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Background and aims: The anti-inflammatory agent colchicine is gaining interest as a treatment for coronary artery disease. However, the effects of colchicine in atherosclerotic animal models are mostly unknown. This study aimed to evaluate colchicine in a rabbit model of atherosclerosis. Methods: Twenty-two rabbits were fed a 0.5% cholesterol-enriched diet for 10 weeks and then randomized to receive either oral saline (n=11) or colchicine (350 μg/kg/day; n=11) for 6 weeks, with 0.2% cholesterol-diet during the treatment period. We performed intravascular ultrasound imaging (at start and end of treatment) and histology analyses of the descending thoracic aorta. Leucocyte activation was assessed in vitro on blood samples obtained during treatment. Results: Colchicine prevented positive aortic vascular remodelling (p=0.029 vs placebo). This effect was even more marked at high plasma cholesterol level (third quartile of plasma cholesterol, p=0.020). At high cholesterol level, both atherosclerotic plaque and media areas on histomorphology were reduced by colchicine compared to placebo (p=0.031 and p=0.039, respectively). Plaque fibrosis and macrophage area were reduced by colchicine (Masson's trichrome stain: p=0.038; RAM-11: p=0.026). The plaque vulnerability index, assessed by histology, was reduced by colchicine (p=0.040). Elastin/type I collagen ratio in media was significantly higher with colchicine compared to placebo (p=0.013). At a high level of plasma cholesterol, in vitro LPS challenge revealed a decrease in monocyte activation following treatment with colchicine (p

Massive rotator cuff tears have always been a worrisome situation to every orthopaedic surgeon. Patients’ functional demands are increasing with time, and this is why we aim to offer them the best options to preserve their quality of life. We found that using the Banana SutureLasso (Arthrex) has made this type of surgery much easier. We think that with the Banana SutureLasso (Arthrex) we have more access to the medial part of the rotator cuff, and that we can grab both the deep and superficial layers of the tendons while diminishing the risk of laceration. We combined an X-suture with a double-row fixation using a Corkscrew (Arthrex) on the humeral tuberosity and a SwiveLock (Arthrex) screw on lateral side of the humerus. We used only 3 portals with an extra parking portal. Another advantage is that we can adjust the sutures so they would be perpendicular to both ends of the tear. Our technique is simple, safe, and reproducible., Technique Video Video 1 The patient is at a beach chair position. The scope and the shaver are introduced laterally just over the tear. The first step is to have an interrupted X-suture. This why we introduce the Banana SutureLasso anteriorly through the tear. We use the tracking wire in order to pass the fibertape from the deep into the superficial layer of the rotator cuff tissue. Then we leave the fibertape in the parking portal just over the tear. We do the same posteriorly; you can see how the Banana Lasso passes through both the superficial and the deep layers of the rotator cuff tear, something you can't do while using the scorpion forceps. Note how easily the fibertape is passed while using the tracking wire. The first part of the X-suture is now complete. Contrary to it, we proceed to the second part by inverting the loop of the tracking in order to pass the fibertape from the superficial into the deep layer of the rotator cuff tissue. In that way enough tissue is taken and no tension will be applied while tying the knots. We do the same on the posterior part, also by inverting the loop of the tracking wire so we can have a complete X-suture. The tracking wire is then passed through the canula and the fibertape is inserted through the tear and again put on hold in the parking portal. With this X-suture technique, using the Banana Lasso, we have enough tissue taken medially to ensure a better fixation with no tissue laceration. After preparing the footprint, a corkscrew is then inserted in the humeral tuberosity, to begin the double row fixation. The corkscrew and the fibertape wires are taken together with a grasping forceps through the canula and this what makes the originality of this technique. Then again, the Banana Lasso is inserted anteriorly, this time the tracking wire holding both the fibertape and the corkscrew wires are again passed anteriorly from the deep into the superficial layer of the anterior of the rotator cuff tear. We do the same posteriorly by passing the 2 wires from the deep into the superficial layer of the posterior part of the rotator cuff tear. After passing both ends of the tear, the fibertape wire is put on hold in the parking portal while the corkscrew wire is passed through the canula and is tightened with half surgical hitches so we can slide them and then lock them with an inverted half hitch. Now we have a rotator cuff that is sutured and pinned down to the greater tuberosity. An external rotation and abduction is performed in order to have a better exposure of the lateral side of the humerus. All 4 sutures are passed through the canula and through the eyelet of the swivelock screw, then pinned down to the lateral side of the humerus. You can see the parachute effect of the wires on the rotator cuff, grabbing it and covering all the head of the humerus without any tension.

People living with HIV (PLWH) are at risk of noninfectious comorbidities. It is important to individualize those at higher risk. In a single-center cohort of PLWH, we performed a cross-sectional analysis of comorbidities, diagnosed according to standard procedures. The primary endpoint was the prevalence of subclinical carotid/coronary atherosclerosis. Secondary endpoints were its association with selected inflammatory/immune activation biomarkers and with other comorbidities. Associations were examined by using Chi-square or Fisher's exact test for categorical variables and Student or Wilcoxon tests for quantitative variables, and a stepwise multivariate logistical model was performed for further exploration. Among 790 participants [median age: 49.8 years (interquartile range, IQR: 44.5-55.6), 77.1% males, median CD4: 536/mm

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).

Sickle cell disease (SCD) patients display skeletal muscle hypotrophy, altered oxidative capacity, exercise intolerance and poor quality of life. We previously demonstrated that moderate-intensity endurance training is beneficial for improving muscle function and quality of life of patients. The present study evaluated the effects of this moderate-intensity endurance training program on skeletal muscle structural and metabolic properties. Of the 40 randomized SCD patients, complete data sets were obtained from 33. The training group (n = 15) followed a personalized moderate-intensity endurance training program, while the non-training (n = 18) group maintained a normal lifestyle. Biopsies of the vastus lateralis muscle and submaximal incremental cycling tests were performed before and after the training program. Endurance training increased type I muscle fiber surface area (P = .038), oxidative enzyme activity [citrate synthase, P

Resume Objectifs L’objectif de cette etude etait de quantifier les risques de morbidite maternelle et perinatale en fecondation in vitro (FIV) par rapport aux grossesses non issues de FIV sur une cohorte nationale francaise recente. Methode Les donnees etaient issues du systeme d’information des donnees d’hospitalisation incluant toutes les grossesses ayant conduit a un accouchement et les naissances de 2013 a 2016. Les risques d’accouchement premature, de morbidite maternelle (thrombose veineuse et arterielle, diabete gestationnel, troubles vasculaires, placenta praevia, hematome retroplacentaire), d’hypotrophie et de malformation congenitale ont ete compares entre les deux groupes en analyse univariee et multivariee apres ajustement sur les caracteristiques des femmes (l’âge, la primiparite, l’obesite, la dependance au tabac, les antecedents de diabete ou d’hypertension arterielle), les accouchements multiples et le sexe des enfants. Resultats Au total, 2 875 662 grossesses ayant conduit a un accouchement et 2 922 712 naissances ont ete analysees, dont 49 224 (1,7 %) issues de FIV avec transfert d’embryons frais. En analyse multivariee, tous les risques de morbidite etaient significativement plus eleves en FIV : les accouchements prematures (ORajuste = 1,28 ; IC95 % = 1,24–1,32), la morbidite maternelle (ORajuste = 1,24 ; IC95 % = 1,21–2,28) (principalement pour les thromboses veineuses dans les accouchements multiples, le placenta praevia et les hematomes retroplacentaires). Les risques d’hypotrophie (ORajuste = 1,13 ; IC95 % = 1,10–1,16) et de malformations congenitales (ORajuste = 1,11 ; IC95 % = 1,05–1,17) etaient faiblement augmentes. Conclusion Les resultats de cette premiere etude portant sur un large effectif de naissances recentes en France confirment qu’il existait une augmentation des risques de morbidite maternelle et perinatale en FIV. Ces risques etaient comparables a ceux publies dans la litterature internationale. Cette etude constitue le point de depart d’une surveillance de la morbidite maternelle et perinatale en FIV.

