Metabolic-associated fatty liver disease and hepatocellular carcinoma: a prospective study of characteristics and response to therapy.

BACKGROUND AND AIM: The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population. METHOD: Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period. RESULTS: Three hundred and thirteen (313) newly diagnosed HCC patients with MAFLD (n = 77), MAFLD plus other liver disease (n = 57) (the "mixed" group), and non-MAFLD (n = 179) were included in the study. Alcohol-associated liver disease (ALD) (43%) and MAFLD (43%) were the most common underlying liver diseases. MAFLD-HCC patients were older (73 years vs 67 years vs 63 years), more likely to be female (40% vs 14% vs 20%), less likely to have cirrhosis (69% vs 88% vs 85%), showed higher ECOG, and were less likely to be identified by screening (29% vs 53% vs 45%). Metabolic syndrome was more prevalent in the MAFLD and mixed groups. The severity of underlying liver disease and HCC characteristics were the same across groups. While the MAFLD population self-reported more sedentary lifestyles, reported dietary patterns were no different across the groups. Dyslipidemia was associated with tumor size, and those taking statins had a lower recurrence rate. CONCLUSION: Equal to ALD, MAFLD is now the most common underlying liver disease seen in HCC patients in Australia. Future HCC prevention screening and treatment strategies need to take this important group of patients into consideration.

Candidatus Actinochlamydia pangasiae sp. nov. (Chlamydiales, Actinochlamydiaceae), a bacterium associated with epitheliocystis in Pangasianodon hypophthalmus.

Chlamydial infections are recognised as causative agent of epitheliocystis, reported from over 90 fish species. In the present study, the farmed striped catfish Pangasianodon hypophthalmus (14-15 cm, 70-90 g) with a history of cumulative mortality of about 23% during June and July 2015, were brought to the laboratory. The histopathological examination of gills from the affected fish revealed presence of granular basophilic intracellular inclusions, mostly at the base of the interlamellar region and in gill filaments. A concurrent infection with Trichodina spp., Ichthyobodo spp. and Dactylogyrus spp. was observed in the gills. The presence of chlamydial DNA in the gills of affected fish was confirmed by amplification and sequencing of 16S rRNA gene. BLAST-n analysis of these amplicons revealed maximum similarity (96%) with Candidatus Actinochlamydia clariae. On the basis of phylogenetic analysis, it was inferred that the epitheliocystis agents from striped catfish were novel and belonged to the taxon Ca. Actinochlamydia. It is proposed that epitheliocystis agents from striped catfish will be named as Ca. Actinochlamydia pangasiae. The 16S rRNA gene amplicons from novel chlamydiae were labelled and linked to inclusions by in situ hybridisation. This is the first report of epitheliocystis from India in a new fish host P. hypophthalmus.

Factors associated with poor adherence to antiviral treatment for hepatitis B.

Antiviral therapy for hepatitis B is effective and reduces the risk of progression to cirrhosis and liver cancer but is often required for an indefinite duration. Treatment adherence is important to prevent the development of resistance and optimize outcomes. Pharmacy adherence measures can be used to assess treatment adherence, with the medication possession ratio being less susceptible to bias than physician- or self-reported adherence. The aim of this study was to measure adherence in public hospital outpatients over a 3-year period and to examine factors associated with nonadherence. A retrospective study of pharmacy records of patients dispensed antiviral therapy for hepatitis B from four major hospitals in Melbourne between 2010 and 2013. Hospital record numbers were linked with and de-identified demographic information including age, sex, Indigenous status, country of birth, interpreter requirement, spoken language and postcode of residence. The medication possession ratio was the outcome measure with poor adherence defined <.90. Univariate logistic regression and multivariate logistic regression were performed to examine associations with nonadherence. Records of 1026 patients were included in the analysis. Twenty per cent of all participants met the definition of poor adherence. Significant factors affecting adherence included age <35 years (P=.002), hospital site and treatment by multiple doctors within shorter time periods. This is the largest study examining detailed factors associated with adherence to hepatitis B treatment. Understanding poor adherence in clinical settings, and the factors associated with lower adherence, is important to inform efforts towards promoting treatment adherence for hepatitis B.

Impact of viral hepatitis aetiology on survival outcomes in hepatocellular carcinoma: A large multicentre cohort study.

