Factors Associated with Death in Subjects Admitted for a Diabetological Emergency: Experience of the Medical Clinic II of the Abass Ndao Hospital Center in Dakar (Senegal) —Death in Diabetic Emergencies

Introduction: Metabolic and vascular emergencies constitute a risk of lethality in diabetic subjects admitted to hospital. The objective was to evaluate the factors associated with death in subjects admitted for a diabetological emergency to improve management. Materials and Methods: It was a 12-month retrospective, descriptive and analytical study at Dakar’s Marc Sankale Diabetes Center. The study concerned any type of diabetics subjects admitted for a diabetological emergency. We evaluated the profile of diabetes, the pathologies found and factors associated with death. Results: We identified 697 cases of diabetic emergencies with a prevalence of 13.8%. The sex ratio (M/F) was 0.82, the mean age was 49.6 years, and the mean duration of diabetes was 7.1 years. The metabolic profile was hypoglycemia (11.3%), ketoacidosis (34.6%), and hyperosmolar hyperglycemia syndrome (5%). The associated pathologies were vascular (51.1%), infectious (65.3%), kidney function impairment (7.6%), anaemia (13.8%). During the follow-up, 94 patients died, as an annual frequency of 13.5% among diabetological emergencies. In univariate analysis, the factors significantly associated with death were age > 60 years [OR = 4.09 (2.6 - 6.41)], hyperglycemia [OR = 2.58 (1.50 - 4.4)], hyperosmolar hyperglycemia syndrome [OR = 10.5 (5.19 - 21.5)], septic diabetic foot [OR = 3.57 (2.24 - 5.66)]. Vascular pathologies that significantly associated with death were stroke [OR = 4.06 (2.10 - 7.81)], lower limb arteriopathy [OR = 3.25 (1.84 - 5.73)], cardiovascular collapse [OR = 6.85 (2.34 - 20)]. In addition to diabetes, the deceased patients had one (18%), two (34%) and at least three (45.7%) known factors of poor prognosis. Conclusion: Emergencies in diabetology remain frequent in our practice. The comorbidity (vascular and infectious) constitutes a risk of abnormally high death rate. A particular attention must concern on old diabetics subjects with several pathologies.

Hepatic Cirrhosis: Diagnostic and Prognosis in Internal Medicine

Introduction: Cirrhosis is a public health problem and the causes are dominated by viral hepatitis and alcoholism. Deaths due to cirrhosis represented 2.4% of deaths worldwide in 2017. The aim of this work was to study the diagnostic and prognosis of cirrhosis at the department of internal medicine of the Abass Ndao hospital center. Patients and Methods: This is a retrospective, descriptive study, carried out on the basis of patient files followed from May 1, 1999 to February 28, 2018 (19 years) and included all patients for whom the diagnosis of cirrhosis was accepted. The diagnosis of cirrhosis was made on the basis of clinical, biological and ultrasound (portal hypertension, signs of hepatocellular insufficiency, a diffuse heterogeneous aspect, and irregularity of the liver contours). Results: 60 patient files were listed with an average age of 46.9 years, a sex ratio of 2.2 and alcoholism in 11.7% of the cases. The reasons for consultation were dominated by an increase in the size of the abdomen (55%), lose weight (50%). On physical examination, it was a hepatomegaly (43.3%) and jaundices (33.3%). Exploration of liver function showed a cholestasis (48%), a cytolysis (58%) and a hepatocellular insufficiency (46.2%). Anemia was found in (24%). The abdominal ultrasound found in all cases a dysmorphic, heterogeneous liver with irregular contours. Hepatic atrophy was found in 20%. Among the 34 patients who underwent upper gastrointestinal endoscopy, they were grade 2 to 3 esophageal varicose vein in 67.6%, an erosive gastropathy in 29.4%. The etiology was viral hepatitis B in 45%, alcoholism in 11.7% and undetermined in 43.3%. A hematemesis complicated the evolution in 16.7%. Carcinomatous degeneration was found in 5% and 16.7% of the patients had died. Conclusion: our experience with cirrhosis was marked by advanced forms at the stage of complications. The viral etiology B remains dominant. Prevention will involve early detection and vaccination.