The appropriate management of early treatment failures in patients with elbow injuries requires the identification of the cause of failure. In this work, six types of elbow injury are considered: (i) identification of early failed reduction of a dislocation or fracture-dislocation of the elbow should lead to a repeat reduction procedure, testing for elbow instability, and ligament repair, followed by the use of a hinged external fixator to allow early mobilisation. Differentiating an isolated dislocation from a dislocation combined with a fracture of the coracoid process is crucial. Re-implantation of the coronoid process allows repair of the ligaments and restoration of stability in the sagittal plane; (ii) early secondary displacement of a distal humeral fracture after internal fixation is usually due to insufficient fixation confined to a single humeral pillar. If both humeral pillars are fractured, then both must be repaired; (iii) early treatment failure of an intra-articular distal humeral fracture in an elderly patient with bone loss warrants distal humeral hemiarthroplasty or total elbow arthroplasty; (iv) in fractures of the olecranon, treatment failures are due to insufficient fixation or to a mistaken diagnosis of trans-olecranon fracture-dislocation; (v) in fractures of the radial head, causes of early revision include excessive tilting of the head in radial neck fractures, with secondary displacement due to insufficient internal fixation, and adverse effects on the wrist of radial head resection performed without assessing the ulnar variance. In patients with radial head fractures, no treatment decisions can be made before performing an anteroposterior radiograph of the wrist; (vii) in fracture-dislocations of both the radius and ulna, accurate reduction of the ulnar fracture is a pre-requisite to proper reduction of the radio-humeral and proximal radio-ulnar joints. An early postoperative assessment, within 10 days after surgery, is of paramount importance to re-evaluate the initial treatment and, if needed, to introduce modifications. Early failure of the initial treatment of an elbow injury should lead to the prompt implementation of corrective measures: follow-up anteroposterior and lateral radiographs must be obtained on day 8 to ensure the diagnosis of initial treatment failure and to allow the institution of an appropriate management strategy; the dogma stating that the elbow should never be immobilised remains valid, and every effort should be made to ensure that mobilisation starts as early as possible.

Background:Rotator cuff tears are common shoulder injuries that often cause pain and loss of function. Nonanatomic side-to-side techniques facilitate repair by minimizing tensions within tendons to improve healing and optimize the thickness of sutured tissues.Purpose/Hypothesis:The purpose was to evaluate long-term clinical and radiographic outcomes of arthroscopic side-to-side repair of massive rotator cuff tears (mRCTs). The hypothesis was that, at a minimum follow-up of 12 years, arthroscopic side-to-side repair maintains clinically important improvements.Study Design:Case series; Level of evidence, 4.Methods:The authors reviewed records of all patients who underwent arthroscopic repair of mRCTs over 2 consecutive years. A total of 30 adult patients met the eligibility criteria and underwent side-to-side repair. Patients were evaluated clinically using the Constant score (CS) and ultrasound to assess retears at 3 timepoints after surgery: 2 to 4 years, 5 to 7 years, and 12 to 14 years.Results:At first follow-up (3.2 ± 0.5 years), all 30 patients had clinical and ultrasound assessment, which revealed 13 retears (43%). At second follow-up (6.2 ± 0.5 years), all 30 patients had clinical and ultrasound assessment, which revealed 2 new retears (total 50%). At final follow-up (13.0 ± 0.7 years), only 21 patients had clinical assessment (1 died and 8 could not be reached), and only 19 patients had ultrasound assessment, which revealed 6 new retears (total 79%). Both absolute CS and age-/sex-adjusted CS improved significantly from baseline values at first follow-up (73.5 and 96.6, respectively), and remained stable at second follow-up (69.0 and 91.9, respectively), and final follow-up (64.4 and 87.0, respectively). Compared to shoulders with intact repairs, those with retears tended to have lower absolute CS at all follow-up visits, although differences were not statistically significant.Conclusion:Patients with mRCTs maintain satisfactory clinical scores at 12 to 14 years after arthroscopic side-to-side repair despite a high incidence of retears. Repair is a safe and effective treatment for mRCTs, providing a less invasive and less complex alternative to reverse shoulder arthroplasty and tendon transfer procedures.

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Background In 2017, New Caledonia experienced an outbreak of severe dengue causing high hospital burden (4379 cases, 416 hospital admissions, 15 deaths). We decided to build a local operational model predictive of dengue severity, which was needed to ease the healthcare circuit. Methods We retrospectively analyzed clinical and biological parameters associated with severe dengue in the cohort of patients hospitalized at the Territorial Hospital between January and July 2017 with confirmed dengue, in order to elaborate a comprehensive patient’s score. Patients were compared in univariate and multivariate analyses. Predictive models for severity were built using a descending step-wise method. Results Out of 383 included patients, 130 (34%) developed severe dengue and 13 (3.4%) died. Major risk factors identified in univariate analysis were: age, comorbidities, presence of at least one alert sign, platelets count 9/L, prothrombin time 10 N, and previous dengue infection. Severity was not influenced by the infecting dengue serotype nor by previous Zika infection. Two models to predict dengue severity were built according to sex. Best models for females and males had respectively a median Area Under the Curve = 0.80 and 0.88, a sensitivity = 84.5 and 84.5%, a specificity = 78.6 and 95.5%, a positive predictive value = 63.3 and 92.9%, a negative predictive value = 92.8 and 91.3%. Models were secondarily validated on 130 patients hospitalized for dengue in 2018. Conclusion We built robust and efficient models to calculate a bedside score able to predict dengue severity in our setting. We propose the spreadsheet for dengue severity score calculations to health practitioners facing dengue outbreaks of enhanced severity in order to improve patients’ medical management and hospitalization flow.

Constitutional thinness (CT) is a nonpathological state of underweight. The current study aimed to explore skeletal muscle energy storage in individuals with CT and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsy specimens before and after overfeeding. In the skeletal muscle of CT participants compared with controls, we observed a lower content of intramuscular triglycerides for type I (−17%, p < 0.01) and type IIA (−14%, p < 0.05) muscle fibers, a lower glycogen content for type I (−6%, p < 0.01) and type IIA (−5%, p < 0.05) muscle fibers, a specific fiber-type distribution, a marked muscle hypotrophy (−20%, p < 0.001), a low capillary-to-fiber ratio (−19%, p < 0.001), and low citrate synthase activity (−18%, p < 0.05). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (+10%, p < 0.01) and type IIA (+9%, p < 0.01) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared with normal-weight individuals, suggesting a specific energy metabolism and muscle adaptations. ClinicalTrials.gov registration no. NCT02004821. Novelty Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals. Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin individuals. Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding.

Background We previously demonstrated that high-density lipoprotein (HDL) infusions may improve left ventricular diastolic dysfunction (LVDD) in an aortic valve stenosis (AVS) model. Whether the benefit was direct or mediated by the observed reduction in AVS severity is not clear. Here, we aimed to test the direct effect of an ApoA-I mimetic on LVDD in the absence of AVS. Methods Rabbits were exposed to three different protocols to develop LVDD. First, rabbits were exposed to 0.5% cholesterol-rich diet for an average of 17 weeks. Second, rabbits were subjected to surgical ascending aortic constriction (AAC), to mimic the effect of fixed reduced aortic valve area, and studied after 10 weeks. The third model combined both cholesterol-enriched diet (for 12 weeks) and surgical AAC. The control group consisted of age-matched rabbits under normal diet. After development of LVDD, rabbits were randomized to receive infusions of saline or apoA-I mimetic (25 mg/kg) 3 times per week for 4 weeks. Detailed cardiac structure and function measurements were assessed at baseline and weekly during treatment period. Histological and molecular analyses were performed on LV samples. Results In the three models, echocardiographic results showed development of LVDD over time, with preserved LV systolic and aortic valve functions versus controls. ApoA-I mimetic infusions did not significantly improve echocardiographic parameters nor molecular markers of cardiac inflammation, oxidative stress and fibrosis. Conclusion ApoA-I mimetic therapy did not directly improve LVDD. These results indicate that previously observed changes of LVDD were caused by AVS improvement induced by this treatment.

