Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis

The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. The dysfunction of lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes lipid accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress would further contribute to hepatocyte injury and death, leading to inflammation and immune dysfunction in the liver. During the healing process, the accumulation of an excessive amount of fibrosis might occur while healing. During the development of NASH and liver fibrosis, the gut-liver axis, adipose-liver axis, and renin-angiotensin system (RAS) may be dysregulated and impaired. Translocation of bacteria or its end-products entering the liver could activate hepatocytes, Kupffer cells, and hepatic stellate cells, exacerbating hepatic steatosis, inflammation, and fibrosis. Bile acids regulate glucose and lipid metabolism through Farnesoid X receptors in the liver and intestine. Increased adipose tissue-derived non-esterified fatty acids would aggravate hepatic steatosis. Increased leptin also plays a role in hepatic fibrogenesis, and decreased adiponectin may contribute to hepatic insulin resistance. Moreover, dysregulation of peroxisome proliferator-activated receptors in the liver, adipose, and muscle tissues may impair lipid metabolism. In addition, the RAS may contribute to hepatic fatty acid metabolism, inflammation, and fibrosis. The treatment includes lifestyle modification, pharmacological therapy, and non-pharmacological therapy. Currently, weight reduction by lifestyle modification or surgery is the most effective therapy. However, vitamin E, pioglitazone, and obeticholic acid have also been suggested. In this review, we will introduce some new clinical trials and experimental therapies for the treatment of NASH and related fibrosis.

Proton Pump Inhibitor-unresponsive Laryngeal Symptoms Are Associated With Psychological Comorbidities and Sleep Disturbance: A Manometry and Impedance-pH Monitoring Study

Background/Aims@#Laryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms. @*Methods@#Patients with persistent laryngeal symptoms despite PPI treatment for ≥ 8 weeks were recruited. A multidisciplinary evaluationcomprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed.Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances. @*Results@#Ninety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, P < 0.001) and sleep disturbance (82.5% vs 37.5%, P < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores (r = 0.26, P = 0.010, and r = 0.29, P = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, P < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility. @*Conclusions@#PPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients.

Nuclear Theranostics in Taiwan / 대한핵의학회잡지

Boron neutron capture therapy and Y-90 radioembolization are emerging therapeutic methods for uncontrolled brain cancers and hepatic cancers, respectively. These advanced radiation therapies are heavily relied on theranostic nuclear medicine imaging before the therapy for the eligibility of patients and the prescribed-dose simulation, as well as the post-therapy scanning for assessing the treatment efficacy. In Taiwan, the Taipei Veterans General Hospital is the only institute performing the BNCT and also the leading institute performing Y-90 radioembolization. In this article, we present our single institute experiences and associated theranostic nuclear medicine approaches for these therapies.

Nuclear Theranostics in Taiwan / 대한핵의학회잡지

Boron neutron capture therapy and Y-90 radioembolization are emerging therapeutic methods for uncontrolled brain cancers and hepatic cancers, respectively. These advanced radiation therapies are heavily relied on theranostic nuclear medicine imaging before the therapy for the eligibility of patients and the prescribed-dose simulation, as well as the post-therapy scanning for assessing the treatment efficacy. In Taiwan, the Taipei Veterans General Hospital is the only institute performing the BNCT and also the leading institute performing Y-90 radioembolization. In this article, we present our single institute experiences and associated theranostic nuclear medicine approaches for these therapies.

Imaging Spectrum after Pancreas Transplantation with Enteric Drainage

Since the introduction of pancreas transplantation more than 40 years ago, surgical techniques and immunosuppressive regiments have improved and both have contributed to increase the number and success rate of this procedure. However, graft survival corresponds to early diagnosis of organ-related complications. Thus, knowledge of the transplantation procedure and postoperative image anatomy are basic requirements for radiologists. In this article, we demonstrate the imaging spectrum of pancreas transplantation with enteric exocrine drainage.

