinary research is the key to unraveling the relationships between CT traits and bioactivities and will enable future on-farm exploitation of these natural plant compounds. Research is also needed to provide plant breeders with guidelines and screening tools to optimize CT traits, in both the forage and the whole diet. In addition, improvements are needed in the competitiveness and agronomic traits of CT-containing legumes and our understanding of options for their inclusion in ruminant diets. Farmers need varieties that are competitive in mixed swards and have predictable bioactivities. This review covers recent results from multidisciplinary research on sainfoin (Onobrychis Mill. spp.) and provides an overview of current developments with several other tanniniferous forages. Tannin chemistry is now being linked with agronomy, plant breeding, animal nutrition, and parasitology. The past decade has yielded considerable progress but also generated more questions — an enviable consequence of new knowledge

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (eNPP1), preventing the hydrolysis of ATP into pyrophosphate (PPi). The importance of PPi for inhibiting arterial calcification has been reinforced by the protective effects of PPi in various mouse models displaying ectopic calcifications. Besides PPi, Matrix Gla Protein (MGP) has been shown to be another potent calcification inhibitor as Keutel patients carrying a mutation in the encoding gene or Mgp-deficient mice develop spontaneous calcification of the arterial media. Whereas PPi and MGP represent locally produced calcification inhibitors, also systemic factors contribute to protection against arterial calcification. One such example is Fetuin-A, which is mainly produced in the liver and which forms calciprotein particles (CPPs), inhibiting growth of calcium-phosphate crystals in the blood and thereby preventing their soft tissue deposition. Other calcification inhibitors with potential importance for arterial calcification include osteoprotegerin, osteopontin, and klotho. The aim of the present review is to outline the latest insights into how different calcification inhibitors prevent arterial calcification both under physiological conditions and in the case of disturbed calcium-phosphate balance, and to provide a consensus statement on their potential therapeutic role for arterial calcification

Promotion of avian endothelial cell differentiation by GATA transcription factors

AbstractIn the avian embryo, endothelial cells originate from several sources, including the lateral plate and somite mesoderm. In this study, we show that Gata transcription factors are expressed in the lateral plate and in vasculogenic regions of the avian somite and are able to promote a vascular endothelial fate when ectopically expressed in somite precursors. A fusion of GATA4 to the transcriptional activator VP16 promoted endothelium formation, indicating that GATA transcription factors promote vasculogenesis via activation of downstream targets, while a fusion of GATA4 to the transcriptional repressor engrailed repressed expression of Vascular Endothelial Growth Factor Receptor 2, a marker of endothelial precursors. These findings indicate a role for GATA transcription factors in the differentiation of the endothelium

Angiopoietin 2 Alters Pancreatic Vascularization in Diabetic Conditions

Islet vascularization, by controlling beta-cell mass expansion in response to increased insulin demand, is implicated in the progression to glucose intolerance and type 2 diabetes. We investigated how hyperglycaemia impairs expansion and differentiation of the growing pancreas. We have grafted xenogenic (avian) embryonic pancreas in severe combined immuno-deficient (SCID) mouse and analyzed endocrine and endothelial development in hyperglycaemic compared to normoglycaemic conditions. 14 dpi chicken pancreases were grafted under the kidney capsule of normoglycaemic or hyperglycaemic, streptozotocin-induced, SCID mice and analyzed two weeks later. Vascularization was analyzed both quantitatively and qualitatively using either in situ hybridization with both mouse- and chick-specific RNA probes for VEGFR2 or immunohistochemistry with an antibody to nestin, a marker of endothelial cells that is specific for murine cells. To inhibit angiopoietin 2 (Ang2), SCID mice were treated with 4 mg/kg IP L1-10 twice/week. In normoglycaemic condition, chicken-derived endocrine and exocrine cells developed well and intragraft vessels were lined with mouse endothelial cells. When pancreases were grafted in hyperglycaemic mice, growth and differentiation of the graft were altered and we observed endothelial discontinuities, large blood-filled spaces. Vessel density was decreased. These major vascular anomalies were associated with strong over-expression of chick-Ang2. To explore the possibility that Ang2 over-expression could be a key step in vascular disorganization induced by hyperglycaemia, we treated mice with L1-10, an Ang-2 specific inhibitor. Inhibition of Ang2 improved vascularization and beta-cell density. this work highligghted an important role of Ang2 in pancreatic vascular defects induced by hyperglycemia