Brain metastasis in advanced colorectal cancer： results from the South Australian metastatic colorectal cancer (SAmCRC) registry

Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.

Mannose-binding lectin and maladies of the bowel and liver

Mannose-binding lectin (MBL) is a pattern-recognition molecule that binds to characteristic carbohydrate mo-tifs present on the surface of many different pathogens. MBL binding stimulates the immune system via the lectin pathway of complement activation. In certain clinical situations, often characterized by pre-existing immune compromise, MBL deficiency increases the risk of infec-tious and other disease-specific complications. Many of the key pathogenic processes inherent to common gastroenterological diseases, such as infection, immuno-logical damage, and carcinogenesis, have been linked to MBL. This editorial reviews the biology of MBL, outlines key disease associations to document the breadth of influence of MBL, and finally, highlights the relevance of MBL to both gastroenterological health and disease.

Prolonged cholestasis following successful removal of common bile duct stones:Beware patients on estrogen therapy

有在成年人的长期的胆汁郁积的黄疸的各种各样的很好描述的形式，例如自体免疫的胆管炎，导致药的胆管炎和怀孕的肝内胆汁郁积。我们在场胆石在的延长胆汁郁积追随者移动的二个盒子内视镜后退 cholangiopancreatography (ERCP ) 和随后的清楚的胆管造影术。两个病人在表示的时候正在拿口头的雌激素，它随后被撤退。第一个盒子对皮质甾治疗很快作出回应，并且第二个盒子与 ursodeoxycholic 酸有一个慢得多的决定。两个盒子与延长黄疸追随者 ERCP 和 intra-ductal 石头的移动在女病人加亮导致雌激素的胆汁郁积的意义。在口头的雌激素被中止以后，类固醇的一堂短功课需要被考虑。

The impact of intra-operative cell salvage during open nephrectomy

Objective:To assess the impact of intra-operative cell salvage on outcomes in open nephrectomy.Methods:A retrospective cohort study was performed of all patients undergoing open nephrectomy for suspected malignancy from 1 October 2013 to 1 October 2017.Patients were grouped and compared based on whether they received intra-operative cell salvage(ICS).Primary outcomes were allogeneic transfusion rates(ATRs),and if histology confirmed cancer,disease recurrence.Secondary outcomes were complications and transfusion-related cost.Results:Forty patients underwent open nephrectomy for suspected malignancy during the enrolment period.Sixteen patients received ICS while 24 did not(standard group).Compared with the standard group,ICS patients had similar median age(63.5 vs.61.0 years;p=0.83)but fewer females(19%vs.58%;p=0.013).The groups were similar in pre-operative and discharge haemoglobin,Charlson Comorbidity Index,length of hospital stay and proportion with thoracoabdominal surgical approach.The ICS group had a smaller proportion undergoing partial nephrectomy(19%vs.54%;p=0.025)and shorter median follow-up(278 vs.827 days;p=0.0005).Histology was malignant for 14 ICS and 15 standard patients.The ICS group had more frequent
T2 disease(79%vs.27%;p=0.005).There were no positive margins.Both groups had similar ATRs(6%vs.4%;p=0.96),complication rates(19%vs.29%;p=0.46)and recurrence rates(18%vs.7%;p=0.40).Transfusion costs were higher amongst ICS patients(AUD$878.18 vs.$49.65 per patient).Conclusion:ICS appears safe,with low rates of recurrence and complication.Both groups had low ATRs,and therefore cost benefit for ICS was not seen.

Missed opportunities for hepatitis C treatment at a tertiary care hospital in South Australia

