Changes of concave and convex rib�Cvertebral angle, angle difference and angle ratio in patients with right thoracic adolescent idiopathic scoliosis

The aim of this study is to describe the radiological changes in rib–vertebral angles (RVAs), rib–vertebral angle differences (RVADs), and rib–vertebral angle ratios (RVARas) in patients with untreated right thoracic adolescent idiopathic scoliosis and to compare with the normal subjects. The concave and convex RVA from T1 to T12, the RVADs and the RVARas were measured on AP digital radiographs of 44 female patients with right convex idiopathic scoliosis and 14 normal females. Patients were divided into three groups: normal subjects (group 1), scoliotic patients with Cobb’s angle equal or <30° (group 2) and scoliotic patients with Cobb’s angle over 30° (group 3). Overall values (mean ± SD) of the RVAs on the concave side were 90.5° ± 17° in group 1, 90.3° ± 15.8° in group 2 and 88.8° ± 15.4° in group 3. On the convex side, values were 90.0° ± 17.3° in group 1, 86.3° ± 13.7° in group 2 and 80.7° ± 14.4° in group 3. Overall values (mean ± SD) of the RVADs at all levels were 0.5° ± 0.7° in group 1, 4.0° ± 4.8° in group 2 and 8.0° ± 4.0° in group 3. The RVARa values (mean ± SD) at all levels was 1.008° ± 0.012° in group 1, 1.041° ± 0.061° in group 2 and 1.102° ± 0.151° in group 3. RVAD and RVARa values in the scoliotic segment were greater in patients with untreated scoliosis over 30° than in patients with an untreated deformity of <30° or normal subjects. A significant effect between groups was observed for the RVA, RVAD and RVARa variables. Measurement of RVA, RVAD and RVARa should not only be performed at and around the apex of a thoracic spinal deformity, but also extended to the whole thoracic spine.     

Association between Staphylococcus aureus alone or combined with Pseudomonas aeruginosa and the clinical condition of patients with cystic fibrosis

BackgroundThe prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients has increased and MRSA seems to be associated with a poorer prognosis. The aim of this study was to assess the prevalence and clinical consequences of MRSA and methicillin-susceptible Staphylococcus aureus (MSSA), associated or not associated with Pseudomonas aeruginosa (PA).MethodsIn a retrospective study on 419 sputum producer patients (293 adults and 126 children > 7 years of age), we recorded patient characteristics, lung function, nutritional status, IV antibiotics and hospitalisations, the presence of SA and/or PA and FEV1 decline over 2 years.ResultsSA was found in 72% of the patients: MSSA in 68.2% of children and 48.8% of adults; MRSA in 17.5% of children and 17.8% of adults. Sixty percent of MRSA patients and 60.4% of MSSA patients also harboured PA. The rate of deterioration of clinical status of the various groups, as assessed from respiratory function, IV antibiotic courses and hospitalisations, increased in the order: no SA/no PA, MSSA alone, MRSA alone, MSSA/PA, MRSA/PA, and PA alone. Nutritional status did not differ between groups. Results were roughly similar for children and adults. The yearly FEV1 decline was significantly higher only for MRSA/PA patients (p = 0.03) compared to no SA/no PA patients.ConclusionClinical condition of CF patients with MSSA only or MRSA only appeared similar, whereas MRSA/PA patients had more severe respiratory function than MSSA/PA patients. In CF patients, MRSA might be more deleterious than MSSA only when associated with PA.     

Protection Against Type 1 Diabetes Upon Coxsackievirus B4 Infection and iNKT-Cell Stimulation: Role of Suppressive Macrophages

