1.15 PW-850 J compressed beam demonstration using the PETAL facility.

The Petawatt Aquitaine Laser (PETAL) facility was designed and constructed by the French Commissariat à l'énergie atomique et aux énergies alternatives (CEA) as an additional PW beamline to the Laser MegaJoule (LMJ) facility. PETAL energy is limited to 1 kJ at the beginning due to the damage threshold of the final optics. In this paper, we present the commissioning of the PW PETAL beamline. The first kJ shots in the amplifier section with a large spectrum front end, the alignment of the synthetic aperture compression stage and the initial demonstration of the 1.15 PW @ 850 J operations in the compression stage are detailed. Issues encountered relating to damage to optics are also addressed.

The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P < 0.001). At diagnosis, the Rodnan skin score evaluating the cutaneous manifestations was higher (13.3 versus 8.7; P = 0.01) and myositis was also more common in the AFA+ group (31.4% versus 12.2%; P < 0.01). Patients with AFA+ were not associated with diffuse cutaneous SSc or with lung involvement and no difference in survival was observed. Antifibrillarin autoantibodies are associated with patients of Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis.

[Cystectomy and urinary diversion: Technique and support]. / Cystectomie et dérivations urinaires : techniques et accompagnement.

Cystectomy and urinary diversion (Bricker ileal conduit or neobladder) are common modalities of care in urology requiring their attention. Oncological surgery as well as functional disorders in particular for neurogenic bladder are the main directions. The optimal decision must be multidisciplinary and requires the fundamental of stomatherapy that urology teams need to know in order to improve the management of the care plan. After cystectomy whose surgical approach depends on the cause (oncological vs other causes), urinary diversions may be non continent (cutaneous ureterostomy or Bricker ileal conduit) or continent (ileal neobladder most of the time.) The monitoring and patient's support remain two most important steps, particularly in cases of bladder diversion to monitor (protection of upper urinary tract, neobladder capacity) and patient education (learning of continence and good emptying). The choice of many surgical techniques must be adapted to the characteristics of the patient, after an informed discussion with the patient.

Gonococcemia mimicking a lupus flare in a young woman.

Gonorrhea is a common sexually transmitted infection, which can present as the 'arthritis-dermatitis syndrome'. Patients with systemic lupus erythematosus often develop disseminated neisserial infections, because of inherited and acquired complement deficiencies. Neisserial infection, and particularly gonococcemia, can mimic a lupus flare. We report one case of gonococcemia presenting as acral papulo-vesiculous lesions of the digits in a young woman with lupus.

Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature.

BACKGROUND: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation. METHODS: Primary CD44⁺CD24⁻ breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques. RESULTS: Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44⁻CD24⁺ and showed tumorigenic abilities after injection in secondary mice. CD44⁻CD24⁺ CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs. CONCLUSION: Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.

Overexpression of histamine H4 receptors in the kidney of diabetic rat.

OBJECTIVE AND DESIGN: The renal expression of H1 and H2 receptors has previously been demonstrated, while that of the H4 receptor has been poorly investigated, and thus the aim of this research was to investigate the expression of the H4 receptor in the kidney of diabetic rats. MATERIAL OR SUBJECTS: 24 8-week-old male Wistar rats. TREATMENT: Diabetes was induced in 12 rats by a single intravenous injection of streptozotocin, and animals were killed 6 weeks later. METHODS: Kidneys were collected and processed for quantitative PCR or immunohistochemical analyses. To ascertain the renal topology of the H4 receptor, colocalization experiments were performed with a series of markers. RESULTS: H4 receptor is expressed in healthy rats, although at a very low level, and is strongly upregulated in diabetic animals. Immunohistochemical analysis revealed the highest immune-positivity in the medulla. Colocalization experiments revealed a close overlap in expression topology of the H4 receptor and both Tamm-Horsfall glycoprotein and aquaporin 1 was observed. CONCLUSIONS: The results demonstrate, for the first time, that the H4 receptor is expressed in the kidney mainly by resident renal cells of the loop of Henlé and that this receptor is significantly overexpressed in diabetic animals, thus suggesting a possible role in the pathogenesis of diabetes-associated renal disease.

Endothelial progenitor cell-derived microvesicles improve neovascularization in a murine model of hindlimb ischemia.