BACKGROUND Hepatitis C is a global epidemic and an estimated 230000 Australians were living with chronic hepatitis C in 2016.Through effective public health policy and state commitment,Australia has utilised the advent of direct acting antiviral(DAA)therapy to transform the therapeutic landscape for hepatitis C virus(HCV).However,treatment rates are falling and novel public health approaches are required to maintain momentum for HCV elimination.Contemporary discourse in cascades of care have focused on expanding testing capabilities but less attention has been given to linking previously diagnosed patients back to care.Our simple and focused study rests on the premise that hospital admissions are an excellent opportunity to identify and refer previously diagnosed patients for HCV treatment.AIM To assess whether inpatients with HCV are appropriately referred on for treatment.METHODS We conducted a retrospective single centre cohort study that examined all patients with HCV presenting to The Queen Elizabeth Hospital(QEH)inpatient service between January 1 and December 31,2017.QEH is a tertiary care hospital in South Australia.The main inclusion criteria were patients with active HCV infection who were eligible for DAA therapy.Our study cohort was identified using a comprehensive list of diagnosis based on international classification of diseases-10 AM codes for chronic viral hepatitis.Patients were excluded from the analysis if they had previously received DAA therapy or spontaneously cleared HCV.Patients presenting with decompensated liver cirrhosis or other systemic medical conditions conferring poor short-term prognosis were also excluded from the analysis.The primary outcome of our study was referral of patients for HCV treatment.Secondary outcomes included assessment of factors predicting treatment referral.RESULTS There were 309 inpatients identified with hepatitis C as a principal or additional diagnosis between January 1 and December 31,2017.Of these patients,148 had active HCV infection without prior treatment or spontaneous clearance.Overall,131 patients were deemed eligible for DAA treatment and included in the main analysis.Mean patient age was 47.75±1.08 years,and 69%of the cohort were male and 13%identified as Aboriginal or Torres Strait Islander.Liver cirrhosis was a complication of hepatitis C in 7%of the study cohort.Only 10 patients were newly diagnosed with HCV infection during the study period with the remainder having been diagnosed prior to the study.CONCLUSION Under 25%of hepatitis C patients presenting to an Australian tertiary hospital were appropriately referred for treatment.Advanced age,cirrhosis and admission under medical specialties were predictors of treatment referral.

Cognitive Behavior Therapy for Heart Failure Patients with Depression

The purpose of this systematic review was to examine the effectiveness of cognitive behavior therapy (CBT) in minimizing the depressive symptoms and improving quality of life in heart failure (HF) patients with depression. This systematic review was conducted in accordance with the Joanna Briggs Institute methodology for systematic reviews of effectiveness evidence. This review only considered randomized controlled trial, assessing the effectiveness of CBT as a treatment for depression in adults (aged above 18) with HF, compared with usual care, which may include medications. This systematic review includes five RCTs involving 379 HF patients with depression (CBT = 192;Control = 187). Two RCTs compared CBT versus usual care using BDI, and no statistically significant differences were observed in reduction of depression after three months of the intervention (MD ?0.92, 95% CI ?1.89 to ?0.05) (p = 0.06). However, a significant difference of depression level was identified between CBT and control groups in a meta-analysis of two RCTs after 6-months of intervention measured by Hamilton Depression Scale (HAM-D) (MD ?3.34, 95% CI ?5.00 to ?1.68) (p = 0.0001) with moderate heterogeneity (I2 = 43%). Quality of life was assessed at three months between intervening groups undergoing CBT and the control group with usual care in two RCTs. A statistically significant improvement was observed in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) in the CBT group compared with usual care (MD ?9.44, 95% CI ?13.02 to ?5.87) (p < 0.0001). The key finding of this review is that CBT is likely to be helpful in improving the depressive symptoms and quality of life in HF patients with depression. Moreover, long-term continued CBT sessions may help in minimizing the depression level and improving the QoL.

New Developments in Anti-Anginal Therapy: Roles of Ivabradine, Allopurinol and of Agents Modifying Myocardial Metabolism

Over the last 20 years, it has emerged that, while surgical revascularisation of extensive ischaemic heart disease may have prognostic advantages, the main issues considered regarding individual management are usually those of symptomatic improvement only. The major impetus towards invasive intervention is therefore failure of prophylactic anti-anginal therapy. On the other hand, many patients, especially the elderly, now present the clinical problem of ongoing angina without residual invasive options. There is an ongoing need for more effective anti-anginal therapies. Of the currently available major classes of prophylactic anti-anginal agents, neither nitrates, β-blockers nor calcium antagonists generally produce marked improvements in exercise duration. Three areas of new therapeutic development in anti-anginal therapy are worthy of note. These involve the sinus node inhibitor ivabradine, high dose allopurinol (xanthine oxidase inhibitor) and a new class of “metabolic modulators” represented by perhexiline, trimetazidine and probably ranolazine. The current review addresses the therapeutic potential of these agents. Notably, all of these “new” drugs are potentially suitable for management of angina in the setting of impaired left ventricular systolic function, and they may also be utilized in patients with angina independent of the presence of coronary disease (for example in hypertrophic cardiomyopathy). The current evidence for efficacy and potential future development in this area are reviewed.

