Clinical predictors of Covid-19 mortality in a tertiary hospital in Lagos, Nigeria: A retrospective cohort study.

Background: The predictors of mortality among patients presenting with severe to critical disease in Nigeria are presently unknown. Aim: The aim of this study was to identify the predictors of mortality among patients with COVID-19 presenting for admission in a tertiary referral hospital in Lagos, Nigeria. Patients and Methods: The study was a retrospective study. Patients' sociodemographics, clinical characteristics, comorbidities, complications, treatment outcomes, and hospital duration were documented. Pearson's Chi-square, Fischer's Exact test, or Student's t-test were used to assess the relationship between the variables and mortality. To compare the survival experience across medical comorbidities, Kaplan Meir plots and life tables were used. Univariable and multivariable Cox-proportional hazard analyses were conducted. Results: A total of 734 patients were recruited. Participants' age ranged from five months to 92 years, with a mean ± SD of 47.4 ± 17.2 years, and a male preponderance (58.5% vs. 41.5%). The mortality rate was 9.07 per thousand person-days. About 73.9% (n = 51/69) of the deceased had one or more co-morbidities, compared to 41.6% (252/606) of those discharged. Patients who were older than 50 years, with diabetes mellitus, hypertension, chronic renal illness, and cancer had a statistically significant relationship with mortality. Conclusion: These findings call for a more comprehensive approach to the control of non-communicable diseases, the allocation of sufficient resources for ICU care during outbreaks, an improvement in the quality of health care available to Nigerians, and further research into the relationship between obesity and COVID-19 in Nigerians.

Pro- and anti-inflammatory macrophages express a sub-type specific purinergic receptor profile.

Extracellular nucleotides act as danger signals that orchestrate inflammation by purinergic receptor activation. The expression pattern of different purinergic receptors may correlate with a pro- or anti-inflammatory phenotype. Macrophages function as pro-inflammatory M1 macrophages (M1) or anti-inflammatory M2 macrophages (M2). The present study found that murine bone marrow-derived macrophages express a unique purinergic receptor profile during in vitro polarization. As assessed by real-time polymerase chain reaction (PCR), Gαs-coupled P1 receptors A2A and A2B are upregulated in M1 and M2 compared to M0, but A2A 15 times higher in M1. The ionotropic P2 receptor P2X5 is selectively upregulated in M1- and M2-polarized macrophages. P2X7 is temporarily expressed in M1 macrophages. Metabotropic P2Y receptors showed a distinct expression profile in M1 and M2-polarized macrophages: Gαq coupled P2Y1 and P2Y6 are exclusively upregulated in M2, whereas Gαi P2Y13 and P2Y14 are overexpressed in M1. This consequently leads to functional differences between M1 and M2 in response to adenosine di-phosphate stimulation (ADP): In contrast to M1, M2 showed increased cytoplasmatic calcium after ADP stimulation. In the present study we show that bone marrow-derived macrophages express a unique repertoire of purinergic receptors. We show for the first time that the repertoire of purinergic receptors is highly flexible and quickly adapts upon pro- and anti-inflammatory macrophage differentiation with functional consequences to nucleotide stimulation.

Development and practice of laparoscopic surgery in a Nigerian tertiary hospital.

BACKGROUND: For the benefits of less postoperative pain, early recovery and discharge, and better cosmesis, laparoscopic surgery is rapidly gaining acceptance amongst surgeons as a better alternative to traditional open procedures. In January 2015, bookings for laparoscopic surgery became a more regular feature on our operation list. AIMS: We reported the indications, management outcome, and challenges in patients who had laparoscopic surgery in our institution. This is to document the trends in our surgical practice. METHODOLOGY: This is a descriptive study of 137 patients who had laparoscopic surgery for general surgical indications in our institution over a period of 5 years. Patients data as collected from the records department were evaluated for demographic characteristics, medical comorbidities, type of procedures done, and perioperative outcome. Data analysis was performed using Statistical Package for Social Sciences (SPSS). RESULTS: A total of 137 Patients had laparoscopic general surgery between January 2015 and December 2019. There were 48 males and 89 females with a male-to-female ratio of 1:1.9. The mean age of the patients was 38.8 ± 3.4 years (range 16-87 years). Laparoscopic cholecystectomy (35%) and laparoscopic appendicectomy (29.9%) were the most common procedures performed. Five (3.7%) cases were converted to open surgery. Superficial surgical site infection (5.8%) following laparoscopic appendicectomy was the most common postoperative complication. There was no 30-day postoperative mortality. CONCLUSION: Laparoscopic surgery is safe and can be applied to wide variety of general surgical conditions in developing countries. Minimal postoperative morbidity of laparoscopy is a major benefit to the patients.

