Gonadotoxic Effect of Combined Chemotherapy on Anti Müllerian Hormone (AMH) Level in non-Gynecologic Cancer Patients in Reproductive Age

Objective: To assess the effect of combined chemotherapy on levels of Anti-Müllerian Hormone (AMH). Method: This is a prospective cohort study on 12 non-gynecologic cancer women aged 20 - 40 years who received combined chemotherapy treatment. AMH levels and menstrual pattern before and after three months of chemotherapy were examined. The relationships between age, chemotherapy regimens and the cumulative doses on the change of AMH were also analyzed. Result: The median age of subjects was 37 years (range 20 - 40 years). Pre chemotherapy AMH analysis revealed an inverse correlation between age and AMH levels (r = -0.715; p = 0.009). AMH levels after 3 months of combined chemotherapy drastically declined to 84.6% (p = 0.002). Multivariate analysis indicated that age and total cumulative dose were the main factors contributing to the AMH levels reduction (r = -0.679; p = 0.002 and r = 0.405; p = 0.027). Ten of 12 subjects (83.3%) experienced amenorrhea after 3 months of chemotherapy and had lower level of pre and postchemotherapy AMH compared to those who still maintained normal periods (p = 0.03 and 0.02). Conclusion: AMH levels in non-gynecological cancer women who received combined chemotherapy decreased dramatically after 3 months of chemotherapy. Main factors that contribute to this were the cumulative dose and age. Most of these subjects experienced amenorrhea after 3 months of chemotherapy. [Indones J Obstet Gynecol 2010; 34-3: 119-24] Keywords: ovarian reserve, chemotherapy, Anti Müllerian Hormone (AMH), ovarian function, gonadotoxi

Characterization of the human herpesvirus 6A U23 gene

AbstractHuman herpesvirus 6 (HHV-6), which replicates abundantly in T cells, belongs to the Roseolovirus genus within the betaherpesvirus subfamily. Members of the Roseolovirus genus encode seven unique genes, U20, U21, U23, U24, U24A, U26, and U100. The present study focused on one of these, U23, by analyzing the characteristics of its gene product in HHV-6A-infected cells. The results indicated that the U23 protein was expressed at the late phase of infection as a glycoprotein, but was not incorporated into virions, and mostly stayed within the trans Golgi network (TGN) in HHV-6A-infected cells. Furthermore, analysis using a U23-defective mutant virus showed that the gene is nonessential for viral replication in vitro

Is Higher BMI Associated with Worse Overall Mortality in Hepatocellular Carcinoma Patients? An Evidence Based Case Report

Background: liver cancer is currently the second deadliest cancer in the world with hepatocelullar carcinoma (HCC) being the commonest form—accounting 90% of all its cases. With the current global alarming increase of obesity, there is hence an increase of fatty liver disease cases, which is one of the major non-viral etiology of cirrhosis in the world. The objective of this study is to evaluate whether obese HCC patients have worse survival outcome. Methods: PubMed, Cochrane, Scopus, ProQuest, and EBSCOhost were comprehensively searched for systematic review and cohort prognostic researches studying overall survival of HCC patients who are underweight and obesity according to their BMI. Three studies were selected and critically appraised. Data were then summarized descriptively. Results: the three studies included consist of one meta-analysis and two cohort studies. Meta-analysis study stated no association between overweight and obesity status with higher mortality rate in Asian race HCC patients (aHR, 1.10; 95% CI, 0.63-1.92). A cohort study from Japan reported while there was a significant difference of mortality rate in obese HCC patients in bivariate analysis, adjustment with other important prognostic factors with multivariate analysis found no significant correlation between obesity and HCC-related mortality rate (aHR, 1.00; 95% CI, 0.83-1.22). Another cohort study from China reported that HCC-related mortality rate in patients with higher BMI was lower than in patients with lower BMI (aHR, 0.347; 95% CI, 0.239-0.302). Conclusion: there is no association between higher BMI with HCC-related mortality in Asian race patients

Evaluation of Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Chronic Liver Diseases