Quality of colonoscopy performed by medical or surgical specialists and trainees in five Australian hospitals

BACKGROUND Ensuring colonoscopy procedure quality is vital to the success of screening and surveillance programmes for bowel cancer in Australia. However, the data on the performance of quality metrics, through adequate adenoma detection, bowel preparation, and procedure completion rates, in the Australian public sector is limited. Understanding these can inform quality improvement to further strengthen our capacity for prevention and early detection of colorectal cancer.AIM To determine the quality of colonoscopy in Australian teaching hospitals and their association with proceduralist specialty, trainee involvement, and location.METHODS We retrospectively evaluated 2443 consecutive colonoscopy procedure reports from 1 January to 1 April, 2018 from five public teaching tertiary hospitals in Australia(median 60 years old, 49% male). Data for bowel preparation quality,procedure completion rates, and detection rates of clinically significant adenomas, conventional adenomas, and serrated lesions was collected and compared to national criteria for quality in colonoscopy. Participating hospital, proceduralist specialty, and trainee involvement indicators were used for stratification. Data was analysed using Chi-squared tests of independence, MannWhitney U, One-way ANOVA, and multivariate binary logistic regression.RESULTS Fifty-two point two percent(n = 1276) and 43.3%(n = 1057) were performed by medical and surgical proceduralists respectively, whilst 29.8%(n = 728) involved a trainee. Inadequate bowel preparation affected 7.3% of all procedures. The procedure completion rate was 95.1%, which increased to 97.5% after adjustment for bowel preparation quality. The pooled cancer, adenoma, and serrated lesion detection rates for all five hospitals were 3.5%, 40%, and 5.9% respectively. Assessed hospitals varied significantly by patient age(P < 0.001), work-force composition(P < 0.001), adequacy of bowel preparation(P < 0.001), and adenoma detection rate(P < 0.001). Two hospitals(40%) did not meet all national criteria for quality, due to a procedure completion rate of 94.5% or serrated lesion detection rate of 2.6%. Although lower than the other hospitals, the difference was not significant. Compared with surgical specialists, procedures performed by medical specialists involved older patients [65 years(inter-quartile range, IQR 58-73) vs 64 years(IQR 56-71);P = 0.04] and were associated with a higher adenoma detection rate [odds ratio(OR) 1.53;confidence interval: 1.21-1.94;P < 0.001]. Procedures involving trainee proceduralists were not associated with differences in the detection of cancer, adenoma, or serrated lesions, compared with specialists, or according to their medical or surgical background. On multivariate analysis, cancer detection was positively associated with patient age(OR 1.04;P < 0.001) and negatively associated with medical compared to surgical proceduralists(OR 0.54;P = 0.04). Conventional adenoma detection rates were independently associated with increasing patient age(OR 1.04;P < 0.001), positively associated with medical compared to surgical proceduralists(OR 1.41;P = 0.002) and negatively associated with male gender(OR 0.53;P < 0.001).CONCLUSION Significant differences in the quality of colonoscopy in Australia exist, even when national benchmarks are achieved. The role of possible contributing factors, like procedural specialty and patient gender need further evaluation.

Risk stratification for coronary artery disease in multi-ethnic populations:Are there broader considerations for cost efficiency?

Coronary artery disease(CAD) screening and diagnosis are core cardiac specialty services.From symptoms,autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory coronaries artery disease as etiologies.While angina remains a clinical diagnosis,most cases require correlation with a diagnostic modality.At the onset of the evidence building process much research,now factored into guidelines were conducted among population and demographics that were homogenous and often prior to newer technologies being available.Today we see a more diverse multi-ethnic population whose characteristics and risks may not consistently match the populations from which guideline evidence is derived.While it would seem veryunlikely that for the majority,scientific arguments against guidelines would differ,however from a translational perspective,there will be populations who differ and importantly there are cost-efficacy questions,e.g.,the most suitable first-line tests or what parameters equate to an adequate test.This article reviews non-invasive diagnosis of CAD within the context of multi-ethnic patient populations.