Invariant natural killer T (iNKT) cells belong to the innate immune system and exercise a dual role as potent regulators of autoimmunity and participate in responses against different pathogens. They have been shown to prevent type 1 diabetes development and to promote antiviral responses. Many studies in the implication of environmental factors on the etiology of type 1 diabetes have suggested a link between enteroviral infections and the development of this disease. This study of the pancreatropic enterovirus Coxsackievirus B4 (CVB4) shows that although infection accelerated type 1 diabetes development in a subset of proinsulin 2–deficient NOD mice, the activation of iNKT cells by a specific agonist, α-galactosylceramide, at the time of infection inhibited the disease. Diabetes development was associated with the infiltration of pancreatic islets by inflammatory macrophages, producing high levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and activation of anti-islet T cells. On the contrary, macrophages infiltrating the islets after CVB4 infection and iNKT-cell stimulation expressed a number of suppressive enzymes, among which indoleamine 2,3-dioxygenase was sufficient to inhibit anti-islet T-cell response and to prevent diabetes. This study highlights the critical interaction between virus and the immune system in the acceleration or prevention of type 1 diabetes.Type 1 diabetes is characterized by the destruction of pancreatic islet β-cells by autoreactive CD4 and CD8 T cells, leading to low insulin production and incapacity to regulate blood glucose levels (1). Despite numerous studies, the etiology of type 1 diabetes remains elusive. Besides genetics (2–4), environmental factors such as viral infections have been suggested as triggers of type 1 diabetes (5–7). Most striking of these infections are the type B Coxsackieviruses belonging to the enterovirus genus whose genome and anti-Coxsackievirus antibodies were detected more frequently in the blood of recently diagnosed patients compared with healthy controls (8,9). Besides, enteroviral RNA or enteroviral particles were directly detected in the pancreas of type 1 diabetic patients, whereas they were undetectable in the pancreas of healthy donors (9,10). In a mouse model of type 1 diabetes, Serreze et al. (11) showed that diabetes can develop rapidly after Coxsackievirus B4 (CVB4) infection if mice had an advanced age and sufficient insulitis. Others have reported that inefficient islet β-cell response, viral dose, and replication rate as well as a lack of islet neogenesis could also promote accelerated diabetes development after CVB4 infection (12–14).Natural killer T (NKT) cells are CD1d-restricted, nonconventional T cells recognizing self and exogenous glycolipids. Most NKT cells express an invariant T-cell receptor α chain, Vα14-Jα18 (Vα14) in mice and Vα24-Jα18 in humans, and are named invariant NKT (iNKT) cells. They can promptly secrete copious amounts of interferon-γ (IFN-γ) and interleukin (IL)-4 and provide maturation signals to dendritic cells (DCs) and lymphocytes, thereby contributing to both innate and acquired immunity (15,16). iNKT cells are potent regulatory cells that can inhibit autoimmunity and promote immune responses against pathogens (1,17). Diabetes can be prevented in NOD mice by increasing iNKT cell numbers and by iNKT-cell stimulation with exogenous ligands such as α-galactosylceramide (αGalCer) (15,18,19). NOD mice protected from diabetes by iNKT cells have weak T helper 1 anti-islet β-cell responses (20). Indeed, iNKT cells can impair the differentiation of anti-islet CD4 and CD8 T cells, which become hyporesponsive or anergic (21). Contrary to their suppressive role in type 1 diabetes, iNKT cells can enhance immune responses to pathogens such as parasites, bacteria, and viruses (22,23).Our previous studies conducted in a murine model of type 1 diabetes with lymphocytic choriomeningitis virus infection revealed that iNKT cells could promote systemic antiviral CD8 T-cell responses while inhibiting deleterious anti-islet T-cell responses, thereby preventing type 1 diabetes (24,25). In the present study, we investigated the role of iNKT cells after CVB4 infection, revealing that diabetes development following CVB4 infection is associated with the infiltration of inflammatory macrophages into the pancreatic islets with subsequent activation of anti-islet T cells. However, the activation of iNKT cells during CVB4 infection results in the infiltration of suppressive macrophages into pancreatic islets. Indoleamine 2,3-dioxygenase (IDO) expressed by these macrophages was critical for the inhibition of diabetes development.     

Elastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse?

Introduction and hypothesis

The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP).

Methods

Tissue samples were collected from the anterior [point Ba; POP Questionnaire (POP-Q)] and/or posterior (point Bp; POP-Q) vaginal wall of 15 women who underwent vaginal surgery for POP. Both histological and biomechanical assessments were performed from the same tissue samples in 14 of 15 patients. For histological assessment, the density of collagen and elastin fibers was determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. For biomechanical testing, uniaxial tension tests were performed to evaluate vaginal tissue stiffness at low (C₀) and high (C₁) deformation rates.

Results

Biomechanical testing highlights the hyperelastic behavior of the vaginal wall. At low strains (C₀), vaginal tissue appeared stiffer when elastin density was low. We found a statistically significant inverse relationship between C₀ and the elastin/collagen ratio (p?=?0.048) in the lamina propria. However, at large strain levels (C₁), no clear relationship was observed between elastin density or elastin/collagen ratio and stiffness, likely reflecting the large dispersion of the mechanical behavior of the tissue samples.