While HBV and HCV are risk factors for HCC, uncertainty exists as to whether these viral infections have prognostic significance in HCC. Thus, we compared the overall survival of patients with HBV, HCV and nonviral HCC, and evaluated whether the presence of HBV and HCV predicts patient outcomes. We conducted a multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour characteristics and patient outcomes were obtained from hospital databases, computer records and the Victorian Death Registry. Survival outcomes were compared between HBV, HCV and nonviral hepatitis cases and predictors of survival determined using Cox proportional hazards regression. There were 1436 new HCC cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV 30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On multivariate analysis, independent risk factors for survival included HCC aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and serum creatinine and albumin. After adjusting for these and method of detection, HBV remained an independent predictor of improved overall survival when compared to both nonviral (HR 0.60%, 95% CI 0.35-0.98; P=.03) and HCV-related HCC (HR 0.51%, 95% CI 0.30-0.85; P=.01). In this large multicentre study, HBV is independently associated with improved overall survival compared with HCV and nonviral-related HCC. Further studies are needed to determine the underlying factor(s) responsible.

Lower treatment targets for gestational diabetes: is lower really better?

Proposed lower diagnostic thresholds and lower treatment targets for gestational diabetes have been controversial internationally. Intervention trials for the recently revised lower Australian treatment targets are currently lacking. While there may be benefits, lowering treatment targets may cause a number of harms including increased risk of hypoglycaemia in pregnant women, greater medicolegal risk for health practitioners, and heavier economic costs for the health system. Regional and remote care providers in particular will have greater costs, and may be overwhelmed in attempts to implement new treatment targets. An excessively glucose-centric focus may divert attention and resources from identifying and addressing other important and growing contributors to adverse pregnancy outcomes, such as obesity. Important groups such as Aboriginal and Torres Strait Islander Australians may not gain overall benefit from lowering treatment targets for gestational diabetes because of current low birthweights and the effect of social costs. It has not yet been established whether implementing lower treatment targets for gestational diabetes will create more benefit than harm. Implementation at this stage is premature.

Safer hours for doctors and improved safety for patients.

An increasing weight of evidence is demonstrating that sleep deprivation and circadian rhythm disruption in doctors are associated with human error and harm to both patients and doctors. The increasing junior doctor workforce entering the hospital system in Australia provides a rare opportunity for workplace and roster reforms. There are cultural, educational and industrial challenges to reforming working hours. Any changes should be evidence-based and monitored to ensure that training for junior doctors and patient care are not compromised.

Paraduodenal pancreatitis.

Paraduodenal pancreatitis is a distinct clinicopathological entity involving the duodenum and the pancreatic tissue in the vicinity of the minor papilla. Most afflicted patients are young alcoholic males who present clinically with upper abdominal pain, weight loss, nausea, and vomiting. Pancreatic tissue elements in the duodenal wall and impedance to exocrine pancreatic secretions at the minor papilla are key factors in the pathogenesis of this condition. On imaging, the condition may manifest as a solid fibrotic mass around the minor papilla or as cysts in the duodenum and the pancreaticoduodenal groove. Duodenal stenosis, biliary strictures, chronic calcifying pancreatitis, and pancreatic ductal dilatation are also often observed.

Rotator Cuff Tears: Correlation Between Clinical Examination, Magnetic Resonance Imaging and Arthroscopy.

Background Arthroscopy in diagnosing a rotator cuff injury has surgical and anaesthesia-related risks. Magnetic resonance imaging (MRI), a non-invasive procedure, is expensive, and lacks dynamic components making it less favourable. Clinical examination narrows the diagnosis, but lacks diagnostic accuracy due to overlap of clinical signs and symptoms. We aimed to determine the diagnostic accuracy of clinical examination and MRI in rotator cuff tears by correlating it with arthroscopy. Methods This prospective, cross-sectional validation study included patients (N=28) with shoulder pain with clinical characteristics suggestive of rotator cuff tears. Clinical diagnoses and MRI were done preoperatively, following which each patient underwent arthroscopic surgery. Shoulder arthroscopy findings were correlated with those of clinical examination and MRI. Results The mean age of patients was 50.21±9.66 years, with 60.71% being males. Clinical examination was 100% sensitive and 73.8% specific for detecting rotator cuff tears. MRI was 92.85% sensitive and 98.8% specific in detecting rotator cuff tears. Shoulder MRI demonstrated a higher agreement with arthroscopy than clinical results for subscapularis, supraspinatus, infraspinatus, teres, and biceps tendon appearance. Conclusion MRI results in identifying rotator cuff pathologies are comparable with arthroscopy. Clinical examination findings are variable due to an examiner's bias and therefore its diagnostic scope is limited. However, clinical examination with MRI together might accurately identify the rotator cuff injury.