Laparoendoscopic Single Site Donor Nephrectomy: The Preliminary Experience

Methods: In our endeavour to give patients visibly scarless surgery we have raised the bar to the next level in laparoscopic donor nephrectomy. We have moved from standard laparoscopy to LESS Laparoendoscopic single site donor nephrectomy. 1997 we introduced laparoscopic donor nephrectomy in Australia. In September 2008 we did our first LESS donor nephrectomy. September 2008 to October 2009, 6 laparoscopic donor nephrectomies were performed using a single port. Two types of devices have been used R-port and SILSTM Port. The device was inserted through an intra umbilical incision using open technique. Surgical technique was similar to the laparoscopic method and standard rigid and roticulator laparoscopic instruments were used. Results: All were completed with no major complications. In 3 an additional 5mm port was added to reduce the dissection time. Average operating time was 4.4 hours, warm ischemia time was an average of 7.16 minutes and post surgery hospital stay was an average of 1.41 days. All grafts functioned immediately after transplantation. Conclusion: Initial experience with this technique is promising. It is too early to draw any conclusions on its benefits to the donor in terms of reduced morbidity. However the donors appreciated the cosmesis. It is yet another learning curve for the transplant surgeon.

端粒酶逆转录酶在结肠癌组织中表达的临床意义

背景与目的:尽管能够在70%～90%的恶性肿瘤细胞中可检测到端粒酶活性,但其活性与恶性肿瘤患者预后的关系仍存在争议。本研究旨在探讨端粒酶逆转录酶(humantelomerasereversetranscriptase,hTERT)在结肠癌组织中表达的临床意义。方法:用定量实时RT-PCR检测59例大肠癌标本的癌组织和癌旁非癌组织hTERT表达。结果:癌组织和癌旁非癌组织hTERT表达与临床病理学特征无相关性。32例DukesA和B期患者中,18例(56%)癌组织hTERT表达低于0.6,14例(44%)表达高于0.6,前者的预后较后者好。20例(62%)癌组织/癌旁非癌组织hTERT表达差异低于0.5,12例(38%)表达差异高于0.5,前者的预后较后者好。27例DukesC和D期患者中,癌组织hTERT表达和癌组织/癌旁非癌组织hTERT表达差异对预测患者的预后无意义。结论:结肠癌组织hTERT表达和癌组织/癌旁非癌组织hTERT表达差异可作为DukesA和B期结肠癌患者预后的指标之一。

Colorectal cancer:Metastases to a single organ

Colorectal cancer(CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site(solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ.

Single-center study comparing computed tomography colonography with conventional colonoscopy

AIM:To compare the results from computed tomography (CT) colonography with conventional colonoscopy in symptomatic patients referred for colonoscopy. METHODS: The study included 227 adult outpatients, mean age 60 years, with appropriate indications for colonoscopy. CT colonography and colonoscopy were performed on the same day in a metropolitan teaching hospital. Colonoscopists were initially blinded to the results of CT colonography but there was segmental unblinding during the procedure. The primary outcome measures were the sensitivity and specificity of CT colonography for the identification of polyps seen at colonoscopy (i.e. analysis by polyp). Secondary outcome measures included an analysis by patient, extracolonic findings at CT colonography, adverse events with both procedures and patient acceptance and preference. RESULTS: Twenty-five patients (11%) were excluded from the analysis because of incomplete colonoscopy or poor bowel preparation that affected either CT colonography, colonoscopy or both procedures. Polyps and masses (usually cancers) were detected at colonoscopy and CT colonography in 35% and 42% of patients, respectively. Of nine patients with a finaldiagnosis of cancer, eight (89%) were identified by CT colonography as masses (5) or polyps (3). For polyps analyzed according to polyp, the overall sensitivity of CT colonography was 50% (95% CI, 39%-61%) but this increased to 71% (95% CI, 52%-85%) for polyps ≥ 6 mm in size. Similarly, specificity for all polyps was 48% (95% CI, 39%-58%) increasing to 67% (95% CI, 56%-76%) for polyps ≥ 6 mm. Adverse events were uncommon but included one colonic perforation at colonoscopy. Patient acceptance was high for both procedures but preference favoured CT colonography. CONCLUSION: Although CT colonography was more sensitive in this study than in some previous studies, the procedure is not yet sensitive enough for widespread application in symptomatic patients.