Blood transfusion and ischaemic outcomes according to anemia and bleeding in patients with non-ST-segment elevation acute coronary syndromes: Insights from the TAO randomized clinical trial.

BACKGROUND: The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI). METHODS: The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status. RESULTS: 12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001). CONCLUSION: In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.

IgG4-related disease in patients with newly diagnosed idiopathic retroperitoneal fibrosis: a population-based Danish study.

Objectives: IgG4-related disease (IgG4-RD) may present as 'idiopathic' retroperitoneal fibrosis (IRPF). We aimed to determine the occurrence of IgG4-retroperitoneal fibrosis (IgG4-RPF) in a nationwide study on patients with newly diagnosed IRPF, and to compare histopathological, imaging, and clinical features in the IgG4-RPF and non-IgG4-RPF subsets. Method: The National Danish Pathology Register was searched for biopsy codes relating to retroperitoneal tissue from 1 January 2004 to 31 December 2013. Secondary causes of RPF were excluded. Among 724 candidate cases, 68 were identified with IRPF. Clinical, laboratory, and imaging recordings were reviewed, and tissue blocks were scrutinized for IgG4-RPF features according to international consensus. Results: Forty-two patients (28 males), median age 56 (25-74) years were included. Nineteen (45%) met the criteria for IgG4-RPF, seven with definite and 12 with possible IgG4-RPF, while 23 had non-IgG4-RPF. Local manifestations and laboratory measures did not differ between RPF subsets. Arterial hypertension (p = 0.037) and periaortic fibrosis (p = 0.024) were more common in IgG4-RPF vs non-IgG4-RPF. Plasma cell IgG4/total IgG ratios ≥ 40% were associated more with core histopathological features of IgG4-RD compared to ratios < 40% (p < 0.001). There was a positive correlation between tissue IgG4-positive plasma cells and eosinophil cell count in patients with IgG4-RPF (rho = 0.50, p = 0.043). Conclusion: Forty-five per cent of this nationwide study population with newly diagnosed IRPF could be reclassified with IgG4-RPF. The association between high numbers of IgG4-bearing plasma cells and histopathological features of IgG4-RPF supports IgG4-bearing plasma cells with a perturbed distribution between IgG4 and total IgG being implicated in the pathogenesis of IgG4-RPF.

Dual targeting improves capture of ultrasound microbubbles towards activated platelets but yields no additional benefit for imaging of arterial thrombosis.

Platelets can be found on the surface of inflamed and ruptured atherosclerotic plaques. Thus, targeting of activated platelets may allow for molecular imaging of vulnerable atherosclerotic lesions. We here investigated microbubbles (MB) functionalized with the selectin ligand sialyl Lewisa individually (MBsLea) or dually with sLea and an antibody targeting ligand-induced binding sites of the activated GPIIb/IIIa receptor (MBDual). Assessed by in vitro flow chamber, targeted MB exhibited increased adhesion to platelets as compared to MBControl. While MBsLea rolled slowly on the platelets' surface, MBDual enhanced the percentage of firm adhesion. In vivo, MB were investigated by ultrasound in a model of ferric chloride induced non-occlusive carotid artery thrombosis. MBsLea and MBDual revealed a higher ultrasound mean acoustic intensity than MBControl (p < 0.05), however MBDual demonstrated no additional increase in mean signal intensity as compared to MBsLea. The degree of carotid artery stenosis on histology correlated well with the ultrasound acoustic intensity of targeted MB (p < 0.05). While dual targeting of MB using fast binding carbohydrate polymers and specific antibodies is a promising strategy to support adhesion to activated platelets under arterial shear stress, these advantages seem not readily translatable to in vivo models.

