Epidemiology and Clonal Spread Evidence of Carbapenem-Resistant Organisms in the Center of Care and Protection of Orphaned Children, Vietnam

Objective: To determine the prevalence of colonization and transmission of carbapenem-resistant Gram-negative organisms in order to develop of an effective infection prevention program. Design: Cross-sectional study with carbapenem-resistant organisms (CRO) colonization detection from the fecal specimens of 20 Health Care Workers (HCWs) and 67 residents and 175 random environment specimens from September 2022 to September 2023. Setting: A Care and Protection Centre of Orphaned Children in South of HCM City. Participants: It included 20 HCWs, 67 residents, and 175 randomly collected environmental specimens. Method: Rectal and environmental swabs were collected from 20 HCWs, 67 residents (most of them were children), and 175 environmental specimens. MELAB Chromogenic CARBA agar plates, Card NID, and NMIC-500 CPO of the BD Phoenix TM Automated Microbiology System and whole genome sequencing (WGS) were the tests to screen, confirm CROs, respectively and determine CRO colonization and transmission between HCWs, residents, and the environment. Result: We detected 36 CRO isolates, including 6, 11 and 19 CROs found in 6 HCWs, 10 residents and 19 environments. The prevalence of detectable CRO was 30% (6/20) in HCWs, 14.92% (10/67) in residents, and 10.86% (19/175) in environmental swabs in our study. WGS demonstrated CRO colonization and transmission with the clonal spread of E. coli and A. nosocomialis, among HCWs and residents (children). Conclusion: Significant CRO colonization and transmission was evident in HCWs, residents, and the center environment. Cleaning and disinfection of the environment and performing regular hand hygiene are priorities to reduce the risk of CRO colonization and transmission.

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study

BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)metformin.During a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related mortality.Statin,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Imaging volumes during COVID-19:A Victorian health service experience

BACKGROUND The World Health Organisation declared the coronavirus disease 2019(COVID-19)a pandemic on March 11,2020.While globally,the relative caseload has been high,Australia’s has been relatively low.During the pandemic,radiology services have seen significant changes in workflow across modalities and a reduction in imaging volumes.AIM To investigate differences in modality imaging volumes during the COVID-19 pandemic across a large Victorian public health network.METHODS A retrospective analysis from January 2019 to December 2020 compared imaging volumes across two periods corresponding to the pandemic’s first and second waves.Weekly volumes across patient class,modality and mobile imaging were summed for periods:wave 1(weeks 11 to 16 for 2019;weeks 63 to 68 for 2020)and wave 2(weeks 28 to 43 for 2019;weeks 80 to 95 for 2020).Microsoft Power Business Intelligence linked to the radiology information system was used to mine all completed examinations.RESULTS Summed weekly data during the pandemic’s first wave showed the greatest decrease of 29.8%in adult outpatient imaging volumes and 46.3%in paediatric emergency department imaging volumes.Adult nuclear medicine demonstrated the greatest decrease of 37.1%for the same period.Paediatric nuclear medicine showed the greatest decrease of 47.8%,with angiography increasing by 50%.The pandemic’s second wave demonstrated the greatest decrease of 23.5%in adult outpatient imaging volumes,with an increase of 18.2%in inpatient imaging volumes.The greatest decrease was 28.5%in paediatric emergency department imaging volumes.Nuclear medicine showed the greatest decrease of 37.1%for the same period.Paediatric nuclear medicine showed the greatest decrease of 36.7%.Mobile imaging utilisation increased between 57.8%and 135.1%during the first and second waves.A strong correlation was observed between mobile and nonmobile imaging in the emergency setting(Spearman’s correlation coefficient=-0.743,P=0.000).No correlation was observed in the inpatient setting(Spearman’s correlation coefficient=-0.059,P=0.554).CONCLUSION Nuclear medicine was most impacted,while computed tomography and angiography were the least affected by the pandemic.The impact was less during the pandemic’s second wave.Mobile imaging shows continuous growth during both waves.

Acute-on-chronic liver failure: Controversies and consensus

Acute-on-chronic liver failure(ACLF)is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease.Consequences include high short-term morbidity,mortality,and healthcare resource utilisation.ACLF encompasses a dysregulated,systemic inflammatory response,which can precipitate extra hepatic organ failures.Common precipitants include infection,alcoholic hepatitis,and reactivation of viral hepatitis although frequently no cause is identified.Heterogenous definitions,diagnostic criteria,and treatment guidelines,have been proposed by international hepatology societies.This can result in delayed or missed diagnoses of ACLF,significant variability in clinical management,and under-estimation of disease burden.Liver transplantation may be considered but the mainstay of treatment is organ support,often in the intensive care unit.This review will provide clarity around where are the controversies and consensus in ACLF including:Epidemiology and resource utilisation,key clinical and diagnostic features,strategies for management,and research gaps.

Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine:Three case reports

BACKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment barriers.DAAs co-prescribed with several firstgeneration anti-epileptic drugs(AEDs)are contraindicated due to drug-drug interactions.A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir,glecaprevir and pibrentasvir due to potent cytochrome P450(CYP)3A4 induction.Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir’s area under curve to infinite time.Sofosbuvirvelpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently,virological treatment failure.This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible,impractical or unacceptable.However,the properties of current generation DAA therapies,including high-potency non-structural protein 5A inhibitory effect,may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction.CASE SUMMARY We present a case series of three patients with non-cirrhotic,treatment-naïve,genotype 1a,1b,and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir,while co-prescribed carbamazepine for seizure disorders.Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants.DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration,and taken with meals to improve absorption.Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes.CONCLUSION DAA therapies,including glecaprevir-pibrentasvir,warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine,particularly if AED substitution is not feasible.

Abnormal liver function tests associated with severe rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided.

Sex steroids and glucose metabolism

Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus （T2DM） and also predict the onset of these adverse metabolic states. Body composition （body mass index, waist circumference） is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter＇s syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/ glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

cytoplasmic domain of tissue factor promotes liver fibrosis in mice

To evaluate the role of tissue factor (TF) and protease activated receptor (PAR)-2 in liver fibrosis. METHODSUsing CCl4 administration for eight weeks, we induced hepatic fibrosis in wild-type C57BL/6 mice and in mice with deletion of the cytoplasmic signalling domain of TF (TF§CT/§CT), deletion of PAR-2 (PAR-2-/-) and combined deletion of TF signalling domain and PAR-2 (TF§CT/§CT/PAR-2-/-). Hepatic fibrosis area was assessed by quantitative imaging of picrosirius red staining. Hepatic collagen content was assessed by hydroxyproline levels. Hepatic stellate cells (αSMA positive) and hepatic macrophages (CD68 positive) were identified by immunohistochemistry. Hepatic gene expression was determined by PCR and liver TGFβ1 content by ELISA. RESULTSCCl4 treated mice with deletion of the PAR-2 gene (PAR-2-/-) and the cytoplasmic domain of TF (TF§CT/§CT) developed significantly less hepatic fibrosis, characterised by reduced liver fibrosis area and hydroxyproline content, compared to control wildtype mice treated with CCl4. The observed reduction in histological fibrosis was accompanied by a significant decrease in the hepatic content of TGFβ, the prototypic fibrogenic cytokine, as well as fewer activated hepatic stellate cells and hepatic macrophages. Deletion of the TF cytoplasmic signalling domain reduced hepatic fibrosis to levels similar to those observed in mice lacking PAR-2 signalling but combined deletion provided no added protection against fibrosis indicating a lack of mutual modulating effects that have been observed in other contexts such as angiogenic responses. CONCLUSIONTissue factor cytoplasmic domain is involved in TF-PAR-2 signalling initiating hepatic fibrosis and is a potential therapeutic target, as its deletion would not impact coagulation.

Clinical characteristics and outcomes of octogenarians presenting with ST elevation myocardial infarction in the Australian population

AIM To investigate the characteristics and outcomes of octogenarians who presented with ST-elevation myocardial infarction(STEMI) compared to non-octogenarians and to investigate the outcomes of octogenarians that received primary percutaneous coronary intervention(PCI) compared to those managed conservatively.METHODS We performed a single center retrospective case controlled study. All octogenarians who presented with STEMI to a tertiary referring hospital between 2007 and 2012 were included. The subsequent non-octogenarian patient who presented with a STEMI following the octogenarian patient was assigned to the control group in a 1:1 manner. The outcomes measured were peri-procedural cardiac arrest, death on table, cerebrovascular accidents(CVA), in-hospital and 30-d mortality. RESULTS A total of 146 patients were analyzed. The octogenarian group had a higher percentage of females, higher overall comorbidities, higher Charlson Comorbidity Index score, worse renal function and were more likely to require residential care and home help. The octogenarian group were also less likely to have PCI attempted and had a longer symptom onset to PCItime. Mortality rate was high amongst octogenarians who presented with STEMI. However, those managed conservatively had a higher in-hospital and 30-d mortality rate CONCLUSION Octogenarians who presented with STEMI that were managed conservatively had a higher mortality rate compared to those who had primary PCI. Therefore,we propose that revascularization may be beneficial to patients in this age group.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care