Dynamic ultrasonography for optimizing treatment position in superior mesenteric artery syndrome:Two case reports and review of literature

BACKGROUND Superior mesenteric artery(SMA)syndrome is a rare cause of duodenal obstruction by extrinsic compression between the SMA and the aorta(SMA-Ao).Although the left lateral recumbent position is considered effective in the treatment of SMA syndrome,individual variations in the optimal patient position have been noted.In this report,we present two elderly cases of SMA syndrome that exhibited rapid recovery due to ultrasonographic dynamic evaluation of the optimal position for each patient.CASE SUMMARY Case 1:A 90-year-old man with nausea and vomiting.Following diagnosis of SMA syndrome by computed tomography(CT),ultrasonography(US)revealed the SMA-Ao distance in the supine position(4 mm),which slightly improved in the lateral position(5.7–7.0 mm)without the passage of duodenal contents.However,in the sitting position,the SMA-Ao distance was increased to 15 mm accompanied by improved content passage.Additionally,US indicated enhanced passage upon abdominal massage on the right side.By day 2,the patient could eat comfortably with the optimal position and massage.Case 2:An 87-year-old woman with vomiting.After the diagnosis of SMA syndrome and aspiration pneumonia by CT,dynamic US confirmed the optimal position(SMA-Ao distance was improved to 7 mm in forward-bent position,whereas it remained at 5 mm in the supine position).By day 7 when her pneumonia recovered,she could eat with the optimal position.CONCLUSION The optimal position for SMA syndrome varies among individuals.Dynamic US appears to be a valuable tool in improving patient outcomes.

Prospective study of hepatitis B and D epidemiology and risk factors in Romania:A 10-year update

BACKGROUND The global burden of hepatitis D virus(HDV)infection represents a major medical challenge and a public health crisis worldwide.However,there is a lack of accurate data on the epidemiology and risk factors for HDV.Hepatitis B virus(HBV)and HDV coinfection causes the most severe form of viral hepatitis,leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection,including the need for liver transplantation and death.AIM To investigate the epidemiology,natural history,risk factors and clinical management of HBV and HDV coinfection in Romanian patients.METHODS This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania.All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled.Patients with acute hepatitis or incomplete data were excluded.Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period,963 met the inclusion criteria.Testing for anti-HDV antibodies and HDV RNA was performed for all participants.Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires.All data were stored in an anonymized online database during the study.RESULTS The prevalence of HBV was 3.8%;among these patients,the prevalence of HBV/HDV coinfection was 33.1%.The median age of the study population was 54.0 years,and it consisted of 55.1%men.A higher prevalence of HBV/HDV coinfection was observed in patients 50–69 years old.Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection(P=0.03).Multivariate multiple regression analysis identified female gender(P=0.0006),imprisonment(P<0.0001),older age at diagnosis(P=0.01)and sexual contact with persons with known viral hepatitis(P=0.0003)as significant risk factors for HDV.CONCLUSION This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors.It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.

Identification of CD13,CD107a,and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-de-pendent upregulation

Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD203c^(+)basophils.Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor(FcεRI).These include antibod-ies against CD164(WS-80160,clone N6B6 and WS-80162,clone 67D2),as well as two reagents with previously unknown specificities that were identified as CD13(WS-80274,clone A8)and CD107a(WS-80280,clone E63-880).The activation patterns followed either the“CD203c-like”or“CD63-like”activation profile.The CD203c profile is characterized by a rapid and significant upregulation(of CD13,CD164,and CD203c),reaching maximum levels after 5-15 min of stimulation.The phosphoinositide-3-kinase(PI3K)-specific inhibitor wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate(TPA)induced a rapid and FcεRI-independent upregulation within 1-2 min.In the CD63 profile,maximum upregulation(of CD63 and CD107a)was detected only after 20-40 min,and upregulation by TPA reached maximum levels after 60 min.In summary,our data identify CD13,CD107a,and CD164 as novel basophil-activation antigens.Based on time kinetics of upregulation,we hypothesize that molecules of the“CD203c group”and the“CD63 group”are linked to two different mechanisms of basophil activation.