Late post liver transplant protein losing enteropathy: Rare complication of incisional hernia

Development of oedema and hypoproteinaemia in a liver transplant recipient may be the first signs of graft dysfunction and should prompt a full assessment. We report the novel case of a patient who, years after liver transplantation developed a functional blind loop in an incisional hernia, which manifested as oedema and hypoproteinaemia secondary to protein losing enteropathy. After numerous investigations, the diagnosis was made by flurodeoxyglucose positron emmision tomography (FDG-PET) imaging. Surgical repair of the incisional hernia was followed several months later by resolution of the protein loss, and confirmed at a post operative FDG-PET scan at one year.

Handgrip strength and health outcomes: Umbrella review of systematic reviews with meta-analyses of observational studies

Purpose:The aim of the present study was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies on handgrip strength and health outcomes.Methods:An umbrella review of systematic reviews with meta-analyses of observational studies was conducted.We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values,95%prediction intervals,heterogeneity,small-study effects,and excess significance.We graded the evidence from convincing(Class I)to weak(Class IV).Results:From 504 articles returned in a search of the literature,8 systematic reviews were included in our review,with a total of 11 outcomes.Overall,nine of the 11 of the outcomes reported nominally significant summary results(p<0.05),with 4 associations surviving the application of the more stringent p value(p<106).No outcome presented convincing evidence.Three associations showed Class II evidence(i.e.,highly suggestive):(1)higher handgrip values at baseline were associated with a minor reduction in mortality risk in the general population(n=34 studies;sample size=1,855,817;relative risk=0.72,95%confidence interval(95%CI):0.670.78),(2)cardiovascular death risk in mixed populations(n=15 studies;relative risk=0.84,95%CI:0.780.91),and(3)incidence of disability(n=7 studies;relative risk=0.76,95%CI:0.660.87).Conclusion:The present results show that handgrip strength is a useful indicator for general health status and specifically for early all-cause and cardiovascular mortality,as well as disability.To further inform intervention strategies,future research is now required to fully understand mechanisms linking handgrip strength scores to these health outcomes.

Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab

AIM:To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease.METHODS:We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts:(1) the AGITG MAX trial(Phase Ⅲ randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine,bevacizumab and mitomycin C);(2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer(TRACC) registry(any first-line regimen ± bevacizumab);and(3) two cancer centres in New South Wales,Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre(NSWCC) from January 2005 to Decenber 2012,(any first-line regimen ± bevacizumab).For the AGITG MAX trial capecitabine was compared to the other two arms(capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycin C).In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases.Secondary endpoints included progression-free survival,chemotherapy duration,and overall survival.Time-toevent outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS:Eighty-four MAX,179 TRACC and 69 NSWCC patients had peritoneal disease.There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts.Of the patients without peritoneal disease in the MAX trial,4/300(1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123(0.8%) in the capecitabine alone arm.In the TRACC registry 3/126(2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53(1.9%) in the chemotherapy alone arm.In a further analysis of patients without peritoneal metastases in the TRACC registry,the rate of gastrointestinal perforations was 9/369(2.4%) in the chemotherapy/bevacizumab group and 5/177(2.8%) in the chemotherapy alone group.The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts:MAX 6.9 m vs 4.9 m,HR = 0.64(95%CI:0.42-1.02);P = 0.063;TRACC 9.1 m vs 5.5 m,HR = 0.61(95%CI:0.37-0.86);P = 0.009;NSWCC 8.7 m vs 6.8 m,HR = 0.75(95%CI:0.43-1.32);P = 0.32.Chemotherapy duration was similar across the groups.CONCLUSION:Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.

Pancreatic, periampullary and biliary cancer with liver metastases: Should we consider resection in selected cases?