Routine hemoglobin electrophoresis for pediatric surgery day case in at-risk populations: Suggested algorithm for screening using clinical risk factors.

BACKGROUND: Hemoglobin electrophoresis (HBE) is a part of the preoperative routine requested by anesthetists. However, the prevalence of hemoglobinopathy in the population is low. This study aims to determine the clinical risk factors for hemoglobinopathies and propose clinical guidelines for preoperative screening of patients for pediatric day care surgery. PATIENTS AND METHODS: A prospective study carried out over 12 months. Consecutive patients aged 6 months and older who had day case surgery were recruited to the study. Biodata and relevant clinical data were collated and documented in a proforma and analyzed using a statistical package for social sciences version 17. RESULTS: There were 124 patients106 boys and 18 girls. The median age was 3 years. Scrotal lesions were the most common conditions managed (71.7%). Seventy-eight percent of patients had HbAA, 15.3% had HbAS, and 4.8% had HbAC while 0.8% each had both HbSC and HbSS. At least one parent of 78.2% knew their Hb phenotype, of which, 79% were HbAA. A history of jaundice (P = 0.0001), hand and foot syndrome (P = 0.0001), frontal bossing (P = 0.0001), and low packed cell volume at surgery (P = 0.001) were found significant in predicting hemoglobinopathies. There was no mortality. CONCLUSION: Risk factors for hemoglobinopathies from this study included a positive history of jaundice, hand and foot syndrome, frontal bossing, and anemia. Proposed guidelines for HBE screening include the presence of hemoglobinopathy in one parent if one parent has sickle cell trait, and the other parent's genotype is unknown or if any of the risk factors is present.

[Antiplatelet therapy after acute coronary syndrome. Therapeutic strategies and treatment duration]. / Antithrombozytäre Therapie nach akutem Koronarsyndrom. Differenzialtherapie und Dauer.

Besides percutaneous coronary interventions, antiplatelet drugs are of overwhelming importance for patients with acute coronary syndrome (ACS). For ACS patients, the guidelines recommend treatment with acetylsalicylic acid and a P2Y12 receptor antagonist. The third generation P2Y12 receptor antagonists prasugrel and ticagrelor provide stronger platelet inhibition than clopidogrel and improve the clinical outcome in patients with ACS; however, it is still under discussion which P2Y12 antagonist fits best to which subgroup of ACS patients. This article summarizes current guidelines and antiplatelet treatment strategies for patients with non-ST-segment elevation (NSTE) ACS or ST-segment elevation myocardial infarction (STEMI). The information is mainly based on the recently published guidelines of the European Society of Cardiology on myocardial revascularization.

[Reconstruction of metadiaphyseal bone defects of the femur with cortical strut allografts in periprosthetic bone loss]. / Metadiaphysäre Femurdefektrekonstruktion mit kortikalen Strut-Allografts bei periprothetischen Knochendefekten.