Influence of antibiotic-regimens on intensive-care unit-mortality and liver-cirrhosis as risk factor

AIM: To assess the rate of infection, appropriateness of antimicrobial-therapy and mortality on intensive care unit(ICU). Special focus was drawn on patients with liver cirrhosis.METHODS: The study was approved by the local ethical committee. All patients admitted to the Internal Medicine-ICU between April 1, 2007 and December 31, 2009 were included. Data were extracted retrospectively from all patients using patient charts and electronic documentations on infection, microbiological laboratory reports, diagnosis and therapy. Due to the large hepatology department and liver transplantation center, special interest was on the subgroup of patients with liver cirrhosis. The primary statistical-endpoint was the evaluation of the influence of appropriate versusinappropriate antimicrobial-therapy on in-hospitalmortality.RESULTS: Charts of 1979 patients were available. The overall infection-rate was 53%. Multiresistantbacteria were present in 23% of patients with infection and were associated with increased mortality(p < 0.000001). patients with infection had significantly increased in-hospital-mortality(34% vs 17%, p < 0.000001). Only 9% of patients with infection received inappropriate initial antimicrobial-therapy, no influence on mortality was observed. Independent risk-factors for in-hospital-mortality were the presence of septicshock, prior chemotherapy for malignoma and infection with pseudomonas spp. Infection and mortality-rate among 175 patients with liver-cirrhosis was significantly higher than in patients without liver-cirrhosis. Infection increased mortality 2.24-fold in patients with cirrhosis. patients with liver cirrhosis were at an increased risk to receive inappropriate initial antimicrobial therapy.CONCLUSION: The results of the present study report the successful implementation of early-goal-directed therapy. Liver cirrhosis patients are at increased risk of infection, mortality and to receive inappropriate therapy. Increasing burden are multiresistant-bacteria.

Recurrence rates after endoscopic resection of large colorectal polyps:A systematic review and meta-analysis

BACKGROUND Complete polyp resection is the main goal of endoscopic removal of large colonic polyps.Resection techniques have evolved in recent years and endoscopic submucosal dissection(ESD),endoscopic mucosal resection(EMR)with margin ablation,cold snare polypectomy(CSP),cold EMR,and underwater EMR have been introduced.Yet,efficacy of these techniques with regard to local recurrence rates(LRRs)vs traditional hot snare polypectomy and standard EMR remains unclear.AIM To analyze LRR of large colonic polyps in a systematic review and meta-analysis.METHODS MEDLINE,EMBASE,EBM Reviews,and CINAHL were searched for prospective studies reporting LRR or incomplete resection rate(IRR)after colonic polypectomy of polyps≥10 mm,published between January 2011 and July 2021.Primary outcome was LRR for polyps≥10 mm.RESULTS Six thousand nine hundred and twenty-eight publications were identified,of which 34 prospective studies were included.LRR for polyps≥10 mm at up to 12 mo’follow-up was 11.0%(95%CI,7.1%-14.8%;15 studies;4904 polyps).ESD(1.7%;95%CI,0%-3.4%;3 studies,221 polyps)and endoscopic mucosal resection with margin ablation(3.3%;95%CI,2.2%-4.5%;2 studies,947 polyps)significantly reduced LRR vs standard EMR without(15.2%;95%CI,12.5%-18.0%;4 studies,650 polyps)or with unsystematic margin ablation(16.5%;95%CI,15.2%-17.8%;6 studies,3031 polyps).CONCLUSION LRR is significantly lower after ESD or EMR with routine margin ablation;thus,these techniques should be considered standard for endoscopic removal of large colorectal polyps.Other techniques,such as CSP,cold EMR,and underwater EMR require further evaluation in prospective studies before their routine implementation in clinical practice can be recommended.