Emerging Therapies in Management of Cholangiocarcinoma.

Cholangiocarcinoma is a heterogeneous group of biliary tract cancers that has a poor prognosis and globally increasing incidence and mortality. While surgical resection remains the only curative option for the treatment of cholangiocarcinoma, the majority of cancers are unresectable at the time of diagnosis. Additionally, the prognosis of cholangiocarcinoma remains poor even with the current first-line systemic therapy regimens, highlighting the difficulty of treating locally advanced, metastatic, or unresectable cholangiocarcinoma. Through recent developments, targetable oncogenic driver mutations have been identified in the pathogenesis of cholangiocarcinoma, leading to the utilization of molecular targeted therapeutics. In this review, we comprehensively discuss the latest molecular therapeutics for the treatment of cholangiocarcinoma, including emerging immunotherapies, highlighting promising developments and strategies.

Generation of substrate-free III-V nanodisks from user-defined multilayer nanopillar arrays for integration on Si.

High material quality InP-based multilayer nanopillar (NP) arrays are fabricated using a combination of self-assembly of silica particles for mask generation and dry etching. In particular, the NP arrays are made from user-defined epitaxial multilayer stacks with specific materials and layer thicknesses. An additional degree of flexibility in the structures is obtained by changing the lateral diameters of the NP multilayer stacks. Pre-defined NP arrays made from InGaAsP/InP and InGaAs/InP NPs are then used to generate substrate-free nanodisks of a chosen material from the stack by selective etching. A soft-stamping method is demonstrated to transfer the generated nanodisks with arbitrary densities onto Si. The transferred nanodisks retain their smooth surface morphologies and their designed geometrical dimensions. Both InP and InGaAsP nanodisks display excellent photoluminescence properties, with line-widths comparable to unprocessed reference epitaxial layers of similar composition. The multilayer NP arrays are potentially attractive for broad-band absorption in third-generation solar cells. The high optical quality, substrate-free InP and InGaAsP nanodisks on Si offer a new path to explore alternative ways to integrate III-V on Si by bonding nanodisks to Si. The method also has the advantage of re-usable III-V substrates for subsequent layer growth.

Emerging inequality and potential unconstitutionality - the case for reform of the intern priority system.

Internship selection is becoming more competitive due to substantial increases in numbers of medical graduates. Australian states operate a "priority system" for medical internship selection which discriminates against Australian interstate applicants. This discrimination arguably infringes section 117 of the Australian Constitution, which seeks to ensure that all citizens are treated equally and promotes national unity. The priority system should be reformed. It is inequitable and inconsistent with other aspects of medical training and regulation.

Epidemiology of hepatitis B-associated hepatocellular carcinoma in Victoria.

BACKGROUND: Chronic hepatitis B (HBV) and cirrhosis are major risk factors for hepatocellular carcinoma (HCC). The proportion and characteristics of cases with cirrhosis are not well documented. AIM: Our aim was to compare demographic, viral and tumour characteristics of HBV-associated HCC in an Australian cohort, in patients with and without cirrhosis. METHODS: Existing HCC databases at six Melbourne teaching hospitals were reviewed for cases associated with HBV. Patient demographics, HBV viral characteristics, presence of cirrhosis, serum alpha-fetoprotein and tumour size were assessed. Mode of diagnosis was recorded through surveillance or symptoms, and treatment was either palliative, percutaneous or surgical. RESULTS: We identified 197 cases of HBV-related HCC. The mean age was 57.9 ± 12.9 years; 83% were male, and 55.3% and 35.3% were of Asian and European descent respectively. Of 168 patient with available data, 146 (87%) had cirrhosis versus 22 (13%) without. Patients with cirrhosis tended to be older (median 60 vs 52 years, P = 0.078). Asian patients were more likely to have HCC without cirrhosis than Europeans (17% vs 6%, P = 0.04). There were no other differences identified between cirrhotic and non-cirrhotic patients. Thirty-four per cent of patients had tumours greater than 5 cm at diagnosis, and 47% were diagnosed after presenting with symptoms. Twelve patients with HBV-HCC were outside current screening guidelines. CONCLUSION: Most patients in Melbourne with HBV-associated HCC have cirrhosis. HCC characteristics in non-cirrhotic and cirrhotic patients were similar. The large number of patients detected through symptoms and with large tumours reinforces the need for vigilance in screening.

Citrus Essential Oils: A Rational View on its Chemical Profiles, Mode of Action of Anticancer Effects/Antiproliferative Activity on Various Human Cancer Cell Lines.