Paracrine mediators released from endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis following ischemia. Recently, we demonstrated that microvesicles (MVs) derived from EPCs are able to activate an angiogenic program in quiescent endothelial cells by a horizontal transfer of RNA. In this study we aim to investigate whether EPC-derived MVs are able to induce neoangiogenesis and to enhance recovery in a murine model of hindlimb ischemia. Hindlimb ischemia was induced in severe combined immunodeficient (SCID) mice by ligation and resection of the left femoral artery and mice were treated with EPC-derived MVs (MVs), RNase-inactivated MVs (RnaseMVs), fibroblast-derived MVs or vehicle alone as control (CTL). Since MVs contained the angiogenic miR-126 and miR-296, we evaluated whether microRNAs may account for the angiogenic activities by treating mice with MVs obtained from DICER-knock-down EPC (DICER-MVs). The limb perfusion evaluated by laserdoppler analysis demonstrated that MVs significantly enhanced perfusion in respect to CTL (0.50±0.08 vs 0.39±0.03, p<0.05). After 7 days, immunohistochemical analyses on the gastrocnemius muscle of the ischemic hindlimb showed that MVs but not fibroblast-MVs significantly increased the capillary density in respect to CTL (MVs vs CTL: 24.7±10.3 vs 13.5±6, p<0.0001) and (fibroblast-MVs vs CTL: 10.2±3.4 vs 13.5±6, ns); RNaseMVs and DICER-MVs significantly reduced the effect of MVs (RNaseMVs vs CTL: 15.7±4.1 vs 13.5±6, ns) (MVs vs DICER-MVs 24.7±10.3 vs 18.1±5.8, p <0.05), suggesting a role of RNAs shuttled by MVs. Morphometric analysis confirmed that MVs enhanced limb perfusion and reduced injury. The results of the present study indicate that treatment with EPC-derived MVs improves neovascularization and favors regeneration in severe hindlimb ischemia induced in SCID mice. This suggests a possible use of EPCs-derived MVs for treatment of peripheral arterial disease.

Twice- or Once-Daily Dosing of Direct Oral Anticoagulants, a systematic review and meta-analysis.

AIM: The direct oral anticoagulants (DOAC) have similar half-lives, but the dosing regimen varies between once daily (QD) or twice daily (BID). For some prescribers, the QD regimen improves compliance. Others prefer BID regimens to promote better stability of plasma concentrations, particularly in the event of missed doses. Limited level of evidence provides guidance about the best treatment strategy. The purpose of this study was to compare the treatment effect of QD vs. BID administration of DOACs in major orthopedic surgery (MOS), non-valvular atrial fibrillation (NVAF), venous thromboembolism (VTE), and acute coronary syndrome (ACS). METHODS: We conducted a systematic review up to April 2020. We included phase II clinical trials comparing DOAC QD vs BID with same daily dose. We extracted data for the occurrence of major thrombosis (proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke) and major hemorrhage (ISTH criteria and recommendations of the European Medicines Agency for surgical patients). Relative risks (RR) were combined using a fixed and random effects weighted meta-analysis. RESULTS: Twelve randomized, controlled, phase II trials were included (10,716 patients), representing 24 dosing regimen comparisons of apixaban, darexaban, edoxaban, rivaroxaban, letaxaban, and dabigatran. There was no difference for major thrombotic event (RRBID/QD = 1.06, 95%IC 0.86-1.30) nor for major bleeding (RRBID/QD = 1.02, 95%IC 0.84-1.23) between the BID vs QD regimens, without heterogeneity (I2 = 0%). CONCLUSION: Our study does not support a global difference in term of efficacy and safety of the BID and QD regimens of DOAC in MOS, NVAF, VTE and ACS.

Acute renal and splenic infarctions: a review.

BACKGROUND: Renal and splenic infarctions are close entities, with few data concerning their clinical, biological and radiological features. AIM: The aim of this study was to compare the clinical presentations, etiologies and outcomes of acute renal infarctions (RI) and splenic infarctions (SI). DESIGN: A retrospective multicentric cohort study included patients of the 6 university hospitals in Lyon with RI, SI, or associated RI-SI infarctions was conducted. METHODS: All consecutive cases diagnosed by CT imaging, between January 2013 and October 2016, were included. The exclusion criteria were causes of infarction that did not require additional investigations. RESULTS: A total of 161 patients were selected for analysis: 34 patients with RI, 104 patients with SI and 23 patients with both RI-SI. Mean ± SD age of patients was 63.2 ± 16.6 years; 59.6% were male. Only 5/161 (3.1%) were healthy prior to the event. The main symptoms were diffuse abdominal pain (26.4%), followed by nausea/vomiting (18.3%) and fever (16.4%).The causes of RI or SI varied significantly within the three groups. Hypercoagulable state was associated with SI, and embolic disease and arterial injury were associated with RI. Extensive (i.e.>2/3 of organ volume) (OR 6.22, 95%CI 2.0119.22) and bilateral infarctions (OR 15.05, 95%CI 1.79-126.78) were significantly associated with hemodynamic shocks. The survival at 1 month follow-up did not significantly differ between the three groups. CONCLUSION: Acute RI and SI are heterogenous entities in regards to their clinical presentation, etiology, associated venous or arterial thrombosis, but prognoses were not different at short term follow-up.

