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.

[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.

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.

Caesarean section in a parturient with Carpenter syndrome and corrected Tetralogy of Fallot.

Carpenter syndrome is an extremely rare congenital disorder characterized by craniofacial malformations, syndactyly, cardiac defects and obesity. Even after surgical correction of cardiac abnormalities, intrapartum care of a parturient with this condition can be challenging because of progression of residual cardiac defects compounded by the haemodynamic changes of pregnancy. We describe the anaesthetic management for caesarean section of a parturient with Carpenter syndrome and corrected Tetralogy of Fallot. Additional complicating issues included worsening cardiac function, asthma, needle-phobia and osteoarthritis.

[Sexual function and quality of life in locally advanced cervical cancer]. / Qualité de vie sexuelle et cancer du col localement avancé

OBJECTIVES: Sexual dysfunction is currently the most common complication of cancer. Most of the time, patients who are concerned by locally advanced cervical cancer are in a period of sexual activity. The primary objective of this study was to assess the quality of life and sexual function of patients with locally advanced cervical cancer who were in remission. The secondary objective was to correlate the prognostic factor with sexual dysfunction. PATIENTS AND METHODS: This multicentric and prospective study included the patients with locally advanced cervical cancer diagnosis from three centres. Thirty-one patients with diagnosis of locally advanced cervical cancer were enrolled from February 2007 to October 2008. The mean age was 49years old. Inclusion criteria were to have received the standard therapy by chemoradiotherapy and have been in remission for 2years. Both self-administered questionnaires BISF-W and EORTC QLQ-CX24 allowed scoring quality of life and sexual function. RESULTS: The rate of completion was 42%. The results confirmed that sexual function was impaired in accordance with sexual satisfaction. After therapy, the frequency of sexual activity was decreased. The functional quality of life was significantly correlated with sexual function. Marital status was a significant prognostic factor. Age, stage and the type of centre were not. DISCUSSION AND CONCLUSION: This preliminary study suggests that after 2years of remission of the disease after treatment, patients and their partners need to be helped as regards their sexual function. We propose to perform a prospective study on a larger cohort.

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.

Health activism in Cape Town: a case study of the Health Workers Society.

The Health Workers Society (HWS), founded in 1980, was one of several progressive health organisations that fought for a democratic health system in South Africa. We document the sociopolitical context within which it operated and some of its achievements. HWS, many of whose members were staff and students of the University of Cape Town (UCT), provided a forum for debate on health-related issues, politics and society, and worked closely with other organisations to oppose the apartheid state's health policies and practices. They assisted with the formation of the first dedicated trade union for all healthcare workers and were one of the first to pioneer the primary healthcare approach in an informal settlement in Cape Town.

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.

[Unilateral adrenal ischemia during third trimester of pregnancy: about two cases]. / Ischémie aiguë unilatérale de la glande surrénale en cours du 3e trimestre de grossess: à propos de deux cas.

Unilateral adrenal ischemia by venous thrombosis during pregnancy is an extremely rare event. We report the case of two women, in their third trimester who presented intense abdominal pain located on their right flank. Obstetric and clinical examination are normal, so as are the biological check-up and hepatic and renal imaging. The thoraco-abdominal CAT scan shows the right adrenal necrosis associated with the vein thrombosis. A C-section was decided to allow administration of appropriate treatment: analgesics and anticoagulants. Clinical evolution was rapidly favorable. Protein S deficiency was diagnosed in one of the patients. The follow-up CAT scan shows the vein re-permeabilisation and disappearing of necrosis signs.

Proximal row carpectomy: Is early postoperative mobilisation the right rehabilitation protocol?

PURPOSE OF THE STUDY: To determine the feasibility and interest of an early rehabilitation protocol with no initial immobilisation after proximal row carpectomy. MATERIAL AND METHODS: Thirteen patients were included in this retrospective study. Range of motion (ROM) and wrist strength (grip strength and grasp strength) were evaluated 3 and 6 weeks after surgery on the both wrists (operated and non-operated). Postoperatively, patients had no immobilisation of the wrist, and began a rehabilitation program immediately after surgery in the department of Physical Therapy and Rehabilitation under multidisciplinary team supervision. The same surgical technique was used for all patients by the same surgeon. RESULTS: Six weeks after PRC, there was a 25-51% deficit in passive ROM and 54-64% deficit in active ROM compared to the corresponding non-operated wrist. Six weeks after PRC, mean overall grip strength was nearly 55% and Jamar dynamometer grip strength was 51% of the contralateral side. DISCUSSION: This study shows that immediate immobilisation following PRC is unnecessary, and that early rehabilitation is of the essence. Early rehabilitation could reduce the delay necessary to recover range of motion and strength, and probably the time to return to work. LEVEL OF EVIDENCE: Level 4, prospective cohort study.

[Adrenal vein thrombosis during pregnancy]. / Thrombose veineuse surrénalienne en cours de grossesse.

Pregnancy represents an inner transitional prothrombotic state; that is why other coagulation abnormalities may be revealed during this time. Factor V Leiden mutation is the most frequent inherited thrombophilia in the general population. We report the case of a patient by whom this mutation has been revealed during pregnancy by an adrenal vein thrombosis. Through this case, we will review the physiopathology of resistance to activated protein C and its consequences.

Anaesthetic management of an obstetric patient with idiopathic acute transverse myelitis.

Idiopathic acute transverse myelitis is a rare focal inflammatory disorder of the spinal cord causing motor, sensory and autonomic dysfunction. We report the successful use of general anaesthesia for caesarean section in a patient with this disease. Potential anaesthetic concerns include autonomic dysreflexia and hyperkalaemia following the use of suxamethonium. Further complicating issues with this patient included psychotic depression and new-onset neuropathic pain on a background of chronic pain symptoms.