We describe the first case report of a patient with COVID19 infection and metastatic breast cancer, while on systemic therapy with a CDK4/6 inhibitor. The patient had unique disease course, characterized with delayed symptomatology. The case highlights novel findings and stress careful and extended follow-up during COVID19 infection in patients taking biologic therapies affecting the immune system.

The phonological deficit in dyslexia is associated with altered low-gamma oscillatory function in left auditory cortex, but a causal relationship between oscillatory function and phonemic processing has never been established. After confirming a deficit at 30 Hz with electroencephalography (EEG), we applied 20 minutes of transcranial alternating current stimulation (tACS) to transiently restore this activity in adults with dyslexia. The intervention significantly improved phonological processing and reading accuracy as measured immediately after tACS. The effect occurred selectively for a 30-Hz stimulation in the dyslexia group. Importantly, we observed that the focal intervention over the left auditory cortex also decreased 30-Hz activity in the right superior temporal cortex, resulting in reinstating a left dominance for the oscillatory response. These findings establish a causal role of neural oscillations in phonological processing and offer solid neurophysiological grounds for a potential correction of low-gamma anomalies and for alleviating the phonological deficit in dyslexia., The phonological deficit in dyslexia is associated with altered low-gamma oscillatory function in left auditory cortex; this study shows that enhancing low-gamma neural oscillations by applying 30-Hz transcranial electrical stimulation to the left auditory cortex improves phonemic processing and reading accuracy in dyslexia.

Background: Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the CETP (cholesteryl ester transfer protein) inhibitor dalcetrapib on cardiovascular events and atherosclerosis imaging. The underlying mechanisms responsible for the interactions between ADCY9 and CETP activity have not yet been determined. Methods: Adcy9 -inactivated ( Adcy9 Gt/Gt ) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETPtg Adcy9 Gt/Gt and CETPtg Adcy9 WT ), were submitted to an atherogenic protocol (injection of an AAV8 [adeno-associated virus serotype 8] expressing a PCSK9 [proprotein convertase subtilisin/kexin type 9] gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, vasorelaxation, telemetry, and adipose tissue magnetic resonance imaging were evaluated. Results: Adcy9 Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P Adcy9 Gt/Gt mice compared to WT animals ( P Adcy9 Gt/Gt mice (versus WT, P Adcy9 Gt/Gt ( P Adcy9 Gt/Gt mice allowed significantly less adhesion of splenocytes compared to WT ( P Adcy9 Gt/Gt mice gained more weight than WT with the atherogenic diet; this was associated with an increase in whole body adipose tissue volume ( P Adcy9 Gt/Gt compared to WT mice ( P P P =0.0572). Adcy9 inactivation–induced effects on atherosclerosis, endothelial function, weight gain, adipose tissue volume, and feed efficiency were lost in CETPtg Adcy9 Gt/Gt mice ( P >0.05 versus CETPtg Adcy9 WT ). Conclusions: Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, and improved endothelial function and autonomic tone.

Aims Endothelial dysfunction is one of the earliest symptoms in septic patients and plays an important role in the cardiovascular alterations. However, the endothelial mechanisms involved in the impaired sympathetic regulation of the cardiovascular system are not clear. This study aimed to determine the role of the endocardial endothelium (EE) in the cardiac β-adrenergic (β-AR) remodeling at the early phase of endotoxemic shock. Main methods Rats received either lipopolysaccharide (LPS) or saline (control) intravenously. Three hours later, β-AR cardiac contractility was evaluated on papillary muscles with or without a functional EE. Key findings Isoproterenol-induced contractility was strongly increased in papillary muscles from LPS rats. A similar increase was observed with a β1-AR stimulation, whereas β2-AR and β3-AR produced similar contractility in control and LPS treatments. The removal of the EE did not modify β1-AR-induced contractility in controls, whereas it abolished the increased β1-AR response in LPS-treated muscles. In LPS-treated papillary muscle, the increased β1-AR-induced contractility was not modified by pretreatment with a NOS inhibitor or an endothelin receptor antagonist. Conversely, the increased β1-AR-induced contractility was abolished by indomethacin, a non-selective cyclooxygenase (COX) inhibitor, as well as by selective inhibitors of COX1 and COX2. An early treatment with indomethacin improved the survival of LPS rat. Significance Our results suggest that the EE is involved in the increased cardiac β1-AR contractility in the early phase of endotoxemic shock. This effect is mediated through the activation of COX1 and COX2 and suggests these may be novel putative therapeutic targets during endotoxemic shock.

Background: The efficacy of neoadjuvant chemotherapy regimens in advanced luminal breast cancer patients is difficult to predict. Intrinsic properties of breast tumors, including altered gene expression profile and dynamic evaluation of metabolic properties of tumor cells using positron emission tomography/computed tomography (PET/CT) of tumor cells, have been identified to guide patient's prognosis. The aim of this study is to determine if both analyses may improve the prediction of response to neoadjuvant chemotherapy in ER-positive / HER2-negative breast cancers (BCs) patients. Methods: We used metabolic PET parameters, at diagnosis and after two cycles of chemotherapy and proliferation gene expression profile on biopsy at diagnosis, in particular, the genomic grade index (GGI) analyzed by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The pathological response was the surrogate endpoint. Results: The change of FDG uptake between baseline PET and interim PET after 2 cycles of neoadjuvant chemotherapy (ΔSUVmax) was highly associated with pCR (p=0.008). We also observed an ability of P53 mutated status (p=0.042), in addition to histological grade (p=0. 0004), and PR expression (p=0.01) to predict pCR in ERpositive BCs, whereas no proliferation marker predicted pCR (P=0.39 for GGI). Finally, only ΔSUVmax was significantly associated with event free survival (p=0.047). Conclusions: Our results confirm the predictive and prognostic value of tumor ΔSUVmax in ER-positive /HER2-negative advanced BCs patients. These findings can be helpful to select high-risk patients within trials investigating novel treatment strategies., SCOPUS: ar.j, info:eu-repo/semantics/published

No methodical assessment of the lung, cardiac, and sleep function of patients surviving an acute hypercapnic respiratory failure episode requiring admission to the intensive care unit (ICU) has been reported in the literature.To prospectively investigate the prevalence and impact of comorbidities in patients treated by mechanical ventilator support (invasive or noninvasive) for acute hypercapnic respiratory failure in the ICU.Seventy-eight consecutive patients admitted for an episode of acute hypercapnic respiratory failure underwent an assessment of lung, cardiac, and sleep function by pulmonary function tests, transthoracic echocardiography, and polysomnography 3 months after ICU discharge.Sixty-seven percent (52 of 78) of patients exhibited chronic obstructive pulmonary disease (COPD), although only 19 had been previously diagnosed. Patients without COPD were primarily obese. Prevalence of severe obstructive sleep apnea was 51% (95% confidence interval, 34-69) in patients with COPD and 81% (95% confidence interval, 54-96) in patients without COPD. Previously undiagnosed cardiac dysfunction with preserved ejection fraction was highly prevalent (44%), as was hypertension (67%). More than half of the population demonstrated at least three major comorbidities known to precipitate acute hypercapnic respiratory failure. Multimorbidity was associated with longer time to hospital discharge. Hospital readmission or death occurred in 46% of patients over an average of 3.5 months after discharge.Severe hypercapnic respiratory failure requiring ICU admission resulted primarily from COPD or obesity. Major comorbidities are highly prevalent in both cases and most often ignored. Surviving acute hypercapnic respiratory failure should be an opportunity to systematically evaluate lung, heart, and sleep functions to improve poor outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 02111876).

