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Chronic hepatitis B virus (HBV) infection is a serious public health problem because of its worldwide prevalence and potential to cause adverse consequences. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer‐Hepatitis B Virus (REVEAL‐HBV) study carried out in Taiwan was used to investigate the natural history of chronic hepatitis B. The REVEAL‐HBV study has established an HBV viral load paradigm in the natural history of chronic hepatitis B (CHB). Serum HBV DNA level has been shown to be significantly and independently associated with incidence of hepatocellular carcinoma (HCC) and cirrhosis and liver‐related mortality across a biological gradient. It is also a major predictor of HBsAg seroclearance. Genetic features including HBV genotype and basal core promoter A1762T/G1764A mutant, and precore G1896A mutant were documented as predictors of HCC risk. Inactive HBV carriers still had an increased risk on HCC development and liver‐related mortality compared with HBsAg ‐seronegatives. Nomograms focusing on facilitating risk communication between patients and clinicians were developed incorporating non‐invasive clinical parameters to predict long‐term HCC risk. These will hopefully contribute to evidence‐based decisions in the clinical management of CHB patients. A somewhat provocative and novel finding from the REVEAL‐HBV study is the association of chronic HBV infection in active replication with an increased pancreatic cancer risk especially in women less than 50 years old. This finding will hopefully spur further research in this area seeking confirmatory evidence. Finally, we hope that the REVEAL‐HBV study will continue to be a source of data to answer other important questions in chronic hepatitis B research going forward. 相似文献
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Carrie McAdam-Marx Jayanti Mukherjee Brandon K. Bellows Sudhir Unni Xiangyang Ye Uchenna Iloeje Diana I. Brixner 《Diabetes research and clinical practice》2014
Aims
This study evaluates the relationship between HbA1c and weight change outcomes by anti-diabetic weight-effect properties in patients newly treated for type 2 diabetes; a relationship not previously characterized.Methods
Electronic medical records of patients with type 2 diabetes newly prescribed anti-diabetic monotherapy were assessed to identify HbA1c goal attainment [(<53 mmol/mol)] and weight change at 1-year. Anti-diabetics were categorized by weight-effect properties: weight-gain (sulfonylureas, thiazolidinediones) and weight-loss/neutral (metformin, DPP-4 inhibitors, GLP-1 agonists). Logistic regression analyses identified likelihood of attaining HbA1c goal or ≥3% weight loss by anti-diabetic category controlling for baseline characteristics. MANOVA was used to identify correlation between changes in weight and HbA1c.Results
The study included 28,290 patients. Mean age ± sd was 61 years ± 11.8. Baseline HbA1c was 7.4% ± 1.6 (57 mmol/mol ± 17); 67.3% were prescribed a weight-loss/neutral anti-diabetic. At 1-year, more patients in the weight-loss/neutral anti-diabetic category lost weight (≥3%) than in the weight-gain anti-diabetic category (40.4% vs. 24.2%, p < 0.001) or had an HbA1c < 7.0% (<53 mmol/mol) (71.1% vs. 63.8%, p < 0.001). Those prescribed a weight-gain anti-diabetic were 53% less likely to lose weight and 29% less likely to be at HbA1c goal than those prescribed a weight-loss/neutral anti-diabetic (p < 0.001). Weight loss and HbA1c outcomes were significantly correlated (p < 0.001).Conclusions
Weight loss of ≥3% was associated with better glycemic control in patients newly treated for type 2 diabetes. Anti-diabetics associated with weight-loss/neutrality were associated with greater weight loss and HbA1c goal attainment and may facilitate efforts to co-manage weight and glycemia in the ambulatory-care setting. 相似文献5.