Significance of scintigraphy for the localisation of obscure gastrointestinal bleedings

AIM： To determine the role of scintigraphy in patients with gastrointestinal （GI） bleeding of unknown Iocalisation. METHODS： We performed retrospective analyses on 92 patients receiving scintigraphies from 1993 to 2000 in the University of Regensburg hospital, which were done for Iocalisation of GI bleeding as a diagnostic step after an unsuccessful endoscopy. In addition to the scintigraphies, further diagnostic steps such as endoscopy, angiography or operations were performed. In some of the scintigraphies with negative results, a provocation test for bleeding with heparinisation was carried out. RESULTS： 73% of all scintigraphies showed a positive result. In 4.5% of the positive results, the source was located in the stomach, in 37% the source was the small bowel, in 25% the source was the right colon, in 4.5% the source was the left colon, and in 20% no clear Iocalisation was possible. Only 4% of all scintigraphies were false positive. A reliable positive scintigraphy was independent of the age of the examined patient. A provocation test for bleeding with heparin resulted in an additional 46% of positive scintigraphies with a reliable Iocalisation in primary negative scintigraphies. CONCLUSION- Our results show that scintigraphy and scintigraphy with heparin provocation tests are reliable procedures. They enable a reliable Iocalisation in about half of the obscure GI-bleeding cases. Scintigraphy is superior to angiography in locating a bleeding. It is shown that even in the age of video capsule endoscopy and double-balloon enteroscopy, scintigraphy provides a reliable and directed localization of GI bleeding and offers carefully targeted guidance for other procedures.

Experimental treatment of pancreatic cancer with two novel histone deacetylase inhibitors

AIM:To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer. METHODS:Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 8 human pancreatic cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT) assay. In addition,the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral activity of the drugs was assessed by immunoblotting for p21WAF-1,acH4,cell cycle analysis,TUNEL assay,and immunohistochemistry for MIB-1. RESULTS:In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines and was associated with hyperacetylation of nucleosomal histone H4,increased expression of p21WAF-1,cell cycle arrest at G2/M-checkpoint,and increased apoptosis. In vivo,NVP-LBH589 alone significantly reduced tumor mass and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed slightly increased apoptosis and no significant reduction of cell proliferation.CONCLUSION:Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human pancreatic cancer,although the precise mechanism of in vivo drug action is not yet completely understood. Therefore,further preclinical and clinical studies for the treatment of pancreatic cancer are recommended.

New flexible endoscopic controlled stapler technique for the treatment of Zenker's diverticulum:A case series

AIMTo report about the combination and advantages of a stapler-assisted diverticulotomy performed by flexible endoscopy.METHODSFrom November 2014 till December 2015 17 patients (8 female, 9 male, average age 69.8 years) with a symptomatic Zenker diverticulum (mean size 3.5 cm) were treated by inserting a new 5 mm fully rotatable surgical stapler (MicroCutter30 Xchange, Cardica Inc.) next to an ultrathin flexible endoscope through an overtube. The Patients were under conscious sedation with the head reclined in left position, the stapler placed centrally and pushed forward to the bottom of the diverticulum. The septum was divided by the staple rows under flexible endoscopic control.RESULTSIn eleven patients (64.7%) the stapler successfully divided the septum completely. Mean procedure time was 21 min, medium size of the septum was 2.8 cm (range 1.5 cm to 4 cm). In four patients the septum was shorter than 3 cm, in seven longer than 3 cm. To divide the septum, averagely 1.3 stapler cartridges were used. Two minor bleedings occurred. Major adverse events like perforation or secondary haemorrhage did not occur. After an average time of two days patients were discharged from the hospital. In 6 patients (35.3%) the stapler failed due to a thick septum or insufficient reclination of the head. Follow up endoscopy was performed after an average of two months in 9 patients; 4 patients (44.4%) were free of symptoms, 5 patients (55.6%) stated an improvement. A relapse of symptoms did not occur.CONCLUSIONFlexible endoscopic Zenker diverticulotomy by using a surgical stapler is a new, safe and efficient treatment modality. A simultaneously tissue opening and occlusion prevents major complications.