Background Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies can reduce low-density lipoprotein cholesterol (LDL-C) to very low levels when added to background lipid-lowering therapy. Objectives The safety of alirocumab was evaluated in patients with at least 2 consecutive LDL-C values Methods Pooled data from 14 trials were analyzed (double-blind treatment 8 to 104 weeks; n = 3,340 alirocumab, n = 1,894 control [placebo or ezetimibe]; representing 4,029 [alirocumab] and 2,114 [control] double-blind patient-years’ exposure). Results In alirocumab-treated patients, 839 (25.1%) achieved 2 consecutive LDL-C values Conclusions LDL-C levels NCT01288443 , NCT01288469 , NCT01266876 , NCT01812707 , NCT01507831 , NCT01617655 , NCT01623115 , NCT01709500 , NCT01644175 , NCT01644188 , NCT01730040 , NCT01730053 , NCT01644474 , and NCT01709513 )

Hypotension frequently occurs during spinal anesthesia (SA), especially in the elderly. Phenylephrine is effective to prevent SA-induced hypotension during cesarean delivery. The objective of this study was to evaluate the efficacy and safety of prophylactic infusion of phenylephrine after SA for orthopedic surgery in the elderly.This prospective, randomized, double-blind, and placebo-controlled study included 54 patients older than 60 years undergoing elective lower limb surgery under SA (injection of 10 mg of isobaric bupivacaine with 5 μg of sufentanyl).Patients were randomized to group P (100-μg/mL solution of phenylephrine solution at 1 mL/min after placement of SA) or the control group C (0.9% isotonic sodium chloride solution). The flow of the infusion was stopped if the mean arterial blood pressure (MAP) was higher than the baseline MAP and maintained or restarted at 1 mL/min if MAP was equal to or lower than the baseline MAP. Heart rate and MAP were collected throughout the case.Hypotension was defined by a 20% decrease and hypertension as a 20% increase from baseline MAP. Bradycardia was defined as a heart rate lower than 50 beats per minute.Twenty-eight patients were randomized to group P and 26 patients to group C. MAP was higher in group P than in group C (92 ± 2 vs 82 ± 2 mm Hg, mean ± SD, P.001). The number of hypotensive episodes per patient was higher in group C compared with group P (9 [0-39] vs 1 [0-10], median [extremes], P.01), but the number of hypotensive patients was similar between groups (19 [73%] vs 20 [71%], P= 1). The time to onset of the first hypotension was shorter in group C (3 [1-13] vs 15 [1-95] minutes, P= .004). The proportion of patients without hypotension (cumulative survival) was better in group P (P= .04). The number of hypertensive episodes per patient and the number of bradycardic episodes per patient were similar between groups (P= not significant).Prophylactic phenylephrine infusion is an effective method of reducing SA-induced hypotension in the elderly. Compared with a control group, it delays the time to onset of hypotension and decreases the number of hypotensive episodes per patient. More data are needed to evaluate clinical outcomes of such a strategy.

Introduction Melanoma is a highly malignant cutaneous tumor of melanin-producing cells. MEL050 is a synthetic benzamide-derived molecule that specifically binds to melanin with high affinity. Our aim was to implement a fully automated radiosynthesis of [ 18 F]MEL050, using for the first time, the AllInOne™ synthesis module (Trasis), and to evaluate the potential of [ 18 F]MEL050 for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases, and to compare it with that of [ 18 F]FDG. Methods Automated radiosynthesis of [ 18 F]MEL050, including HPLC purification and formulation, were performed on an AllInOne™ synthesis module. [ 18 F]MEL050 was synthesized using a one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumor) or intravenous (pulmonary metastases) injection of B16-F10-luc2 cells in NMRI mice. The maximum percentage of [ 18 F]MEL050 Injected Dose per g of lung tissue (%ID/g Max) was determined on PET images, compared to [ 18 F]FDG and correlated to in vivo bioluminescence imaging. Results The automated radiosynthesis of [ 18 F]MEL050 required an overall radiosynthesis time of 48 min, with a yield of 13–18% (not-decay corrected) and radiochemical purity higher than 99%. [ 18 F]MEL050 PET/CT images were concordant with bioluminescence imaging, showing increased radiotracer uptake in all primary subcutaneous tumors and pulmonary metastases of mice. PET quantification of radiotracers uptake in tumors and muscles demonstrated similar tumor-to-background ratio (TBR) with [ 18 F]MEL050 and [ 18 F]FDG in subcutaneous tumors and higher TBR with [ 18 F]MEL050 than with [ 18 F]FDG in pulmonary metastases. Conclusion We successfully implemented the radiosynthesis of [ 18 F]MEL050 using the AllInOne™ module, including HPLC purification and formulation. In vivo PET/CT validation of [ 18 F]MEL050 was obtained in mouse models of pigmented melanoma, where higher [ 18 F]MEL050 uptake was observed in sub-millimetric pulmonary metastases, comparatively to [ 18 F]FDG.

BackgroundLeft ventricular diastolic dysfunction (LVDD) is present in more than 50% of patients suffering from heart failure. LVDD animal models are limited and its underlying mechanisms remain largely unknown. Aortic valve stenosis (AVS) may cause LVDD, and we recently reported LVDD in an AVS rabbit model. Here we aimed to develop a rabbit model of LVDD without AVS.MethodsRabbits were fed with a 0.5% cholesterol-enriched diet (n = 9) or normal diet (n = 8) until they developed LVDD defined by a value of the echocardiographic parameter E/Em ratio higher than the mean at baseline + 2SD. Rabbits were then fed a 0.2% cholesterol-enriched diet for 4 weeks (average total diet duration: 20 weeks). Detailed cardiac structure and function measurements were assessed by echocardiography at baseline, weeks 8, 12 and 14 to 20, when applicable. Histological analyses and RT-qPCR were performed on LV samples.ResultsThe hypercholesterolemic diet induced LVDD without systolic dysfunction or AVS, as shown by multiple echocardiographic parameters, including early filling mitral peak velocity and deceleration rate, Em/Am ratio and E/Em ratio (all pConclusionRabbits fed with a cholesterol-enriched diet develop LVDD with preserved systolic function and evidence of cardiac inflammation and oxidative stress. This rabbit model may be used in future studies to test treatment strategies against LVDD.

This work was presented at the following congresses: SFRA, September 2017 and SRLF, January 2018; International audience; Introduction: Hypermucoviscous Klebsiella pneumoniae (KP) strains are responsible for complicated bacteremia with multiple septic sites (liver, central nervous system, muscles). We aimed to compare the clinical severity of patients presenting with KP bacteremia based on the hypermucoviscous or non-hypermucoviscous characteristic of the strains.Methods: Observational retrospective study successively including all patients with KP bacteremia from May 2013 to March 2015 at the tertiary medical center of New Caledonia. The hypermucoviscous characteristic was defined by the string test results and molecular analysis to determine the capsular serotype.Results: A total of 55 bacteremic patients were included in the study; 27% of isolated strains were hypermucoviscous. Hypermucoviscous strains accounted for two-thirds of community-acquired infections (72.5% vs. 33.4%, p=0.01). The rate of intensive care hospitalization was high (hypermucoviscous 46.7%; standard 52.5%) without any difference between the two groups. No significant difference was observed in case fatality (hypermucoviscous 46.7% vs. standard 15%, p=0.07) but patients with hypermucoviscous strains had longer hospital stays (73.5 days versus 50.7 days, p=0.04) and longer persistence of positive blood cultures despite an appropriate treatment (OR 1.41, 95% CI: 1.0-1.96, p=0.045).Conclusion: Hypermucoviscous KP bacteremia account for most community-acquired Klebsiella infections in New Caledonia and are associated with longer hospital stay and persistence of positive blood cultures despite the implementation of an appropriate treatment.