[Systemic sclerosis in men]. / Sclérodermie systémique chez l'homme.

PURPOSE: To study the initial clinical features and describe the outcome of systemic sclerosis in a cohort of French men. METHODS: Patients with systemic sclerosis based on Leroy's criteria were included. In this retrospective study we compared a cohort of men to a cohort of women, diagnosed between 1997 and 2005 in departments of internal medicine and rheumatology. RESULTS: One hundred and twenty-one patients were included amongst which thirty-six men. The mean follow-up duration was 6.5 years. The time to diagnosis was significantly shorter in men than in women. Diffuse cutaneous systemic sclerosis, cutaneous ulcers and interstitial syndrome on chest radiograph were more frequent at diagnosis in men than in women. An environmental factor (silica) was observed in only nine men. During the follow-up, incidence of restrictive lung disease was significantly higher in men than in women (37% versus 14% p=0.01) with higher rates of oxygen dependency (22% versus 5% p<0.01). Cumulated survival rates in men were 92% at 5 years, 72% at ten years and 43% at 15 years, respectively. The mean survival was 13 years in men (IC 95%: 10-16) versus 23 years in women (IC 95%: 10-36) with no statistical difference (p=0.27). CONCLUSION: If interstitial and restrictive lung disease, oxygen dependency and diffuse systemic sclerosis were more frequent in men than in women, this data did not provide any evidence of survival difference between men and women with systemic sclerosis.

[Doppler ultrasonography of the renal artery: Guidelines and predictive factors for the presence of a tight stenosis. Retrospective analysis of 450 consecutive examinations]. / Échographie Doppler des artères rénales. Recommandations et facteurs prédictifs de la présence d'une sténose serrée. Analyse rétrospective de 450 examens consécutifs.

Duplex ultrasonography screening for renal artery stenosis has been the object of guidelines published by four societies designed to optimize the cost-effectiveness of the examination. OBJECTIVES: To determine how well guideline indications for ultrasonography matched with requests and results in our university hospital; to determine whether compliance with guidelines was predictive of renal artery stenosis; to identify guidelines predictive of presence of stenosis; and to determine whether other predictive factors can be recognized. MATERIAL AND METHODS: Requests and results of 450 Duplex ultrasonography examinations of the renal arteries performed from January 1st 2014 to December 31st 2015 were compared with published guidelines. RESULTS: At least one guideline indication was identified for 212 of the 450 examinations performed (47.1%). Among these examinations, renal artery stenosis≥70% was identified in 18 patients (8.0%). No case of stenosis was identified during examinations performed outside guideline indications. Factors predictive of stenosis were: compliance with guidelines (OR=21.86 [2.88; 165.8]). Predictive guidelines were: resistant hypertension in spite of appropriate treatment (OR=3.85, [1.44; 10.33], P=0.011), accelerated hypertension (OR=7.30, [1.40; 37.99], P=0.049), sudden unexplained pulmonary edema (OR=7.30, [1.40; 37.99], P=0.049), unexplained renal insufficiency (OR=3.58, [1.37; 9.37], P=0.011), unexplained renal hypotrophy (OR=16.69, [4.38; 63.69], P<0.001), renal asymmetry (OR=4.32, [1.45; 12.85], P<0.016). No other factor was predictive of renal stenosis. These examinations had therapeutic consequences in only 50% of patients. CONCLUSION: This study confirms the relevance of published guidelines. The diagnostic-effectiveness of Duplex ultrasonography examinations to search for renal artery stenosis depends upon compliance with these guidelines.

Prevalence of fecal incontinence in a cohort of systemic sclerosis patients within a regional referral network.

BACKGROUND: The prevalence of gastrointestinal involvement in systemic sclerosis is higher than 75%. The estimated prevalence of fecal incontinence varies from 22% to 77%, but suffers from recruitment bias and patient reluctance. Our goal was to evaluate the prevalence of fecal incontinence in systemic sclerosis, and to identify associated risk factors. METHODS: Patients were recruited in the referral systemic sclerosis network of the Lyon University Hospitals, using self-administered questionnaires including constipation, fecal incontinence and Bristol Stool scales, quality of life, anxiety and depression. The cohort was compared with the historical ORALIA cohort that established the prevalence of fecal incontinence in the general population of the Rhône-Alpes region (France). RESULTS: Seventy-seven patients were included (mean age: 60 years, range: 32-84), and 86% were female. These were compared to 153 ORALIA individuals matched for age and sex. Fecal incontinence was present in 38% of patients and 6% of the general population. A longer duration of systemic sclerosis was the only characteristic associated with fecal incontinence. Abnormal stool consistency was more frequent in patients with fecal incontinence. CONCLUSION: Fecal incontinence and abnormal stool consistency are common in systemic sclerosis and should be systematically addressed.