Agu RU Vu Dang H Jorissen M Willems T Kinget R Verbeke N 《International journal of pharmaceutics》2002,237(1-2):179-191
This study examined the potential usefulness of cultured human nasal epithelium as a model to investigate nasal absorption enhancement strategies for therapeutic peptides. The transport of leucine enkephalin (Leu-Enk) in the presence of bestatin and puromycin, respectively and various combinations of these protease inhibitors with absorption enhancers capable of inhibiting proteases or protecting peptides against protease degradation (glycocholate, dimethyl-beta-cyclodextrin (DM beta CD)) was studied. Epithelial membrane perturbation, protein leakage, bestatin/puromycin absorption and rebound aminopeptidase activity were used as toxicological end-points. The combination of puromycin with glycocholate or DM beta CD resulted in a higher absorption enhancement of Leu-Enk (9-14%) than when the absorption enhancers were combined with bestatin (1-3%) or when the inhibitors were used alone (2-4%). The higher absorption enhancement resulting from the combination of protease inhibitors with absorption enhancers caused a significant reduction of epithelial resistance and increased sodium fluorescein transport. Although only puromycin permeated the human nasal epithelium, both protease inhibitors induced a significant rebound aminopeptidase activity (25-61%), which can be associated with protein leakage (21-46%). This study highlighted (i) the potential usefulness of cultured human nasal epithelium as a model to study nasal absorption enhancement of therapeutic peptides; (ii) further studies using in vivo nasal models are required to ascertain whether the membrane perturbation and cytotoxicity observed with various combinations of the protease inhibitors and absorption enhancers really raise safety concerns. 相似文献
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Characterization of human nasal primary culture systems to investigate peptide metabolism 总被引:1,自引:0,他引:1
Hoang VD Uchenna AR Mark J Renaat K Norbert V 《International journal of pharmaceutics》2002,238(1-2):247-256
The objectives of this study were to validate and compare the suitability of different primary cell culture systems as models to investigate peptide enzymatic stability following nasal administration. The degradation kinetics of a model peptide, leucine enkephalin (Tyr-Gly-Gly-Phe-Leu, Leu-Enk), was determined in four nasal cell culture systems: immersion, air-liquid interface, sequential monolayer-suspension, floating collagen. The influence of enzyme inhibitors (bestatin, puromycin) and Leu-Enk metabolite analogs (Tyr-Gly, Phe-Leu, Tyr-Gly-Gly, Gly-Phe-Leu) on the Leu-Enk degradation profile was also investigated. The disappearance of Leu-Enk in all the cell culture systems followed first order kinetics. The specific activity in the cell culture systems followed the rank: sequential monolayer-suspension (32.60 microM min(-1) mg(-1)) >air-liquid interface (15.19 microM min(-1) mg(-1)) >immersion (11.49 microM min(-1) mg(-1)) >floating collagen (4.57 microM min(-1) mg(-1)). At equimolar concentration, bestatin had a higher inhibitory effect than puromycin. The rate of hydrolysis of Leu-Enk was reduced significantly by co-incubation with Leu-Enk metabolite analogs. This study showed that immersion, sequential monolayer-suspension and air-liquid interface culture systems may be potentially suitable for further studies on peptide enzymatic stability following nasal administration. 相似文献
7.
Uchenna Kenneth Ezemagu Chike P. Anibeze Chinedu F. Akpuaka 《Anatomical science international / Japanese Association of Anatomists》2018,93(2):277-283
The biomechanical function of the lumbosacral junction (LSJ) is obscure, but its medical significance is not, as it is the most common site of low back pain. In this study, we analyzed the difference between the mean values of the surface areas of the inferior body and total inferior facet areas of the fourth and fifth lumbar vertebrae. We aimed to define the function of the LSJ during weight transmission and clarify its mechanical significance. Vertebral columns of 45 adult male human cadavers from five anatomy departments in Nigeria were cut at the L3–L4 intervertebral disc and macerated. Using the graph paper method, the mean values of the surface area of the inferior body and total facet area of the fourth and fifth lumbar vertebrae were 1356 ± 26 and 329 ± 6 and 1277 ± 27 and 418 ± 8 mm2, respectively. The relationships between the fourth and fifth lumbar vertebrae paired variables were highly significant (P < 0.001). A sudden reduction in the surface area of the inferior body of the fifth lumbar vertebra was compensated for by a corresponding increase in its total inferior facet area, which indicated that corresponding weight was diverted from the anterior column to the posterior column at the LSJ. This pattern of weight transmission may be a beneficial functional adaptation in man to protect the relatively large intervertebral disc of the LSJ in bipedal posture, or it may predispose the LSJ synovial zygapophyseal joints to mechanical stress. 相似文献
8.