Epub ahead of print; Sickle cell disease (SCD) is a genetic hemoglobinopathy leading to two major clinical manifestations: severe chronic hemolytic anemia and iterative vaso-occlusive crises. SCD is also accompanied by profound muscle microvascular remodeling. The beneficial effects of endurance training on microvasculature are widely known. The aim of this study was to evaluate the effects of an endurance training program on microvasculature of skeletal muscle in SCD patients. A biopsy of the vastus lateralis muscle and submaximal incremental exercise were performed before and after the training period. Of the forty randomized SCD patients, complete data sets from 32 were obtained. The training group (n=15) followed a personalized moderate-intensity endurance training program, while the non-training (n=17) group maintained a normal lifestyle. Training consisted of three 40-minute cycle ergometer exercise sessions per week for 8 weeks. Histological analysis highlighted microvascular benefits in the training SCD patients compared to non-training patients, including increases in capillary density (CD) (P = .003), number of capillaries around a fiber (CAF) (P = .015) and functional exchange surface (LC/PF) (P < .0001). Conversely, no significant between-group difference was found in the morphology of capillaries. Indexes of physical ability also improved in the training patients. The moderate-intensity endurance exercise training program improved the muscle capillary network and partly reversed the microvascular defects commonly observed in skeletal muscle of SCD patients. This trial was registered at www.clinicaltrials.gov as #NCT02571088.

Summary Background Exercise could be a triggering factor for vaso-occlusive crises in patients with sickle-cell disease. We aimed to investigate whether a patient-adapted training programme of moderate endurance exercise could be safe and beneficial for patients with sickle-cell disease. Methods We did a multicentre, prospective, open-label, randomised controlled trial at four university hospitals in France. Eligible patients were older than 18 years, with an HbSS or S/β0-thalassaemia genotype, and with no severe chronic complications. All patients underwent cardiopulmonary exercise tests (CPETs) on a stationary bicycle with cardiac, pulmonary, laboratory, and muscle parameter evaluations at the start and end of the study period. We randomly assigned patients (1:1) to the training group (three 45-min exercise sessions per week, for 8 weeks) or the control group (no lifestyle changes) using a central computer-generated randomisation list. During baseline evaluation, patients and researchers were masked to group assignment; randomisation was done after completion of the baseline evaluation to minimise bias. The primary outcome was difference in power output at a blood lactate concentration of 4 mmol/L during CPET between baseline and the end of the 8-week training period. Patients were analysed on a per-protocol basis, excluding those who missed more than 20% of the training sessions or had other major protocol violations. This trial is registered with ClinicalTrials.gov, number NCT02571088, and is completed. Findings Between Sept 8, 2014, and Dec 11, 2015, 40 patients were enrolled (20 to each group). After exclusion of seven patients (one pregnancy, one appendicitis, one protocol violation, two lost to follow-up, and two incompatibilities with work schedule), 33 patients were analysed (15 in the training group, 18 in the control group). At the 8-week follow-up, the absolute change from baseline in mean power output at 4 mmol/L blood lactate was 7·2 W (SD 8·7) in trained patients (from 70·4 W [SD 16·2] at baseline to 77·6 W [15·1] at end of intervention) compared with −0·3 W (9·4) in controls (from 66·2 W [13·8] to 65·9 W [15·6]; mean difference between groups 7·3 W [95% CI 0·7–13·8], p=0·031). No adverse events requiring hospital admission occurred in the training group, whereas five occurred in the control group: four (20%) vaso-occlusive crises (one complicated by an acute chest syndrome), and one (6%) viral infection with isolated chest pain (hazard ratio 0·143 [95% CI 0·024–0·827; p=0·029). Interpretation Moderate-intensity endurance-exercise training seems to be safe for adults with sickle-cell disease without severe chronic complications and significantly improved their functional capacity, especially for exercise levels close to those needed for daily activities. Our findings support consideration of endurance-exercise training as a novel therapeutic strategy for patients with sickle-cell disease. Funding Societe Francaise de Cardiologie and Institut National du Sport, de l'Expertise et de la Performance (INSEP).

The investigation of solitary pulmonary nodule (SPN) and non-small cell lung cancer (NSCLC) has rapidly become one of the main indications for 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), currently combined with computed tomography (PET-CT). In this literature review, we first attempt to clarify how PET imaging contributes to investigating SPN, in conjunction with conventional CT. We highlight the prospects of research underway to improve our understanding of SPN. In the second part of this review, we analyze the current role of PET-CT in the overall care process for lung cancer. We review the indications for which consensus has been reached, for example initial staging, as well as new indications such as radiation therapy planning or prognostic assessment.

European heart journal 37(39), 2981-2989 (2016). doi:10.1093/eurheartj/ehw292, Published by Oxford University Press, Oxford

Purpose of the study After transplantation, cord blood (CB) hematopoietic stem and progenitor cells (HSPCs) are able to home to the bone marrow niche and to reconstitute the hematopoietic system. PET–CT imaging may be a useful method to monitor this parameter in different conditions. The aim of our study was to set up an efficient method for HSPC radiolabelling with [ 18 F] fluorodeoxyglucose ( 18 F-FDG) and to follow early HSPC homing through PET–CT in mice. Materials and methods Purified CB HSPCs were radiolabelled with 18 F-FDG at 37° C with various conditions of cell concentration, incubation time and radioactivity concentration in order to define the in vitro condition that allows both sufficient 18 F-FDG uptake to get high quality PET imaging, and preservation of HSPC viability and functional properties during 3 h after radiolabelling. Then, 24 h after 2.25 Gy irradiation, eight NOD-scid/γc −/− mice were injected with 18 F-FDG-labelled HSPCs, the biodistribution of which was followed using micro-PET–CT. Results The optimal incubation time was 45 min with a stability of 48.3% ± 12.8% after 180 min. The radio-uptake rate we obtained was 7.2% ± 1.7% with an activity of 5.6 ± 2.1 MBq. Three hours after radiolabelling, viability was 96.7% ± 3.4%. Fifteen hours after radiolabelling, cell viability was 64.0% ± 2.3%, migration ability diminished from 51.0% ± 23.6% to 12.0% ± 9.1%, clonogenic capacity was null, and long-term engraftment in NSG mice also decreased compared to unlabelled cells. Micro-PET–CT experiments showed an accumulation of radiolabelled HSPCs for 2.5 h after injection in the bone marrow and a slight elution of 18 F-FDG. Conclusion The activity of the obtained 18 F-FDG-labelled HSPCs was sufficient to perform the micro-PET–CT imaging. Although the radiolabelling had a significant toxicity on HSPCs 15 h after labelling, this technique allowed monitoring the beginning of HSPC homing into the bone marrow.

Patients with triple-negative breast cancer (TNBC) have poor outcome when pathologic complete response (pCR) is not reached after neoadjuvant chemotherapy. Early prediction would be helpful. We evaluated the association between metabolic response after 2 cycles of neoadjuvant chemotherapy, pCR, and outcome in patients receiving 2 different anthracycline-based regimens (conventional and intensified). Methods: Of 77 consecutive TNBC patients, 23 received EC-D (4 cycles of epirubicin + cyclophosphamide followed by 4 cycles of docetaxel at conventional doses) and 55 received a dose-intensified, dose-dense concomitant regimen of epirubicin + cyclophosphamide (historically called SIM) for 6 cycles. PET/CT with 18F-FDG was performed at baseline and after 2 cycles of neoadjuvant chemotherapy. The associations between clinical factors, biologic factors, early metabolic change, pCR, and event-free survival (EFS) were examined (log-rank test). Results: Of the 78 patients, 29 (37%) achieved pCR. The change in SUVmax (∆SUVmax) after 2 cycles was more pronounced in patients who achieved pCR (−72% vs. −42%; P

Background: Despite their poor prognosis, patients with severe chronic obstructive pulmonary disease (COPD) have little access to palliative care and tend to have a high rate of hospital and intensive care unit (ICU) admissions during their last year of life. Objectives: To determine the feasibility of a home palliative care intervention during 1 year versus usual care, and the possible impact of this intervention on emergency, hospital and ICU admissions, survival, mood, and health-related quality of life (HRQL). Methods: Prospective controlled study of patients with severe COPD (GOLD stage III or IV) and long-term oxygen therapy and/or home noninvasive ventilation and/or one or more hospital admissions in the previous year for acute exacerbation, randomized to usual care versus usual care with add-on monthly intervention by palliative care specialists at home for 12 months. Results: Of 315 patients screened, 49 (15.5%) were randomized (26 to early palliative care; 23 to the control group); aged (mean ± SD) 71 ± 8 years; FEV1 was 37 ± 14% predicted; 88% with a COPD assessment test score > 10; 69% on long-term oxygen therapy or home noninvasive ventilation. The patients accepted the intervention and completed the assessment scales. After 1 year, there was no difference between groups in symptoms, HRQL and mood, and there was a nonsignificant trend for higher admission rates to hospital and emergency wards in the intervention group. Conclusion: Although this pilot study was underpowered to formally exclude a benefit from palliative care in severe COPD, it raises several questions as to patient selection, reluctance to palliative care in this group, and modalities of future trials.