BACKGROUND Hepatic encephalopathy(HE)is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50%of cirrhotic patients.Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis.AIM To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care.METHODS All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over46-mo(2012–2016)were identified via pharmacy dispensing records.Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded.Medical records were reviewed to determine baseline characteristics and survival.The Kaplan-Meier method was used to calculate survival probability.Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis.The primary outcome was 12-mo mortality following commencement of Rifaximin.RESULTS188 patients were included.Median age was 57 years(IQR 50-65),71%were male and median model for end stage liver disease and Child Pugh scores were 25(IQR 18-31)and 11(IQR 9-12)respectively.The most common causes of cirrhosis were alcohol(62%),hepatitis C(31%)and non-alcoholic fatty liver disease(20%).A precipitating cause for HE was found in 92%patients with infection(43%),GI bleeding(16%),medication non-compliance(15%)and electrolyte imbalance(14%)the most common.During a mean follow up period of 12±13 mo 107(57%)patients died and 32(17%)received orthotopic liver transplantation.Themost common causes of death were decompensated chronic liver disease(57%)and sepsis(19%).The probability of survival was 44%and 35%at 12-and 24-mo respectively.At multivariate analysis a model for end stage liver disease>15 and international normalised ratio reached statistical significance in predicting mortality.CONCLUSION Despite advances made in the management of HE patients continue to have poor survival.Thus,in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

Exercise attenuates bone mineral density loss during diet-induced weight loss in adults with overweight and obesity:A systematic review and meta-analysis

Background:Weight-loss-induced fat loss improves cardiometabolic health in individuals with overweight and obesity;however,weight loss can also result in bone loss and increased fracture risk.Weight-loss-induced bone loss may be attenuated with exercise.Our aim was to compare changes in bone mineral density(BMD)in adults with overweight and obesity who undertook diet-induced weight loss alone or in combination with exercise.Methods:We included randomized controlled trials(RCTs)in adults with overweight or obesity(aged-18 years;body mass index-25 kg/m^(2))that prescribed diet-induced weight loss alone or in combination with supervised exercise,and measured any bone structural parameters.Risk of bias was assessed using the Cochrane Risk of Bias tool.Random-effects meta-analyses determined mean changes and net mean differences(95%confidence intervals(95%CIs))in the percentage of areal BMD(aBMD)change between groups.Results:We included 9 RCTs.Diet-induced weight loss led to significant losses in femoral neck aBMD(mean change:-1.73%(95%CI:-2.39%to-1.07%),p<0.001)and total hip aBMD(-2.19%(95%CI:-3.84%to-0.54%),p=0.009).Femoral neck aBMD losses were significantly greater in the diet-induced weight loss group compared to the exercise plus diet-induced weight loss group(net difference:-0.88%(95%CI:-1.73%to-0.03%));however,there were no differences in aBMD changes at any other skeletal site:total hip(-1.96%(95%CI:-4.59%to 0.68%))and lumbar spine(-0.48%(95%CI:-1.81%to 0.86%)).aBMD changes did not differ significantly according to exercise modality(resistance exercise,aerobic exercise,or a combination of the two)during diet-induced weight loss.Conclusion:Diet-induced weight loss led to greater femoral neck bone loss compared to diet-induced weight loss plus exercise.Bone loss at the total hip and lumbar spine was not attenuated by exercise during diet-induced weight loss.The lack of consistent skeletal benefits may be due to the insufficient duration and/or training intensities of most exercise interventions.Additional RCTs with appropriate,targeted exercise interventions should be conducted.

Acute Cholecystitis: Computed Tomography (CT) versus Ultrasound (US)

Acute cholecystitis is a common surgical emergency and ultrasound (US) is currently considered the first-line diagnostic imaging test. The relative accuracy of computed tomography (CT) in detecting acute cholecystitis has received little attention in the literature. We report a case series of 113 patients who underwent emergency laparoscopic cholecystectomy at a tertiary surgical centre in Australia, between 2014 and 2016, after undergoing both US and CT examination for acute right upper quadrant pain. Both US and CT had a relatively low sensitivity in detecting acute cholecystitis in the patients with histologically proven acute cholecystitis (47% and 45% respectively) but high specificity (84% and 79% respectively). As expected, US was much more sensitive in detecting cholelithiasis (92%) in comparison to CT (55%). With the added advantage of CT in excluding other alternative intra-abdominal pathology in patients presenting with acute right upper quadrant pain, and similar accuracy in detecting acute cholecystitis, the need for ultrasound may be negated in cases where acute cholecystitis has been confirmed on CT. However, it is noted that both US and CT had a significant false negative rate for acute cholecystitis, and if there remains a clinical suspicion despite initial normal imaging, repeat delayed imaging and/or surgical opinion may be warranted.