OBJECTIVE: Biological augmentation and stabilization of high-grade bone defects with structural allografts from donor femur halfs. INDICATIONS: Severe bone defects with aseptic loosening of hip prosthesis, periprosthetic femoral fracture or non-union, possibly even in cases of a healed infection. CONTRAINDICATIONS: Local or systemic infection. SURGICAL TECHNIQUE: The two modeled strut allografts are temporary fixed epiperiostal anterolateral and -medial with wire cerclages, while protecting the vascular supplying linea aspera of the femur. With the thus stabilized femur, the leg can be placed in the four-position in order to prepare the medullary canal of the revision prosthesis. Finally, the uncemented revision prosthesis is hammered in under successive tightening of the wire cerclages. With this "cracking technique", stem is stabilized and the grafts have repositioning, augmentative, and supportive function. POSTOPERATIVE MANAGEMENT: Partial weight-bearing postoperatively for 12 weeks. X-ray control during surgery, 10 days postoperatively, after 6 and 12 weeks and every 1-2 years. RESULTS: In four different studies, 123 patients were stabilized from December 1991 to June 2011 due to an extensive periprosthetic femoral bone defect and/or periprosthetic fracture, refracture, or non-union with strut allografts. After an average follow-up of 3.8 years (range 0.3-11 years), the average Harris Hip Score was 80.8 (range 44-100). During this time, there was 1 refracture, 103 stable stems, 20 fibrous stable stems, 9 patients with low graft resorption, and 122 patients with radiographic healing of the strut allografts based on classification according to Emerson et al. (Clin Orthop Relat Res 285:35-44, 1992).

Interruption of classic CD40L-CD40 signalling but not of the novel CD40L-Mac-1 interaction limits arterial neointima formation in mice.

The co-stimulatory immune molecule CD40L figures prominently in a variety of inflammatory conditions including arterial disease. Recently, we made the surprising finding that CD40L mediates atherogenesis independently of its classic receptor CD40 via a novel interaction with the leukocyte integrin Mac-1. Here, we hypothesised that selective blockade of the CD40L-Mac-1 interaction may also retard restenosis. We induced neointima formation in C57/BL6 mice by ligation of the left carotid artery. Mice were randomised to daily intraperitoneal injections of either cM7, a small peptide selectively inhibiting the CD40L-Mac-1 interaction, scM7, a scrambled control peptide, or saline for 28 days. Interestingly, cM7-treated mice developed neointima of similar size compared with mice receiving the control peptide or saline as assessed by computer-assisted analysis of histological cross sections. These data demonstrate that the CD40L-Mac-1 interaction is not required for the development of restenosis. In contrast, CD40-deficient mice subjected to carotid ligation in parallel, developed significantly reduced neointimal lesions compared with respective wild-type controls (2872 ± 843 µm² vs 35469 ± 11870 µm²). Flow cytometry in CD40-deficient mice revealed reduced formation of platelet-granulocyte and platelet-inflammatory monocyte- aggregates. In vitro, supernatants of CD40-deficient platelet-leukocyte aggregates attenuated proliferation and increased apoptosis of smooth muscle cells. Unlike in the setting of atherosclerosis, CD40L mediates neointima formation via its classic receptor CD40 rather than via its recently described novel interaction with Mac-1. Therefore, selective targeting of CD40L-Mac-1 binding does not appear to be a favorable strategy to fight restenosis.

Preoperative localization of undescended testes in children: comparison of clinical examination and ultrasonography.

BACKGROUND: Preoperative localization of the testis aids effective management of undescended testes. Various diagnostic techniques have been applied in the localization of undescended testes with varying results. The aim of this study was to compare clinical assessment and ultrasound evaluation in the preoperative localization of undescended testes in children. METHODS: A prospective evaluation of all boys undergoing operation for undescended testes at the Lagos University Teaching Hospital, Idi Araba, from July 2010 to June 2011 was carried out. The findings on preoperative clinical and ultrasound examinations were compared with intraoperative findings. RESULTS: Forty boys with 52 undescended testes were studied. The median age of the boys at the time of surgery was 4 years (range 1-11 years). Forty-five testes (86.5%) were accurately localized preoperatively by ultrasound while 25 testes (48.1%) were accurately localized on clinical examination. Ultrasound evaluation had an accuracy of 86.5% in preoperative localization of undescended testes. Clinical examination had an accuracy of 48.1% in preoperative localization of undescended testes. Ultrasound was more accurate than physical examination (p < 0.001). CONCLUSIONS: Ultrasonography is more accurate than clinical examination in the preoperative localization of undescended testes in children and could play a role in preoperative evaluation of patients with undescended testes.

Contrast ultrasound for the quantification of deep vein thrombosis in living mice: effects of enoxaparin and P2Y12 receptor inhibition.