Lipoma is the most common soft tissue mesenchymal neoplasm. Its occurrence is low in the oral cavity (1 to 4%) and in head and neck region (20 to 25%). Usually asymptomatic and slowly growing, lipoma can compress neighboring cervico-facial structures causing dysphagia, dyspnea, or obstructive sleep apnea. We describe an unusual case of giant cervico-parapharyngeal lipoma causing an obstructive sleep apnea in a 69-year-old man and with the complete remove of OSA after surgical procedure.

Survival is increased when pathological complete response (pCR) is reached after neoadjuvant chemotherapy (NAC), especially in triple-negative breast cancer (TNBC) patients. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) and the genomic grade index (GGI), each separately, showed good potential to predict pCR. Our study was designed to evaluate the predictive value for the therapeutic response of a combination of parameters based on FDG-PET, histoclinical features and molecular markers of proliferation. Molecular parameters were measured on pre-treatment biopsy. Tumor metabolic activity was measured using two PET/CT scans, one before and one after 2 cycles of NAC. The pCR was determined on specimen after NAC. Event-free survival (EFS) was estimated using the Kaplan Meier method. Of 55 TNBC patients, 19 (35%) reached pCR after NAC. Tumor grade and Ki67 were not associated with pCR whereas GGI (P = 0.04) and its component KPNA2 (P = 0.04) showed a predictive value. The change of FDG uptake between PET1 and PET2 (ΔSUVmax) was highly associated with pCR (P = 0.0001) but the absolute value of baseline SUVmax was not (P = 0.11). However, the AUC of pCR prediction increased from 0.63 to 0.76 when baseline SUVmax was combined with the GGI (P = 0.016). The only two parameters associated with EFS were ΔSUVmax (P = 0.048) and pathological response (P = 0.014). The early tumor metabolic change during NAC is a powerful parameter to predict pCR and outcome in TNBC patients. The GGI, determined on pretreatment biopsy, is also predictive of pCR and the combination GGI and baseline SUVmax improves the prediction.

The objective of this electrophysiological study was to investigate the processing of semantic coherence during encoding in relation to episodic memory processes promoted at test, in schizophrenia patients, by using the N400 paradigm. Eighteen schizophrenia patients and 15 healthy participants undertook a recognition memory task. The stimuli consisted of pairs of words either semantically related or unrelated to a given category name (context). During encoding, both groups exhibited an N400 external semantic coherence effect. Healthy controls also showed an N400 internal semantic coherence effect, but this effect was not present in patients. At test, related stimuli were accompanied by an FN400 old/new effect in both groups and by a parietal old/new effect in the control group alone. In the patient group, external semantic coherence effect was associated with FN400, while, in the control group, it was correlated to the parietal old/new effect. Our results indicate that schizophrenia patients can process the contextual information at encoding to enhance familiarity process for related stimuli at test. Therefore, cognitive rehabilitation therapies targeting the implementation of semantic encoding strategies can mobilize familiarity which in turn can overcome the recollection deficit, promoting successful episodic memory performance in schizophrenia patients.

Background and purpose The early management of the cardiovascular dysfunction of septic shock is critical as it is associated with a poor outcome. Although the use of catecholamines is a common therapy in this syndrome, no data are available on the involvement of β-adrenoceptor (β-AR) subtypes and only few studies report an alteration of β-adrenergic-induced vasodilation in septic shock. The purpose of the study was to evaluate vascular β 1 , β 2 and β 3 -AR expression and function in an endotoxemic rat model. Experimental approach Endotoxemia was induced in rats by intravenous injection of lipopolysaccharide (LPS). β 1 , β 2 and β 3 -AR mRNA expression was evaluated by RT-PCR in aorta and vascular β 1 , β 2 and β 3 -AR responses were determined on conducting (aorta) and/or resistance (mesenteric and renal) arteries by constructing relaxation curves in response to different β-AR agonists. Results The maximal effect of isoproterenol decreased by 31 to 61% in the three vascular beds of LPS-treated rats compared to controls. In aortas from LPS-treated rats, β 1 and β 3 -AR mRNA expression was decreased and associated to a reduced β 1 and β 3 -induced vasodilation. Conversely, albeit β 2 -AR mRNA was unchanged, the maximal β 2 -AR-induced vasodilation increased by 49% in aortas from LPS-treated rats compared to controls. This increase was not affected by endothelium removal but was abolished in the presence of a β 2 -AR antagonist or an adenylate cyclase inhibitor. Conclusions In endotoxemia, β 2 -AR vasodilation was increased by a potential recruitment of β 2 -AR located on smooth muscle cells. This study suggests that vascular β 2 -AR should be a putative new therapeutic target in septic shock.

Rapid communication-no abstract available

Morbidity/mortality in severe COPD are comparable to that of lung cancer. End-of-life in COPD is associated with high use of medical ressources. Palliative care is seldom proposed. Aim of study: impact of palliative care on hospital, ICU and emergency ward admissions. Methods: Pilot RCT; 2 parallel groups; 1 year period. Intervention: monthly early palliative care consultation (EPCC) at home added to standard care (SC). Patients: MMSE>23; stage III or IV COPD (GOLD criteria) and/or long term oxygen therapy (LTOT) and/or home mechanical ventilation (HMV) and/or > 1 hospital admission in previous year for exacerbation. Mood and anxiety (HAD), HRQL (SF-36), ESAS symptom scales and completion of advance care directives (AD) also measured. Results: 49 patients included of 315 screened (mean age: 71±8; 23 men; FEV1: 37±14% predicted; COPD Assessment Test (CAT): 19.4±7.3; 88% had a CAT>10; 26 EPCC/23 SC). Smokers: 44 (90%), 16(33%) active; LTOT and/or HMV: 34 (69%). 36 (73%) hospitalised in previous year. 8 died during study. HAD>10: for anxiety: 13 (26%) ; for depression: 8 (16%). SF-36: decreased for Vitality (36±20), General Health (35±21), and Physical functioning (28±20). There was no effect in the EPCC group on Hospital, ICU or emergency admissions (P>0.05). Both groups improved quality of life (SF-36 and CAT) 3 and 6 months after inclusion; no group effect and no effect overtime after 6 months. No effect of EPCC on mood and anxiety (HAD). Number of ADs completed during study was higher in the EPCC than in the SC group (12 vs 6; P=0.06). Conclusion: In this pilot study, EPPC did not impact on the predefined outcomes. Possible explanations:number of cases and degree of care already provided