Self-regulated running using perceived exertion in children.

AIM: The aim of this study was to examine the ability of 5- to 7-year-old female (n=16) and male (n=16) children to use perceived exertion in order to self-regulate their running intensity. An estimation-production paradigm was used to determine if 1) self-regulation of exercise using OMNI Scale could be administered in young children, 2) children were able to distinguish 3 different intermittent exercise intensities and 3) gender would differentiate the use of perceived exertion. METHODS: Children underwent 1) 1 estimation trial and 2) 3 production trials. During the estimation trial, perceived exertion was estimated at the end of each stage of an incremental running field test. Then, during the production test, the children were requested to run in random order 300 m bouts on an outdoor track at an exercise intensity based on their interpretation of levels 2, 6 and 10 of the OMNI Scale. Heart rate was continuously recorded during both trials. RESULTS: Heart rate did not differ significantly between estimation and production trials at the level 2 (124.1 SD 6 vs 125.3 SD 4 bpm), 6 (164.9 SD 5 vs 166.2 SD 6 bpm) and 10 (200.9 SD 8 vs 203.1 SD 8) of the OMNI scale. Furthermore, HR responses at OMNI 6 were significantly (p<0.05) higher than OMNI 2, and OMNI 10 were significantly (p<0.05) higher that OMNI 6. No significant difference was found between female and male children. CONCLUSIONS: The present investigation supports the view that the young female and male children tested in this study were able to use perceived exertion to self-regulate during intermittent running exercises.

Centrofacial malignant granulomas. Clinicopathologic study of 40 cases and review of the literature.

An important problem in the treatment of centrofacial ulcerations is to establish a precise diagnosis, since similar clinical and microscopic findings can result from many different causes (as in the centrofacial malignant granuloma syndrome [CFMG]). A comprehensive surgical biopsy protocol (known as SNFMI/GMCF), involving microbiology, parasitology, immunology and pathology laboratories, allowed us to evaluate and to treat 40 cases of CFMG, who form the basis of this report. In 13 of them, specific diagnoses were found and curative treatments could be given. In the remaining 27, the optical microscopy pattern met the criteria for CFMG without identifiable origin or the presence of so-called lethal midline granulomas; however, a more precise evaluation with the help of immunofluorescence studies led to the recognition of malignant lymphoma (ulcerative lymphoma of the midface [ULM]). Most of these lymphomas belonged to the T cell lineage; the others were of B lymphoid origin, or, more rarely, of histiocytic origin. Patients with ULM received radiotherapy and chemotherapy with a response rate of 70.3%; however, the toxicity was significant, with frequent occurrence of chemotherapy-induced neutropenia followed by severe infectious facial cellulitis. Six patients were enrolled in a preliminary open trial of treatment with recombinant alpha-2b interferon with little success. Three patients were treated with radiation therapy only, and survived. Thus, CFMG is a syndrome with specific causes and treatments, requiring multiple extensive biopsies to make the correct diagnosis. The recognition of ULM as the cause of the previously called "lethal midline granulomas" leads logically to the use of chemotherapy with growth factors in order to ameliorate its bad prognosis.

General anaesthesia using remifentanil for caesarean section in parturients with critical aortic stenosis: a series of four cases.

Although heart disease is now the joint leading cause of maternal mortality in the UK, critical aortic stenosis is rarely encountered in parturients. Caesarean section is advisable in these patients to minimise the haemodynamic stress of labour and delivery. The use of an opioid-based general anaesthetic technique also helps to maintain cardiovascular stability. During a two-year period, four women with critical aortic stenosis requiring caesarean section presented to our institution. In all women, a rapid sequence induction of anaesthesia was performed using etomidate 0.1 to 0.2 mg.kg(-1), suxamethonium 1.5 mg.kg(-1) and remifentanil 2 to 4 micrograms.kg(-1). Anaesthesia was then maintained with isoflurane, nitrous oxide and a remifentanil infusion at 0.05 to 0.15 micrograms.kg(-1)min(-1). There was good haemodynamic stability throughout, except for a short period in one patient who became hypotensive after a significant post-partum haemorrhage secondary to uterine atony. All parturients were successfully extubated at the end of surgery and made excellent postoperative recoveries. Neonates were born in good condition with Apgar scores of 10, 9, 6 and 5 at 1 min and 10, 10, 10 and 10 at 5 min. We suggest that remifentanil is an ideal agent for parturients with severe aortic stenosis requiring general anaesthesia for caesarean section. Remifentanil provides cardiovascular stability in conjunction with rapid emergence from anaesthesia in the parturient and minimal side effects in the neonate.