Background: acoustic radiation force impulse (ARFI) is a new proposed noninvasive method for liver fibrosis staging. Integrated with B-mode ultrasonography, ARFI can be used to assess liver tissue condition. However its diagnostic accuracy is still being continuously evaluated. Also, there is lack of data regarding the utilization of ARFI in our population. This study aimed to evaluate the diagnostic value of ARFI as an alternative noninvasive modality for fibrosis staging in chronic hepatitis B and hepatitis C patients in our population. Methods: we conducted cross-sectional comparison of ARFI imaging and transient elastography on patients who underwent liver biopsy at Cipto Mangunkusumo Hospital. Fibrosis staging using METAVIR scoring system presented as standard reference. A total of 43 patients underwent liver biopsy was evaluated by ARFI imaging and transient elastography. Cut-off values were determined using receiver-operating characteristic (ROC). Results: both liver stiffness determined by ARFI and transient elastography (TE) were moderately correlated with METAVIR score with value of 0.581 and 0.613, respectively (both P<0.01). Diagnostic accuracy of ARFI predicted significant fibrosis (F≥2) with area under receiver operating characteristic curve (AUROC) of 0.773 (95% CI 0.616-0.930) and even better for cirrhosis (F4 fibrosis), expressed as AUROC of 0.856 (95% CI 0.736–0.975). Transient elastography was better for significant fibrosis with AUROC of 0.761 (95% CI 0.601–0.920) and was best for prediction of cirrhosis, expressed as AUROC of 0.845 (95% CI 0.722–0.968). Conclusion: ARFI is provided with more convenient evaluation of liver tissue condition, and its diagnostic accuracy is not significantly different from TE for staging liver fibrosis

Efficacy of Combination Sofosbuvir, Pegylated-Interferon, and Ribavirin for Treatment of Hepatitis C Virus Genotype 1 Infection in Indonesia

Background: The presence of direct-acting antiviral (DAA) has improved the treatment of HCV infection and making it more preferable than Pegylated-interferon (PegIFN) and Ribavirin (RBV) based treatment. However, treatment with all DAA combination regimen is limited and expensive in low health care affordability country including Indonesia. The appearance of generic sofosbuvir (SOF) facilitate the utilization of SOF plus PegINF with or withour RBV combination. Therefore, in this study we assessed the efficacy of SOF+RBV and SOF+RBV+PegINF combination for treatment of chronic hepatitis C infections patient with genotype 1 in IndonesiaMethod: We performed retrospective study comprising 128 patients in Cipto Mangunkusumo Hospital with chronic hepatitis C, genotype 1, infection. 36 patients was treated with PegINF+SOF+RBV and 92 patients was treated with SOF+RBV with the duration of therapy was 12 and 24 weeks in both arms. The primary endpoint was sustained virologic response after treatment completion (SVR12)Results: In the end of treatment, 99.2% patients achieved undetected HCV RNA in 12 weeks and 24 weeks duration of therapy (100% in PegINF+SOF+RBV group and 98.9% in SOF+RBV group). The SVR12 of PegINF+SOF+RBV reach 100% meanwhile The SVR12 of SOF+RBV reach 88%.  No different in SVR12 between cirrhotic and non-cirrhotic patient in PegINF+SOF+RBV group while in SOF+RBV group, the SVR12 was lower in cirrhotic patients (82.9%) compared to non-cirrhotic patients (92.2%). In multivariate analysis, HIV co-infection is associated with lower SVR12 in SOF+RBV group.Conclusion: 12 weeks and 24 weeks of PegINF+SOF+RBV and SOF+RBV is effective in the treatment of genotype 1 chronic hepatitis C infectio

3D Co-Culture of Hepatocyte, a Hepatic Stellate Cell Line, and Stem Cells for Developing a Bioartificial Liver Prototype