Background Zika virus (ZIKV) is an arthropod-borne virus of the family Flaviviridae, genus Flavivirus. ZIKV is currently the focus of an ongoing pandemic and worldwide public health emergency. Although originally isolated in 1947, its pathogenesis was poorly known and very few documented infections were published until recently. Its route of transmission and its impact on reproduction and pregnancy have only recently begun to be disclosed. Objective and rationale This review summarizes the most recent knowledge about ZIKV infection and pathogenesis and focuses on its impacts on male and female genital tracts, including the risks of sexual transmission and to pregnancy. The consequences of ZIKV infection for pregnancy planning and ART are also discussed. Search methods The PubMed and EMBASE databases were inter-rogated using specific terms, such as 'ZIKV', 'transmission', 'male', 'female', fertility', 'pregnancy, 'semen', 'testis', 'ovary' and 'genital tract', up to 17 March 2017. Outcomes ZIKV has long been considered a harmless virus, but increasing evidence suggests that it has adverse effects on the neurological system and on pregnancy outcomes. In mice, ZIKV slows foetal growth and damages the foetal brain. In humans, the virus is able to cross the placental barrier and to induce foetal death and major anomalies, such as microcephaly, brain defects and long-term neurologic sequelae, i.e. the 'congenital Zika syndrome'. In addition to its transmission by mosquitoes, ZIKV may be transmitted sexually. Currently available data indicate that ZIKV RNA can remain detectable in semen for several months, whereas shedding in the female genital tract appears to be rare and of short duration. Current guidance on preventing the sexual transmission of ZIKV is based on the assumption that transmission occurs from a male partner to a receptive partner. Furthermore, in mouse models, the virus can actively replicate in male genital organs and induce severe orchitis, which raises concerns about its possible impact on human male fertility. Wider implications These new and relevant findings have led many countries and institutions to release updated and regular guidance for preconception counselling and ART to prevent the sexual transmission of ZIKV. Progress in understanding the sexual transmission of ZIKV and its dissemination to genital systems would also help to better anticipate and control outbreaks of potentially sexually transmissible infectious agents.

Chronic ulnar nerve entrapment worsened by elbow flexion is the most common injury, but rare painful conditions may also be related to ulnar nerve instability. The posterior bundle of the medial collateral ligament (pMCL) and the retinaculum, respectively form a soft floor and a ceiling for the cubital tunnel. The aim of our study was to dynamically assess these soft structures of the cubital tunnel focusing on those involved in the biomechanics of the ulnar nerve. Forty healthy volunteers had a bilateral ultrasonography of the cubital tunnel. Elbows were scanned in full extension, 45° and 90°, and maximal passive flexion. Morphological changes of the nerve and related structures were dynamically assessed on transverse views. Both the pMCL and the retinaculum tightened with flexion. During elbow flexion, the tightening of the pMCL superficially moved the ulnar nerve remote from the osseous floor of the retroepicondylar groove. A retinaculum was visible in all 69 tunnels with stable nerves (86.3%), tightened in flexion, but absent in 11 tunnels with unstable nerves (13.7%). The retinaculum was fibrous in 60 elbows and muscular in nine, the nine muscular variants did not significantly influence the biomechanics of stable nerves. Stable nerves flattened in late flexion between the tightened pMCL and retinaculum, whereas unstable nerves transiently flattened when translating against the anterior osseous edge of the groove. The retinaculum and the pMCL are key structures in the biomechanics of the ulnar nerve in the cubital tunnel of the elbow.

Purpose Male breast cancer (BC) is a rare disease, with patterns different from those found in women. Most tumors are detected at more advanced stages than in women. The aim of this study was to analyze the performance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) in staging, restaging, and therapy response assessment. Methods We performed a systematic analysis in the database of Saint-Louis Hospital to identify male patients with BC referred for PET/CT. 18 F-FDG-PET/CT findings considered suspicious for malignancy were compared to biopsy results, further work-up and/or patient follow-up of at least 6 months. Performances of 18 F-FDG-PET/CT were compared to that of conventional imaging (CI) using the McNemar test. The impact of PET/CT on management was evaluated. Results During 6 consecutive years, among 12,692 18 F-FDG-PET/CT oncology studies, 30 were performed in 15 men with BC: 7 examinations for initial staging, 11 for restaging, and 12 for response assessment. Tumors profile was ER+ and one had HER2 overexpression. PET/CT sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect distant metastases were 100%, 67%, 86%, 100% and 89%, respectively. PET/CT was more informative than CI in 40% of studies ( p = 0.03; 95% confidence interval: 3.26 – 40%). Findings from 18 F-FDG-PET/CT led to modification in the planned treatment in 13/30 cases (43%). Conclusion Although all the tumors were ER+, primary lesions and metastases were diagnosed with high sensitivity. 18 F-FDG-PET/CT seems to be a powerful imaging method to perform staging, restaging and treatment response assessment in male patients with BC.

In patients with triple-negative breast cancer (TNBC), pathology complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This prospective study was designed and powered to investigate the ability of interim (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) to predict pathology outcomes to NAC early during treatment.Consecutive TNBC women underwent (18)FDG-PET/CT at baseline and after two courses of NAC. Maximum standardised uptake value (SUV(max)) in the primary tumour and lymph nodes at each examination and the evolution (ΔSUV(max)) between the two scans were measured. NAC was continued irrespective of PET results. Correlations between PET parameters and pathology response, and between PET parameters and event-free survival (EFS), were examined.Fifty patients without distant metastases were enroled. At completion of NAC, surgery showed pCR in 19 patients, while 31 had residual tumour. Mean follow-up was 30.3 months. Thirteen patients, all with residual tumour, experienced relapse. Of all assessed clinical, biological and PET parameters, ΔSUV(max) in the primary tumour was the most predictive of pathology results (p0.0001; Mann-Whitney-U test) and EFS (p=0.02; log rank test). A threshold of 42% decrease in SUV was identified because it offered the best accuracy in predicting EFS. There were 32 metabolic responders (⩾ 42% decrease in SUV(max)) and 18 non-responders. Within responders, the pCR rate was 59% and the 3-year EFS 77.5%. In non-responders, the pCR rate was 0% and the 3-year EFS 47.1%.Interim (18)FDG can early predict the inefficacy of NAC in TNBC patients. It shows promise as a potential contributory biomarker in these patients.

Afin de soulager les symptomes de l’insuffisance veineuse, le pharmacien dispose de moyens mecaniques et de medicaments. La compression veineuse est un domaine en pleine croissance et le pharmacien represente souvent la personne ressource pour choisir le type de contention le plus adapte, en definir la taille par la prise de mesures et conseiller les patients sur les differentes matieres et textures. Le choix du medicament veinotonique ou complement alimentaire doit prendre en compte chaque cas particulier, notamment les potentiels traitements chroniques associes.

Background— Phenotypic modulation or switching of vascular smooth muscle cells from a contractile/quiescent to a proliferative/synthetic phenotype plays a key role in vascular proliferative disorders such as atherosclerosis and restenosis. Although several calcium handling proteins that control differentiation of smooth muscle cells have been identified, the role of protein phosphatase inhibitor 1 (I-1) in the acquisition or maintenance of the contractile phenotype modulation remains unknown. Methods and Results— In human coronary arteries, I-1 and sarco/endoplasmic reticulum Ca 2+ -ATPase expression is specific to contractile vascular smooth muscle cells. In synthetic cultured human coronary artery smooth muscle cells, protein phosphatase inhibitor 1 (I-1 target) is highly expressed, leading to a decrease in phospholamban phosphorylation, sarco/endoplasmic reticulum Ca 2+ -ATPase, and cAMP-responsive element binding activity. I-1 knockout mice lack phospholamban phosphorylation and exhibit vascular smooth muscle cell arrest in the synthetic state with excessive neointimal proliferation after carotid injury, as well as significant modifications of contractile properties and relaxant response to acetylcholine of femoral artery in vivo. Constitutively active I-1 gene transfer decreased neointimal formation in an angioplasty rat model by preventing vascular smooth muscle cell contractile to synthetic phenotype change. Conclusions— I-1 and sarco/endoplasmic reticulum Ca 2+ -ATPase synergistically induce the vascular smooth muscle cell contractile phenotype. Gene transfer of constitutively active I-1 is a promising therapeutic strategy for preventing vascular proliferative disorders.