AIM To analyse the safety and efficacy of curative intent surgery in biliary and pancreatic cancer.METHODS An extensive literature review was performed using MEDLINE, Google Scholar and EMBASE to identify articles regarding hepato-pancreatoduodenectomy or resection of liver metastasis in patients with pancreatic, biliary tract, periampullary and gallbladder cancers.RESULTS A total of 19 studies were identified and reviewed. Major hepatectomy was undertaken in 391 patients. The median overall survival for pancreatic cancer ranged from 5-36 mo and for biliary tract/gallbladder cancer, it was 8-38 mo. The 30 d mortality rate was only 1%-9%. Overall Survival was significantly better for patients, who had good response to neoadjuvant chemotherapy, underwent metachronous liver resection and who had intestinal type tumours.CONCLUSION Resection of liver metastases in pancreatic and biliary cancers may provide survival benefit without compromising safety and quality of life in a very select group of patients. These data may be utilised to formulate selection criteria that may allow future investigation of resection in the era of more effective systemic therapy.

Outcomes of Pringle maneuver in patients undergoing hepatic resection for colorectal liver metastases

To the Editor:The Pringle maneuver(PM)was initially described more than a century ago to control bleeding associated with hepatic trauma and it remains the most common method to block hepatic inflow and minimize blood loss during hepatic resections[1].

Relationship between perioperative anaemia and outcomes in older people with hip fractures: A systematic review and meta-analysis protocol

BACKGROUND Hip fractures are common with increasing age and is associated with decline in mobility. Both the fracture and the surgery can lead to blood loss, resulting in anaemia. However, it is uncertain at which time point haemoglobin is most strongly associated with different clinical outcomes after hip fracture. Our hypothesis is perioperative anaemia (admission, postoperative and discharge) during hip fracture surgery is associated with poor clinical outcomes. AIM To determine the effects of perioperative anaemia during hip fracture surgery on mortality, functional status and other clinical outcomes. METHODS Electronic databases will be searched to identify studies evaluating perioperative anaemia and outcomes of hip fracture surgery. Reference lists of included studies will also be searched to identify additional published studies. Eligibility criteria are as follows: Population: People who underwent hip fracture surgery;Exposure: Perioperative anaemia;Comparison: No anaemia before or after hip fracture surgery;Outcome: Mortality, hospital length of stay, postoperative complications, hospital readmission, change of discharge destination, quality of life and functional status. Risk of bias assessment will be assessed using the Cochrane Collaboration’s tool for randomized controlled trials and the modified version of the Epidemiological Appraisal Instrument for observational studies. Data will be pooled for meta-analysis if deemed appropriate. CONCLUSION This review seeks to clarify outcomes associated with perioperative anaemia at various time-points around hip fracture surgery. These findings will potentially inform evidence-based clinical practice on interventions in those with anaemia.

Volatility in High-Frequency Intensive Care Mortality Time Series: Application of Univariate and Multivariate GARCH Models

Mortality time series display time-varying volatility. The utility of statistical estimators from the financial time-series paradigm, which account for this characteristic, has not been addressed for high-frequency mortality series. Using daily mean-mortality series of an exemplar intensive care unit (ICU) from the Australian and New Zealand Intensive Care Society adult patient database, joint estimation of a mean and conditional variance (volatility) model for a stationary series was undertaken via univariate autoregressive moving average (ARMA, lags (p, q)), GARCH (Generalised Autoregressive Conditional Heteroscedasticity, lags (p, q)). The temporal dynamics of the conditional variance and correlations of multiple provider series, from rural/ regional, metropolitan, tertiary and private ICUs, were estimated utilising multivariate GARCH models. For the stationary first differenced series, an asymmetric power GARCH model (lags (1, 1)) with t distribution (degrees-of- freedom, 11.6) and ARMA (7,0) for the mean-model, was the best-fitting. The four multivariate component series demonstrated varying trend mortality decline and persistent autocorrelation. Within each MGARCH series no model specification dominated. The conditional correlations were surprisingly low (<0.1) between tertiary series and substantial (0.4 - 0.6) between rural-regional and private series. The conditional-variances of both the univariate and multivariate series demonstrated a slow rate of time decline from periods of early volatility and volatility spikes.