A liver organoid is an in vitro reconstruction of the liver that mimics the in vivo liver microstructure and performs liver functions. Liver organoids can be used for drug testing, as a model of liver disease pathogenesis, and as a bioartificial liver prototype material to develop promising alternative therapies for liver failure. In this study, we reconstructed liver organoids using primary rat hepatocytes, a hepatic stellate cell line (LX2), human umbilical cord-mesenchymal stem cells (UC-MSCs), and human umbilical cord blood (UCB)-CD34+ hematopoietic stem/progenitor cells. Suspensions of primary rat hepatocytes, LX2 cells, UC-MSCs, and UCB-CD34+ cells were co-cultured using 11 ratio sets, and spheroid formation was evaluated for 2 days. Ratio sets with a positive liver organoid appearance were cultured in four different culture media, and after they were harvested, their viability was compared with that of a hepatocyte monoculture. Liver organoids were further analyzed for 14 days to assess albumin and urea production as well as relative gene expression. We found that a 5:1:2:2 cellular density ratio of hepatocytes:LX2 cells:UC-MSCs:UCB-CD34+ cells, respectively, and Williams E medium supplemented with platelet lysate, ITS, and dexamethasone were the most suitable conditions for liver organoid reconstruction. Expression of the albumin and GPT1 genes and CD31 in the liver organoid increased until day 14, while urea secretion increased until day 5. Liver organoids reconstructed through the 3D co-culture of primary rat hepatocytes, LX2 cells, UC-MSCs, and UCB-CD34+ cells at a specific cellular ratio using an economical medium with a simple composition maintained their functions until day 14. As a future direction, these organoids can be used to develop a bioartificial liver

Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres

The genomes of human herpesviruses 6A and 6B (HHV-6A and HHV-6B) have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes. Here, we report an analysis of 28 ciHHV-6 genomes and show that they are significantly divergent from the few modern non-integrated HHV-6 strains for which complete sequences are currently available. In addition ciHHV-6B genomes in Europeans are more closely related to each other than to ciHHV-6B genomes from China and Pakistan, suggesting regional variation of the trait. Remarkably, at least one group of European ciHHV-6B carriers has inherited the same ciHHV-6B genome, integrated in the same telomere allele, from a common ancestor estimated to have existed 24,500 ±10,600 years ago. Despite the antiquity of some, and possibly most, germline HHV-6 integrations, the majority of ciHHV-6B (95%) and ciHHV-6A (72%) genomes contain a full set of intact viral genes and therefore appear to have the capacity for viral gene expression and full reactivation. IMPORTANCE: Inheritance of HHV-6A or HHV-6B integrated into a telomere occurs at a low frequency in most populations studied to date but its characteristics are poorly understood. However, stratification of ciHHV-6 carriers in modern populations due to common ancestry is an important consideration for genome-wide association studies that aim to identify disease risks for these people. Here we present full sequence analysis of 28 ciHHV-6 genomes and show that ciHHV-6B in many carriers with European ancestry most likely originated from ancient integration events in a small number of ancestors. We propose that ancient ancestral origins for ciHHV-6A and ciHHV-6B are also likely in other populations. Moreover, despite their antiquity, all of the ciHHV-6 genomes appear to retain the capacity to express viral genes, and most are predicted to be capable of full viral reactivation. These discoveries represent potentially important considerations in immune-compromised patients, in particular in organ transplantation and in stem cell therapy

The Correlation of Short-Chain Fatty Acids with Peripheral Arterial Disease in Diabetes Mellitus Patients

Diabetes mellitus (DM) is a significant risk factor for peripheral arterial disease (PAD). PAD affects 20% of DM patients over 40 and has increased by 29% in the last 50 years. The gut microbiota produces short-chain fatty acids (SCFAs) that affect atherosclerosis. SCFA inhibits inflammation, which contributes to atherosclerosis. This study tried to link feces SCFA levels to atherosclerosis in people with diabetes with peripheral arterial disease (PAD). The study included 53 people with diabetes and PAD: gas chromatography-mass spectrometry measured acetate, butyrate, and propionate levels in feces samples (GC-MS). There was a positive correlation between random blood glucose (RBG) levels, peak systolic velocity (PSV), volume flow (VF), plaque, relative and absolute acetate, relative valerate, butyrate, and propionate. This supports the idea that elevated SCFA levels in type 2 diabetic (T2D) patients reduce adipose tissue inflammation and cholesterol metabolism, contributing to atherosclerosis pathogenesis. We conclude that increased fecal SCFA excretion is linked to cardiovascular disease. To determine the causal effect correlation of the SCFA with clinical and laboratory parameters for PAD in DM patients, compare the SCFA in plasma and feces, and account for confounding variables, a specific method with larger sample sizes and more extended follow-up periods is required