Fracture Risks Related to Parity and Breastfeeding Effect in Post-Menopausal Women Aged Sixty and Over: Results from the “Quality of Bone in Lorraine” Register

Introduction: The long term effect of accumulation of genital events as repeated pregnancy and longer breastfeeding in bone heath later in women’s life is still disputed. The objective was to assess the impact of parity and cumulated duration of breastfeeding on fracture risk in post-menopausal women aged sixty an over. Patients and Methods: It was a leading study from the register “Quality of Bone in Lorraine (QBL)” achieved in the department of endocrinology and osteoporotic disease of Nancy (France). This register included all patients sent for an assessment of the bone mass density from January 1, 2006 to December 31, 2014 (9 years). It was about post-menopausal women aged sixty an over suffering or not from osteoporosis fracture or bone fragility just after the age of 45. The genital events of patients to their age (from puberty to menopause) as well as the existence of hormone replacement therapy use, parity, and breastfeeding duration were taken into account. The assessment of bone fracture was clinical, radiological or by using the vertebral fracture assessment method. Results: 861 post-menopausal women were included. In comparison to the control group, the fractured population had a mean age of (74.3 ± 9 vs. 72 ± 8 years), a family history of fracture (32.1% vs. 26%), and an average input of calcium (2.4 ± 1 vs. 2.3 ± 0 portions per day). The age at menarche was of 12.8 ± 1 years in each group, a mean genital activity duration of (36.8 ± 3 vs. 37.2 ± 3 years), a parity of (2.1 ± 1 vs. 1.8 ± 1 children), a cumulated breastfeeding duration (4.2 ± 16 vs. 3.1 ± 5 months) and an age of menopause of (48.6 ± 4 vs. 48.6 ± 4 years) were respectively found in fractured and witness population. Overall, an osteoporotic fracture has been rediscovered in 50.9%. In multivariate analysis, only a cumulative duration of breastfeeding of 6 months and over was associated with a higher fracture risk (OR = 1.5 [1.1 - 2.2]). The impact of parity was not significant (OR = 1.1 [0.7 - 1.8]). Association with obesity was quasi significant (OR = 1.3 [0.9 - 1.9]). There was no correlation between the fracture risk and the genital activity duration (OR = 0.7 [0.5 - 1.0]), hormone replacement therapy use (OR = 1.0 [0.8 - 1.4]), daily calcium input (OR = 0.8 [0.6 - 1.3]), and age of menarche (OR = 1.0 [0.9 - 1.1]). Conclusion: This work confirms a negative impact from 6 months of cumulative breastfeeding. The modest effects observed may be related to the selection of Caucasian patients who live in an economically developed country with a limited number of pregnancies and limited duration of breastfeeding.

Carcinoid syndrome caused by a pulmonary carcinoid mimics intestinal manifestations of ulcerative colitis:A case report

BACKGROUND Pulmonary carcinoids are rare,low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior.Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi.Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5%of patients with neuroendocrine tumors.Due to such nonspecific presentation,most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed.CASE SUMMARY We report the case of a 48-year-old male who presented with cough,dyspnea,a history of recurrent pneumonitis,and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid.CONCLUSION We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

Endoscopic radiofrequency ablation for malignant biliary obstruction

Cholangiocarcinoma and pancreatic cancer are the most common causes of malignant biliary obstruction.The majority of patients are diagnosed at a late stage when surgical resection is rarely possible.In these cases,palliative chemotherapy and radiotherapy provide only limited benefit and are associated with poor survival.Radiofrequency ablation(RFA)is a procedure for locoregional control of tumours,whereby a high-frequency alternating current turned into thermal energy causes coagulative necrosis of the tissue surrounding the catheter.The subsequent release of debris and tumour antigens by necrotic cells can stimulate local and systemic immunity.The development of endoluminal RFA catheters has led to the emergence of endoscopically delivered RFA,a treatment mainly used for malignant biliary strictures to prolong survival and/or stent patency.Other indications include recanalisation of occluded biliary stents and treatment of intraductal ampullary adenoma or benign biliary strictures.This article presents a comprehensive review of endobiliary RFA,mainly focusing on its use in patients with malignant biliary obstruction.The available data suggest that biliary RFA may be a promising modality,having positive impacts on survival and stent patency and boasting a reasonable safety profile.However,further studies with better characterised and stratified patient populations are needed before the method becomes accepted within routine clinical practice.