BACKGROUND/OBJECTIVES: We examined the applicability of contrast-enhanced ultrasound (CEUS) for imaging of murine deep vein thrombosis (DVT) and measured the effects of enoxaparin, ticagrelor and P2Y(12) receptor deficiency in vivo. METHODS: Deep vein thrombosis was induced by exposure to ferric chloride or ligation of the infrarenal vena cava of C57BL/6 mice after pretreatment with enoxaparin, ticagrelor or vehicle and in P2Y(12-/-) mice. Initial thrombus growth was visualized by intravital microscopy. Thrombi were weighed and examined by immunohistochemistry. CEUS was performed with a standard ultrasound system (Vivid 7, GE Healthcare) in the open abdominal cavity after injection of stabilized sulphur hexafluoride microbubbles. RESULTS: Incubation with ferric chloride resulted in non-occluding platelet-containing thrombus growth within 15-25 min. Sham-operated mice, enoxaparin- and ticagrelor-pretreated wild-type and P2Y(12-/-) mice developed only small thrombi. After injection of the contrast agent, growing thrombi were delineated clearly as negative contrast on CEUS. Thrombus size on CEUS after 25 min was significantly smaller in enoxaparin- (0.3 ± 0.1 mm(2)) and ticagrelor-treated (0.5 ± 0.1 mm(2)) wild-type and in P2Y(12-/-) mice (0.4 ± 0.1 mm(2)) as compared with vehicle-treated wild-type mice (2.0 ± 0.3 mm(2)) in the maximal sagittal plane (P < 0.001, n = 5-10). CEUS-derived thrombus size correlated linearly with thrombus weight and also reflected the extent of ligation-induced DVT. CONCLUSIONS: Contrast-enhanced ultrasound allowed the real-time quantification of DVT in living mice. Genetic and pharmacologic antithrombotic interventions were well reflected by CEUS and suggested an important role of the platelet P2Y(12) receptor in early DVT formation.

Routine haemoglobin electrophoresis screening in day case herniotomy in Nigerian children: Is it evidence-based?

BACKGROUND: To determine the prevalence of haemoglobinopathies in children who require day case herniotomy in our centre and ascertain if routine screening is necessary in all patients who require herniotomy. MATERIALS AND METHODS: A 12-month retrospective analysis of patients requiring herniotomy in our centre. Data including age, sex, diagnosis, haemoglobin electrophoresis status, surgical outcome and hospital stay were analysed. RESULTS: Ninety-five patients had complete records. There were 84 boys and 11 girls. M:F ratio: 7.6:1. The mean age was 3.2 ± 0.6 years. Fifty-five point eight per cent of the patients had right inguinal hernias while 35.8% had left inguinal hernias. Eight patients (8.4%) had bilateral inguinal hernias. Twenty-six patients (27.4%) had haemoglobinopathies while 69 patients (72.6%) had homozygous Haemoglobin A. The Sickle Cell trait (HbAS) was found in 22 patients (23.2%) while the HbAC was found in three patients (3.2%). One patient (1.1%) had Sickle Cell disease (Haemoglobin SS). He had had blood transfusion and previous history of jaundice. All patients survived and all patients were discharged on the day of surgery (mean hospital stay: 4hrs (range: 2.5 hrs-12 hrs)) except the patient with Sickle Cell disease who was admitted a day before surgery and discharged a day after the operation. CONCLUSION: One in four children coming for day case herniotomy in our centre had the Sickle Cell trait while only 1% had the Sickle Cell disease. These findings are in keeping with the prevalence in the Nigerian population. Routine screening may not be necessary for all patients coming for herniotomy in our centre. Clear indication(s) should be outlined for screening.

[Dabigatran therapy--perioperative management and interpretation of coagulation tests]. / Therapie mit Dabigatran. Periinterventionelles Management und Interpretation von Gerinnungstests.