Cancer is a complex genetic disorder due to uncontrolled growth of abnormal cells in the body, causes damage to the immune system, and may lead to life-threatening situations. Common approaches to cancer treatment includes chemotherapy, hormone therapy, immunotherapy, radiation therapy etc. Development of novel and natural chemotherapeutic agents is highly demanded because of the side effects of synthetic drugs. Essential oils from aromatic plants exhibited antioxidant, antimutagenic, antiproliferative and immunomodulating activities. Mechanism of multidrug resistance and synergistic action of these volatile constituents are responsible for their chemopreventive properties. These oils primarily comprising of terpenoid constituents and are characterized by volatility, aroma, low molecular weight etc. The chemical composition of these oils varies depending on the environmental condition, species, plant part and geographical region. Literature analysis revealed that plant essential oils play an important role in cancer prevention and treatment. Cancer patients exposed to essential oils via inhaler devices were found to have less anxiety, stress, and nausea and insomnia. Nowadays, there is an increasing demand for investigating the biological properties of aromatic plants due to their availability, chemical diversity, and low toxicity. In aromatherapy, Citrus essential oils repress cancer related pain and enhance immune system. Current review summarizes existing variability of the chemical composition of Citrus essential oils and its molecular level anticancer mechanism against various human cancer cell lines. Citrus essential oils enhance cytotoxicity, antiproliferative and apoptotic behavior of cancer cell lines. Since essential oils exhibiting significant anticancer potential is worthy of further investigation for cancer chemoprevention. The findings of various research activities can be exploited by cancer researchers world wide for the development of anticancer drugs which can relieve cancer symptoms.

Troponin I Elevation after Elective Percutaneous Coronary Interventions: Prevalence and Risk Factors.

Percutaneous coronary intervention (PCI) is one of the most important modalities of treatment for coronary artery disease (CAD). Minor extents of injury to the myocardium have been observed even after successful PCI. This peri-procedural injury might therefore reduce some of the beneficial effects of coronary revascularization. The objective of this hospital based comparative observational study was to determine the prevalence of post procedural Cardiac troponin I (cTnI) elevation after elective PCI and also to find out the relation with risk factors such as age, sex, body mass index (BMI), smoking, anemia, diabetes mellitus, hypertension, dyslipidemia, family history, left ventricular dysfunction, renal insufficiency, type of stent, number of stent and length of stent. This was a hospital based comparative observational study carried out in the Department of Cardiology, Chattogram Medical College Hospital (CMCH), Chattogram, Bangladesh from July 2018 to June 2019. A total of 50 patients who underwent elective PCI were included as sampled by purposive sampling method. Serum cTnI was measured by FIA8000 quantitative immunoassay analyzer with an analytical measurement before and at 24 hours of PCI. Value >1.0ng/ml was considered elevated. Univariate and multivariate analysis were applied to assess predictors for the occurrence of post-procedural elevation of cTnI. The mean±SD age of the study population was 54.96±9.1 years (range 35-74 years) and 34(68.0%) patients were male. Regarding cardiovascular risk factors, 17(34.0%) patients had diabetes mellitus, 27(54.0%) had dyslipidemia, 30(60.0%) had hypertension, 32(64.0%) were current or ex-smokers and 20(40.0%) had a family history of CAD. Eighteen patients (36.0%) had post-procedural cTnI elevation but only 8(16.0%) had significant (>1.0ng/ml) elevation. Change of cTnI before and at 24 hours of PCI was not significant (p=0.057). Cardiac Troponin I increase was related to age, pre-procedural serum creatinine and multi-vessel stenting. Minor elevation of cTnI was common following elective PCI and associated with few risk factors such as elderly patient (more than 50 years), raised serum creatinine and multi-vessel stenting. So, early detection of these risk factors, as well as effective intervention may help to prevent injury to cardiac tissue hence stop elevation of cardiac TnI following elective PCI.

Comparison of Risk Factors and Angiographic Profile between Younger and Older Patients with Acute Myocardial Infarction.