Successful management of therapy-refractory pseudoachalasia after Ivor Lewis esophagectomy by bypassing colonic pull-up:A case report

BACKGROUND Gastric pull-up after esophagectomy is still a demanding surgical procedure and associated with considerable morbidity such as anastomotic leaks,fistulas or stenoses.These complications are usually managed by endoscopy,but in extreme cases multidisciplinary management including reoperations may be necessary.Here,we report managing therapy-refractory pseudoachalasia after Ivor Lewis esophagectomy by bypassing colonic pull-up.CASE SUMMARY A 70-year-old male with dysphagia and regurgitation after esophagectomy with gastric pull-up reconstruction was transferred to our tertiary hospital.Since endoscopic approaches including balloon dilatation and stenting failed,retrosternal colonic pull-up with Roux-en-Y reconstruction was performed with no subsequent adverse events.CONCLUSION Secondary colonic pull-up is a demanding but successful surgical procedure in patients suffering from therapy-refractory complaints after esophagectomy with gastric pull-up reconstruction.

Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy:Two case reports and literature review

BACKGROUND Muscle growth promoters are being developed for the treatment of diseaseinduced loss of muscle mass.Ligandrol and ostarine are selective androgen receptor modulators(SARMs)with a non-steroidal structure and a presumably more favorable side effect profile.In recent years,these substances with or without“post-cycle therapy”(PCT)are often misused by amateur athletes aiming to promote muscle growth.At the same time,reports on their toxic effects on organ systems are emerging.CASE SUMMARY We report two cases of liver injury in young men who used ligandrol and/or ostarine for a few weeks followed by the use of substances for PCT.Acute liver injury occurred in both cases after stopping SARMs while on PCT.The clinical picture was dominated by jaundice and fatigue.The biochemical pattern showed a mixed type of injury with normal alkaline phosphatase and high concentrations of bilirubin and serum bile acids. Histological evidence showed predominantlycholestatic injury with canalicular bile plugs, ductopenia, and mild hepatocellulardamage without significant fibrosis. The patients recovered from the conditionafter 3 mo. The off target effects of SARMs were likely idiosyncratic, but ourreport highlights the yet unrecognized effects of other toxic substances used forPCT, supra-therapeutic doses, and the complete absence of monitoring foradverse effects.CONCLUSIONAmong muscle-building amateur athletes, SARMs (ligandrol or ostarine) and/orsubstances in PCT may cause cholestatic liver injury with prolonged recovery.

Unmasking lower gastrointestinal bleeding under administration of norepinephrine

BACKGROUND Bleeding in the gastrointestinal tract is common and transarterial embolization enables the clinician to control gastrointestinal bleeding.Contrast extravasation is a prerequisite for successful embolization.Provocative angiography is helpful in the detection of elusive bleeding.AIM We performed a retrospective analysis of angiographic treatment in patients with lower gastrointestinal hemorrhage and initially negative angiographies,as well as the role of norepinephrine(NE)in unmasking bleeding.METHODS We analyzed 41 patients with lower gastrointestinal bleeding after angiography who had undergone treatment over a period of 10 years.All patients had a positive shock index and needed intensive care.RESULTS In three of four patients,angiography disclosed the site of bleeding when NE was used during the procedure for hemodynamic stabilization.CONCLUSION We suggest that angiography performed after the administration of NE in unstable patients with gastrointestinal bleeding and an initially negative angiography has the potential to unmask bleeding sites for successful embolization.However,this statement must be confirmed in prospective studies.