Risk factors and time-trends of cytomegalovirus (CMV), syphilis, toxoplasmosis and viral hepatitis infection and seroprevalence in human immunodeficiency virus (HIV) infected patients

<p><b>INTRODUCTION</b>Chronic bacterial, viral and parasitic infections contribute to the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. This study investigated risk factors and time-trends of the seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly diagnosed HIV individuals in Singapore.</p><p><b>MATERIALS AND METHODS</b>This was a cross-sectional study. A random sample of 50% of HIV infected patients who visited the Communicable Disease Centre (CDC), Singapore for first-time care from January 2006 to December 2011 were analysed.</p><p><b>RESULTS</b>Among the 793 study subjects, 93.4% were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was 41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm³. The prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%; hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C, 73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was significantly more common among men who have sex with men (MSM) (multivariate OR: 2.53, 95% CI, 1.31 to 4.90, P = 0.006).</p><p><b>CONCLUSION</b>This study described the baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore, and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates compared to the general population may have important consequences for disease progression, response to antiretroviral treatment and long-term general health.</p>

Causes of death in hospitalised HIV-infected patients at a National Referral Centre in Singapore: a retrospective review from 2008 to 2010

<p><b>INTRODUCTION</b>Highly active antiretroviral therapy (HAART) has improved outcomes for individuals infected with human immunodeficiency virus (HIV). This study describes the causes of death in hospitalised HIV-positive patients from 2008 to 2010 in Tan Tock Seng Hospital, the national referral centre for HIV management in Singapore.</p><p><b>MATERIALS AND METHODS</b>Data were retrospectively collected from HIV-positive patients who died in Tan Tock Seng Hospital from January 2008 to December 2010.</p><p><b>RESULTS</b>Sixty-seven deaths occurred in the study period. A majority of patients died of non-acquired immune deficiency syndrome (AIDS)-defining illnesses (54.7%). The median CD4 count was 39.5 (range, 20.0 to 97.0), and 7 patients had HIV viral loads of <200 copies/mL. There were 27 deaths due to opportunistic infections, 27 due to non AIDS-defining infections, 4 due to non AIDS-associated malignancies. This study also describes 3 deaths due to cardiovascular events, and 1 due to hepatic failure. Patients who had virologic suppression were more likely to die from non AIDS-defining causes.</p><p><b>CONCLUSION</b>Causes of death in HIV-positive patients have changed in the HAART era. More research is required to further understand and address barriers to testing and treatment to further improve outcomes in HIV/AIDS.</p>

Older age at initial presentation to human immunodeficiency virus (HIV) care and treatment at the Communicable Disease Centre (CDC) in Singapore, 2006 to 2011

<p><b>INTRODUCTION</b>The incidence of newly diagnosed older patients diagnosed with human immunodeficiency virus (HIV) has increased worldwide in recent years. In this study, we compared the demographics and clinical presentation of younger and older patients in our HIV sentinel cohort.</p><p><b>MATERIALS AND METHODS</b>Among all HIV patients presenting to the Communicable Disease Centre (CDC), Singapore from 2006 to 2011, 793 were randomly included in our cohort, representing about 50% of the patients seen during that period. We collected demographic, clinical, laboratory, and outcome data from patient records to compare younger (<50 years old) and older (≥50 years old) HIV patients.</p><p><b>RESULTS</b>Older patients comprised 27.1% of our HIV cohort and presented with lower median CD4 T cell counts (65 cells/mm³, interquartile range [IQR]: 27 to 214 cells/mm³) compared to younger patients (250 cells/mm³, IQR: 74 to 400 cells/mm³; P <0.001). The median time from HIV diagnosis to initiation of antiretroviral therapy (ART) differed significantly for both age groups as well (49 days for patients <50 years old, IQR: 18 to 294 days; versus 35 days for patients ≥50 years old, IQR: 14 to 102 days; P = 0.008). More of our younger patients were single (72.2%) or homosexual (44.1%), in contrast to older patients, of whom 48.8% were married and 84.7% were heterosexual.</p><p><b>CONCLUSION</b>Upon comparison of our younger and older patients, we identified distinct differences in risk transmission and clinical presentation. Increased awareness of older patients at risk of HIV may improve time to diagnosis among this age group.</p>

Prediction of Mortality after Emergent Transjugular Intrahepatic Portosystemic Shunt Placement: Use of APACHE II, Child-Pugh and MELD Scores in Asian Patients with Refractory Variceal Hemorrhage