Incidence of non-Hodgkin's lymphoma among individuals with chronic hepatitis B virus infection 总被引:4,自引:0,他引:4
Ulcickas Yood M Quesenberry CP Guo D Caldwell C Wells K Shan J Sanders L Skovron ML Iloeje U Manos MM 《Hepatology (Baltimore, Md.)》2007,46(1):107-112
Although hepatitis C virus (HCV) infection has been shown to be associated with development of non-Hodgkin's lymphoma (NHL), few studies have investigated the association between chronic HBV infection and NHL. The purpose of this study was to compare the incidence of NHL between patients with and without chronic hepatitis B virus (HBV) infection. Using automated laboratory result and clinical data from two United States health systems, we identified individuals with chronic HBV infection from January 1, 1995 through December 31, 2001. Using each health system's population-based tumor registry, we identified all cases of NHL diagnosed through December 31, 2002. We excluded any individual with a history of NHL or human immunodeficiency virus (HIV). We fit Cox proportional hazards models to calculate hazard ratios comparing the incidence of NHL between chronic HBV-infected patients (N = 3,888) and patients without HBV (N = 205,203) drawn from the source populations. We identified 8 NHL cases in the chronic HBV infection cohort and 111 cases in the comparison cohort. Patients with chronic HBV infection were 2.8 times more likely to develop NHL than matched comparison patients (adjusted hazard ratio = 2.80, 95% confidence interval = 1.16-6.75), after controlling for age, race, sex, income, Charlson comorbidity index, study site, and HCV infection. CONCLUSION: chronic HBV-infected patients were nearly 3 times more likely to develop NHL than comparison patients. 相似文献
9.
Anti-Hu antibodies, also known as ANNA-1, are well characterized in paraneoplastic neuropathies. We present here the first known case of anti-Hu seropositivity, cerebellar ataxia, and sensory neuropathy in association with cervical cancer. 相似文献
10.
Kristen Cagino Xuan Li Charlene Thomas Diana Delgado Paul Christos Uchenna Acholonu 《Journal of minimally invasive gynecology》2021,28(6):1171-1182.e2
ObjectiveThe incidence of adnexal masses in pregnancy is 1% to 6%. Although surgery is often indicated, there are no definitive management guidelines. We aimed to investigate the optimal approach to surgical management of adnexal masses in pregnancy on the basis of a meta-analysis of previous studies.Data SourcesWe performed a systematic review using MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov from inception to July 17, 2020.Methods of Study SelectionThere were no restrictions on study type, language, or publication date. Comparative and noncomparative retrospective studies that reviewed operative techniques used in surgery of adnexal masses in pregnancy were included. Meta-analyses were performed to assess outcomes. This study was registered in the International Prospective Register of Systematic Reviews (CRD42019129709).Tabulation, Integration, and ResultsComparative studies were identified for laparoscopy vs laparotomy and elective vs emergent surgery (11 and 4, respectively). Elective surgery is defined as a scheduled antepartum procedure. For laparoscopy vs laparotomy, the mean maternal ages and gestational ages at time of surgery were similar (27.8 years vs 27.7 years, p = .85; 16.2 weeks in laparoscopy vs 15.4 weeks in laparotomy, p = .59). Mass size was larger in those undergoing laparotomy (mean 8.8 cm vs 7.8 cm, p = .03). The most common pathologic condition was dermoid cyst (36%), and the risk of discovering a malignant tumor was 1%. Laparoscopy was not associated with a statistically increased risk of spontaneous abortion (SAB) or preterm delivery (PTD) (odds ratio [OR] 1.53; 95% confidence interval [CI], 0.67–3.52; p = .31 and OR 0.95; 95% CI, 0.47–1.89; p = .88, respectively). The mean length of hospital stay was 2.5 days after laparoscopy vs 5.3 days after laparotomy (p <.001). The decrease in estimated blood loss in laparoscopy was not statistically significant (94.0 mL in laparotomy vs 54.0 mL in laparoscopy, p = .06). Operative times were similar in laparoscopy and laparotomy (80.0 minutes vs 72.5 minutes, p = .09). Elective surgery was associated with a decreased risk of PTD (OR 0.13; 95% CI, 0.04–0.48; p = .05). Noncomparative studies were identified for laparoscopy and laparotomy. Laparotomy had more SABs and PTDs than laparoscopy (pooled proportion = 0.02 vs 0.07 and pooled proportion = 0.02 vs 0.14, respectively).ConclusionLaparoscopy for the surgical management of adnexal masses in pregnancy is associated with shorter length of hospital stay and similar risk of SAB or PTD. Elective surgery is associated with a decreased risk of PTD. 相似文献