Evolution of Graves’s Disease: Impact of Socio-Demographic and Clinical Factors in Senegalese Subject

Background: In Graves’s disease, there is a lack of description specific to the gender and age among sub-Saharan African subject. The objective was to evaluate the impact of gender and age on the profile of Graves’ disease in Senegalese subject in order to understand the evolution and improve the therapeutic choices. Methods: This is a retrospective study conducted from January 1, 2010 to December 31, 2017 (07 years) at Abass Ndao University Hospital (Senegal), focused on patients with Graves’ disease followed up under antithyroid drugs treatment for at least 18 months. Results: There were 244 men, 404 subjects between [0 - 25 years], and 101 subjects more than 50 years old. Factors associated with goitre size were male gender (p < 0.001), young age (p < 0.001). Graves orbitopathy was correlated with male gender (p = 0.015), and young age (p < 0.001). Among 580 patients who had stopped medical treatment after more than 18 months of follow-up, relapse involved in 30.3%. Durable remission was achieved in 38.8% of all included patients and 69.7% of subjects who had a cessation of medical treatment. The factors associated with sustained remission were female gender (p = 0.049), absence of orbitopathy (p = 0.011), small goiter (p < 0.001), advanced age (p = 0.006) and early start of the maintenance treatment (p = 0.006). Conclusion: In our Senegalese study, men and young patients are particularized by a trend of voluminous goitre and low rate of remission. These data remain a basis for predicting the outcome of medical treatment and make timely use of radical treatments such as surgery or irratherapy in the presence of risk factors for recurrence.

Hepatitis B virus replication

Hepadnaviruses, including human hepatitis B virus （HBV）, replicate through reverse transcription of an RNA intermediate, the pregenomic RNA （pgRNA）. Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription： it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA, ε, as template, and depends on cellular chaperones; moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids. This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV （DHBV）, now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately, not be complemented by three-dimensional structural information on the involved components. However, at least for the ~ RNA element such information is emerging, raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.

Hepatitis B virus-induced oncogenesis

Hepatocellular carcinoma (HCC) is one of the most com- mon cancers in the world with an annual incidence of more than 500 000 in the year 2000. Its incidence is rising in many countries. Recently, it has been estimated that about 53% of HCC cases in the world are related to hepatitis B virus (HBV). The epidemiological association of HBV with HCC is well established. In recent studies, it was revealed that HBsAg carriers have a 25-37 times increased risk of developing HCC as compared to non-infected people. At present, HBV-associated carcinogenesis can be seen as a multi-factorial process that includes both direct and indirect mechanisms that might act synergistically. The integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion. The integration has been shown in a number of cases to affect a variety of cancer- related genes and to exert insertional mutagenesis. The permanent liver inflammation, induced by the immune response, resulting in a degeneration and regeneration process confers to the accumulation of critical mutations in the host genome. In addition to this, the regulatory proteins HBx and the PreS2 activators that can be encoded by the integrate exert a tumor promoter-like function resulting in positive selection of cells producing a functional regulatory protein. Gene expression profiling and proteomic techniques may help to characterize the molecular mechanisms driving HBV-associated carcino- genesis, and thus potentially identify new strategies in diagnosis and therapy.

Molecular changes in hepatic metabolism and transport incirrhosis and their functional importance

Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function.This review summarizes the regulatory and functional changes in phase Ⅰ and phaseⅡmetabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients.Interestingly,phase Ⅰ enzymes are generally down regulated transcriptionally,while phaseⅡenzymes are mostly preserved transcriptionally but are reduced in their function.Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis.Lipid and glucose metabolism are characterized by insulin resistance and catabolism,leading to the disturbance of energy expenditure and wasting.Possible non-invasive tests,especially breath tests,for components of liver metabolism are discussed.The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients.Additionally,studies in humans are rare,and species differences preclude the transferability of data from rodents to humans.In clinical practice,some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis,but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.