Associations of accelerometer-determined physical activity and sedentary behavior with sarcopenia and incident falls over 12 months in community-dwelling Swedish older adults

Purpose:This study was aimed to determine associations of accelerometer-determined time and bouts of sedentary behavior,light physical activity(LPA),and moderate-to-vigorous PA(MVPA)with sarcopenia and incident falls over 12 months.Methods:A total of 3334 Swedish 70-year-olds were assessed for sarcopenia,as defined by the revised definition of the European Working Group on Sarcopenia in Older People.Assessments were based on low scores for appendicular lean mass(dual-energy X-ray absorptiometry),hand grip strength,and the Timed Up and Go test.For 7 days after baseline,total time and total number of bouts(≥10 min of continuous activity at a given intensity)of activity performed at sedentary,LPA,and MVPA intensities were assessed by accelerometer.Incident falls were self-reported 6 months and 12 months after baseline.Results:Only 1.8%of participants had probable or confirmed sarcopenia.After multivariable adjustment for other levels of activity,only greater MVPA time was associated with a decreased likelihood of having low appendicular lean mass,low hand grip strength,and slow Timed Up and Go time as defined by the European Working Group on Sarcopenia in Older People criteria(all p<0.05),and only MVPA time was associated with lower likelihood of probable or confirmed sarcopenia(odds ratio=0.80,95%confidence interval:0.71-0.91 h/week).Similar associations were identified for total number of bouts,with no evidence of threshold effects for longer duration of bouts of MVPA.A total of 14%of participants reported-1 fall,but neither total time nor bouts of activity was associated with incident falls(all p>0.05).Conclusion:Higher amounts of accelerometer-determined MVPA are consistently associated with a decreased likelihood of sarcopenia and its components,regardless of the length of bouts or amounts of sedentary behavior.

The utility of coronary computed tomography angiography in elderly patients

Background Coronary computed tomography angiography(CCTA)is often avoided in elderly patients due to a presumption that a high proportion of patients will have heavily calcified plaque limiting an accurate assessment.We sought to assess the image quality,luminal stenosis and utility of CCTA in elderly patients with suspected coronary artery disease(CAD)and stable chest pain.Methods Retrospective analysis of elderly patients(>75 years)who underwent 320-detector row CCTA between 2012–2017 at MonashHeart.The CCTA was analysed for degree maximal coronary stenosis by CAD-RADS classification,image quality by a 5-point Likert score(1-poor,2-adequate,3-good,4-very good,5-excellent)and presence of artefact limiting interpretability.Results 1011 elderly patients(62%females,78.8±3.3 years)were studied.Cardiovascular risk factor prevalence included:hypertension(65%),hyperlipidaemia(48%),diabetes(19%)and smoking(21%).The CCTA was evaluable in 68%of patients which included 52%with non-obstructive CAD(<50%stenosis),48%with obstructive CAD(>50%)stenosis.Mean Likert score was 3.1±0.6 corresponding to good image quality.Of the 323(32%)of patients with a non-interpretable CCTA,80%were due to calcified plaque and 20%due to motion artefact.Male gender(P=0.009),age(P=0.02),excess motion(P<0.01)and diabetes mellitus(P=0.03)were associated with non-interpretable CCTA.Conclusion Although CCTA is a feasible non-invasive tool for assessment of elderly patients with stable chest pain,clinicians should still be cautious about referring elderly patients for CCTA.Patients who are male,diabetic and>78 years of age are significantly less likely to have interpretable scans.

Feasibility and clinical outcomes in nonagenarians undergoing transcatheter aortic valve replacement with the LOTUSTM valve

Surgical aortic valve replacement （AVR） is associated with very high peri-operative risk in the nonagenarian populationflI Patients with severe aortic stenosis treated conservatively have high rates of mortality with poor quality of life and loss of independence. Transcatheter aortic valve replacement （TAVR） has been validated in the high risk elderly population as a viable alternative to surgery with comparable outcomes.