Conclusion

Histological and biomechanical properties of the vaginal wall vary from patient to patient. This study suggests that elastin density deserves consideration as a relevant factor of vaginal stiffness in women with POP.

     

Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure

Ischemic acute renal failure is characterized by damages to the proximal straight tubule in the outer medulla. Lesions include loss of polarity, shedding into the tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It was recently shown that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction. Therefore, whether PPARbeta/delta could contribute also to the control of tubular epithelium death after renal ischemia/reperfusion was tested. It was found that PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney dysfunction and injury than wild-type counterparts after a 30-min renal ischemia followed by a 36-h reperfusion. Conversely, wild-type mice that were given the specific PPARbeta/delta ligand L-165041 before renal ischemia were completely protected against renal dysfunction, as indicated by the lack of rise in serum creatinine and fractional excretion of Na+. This protective effect was accompanied by a significant reduction in medullary necrosis, apoptosis, and inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to exert their role by activating the antiapoptotic Akt signaling pathway and, unexpectedly, by increasing the spreading of tubular epithelial cells, thus limiting potentially their shedding and anoikis. These results point to PPARbeta/delta as a remarkable new target for preconditioning strategies.     

Gastric Bypass is not Associated with Protein Malnutrition in Morbidly Obese Patients

Background  Patients undergoing bariatric surgery with a gastric bypass lose about 66% of excess weight. Although this procedure induces weight loss, it is unknown whether it leads to protein malnutrition, which is studied here. Methods  One hundred ten obese patients (body mass index, 47.9 ± 8.6 kg/m²) undergoing gastric bypass had a measurement of plasma albumin and transthyretin (formerly prealbumin) and a calculation of nutritional risk index (NRI) before and throughout the 2 years following the surgery. Results  All but five patients lost more than 15% of initial weight; the mean loss of excess weight was 65.2 ± 26.4% at 2 years. Plasma concentrations of albumin and transthyretin decreased after surgery, but while albumin returned to initial values after 12 months, transthyretin remained low. Only one patient had an albumin below 30 g/l; another one had a transthyretin lower than 110 mg/l. All NRI scores were lower than 83.5 (62 ± 5, ranging 44–70), qualifying patients for severe malnutrition. Conclusion  Malnutrition is difficult to diagnose in obese patients undergoing surgery. The large weight loss is most often not associated with protein malnutrition. Whether gastric bypass induces protein malnutrition remains to be established.     

FVIIa corrects the coagulopathy of fulminant hepatic failure but may be associated with thrombosis: A report of four cases

PURPOSE: During liver transplantation, excessive blood losses are correlated with increased morbidity and mortality. Blood losses are particularly high in the case of urgent liver transplantation for fulminant hepatic failure (FHF). Recombinant activated factor VII (rFVIIa) has shown promise in treating the coagulopathy of liver disease. We review our experience with the use of rFVIIa in treating the coagulopathy of FHF during urgent liver transplantation. CLINICAL FEATURES: We report four patients with FHF who met King's College criteria for liver transplantation and in whom rFVIIa was used after conventional means for treating the associated coagulopathy had failed. In all patients, the coagulation defect was corrected by rFVIIa. However, thrombotic complications occurred in two patients (myocardial ischemia and portal vein thrombosis) and the implication of rFVIIa cannot be excluded. CONCLUSION: We conclude that rFVIIa is effective in the correction of the coagulopathy associated with FHF. However, thrombotic events are of concern and therefore, further studies are warranted to define the safety of rFVIIa in that setting.     

Theoretical study of the flow rate toward the right heart territory in case of total occlusion of the right coronary artery

In this work, patients with severe coronary disease and chronic occlusion of the right coronary artery (RCA) are studied. In this clinical situation, the collateral circulation is an important factor in the preservation of the myocardium until reperfusion of the area at risk. An accurate estimation of collateral flow is crucial in surgical bypass planning as it can influence the outcome of a given treatment for a given patient. The evaluation of collateral flow is frequently achieved using an index (CFI, Collateral Flow Index) based on pressure measurements.Using a model of the coronary circulation based on hydraulic/electric analogy, we demonstrate, through theoretical simulations, that a wide range of fractional collateral flow values can be obtained for any given distal pressure difference depending on the values of the capillary and collateral resistances.