Acute myocardial infarction (AMI) in younger adults (≤40 years) is being increasingly encountered in recent years among the South Asian population. Data regarding the presentation, risk factors and angiographic findings on this important subset of patients is lacking in our country. The aim of this study was to compare the risk factors and pattern of Coronary artery involvement in younger patients presenting with AMI with that of the older age group. This was a cross-sectional observational study conducted during the period from October 2018 to June 2019. Seventy consecutive AMI patients age ≤40 years and another 70 consecutive AMI patients age >40 years undergoing Coronary Angiogram (CAG) were included in the study. After taking informed written consent; demographic, anthropometric, risk factors, CAG findings were recorded in a pre-designed case record form. The severity of Coronary Artery Disease (CAD) was calculated by using Gensini score. The mean age of the younger and older patient groups was 36.89±4.4 years and 57.00±8.4 years respectively. Among the risk factors, smoking (67.1% versus 45.7%, p=0.017), positive family history CAD (38.6% versus 22.9%, p=0.040) and obesity (34.3% versus 20.0%, p= 0.05) were more common in younger group. Whereas, Hypertension (41.4% versus 72.9%, p=0.010) and DM (28.6% versus 50.0%, p=0.024) were more common in older patients. Younger patients mainly presented with STEMI (60.0% versus 48.6%) and predominantly had single vessel disease (42.9%), whereas older patients readily presented with NSTEMI (51.4%) and had a higher incidence of double vessel disease (32.9%) and triple vessel disease (30.0%). The Median Gensini score was significantly higher among the older patients than in the younger age group. Patients in younger age group showed a different pattern of risk factors and coronary artery involvement in comparison to the older age group. Thus, offering younger individuals to make them aware of these risk factors and their early detection, as well as an effective intervention may help to prevent AMI in younger people.

Silver nanoparticles green synthesized with leaf extract of disease-resistant amaranthus genotypes effectively suppress leaf blight (Rhizoctonia solani Kühn) disease in a susceptible red amaranthus cultivar.

Silver nanoparticles (AgNPs) were green synthesized using leaf extract of the leaf blight disease (Rhizoctonia solani) susceptible red amaranthus (Amaranthus tricolor L.) and the disease-resistant green (A. dubius) and the wild amaranthus (A. viridis) genotypes, physically characterized, and assessed for their anti-fungal effects against R. solani. The green synthesized nanostructures showed an absorption maximum typical of silver nanoparticles in spectroscopy, and face-centered cubic structures in X-ray diffraction. Field Emission Scanning Electron Microscopic analysis and High-Resolution Transmission Electron Microscopy revealed the size range to be 35-45 nm for all the samples. In vitro mycelial growth inhibition of the pathogen occurred with 500 and 750 ppm concentrations of the nanoparticles in a poisoned-food assay. Further, detached leaves of red amaranthus variety were sprayed with the nanoparticles, and then challenged with the pathogen. There was significant difference in lesion development on leaves sprayed with Ad-AgNPs and Av-AgNPs compared to those treated with At-AgNPs. In the in vivo assay, challenging with the pathogen after spraying the foliage of the leaf blight susceptible red amaranthus variety with Ad-AgNPs at 750 ppm concentration recorded the lowest disease index (7.40) followed by that received Av-AgNPs spray at the same concentration (17.69), five days after inoculation. At-AgNPs treated plants had a disease index of 49.38. Our findings suggest that application of AgNPs green synthesized with leaf extract of disease-resistant genotypes of amaranthus effectively suppressed leaf blight disease incidence in a susceptible amaranthus genotype. To our knowledge, this is the first report on the improved plant pathogen-suppressive activity of any metal nanoparticle when biogenically synthesized using extracts from a disease-resistant plant genotype.

Epidemiology and outcomes of primary sclerosing cholangitis: an Australian multicentre retrospective cohort study.

BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

Conflict of interest guidelines for clinical guidelines.

• Clinical guidelines are being increasingly produced to improve quality of care, but are vulnerable to bias. • Only 15% of guidelines on the National Health and Medical Research Council portal from the most prolific developers have published conflict of interest statements, and fewer detail the processes used to manage conflicts. • Comprehensive disclosure of conflicts is needed to safeguard the integrity of clinical guidelines and the medical profession. • Peak bodies and clinicians should seek to promote an improvement to current poor practice.

Stable enhancement of near-band-edge emission of ZnO nanowires by hydrogen incorporation.

We report on the photoluminescence properties of ZnO nanowires treated with a mild Ar plasma. The nanowires exhibited stable and strong enhancement of the near-band-edge emission and quenching of the deep level emission. The low temperature PL revealed a strong hydrogen donor-bound-exciton line in the plasma-treated samples indicating unintentional incorporation of hydrogen during the plasma treatment. To confirm the results, hydrogen was implanted into the ZnO nanowires with a low ion energy of 600 eV and different fluences. The observed result can be related to the passivation of deep centers by hydrogen. The absolute photoluminescence intensity measured by an integrating sphere showed stable and strong UV emission from the treated samples even after several weeks.