Natural history and outcomes of patients with liver cirrhosis complicated by hepatic hydrothorax

BACKGROUNDHepatic hydrothorax (HH) is an uncommon and difficult-to-manage complicationof cirrhosis with limited treatment options.AIMTo define the clinical outcomes of patients presenting with HH managed withcurrent standards-of-care and to identify factors associated with mortality.METHODSCirrhotic patients with HH presenting to 3 tertiary centres from 2010 to 2018 wereretrospectively identified. HH was defined as pleural effusion in the absence ofcardiopulmonary disease. The primary outcomes were overall and transplant-freesurvival at 12-mo after the index admission. Cox proportional hazards analysiswas used to determine factors associated with the primary outcomes.RESULTSOverall, 84 patients were included (mean age, 58 years) with a mean model forend-stage liver disease score of 29. Management with diuretics alone achievedlong-term resolution of HH in only 12% patients. At least one thoracocentesis wasperformed in 73.8% patients, transjugular intrahepatic portosystemic shuntinsertion in 11.9% patients and 33% patients received liver transplantation within12-mo of index admission. Overall patient survival and transplant-free survival at12 mo were 68% and 41% respectively. At multivariable analysis, current smoking [hazard ratio (HR) = 8.65, 95% confidence interval (CI): 3.43-21.9, P < 0.001) and acute kidneyinjury (AKI) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were associated with a significantly increasedrisk of mortality.CONCLUSIONCirrhotic patients with HH are a challenging population with a poor 12-mo survival despitecurrent treatments. Current smoking and episodes of AKI are potential modifiable factors affectingsurvival. HH is often refractory of diuretic therapy and transplant assessment should beconsidered in all cases.

Hepatocellular carcinoma surveillance and quantile regression for determinants of underutilisation in at-risk Australian patients

BACKGROUND While clinical guidelines recommend hepatocellular carcinoma(HCC)surveillance for at-risk individuals,reported surveillance rates in the United States and Europe remain disappointingly low.AIM To quantify HCC surveillance in an Australian cohort,and assess for factors associated with surveillance underutilisation.METHODS All patients undergoing HCC surveillance liver ultrasounds between January 1,2018 to June 30,2018 at a tertiary hospital in Melbourne,Australia,were followed until July 31,2020,or when surveillance was no longer required.The primary outcome was the percentage of time up-to-date with HCC surveillance(PTUDS).Quantile regression was performed to determine the impact of factors associated with HCC surveillance underutilisation.RESULTS Among 775 at-risk patients followed up for a median of 27.5 months,the median PTUDS was 84.2%(IQR:66.3%-96.3%).85.0%of patients were followed up by specialist gastroenterologists.Amongst those receiving specialist care,quantile regression demonstrated differential associations at various quantile levels of PTUDS for several factors.Older age at the 25th quantile(estimate 0.002 per percent,P=0.03),and cirrhotic status at the 75th quantile(estimate 0.021,P=0.017),were significantly associated with greater percentage of time up-to-date.African ethnicity(estimate-0.089,P=0.048)and a culturally and linguistically diverse(CALD)background(estimate-0.063,P=0.01)were significantly associated with lower PTUDS at the 50th quantile,and again for CALD at the 75th quantile(estimate-0.026,P=0.045).CONCLUSION While median PTUDS in this Australian cohort study was 84.2%,awareness of the impact of specific factors across PTUDS quantiles can aid targeted interventions towards improved HCC surveillance.

Survival outcomes and predictors of mortality,re-bleeding and complications for acute severe variceal bleeding requiring balloon tamponade