OBJECTIVE: This study was designed to determine if existing methods of grading liver function that have been developed in non-Asian patients with cirrhosis can be used to predict mortality in Asian patients treated for refractory variceal hemorrhage by the use of the transjugular intrahepatic portosystemic shunt (TIPS) procedure. MATERIALS AND METHODS: Data for 107 consecutive patients who underwent an emergency TIPS procedure were retrospectively analyzed. Acute physiology and chronic health evaluation (APACHE II), Child-Pugh and model for end-stage liver disease (MELD) scores were calculated. Survival analyses were performed to evaluate the ability of the various models to predict 30-day, 60-day and 360-day mortality. The ability of stratified APACHE II, Child-Pugh, and MELD scores to predict survival was assessed by the use of Kaplan-Meier analysis with the log-rank test. RESULTS: No patient died during the TIPS procedure, but 82 patients died during the follow-up period. Thirty patients died within 30 days after the TIPS procedure; 37 patients died within 60 days and 53 patients died within 360 days. Univariate analysis indicated that hepatorenal syndrome, use of inotropic agents and mechanical ventilation were associated with elevated 30-day mortality (p 11 or an MELD score > 20 predicted increased risk of death at 30, 60 and 360 days (p 11 or an MELD score > 20 are predictive of mortality in Asian patients with refractory variceal hemorrhage treated with the TIPS procedure. An APACHE II score is not predictive of early mortality in this patient population.

Healthcare workers and HIV health issues

Should healthcare workers (HCWs) be routinely tested for HIV? The authors reviewed the literature on the risk and incidence of HIV transmission from HCW to patients and offer recommendations for HIV testing in HCWs in Singapore. Management of HCWs who are tested seropositive for HIV infection is also discussed in this paper.

A Bionomic Study of Hymenopteran Parasitoids at the Taman Beringin Landfill in Kepong and a Poultry Farm in Sungai Pelek, Selangor, Malaysia / Jurnal Sains Kesihatan Malaysia

A four-month cross-sectional study found five species of parasitoids parasitizing puparia of filth flies breeding at the Taman Beringin landfill in Kepong and a poultry farm in Sungai Pelek, Sepang, Selangor. Effect of monthly rainfalls towards density of flies and percentage of parasitoids emerging from collected puparia were also analyzed. Spalangia sp. was the most common, consisting of Spalangia endius Walker, S. cameroni Perkins and S. gemina Boucek. Other parasitoids collected were Pachycrepoideus vindemmiae Rondani and Exoristobia phillipinensis Ashmead. The parasitized fly hosts were Musca domestica Linn. and Chrysomya megacephala Fabricius. S. endius was the most common parasitoid attacking M. domestica at both locations. M. domestica was the most common fly found at the Sg. Pelek poultry farm whereas C. megacephala was the most numerous at the Taman Beringin landfill. During heavy rainfall month of November 2003, density of flies were high whereas the emerging parasitoids were low at both landfill and poultry farm. The present study revealed the endemic presence of parasitoids especially S. endius in both poultry farm and garbage landfill and the potential of the parasitoid species in fly control in Malaysia.

Cluster of Staphylococcus aureus and dengue co-infection in Singapore

<p><b>INTRODUCTION</b>Singapore saw a resurgence of dengue infections in 2005. Concurrent bacterial co-infections in dengue is rare.</p><p><b>CLINICAL PICTURE</b>We report a cluster of serious methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia or severe soft tissue infection in 5 epidemiologically linked construction workers presenting with dengue and non-resolving fever.</p><p><b>TREATMENT</b>Surgical intervention was indicated in 4 of the 5 patients despite appropriate antistaphylococcal therapy.</p><p><b>OUTCOME</b>All but 1 patient were eventually discharged. Clonality and Panton-Valentine leucocidin genes were not demonstrated. Epidemiological investigations suggested that occupational contact dermatitis could have predisposed the patients to this opportunistic co-infection.</p><p><b>CONCLUSION</b>Clinicians need to be vigilant to unusual manifestations of dengue which may signal a concomitant aetiology.</p>