[Association of Biermer's anemia and gastric carcinoid tumors]. / Association d'une anémie de Biermer et de tumeurs carcinoïdes gastriques.

BACKGROUND: The occurrence of gastric carcinoid tumors during the cure of pernicious anemia has been reported in the literature. Concerning a new case, we review physiopathological data of this infrequent association. CASE REPORT: We report the case of a 47-year-old women with pernicious anemia in which gastroscopy found two small tumors developed from enterochromaffin-like cells. CONCLUSION: These tumors are usually latent and developed from enterochromaffin-like cells. The pathologic and histologic diagnosis is based on positive chromogranin A immunomarking. The physiopathological mechanism studies are in favour of the predominant part of hypergastrinemia following achlorhydria. Usually, evolution is benign and surgical or endoscopic resection recommended.

[Internal medicine DES 10 years after creation. Results of the survey realized by the Association of young internists]. / Le DES de médecine interne 10 ans après sa création. Résultats de l'enquêt réalisée par l'Association des jeunes internistes.

The internal medicine young practitioners association (AJI) did set, during 93 spring, a survey among the registered internal medicine interns since 1984, regarding their training and future. 88 did answer, showing a certain homegeneous training but a deep care in their future. Most would wish a dual activity in general hospitals : internal medicine and an other speciality acquired during their training.

[Constrictive bronchiolitis obliterans. Apropos of a case]. / Bronchiolite oblitérante constrictive. A propos d'un cas.

INTRODUCTION: Constrictive bronchiolitis obliterans is defined histologically as obliteration of the lumina of bronchioles by inflammatory tissue elements and progressive destruction of bronchioles, eventually replaced by fibrotic tissue. Most of the cases, which are not associated with either solid organ or bone marrow transplantation, occur in the development of rheumatoid arthritis. EXEGESIS: We present the case of a 73-year-old woman who developed severe constrictive bronchiolitis obliterans without readily identifiable cause, rapidly fatal despite corticosteroid therapy. The patient had antinuclear antibodies (titer 1/1024) and antiphospholipid antibodies, but there was no anti-DNA, anti-ENA or anti-beta 2GPI antibodies. Tests for rheumatoid factor were negative. Cryoglobulinemia was present (monoclonal IgM Kappa). CONCLUSION: In this case, constrictive bronchiolitis obliterans was associated with serologic abnormalities and cryoglobulinemia. However, were was no clinical evidence of connective tissue disease.

[Porphyria cutanea tarda and hepatitis B and C virus infection]. / Porphyrie cutanée tardive et infection par les virus de l'hépatite B et C.

Porphyria cutanea tarda is a metabolic disorder caused by reduced hepatic uroporphyrinogen decarboxylase activity characterized by skin lesions and liver damage. The high frequency of liver histological damage in patients with porphyria cutanea tarda led us to study hepatitis B and C viral infection which has a striking prevalence in southern Europe. We attempt here to expose different pathophysiological hypotheses: is viral hepatitis a triggering factor precipiting latent decreased uroporphyrinogen decarboxylase activity or does it directly induce the enzyme deficiency?

[Long-term follow-up and therapeutic results of the protocol of the National Society of Internal Medicine in centrofacial malignant granuloma. Report of 40 cases]. / Suivi à long terme et résultats thérapeutiques du protocole de la Société Nationale de Médecine Interne sur les granulomes malins centro-faciaux. A propos de 40 cas.

We have studied 40 cases of mediofacial necrosis with no specific diagnosis on biopsy. After an exhaustive work-up we reached a specific diagnosis in 13 patients (Wegener's granulomatosis in 7, classical malignant lymphoma of the nose in 3, squamous cell carcinoma = "goundou" in 1, syphilis and tuberculosis in 1, aspergillosis in 1). Those patients received the appropriate treatments with good results. The remaining 27 patients, however, had ulcerative lymphomas of the midface (according to the immunofluorescence and molecular biology techniques). Their fate was worse since only 15% remain alive on the long-term, despite intensive treatments with chemotherapy, radiotherapy, interferon, artificial nutrition and antibiotics as needed. We present a new protocol with intensified chemotherapy and growth factor treatment in order to ameliorate the very poor prognosis of these patients.