BACKGROUND Acute severe variceal bleeding(AVB)refractory to medical and endoscopic therapy is infrequent but associated with high mortality.Historical cohort studies from 1970-1980s no longer represent the current population as balloon tamponade is no longer first-line therapy for variceal bleeding;treatments including vasoactive therapies,intravenous antibiotics,endoscopic variceal band ligation are routinely used,and there is improved access to definitive treatments including transjugular intrahepatic portosystemic shunts.However,only a few studies from the current era exist to describe the practice of balloon tamponade,its outcomes,and predictors with a requirement for further updated information.AIM To describe current management of AVB requiring balloon tamponade and identify the outcomes and predictors of mortality,re-bleeding and complications.METHODS A retrospective multi-centre cohort study of 80 adult patients across two large tertiary health networks from 2008 to 2019 in Australia who underwent balloon tamponade using a Sengstaken-Blakemore tube(SBT)were included for analysis.Patients were identified using coding for balloon tamponade.The primary outcome of this study was all-cause mortality at 6 wk after the index AVB.Secondary outcomes included re-bleeding during hospitalisation and complications of balloon tamponade.Predictors of these outcomes were determined using univariate and multivariate binomial regression.RESULTS The all-cause mortality rates during admission and at 6-,26-and 52 wk were 48.8%,51.2%and 53.8%,respectively.Primary haemostasis was achieved in 91.3%and re-bleeding during hospitalisation occurred in 34.2%.Independent predictors of 6 wk mortality on multivariate analysis included the Model for Endstage Liver disease(MELD)score(OR 1.21,95%CI 1.06-1.41,P=0.006),advanced hepatocellular carcinoma(OR 11.51,95%CI 1.61-82.20,P=0.015)and re-bleeding(OR 13.06,95%CI 3.06-55.71,P<0.001).There were no relevant predictors of re-bleeding but a large proportion in which this occurred did not survive 6 wk(76.0%vs 24%).Although mucosal trauma was the most common documented complication after SBT insertion(89.5%),serious complications from SBT insertion were uncommon(6.3%)and included 1 patient who died from oesophageal perforation.CONCLUSION In refractory AVB,balloon tamponade salvage therapy is associated with high rates of primary haemostasis with low rates of serious complications.Re-bleeding and mortality however,remain high.

Clinical outcomes of patients with two small hepatocellular carcinomas

BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or resection.Liver transplantation is often considered for multiple small or single large HCC.Management of two small HCC whether presenting synchronously or sequentially is less clear.AIM To define the outcomes of patients presenting with two small HCC.METHODS Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC≤3 cm between January 2000 and March 2018.Primary outcomes were overall survival(OS)and transplant-free survival(TFS).RESULTS 104 patients were identified(male n=89).Median age was 63 years(interquartile range 58-67.75)and the most common aetiology of liver disease was hepatitis C(40.4%).59(56.7%)had synchronous HCC and 45(43.3%)had sequential.36 patients died(34.6%)and 25 were transplanted(24.0%).1,3 and 5-year OS was 93.0%,66.1% and 62.3% and 5-year post-transplant survival was 95.8%.1,3 and 5-year TFS was 82.1%,45.85% and 37.8%.When synchronous and sequential groups were compared,OS(1,3 and 5 year synchronous 91.3%,63.8%,61.1%,sequential 95.3%,69.5%,64.6%,P=0.41)was similar but TFS was higher in the sequential group(1,3 and 5 year synchronous 68.5%,37.3% and 29.7%,sequential 93.2%,56.6%,48.5%,P=0.02)though this difference did not remain during multivariate analysis.CONCLUSION TFS in patients presenting with two HCC≤3 cm is poor regardless of the timing of the second tumor.All patients presenting with two small HCC should be considered for transplantation.

Shunting,optic nerve sheath fenestration and dural venous stenting for medically refractory idiopathic intracranial hypertension:systematic review and meta-analysis

Background:Cerebrospinal fluid(CSF)-diversion procedures have traditionally been the standard of treatment for patients with medically refractive idiopathic intracranial hypertension(IIH).However,dural venous sinus stent(VSS)placement has been described as a safe and effective procedure for the management of medically refractive IIH.We performed a meta-analysis comparing outcomes and complications of CSF-diversion procedures,VSS and optic nerve sheath fenestration(ONSF)for the treatment of medically refractive IIH.Methods:Electronic searches were performed using six databases from 1988 to January 2017.Data was extracted and meta-analysed from the identified studies.Results:From 55 pooled studies,there were 538 CSF-diversion cases,224 dural venous stent placements,and 872 ONSF procedures.Similar improvements were found in terms of postoperative headaches(CSF vs.VSS vs.ONSF:84%vs.78%vs.62%,P=0.223),papilledema(CSF vs.VSS vs.ONSF:71%vs.86%vs.77%,P=0.192),whilst visual acuity changes favored venous stenting(CSF vs.VSS vs.ONSF:55%vs.69%vs.44%,P=0.037).There was a significantly lower rate of subsequent procedures with venous stent placement(CSF vs.VSS vs.ONSF:37%vs.13%vs.18%,P<0.001),but other complication rates were similar(CSF vs.VSS vs.ONSF:13%vs.8%vs.14%,P=0.28).Subgroup analysis of lumbar-peritoneal vs.ventriculoperitoneal shunts found no differences in symptom improvements,complications and subsequent procedure rates.Conclusions:Our findings suggest that dural venous sinus stenting may be a viable alternative to traditional surgical interventions in patients who are refractory to medical treatment.