UNLABELLED: Dabigatran, an oral, reversible direct factor IIa inhibitor, is approved in Europe for stroke prevention in atrial fibrillation and for the prevention of venous thromboembolism after elective hip and knee replacement. In contrast to vitamin K antagonists, a routine coagulation monitoring during the treatment with dabigatran etexilate is not necessary. However, in specific clinical situations such as invasive emergency procedures or serious haemorrhage, the actual anticoagulant status of dabigatran may be of importance for the treating clinician and can be assessed by clotting tests (aPTT, TT, ECT). The diluted thrombin time test (Hemoclot®), which is specifically calibrated for dabigatran, is useful for quantitative determination of the dabigatran serum concentration. In general, discontinuation of dabigatran etexilate 24 hours before standard elective surgery is sufficient to normalise the bleeding risk in patients with normal renal function. In patients with renal impairment and/or in the case of a high bleeding risk procedure the recommended duration of discontinuation is prolonged. If a bleeding episode occurs in a patient on dabigatran, further treatment should be based on the severity and localisation of the bleeding. A distinct feature of dabigatran is the possibility of effectively removing dabigatran from the circulation by haemodialysis. RECOMMENDATION: In the case of clinically minor bleedings, a delay in the administration of the next dabigatran etexilate dose is recommended. The length of the delay is based on the patient's individual thromboembolic risk. In minor bleedings the use of prothrombin complex concentrates is not indicated. In the case of moderate or major bleedings the main focus should be on stabilising the circulation by using fluids and blood products and, if a lesion can be identified, the local treatment thereof. If time and infrastructure is available, dialysis offers an effective and fast option to remove dabigatran out of the circulation. In the incidence of severe and life threatening bleedings, an additional, more complex haemostasis management is required. Besides haemodynamic stabilisation of the circulation, administration of prothrombin complex concentrates should not be delayed. It has to be kept in mind that standard laboratory coagulation parameters may not accurately reflect the effect of prothrombin complex concentrates in patients on dabigatran. Hence the effect of the prothrombin complex concentrate should be monitored clinically and adjusted by means of onset of coagulation in vivo.

Oral anticoagulation with edoxaban. Focus on current phase III clinical development.

Edoxaban (the former DU176b) an orally available direct factor Xa inhibitor has been engineered from DX-9065a, which was one of the first parenteral Xa inhibitors. Edoxaban has a time to peak plasma concentrations of 1-2 hours and a half-life of approximately 10 hours after multiple doses. Edoxaban is the third new oral anticoagulant in the group of direct factor Xa inhibitors that has gained clinical approval for the prevention of venous thromboembolism after major orthopaedic surgery. Currently, edoxaban is assessed in late stage clinical development for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (ENGAGE AF-TIMI 48, NCT00781391) and for the treatment and prevention of venous thromboembolism in patients with acute deep vein thrombosis and/or pulmonary embolism (HOKUSAI VTE, NCT00986154). Both clinical phase III trials represent the largest single clinical studies in their entity so far with an enrolment of 21107 patients in ENGAGE AF-TIMI 48 and a planned enrolment of 7500 patients in HOKUSAI VTE. The pharmacological properties of edoxaban will be discussed along with the current late stage clinical development focusing on the prevention of stroke and venous thromboembolism.

[Rivaroxaban in the prevention and treatment of thromboembolic disorders]. / Rivaroxaban in der Prävention und Therapie thromboembolischer Erkrankungen.

Rivaroxaban (Xarelto(®)) is a new anticoagulant for the prevention and treatment of thromboembolic disorders. Rivaroxaban inhibits coagulation factor Xa directly, has high oral bioavailability, shows low propensity for drug-drug interactions and requires no routine coagulation monitoring. In patients undergoing elective knee or hip replacement surgery rivaroxaban (10 mg/d) is highly effective to prevent venous thromboembolism. In patients with non-valvular atrial fibrillation rivaroxaban (20 mg/d) has been approved to prevent stroke or systemic embolism. The favourable benefit-risk profile of rivaroxaban in the treatment of deep vein thrombosis (DVT) was shown in EINSTEIN-DVT and led to its clinical approval (twice daily 15 mg for 3 weeks, followed by 20 mg/d). Based on ATLAS-ACS-TIMI-51 which has shown that rivaroxaban (2.5 mg twice daily) reduced thrombotic cardiovascular events and mortality in patients with a recent acute coronary syndrome, the approval of low dose rivaroxaban has been submitted for this indication. Taken together, rivaroxaban may become an effective alternative to standard anticoagulants in the prevention and treatment of thromboembolic disorders.

Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior.

Bone morphogenetic proteins (BMPs) are growth factors that exert important functions in cell proliferation, migration and differentiation. Till date, multiple human tumors have been reported to display a dysregulation of several members of the BMP pathway that is associated with enhanced malignant tumor growth and metastasis. BMPER (BMP endothelial cell precursor-derived regulator) is a direct BMP modulator that is necessary for BMPs to exert their full-range signaling activity. Moreover, BMPER is expressed by endothelial cells and their progenitors, and has pro-angiogenic features in these cells. Here, we describe the expression of BMPER in human specimens of lung, colon and cervix carcinomas and cell lines derived from such carcinomas. In contrast to healthy tissues, BMPER is highly expressed upon malignant deterioration. Functionally, loss of BMPER in the lung tumor cell line A549 impairs proliferation, migration, invasion as well as tumor cell-induced endothelial cell sprout formation. In contrast, stimulation of A549 cells with exogenous BMPER had no further effect. We found that the BMPER effect may be transduced by regulation of the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 9 and 2. These facilitators of cell migration are downregulated when BMPER is absent. To prove the relevance of our in vitro results in vivo, we generated Lewis lung carcinoma cells with impaired BMPER expression and implanted them into the lungs of C57BL/6 mice. In this model, the absence of BMPER resulted in severely reduced tumor growth and tumor angiogenesis. Taken together, these data unequivocally demonstrate that the BMP modulator BMPER is highly expressed in malignant tumors and tumor growth is dependent on the presence of BMPER.

Accreditation of Training Programmes by the West African College of Surgeons.

The establishment of surgical training programmes of the West African College of Surgeons started in six teaching hospitals the early 1970s in Nigeria and Ghana; it was championed by College Fellows, surgeons who had returned to the sub-region after having trained in Europe and America. Surgical programmes accreditation, captured in the College's constitution and mission statement, uses objective guidelines in the identification and encouragement of suitable institutions for surgical training through periodic peer-review audits of installed manpower, facilities, clinical services and academic programmes. This pan-regional model adopted by the five Anglophone countries of West Africa has standardized and nurtured surgical training in the disciplines of surgery, obstetrics and gynaecology, ophthalmology, otorhinolaryngology, dental surgery, radiology and anaesthesia. It has also proven to be a useful template in the current drive for the ongoing harmonization of surgical training programmes with Francophone West African as a prelude to an integrated sub-regional accreditation body. This paper details the evolution of surgical programmes accreditation in West Africa, its progress, challenges, opportunities and future trends.

Oral anticoagulation with edoxaban.

Edoxaban (the former DU176b) an orally available direct factor Xa inhibitor has been engineered from DX-9065a, which was one of the first parenteral Xa inhibitors. Edoxaban has a time to peak plasma concentrations of 1-2 hours and a half-life of approximately 10 hours after multiple doses. Edoxaban is the third new oral anticoagulant in the group of direct factor Xa inhibitors that has gained clinical approval for the prevention of venous thromboembolism after major orthopaedic surgery. Currently, edoxaban is assessed in late stage clinical development for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (ENGAGE AF-TIMI 48, NCT00781391) and for the treatment and prevention of venous thromboembolism in patients with acute deep vein thrombosis and/or pulmonary embolism (HOKUSAI VTE, NCT00986154).Both clinical phase III trials represent the largest single clinical studies in their entity so far with an enrolment of 21 107 patients in ENGAGE AF-TIMI 48 and a planned enrolment of 7500 patients in HOKUSAI VTE.The pharmacological properties of edoxaban will be discussed along with the current late stage clinical development focusing on the prevention of stroke and venous thromboembolism.