Atherosclerotic cardiovascular diseases are characterized by the formation of a plaque in the arterial wall. Intravascular ultrasound (IVUS) provides high-resolution images allowing delineation of atherosclerotic plaques. When combined with near infrared fluorescence (NIRF), the plaque can also be studied at a molecular level with a large variety of biomarkers. In this work, we present a system enabling automated volumetric histology imaging of excised aortas that can spatially correlate results with combined IVUS/NIRF imaging of lipid-rich atheroma in cholesterol-fed rabbits. Pullbacks in the rabbit aortas were performed with a dual modality IVUS/NIRF catheter developed by our group. Ex vivo three-dimensional (3D) histology was performed combining optical coherence tomography (OCT) and confocal fluorescence microscopy, providing high-resolution anatomical and molecular information, respectively, to validate in vivo findings. The microscope was combined with a serial slicer allowing for the imaging of the whole vessel automatically. Colocalization of in vivo and ex vivo results is demonstrated. Slices can then be recovered to be tested in conventional histology.

Purpose To assess the prevalence of adverse drug reactions (ADRs) occurring in patients with Alzheimer’s disease (AD) or other dementia in France. Methods A cross-sectional multicentre study was conducted by the French network of the 31 regional pharmacovigilance centres on a given day. The subjects were selected by random draw to be a representative sample of French patients with dementia: consultations of dementia clinics, nursing-homes, acute and long care geriatric units, rehabilitation care geriatric units. The staff of each medical structure together with that of the pharmacovigilance centre defined a day for including the patients. Socio-demographic data, history, ADR and drugs given were registered. Results There were 1332 subjects included, 51.1% living at home, 48.8% in institutions, aged 82.08.0years (46–108); 61.3% suffered from AD. Meannumber of drugs was 6.33.1. Anti-dementia drugs were given to66.4%subjects. ADR prevalence was 5.0%(95% CI: 3.9–6.2) without a significant difference between at home and institutionalized patients. ADR consisted of gastro-intestinal (23.2%), central nervous system (17.4%) and psychiatric disorders (8.7%). Of the ADR, 31.9% were serious, and 47.8% preventable. The drugs most often involved were anti-dementia (28.9%), cardio-vascular (28.9%) and psychotropic drugs (26.4%, anxiolytics, hypnotics, antidepressants, neuroleptics). Conclusion This national scale study showed that iatrogenesis in patients with AD and related dementia can at times be serious and preventable. Therefore, special attention is required when prescribing psychotropic and anti-dementia drugs, as they are frequently used and induce half of the ADR in this population. Copyright © 2013 John Wiley & Sons, Ltd. key words—Alzheimer’s disease; dementia; adverse drug reaction; pharmacovigilance; cross-sectional study; pharmacoepidemiology

Aims Our aim was to identify new microRNAs (miRNAs) implicated in pathological vascular smooth muscle cells (VSMCs) proliferation and characterize their mechanism of action. Methods and results MicroRNAs microarray and qRT–PCR results lead us to focus on miR-424 or its rat ortholog miR-322 (miR-424/322). In vitro mir-424/322 level was decreased shortly after the induction of proliferation and increased in a time-dependent manner later on. In vivo its expression increased in the rat carotid artery from Day 4 up to Day 30 after injury. miR-424/322 overexpression in vitro inhibited proliferation and migration without affecting apoptosis and prevented VSMC dedifferentiation. Furthermore, miR-424/322 overexpression resulted in decreased expression of its predicted targets: cyclin D1 and Ca2+-regulating proteins calumenin and stromal-interacting molecule 1 (STIM1). Using reporter luciferase assays, we confirmed that cyclin D1 and calumenin mRNAs were direct targets of miR-322, whereas miR-322 effect on STIM1 was indirect. Nevertheless, consistent with the decreased STIM1 level, the store-operated Ca2+ entry was reduced. We hypothesized that miR-424/322 could be a negative regulator of proliferation overridden in pathological situations. Thus, we overexpressed miR-424/322 in injured rat carotid arteries using an adenovirus, and demonstrated a protective effect against restenosis. Conclusion Our results demonstrate that miR-424/322 is up-regulated after vascular injury. This is likely an adaptive response to counteract proliferation, although this mechanism is overwhelmed in pathological situations such as injury-induced restenosis.

Background This study prospectively evaluated the yield of fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET-CT) in patients with clinical stages II and III breast cancer and the impact of PET-CT results on prognosis. Methods In the course of 71 months, 254 consecutive patients with clinical stages II and III breast cancer (based on clinical examination, mammography, breast magnetic resonance imaging, and locoregional ultrasonography) underwent 18FDG-PET-CT. The yield was assessed in the whole population and for each American Joint Committee on Cancer subgroup. The prognostic impact of PET-CT findings was analyzed. Tests of statistical significance were two-sided. Results 18FDG-PET-CT changed the clinical stage in 77 of 254 patients (30.3%; 95% confidence interval [CI] = 25.0% to 36.2%). It showed unsuspected N3 disease (infraclavicular, supraclavicular, or internal mammary nodes) in 40 patients and distant metastases in 53. PET-CT revealed distant metastases in 2.3% (1 of 44) of clinical stage IIA, 10.7% (6 of 56) of stage IIB, 17.5% (11 of 63) of stage IIIA, 36.5% (27 of 74) of stage IIIB, and 47.1% (8 of 17) of stage IIIC patients. Among 189 patients with clinical stage IIB or higher disease and adequate follow-up, disease-specific survival was statistically significantly shorter in the 47 patients scored M1 on 18FDG-PET-CT in comparison with those scored M0, with a three-year disease-specific survival of 57% vs 88% (P < .001). In multivariable analysis, only distant disease on PET-CT and triple-negative phenotype were statistically significant prognostic factors. The relative risk of death was 26.60 (95% CI = 6.60 to 102.62) for M1 vs M0 patients. Conclusions The yield of 18FDG-PET-CT appeared substantial in patients with clinical stage IIB or higher breast cancer. In these patients, 18FDG-PET-CT provided powerful prognostic stratification.

International audience; This study aimed to compare the effect of different types of pressure applied to the stimulation electrode on assessing the efficiency of Ia-α-motoneuron transmission of the soleus muscle and the associated discomfort using electrical nerve stimulation. Twelve healthy young adults participated in three experimental sessions (one for each knee angle). The amplitudes of the maximal Hoffmann reflex (Hmax ) and motor potential (Mmax ) were recorded from the soleus muscle at 0°, 30° and 90° knee angles (0° full extension) through three pressure applications to the stimulation electrode: no pressure, pressure with manual application and pressure using adhesive tape. The soleus Hmax /Mmax were calculated to assess the efficiency of Ia-α-motoneuron transmission during varied knee angles and pressure application to the stimulation electrode. At the stimulation intensity evoking soleus Hmax and Mmax , subjects were asked to orally provide a value between 'no discomfort' (0) and 'worst possible discomfort' (10). The application of pressure on the stimulation electrode, particularly using adhesive tape, decreased both the stimulation intensity needed to evoke an electrophysiological response and the associated self-reported discomfort (P

Background The cecal ligation and puncture (CLP) model, a gold standard in sepsis research, is associated with an important variability in mortality. While the number of punctures and needle size is well described in CLP animal studies, the length of cecal ligation is often not. The relationship between cecal ligation and survival in mice is briefly reported in the literature; therefore, we devised an investigation in mice of the consequences of three standardized cecal ligation lengths on mortality and the severity of the ensued sepsis. Methods Male C57BL/6J mice underwent standardized CLP. The cecum was ligated at 5, 20, or 100 % of its total length and further perforated by a single 20-G puncture. Mortality was analyzed. We assessed blood lactate, serum creatinine levels, and serum cytokines (TNF-α, IL-1β, IL-6, and IL-10) after procedure in a control group and in ligated mice. Results Mortality was directly related to ligation length: median survival was 24 h for the “100 %” group and 44 h for the “20 %” group. Blood lactate increased proportionally with the ligation length. At 6 h post-procedure, pro-inflammatory cytokines significantly increased in the ligated group with significantly higher serum levels of IL-6 in the 100 % group compared to the other ligated groups. The 20 % group exhibited the characteristics of septic shock with hypotension below 65 mmHg, pro-inflammatory balance, organ dysfunction, and hyperlactatemia. Conclusions Cecal ligation length appears to be a major limiting factor in the mouse CLP model. Thus, this experimental model should be performed with high consistency in future protocol designs.