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BACKGROUND: Older people with chronic kidney disease (CKD) may be anaemic due to various reasons, and they are vulnerable to various consequences. One of the most important causes of anaemia to be recognised in this population is gastrointestinal loss. The outcome can be improved by early detection, careful investigation, and suitable therapies. There is currently no standardised grading scale or reliable indicators to assist clinicians on handling gastrointestinal workup in elderly CKD patients who are anaemic. METHODS: A cross-sectional study of 171 people aged 60 and over who had CKD (stages 3-5), including those on Renal Replacement Therapy (RRT) and anaemia. Using oesophagogastroduodenoscopy, colonoscopy, and double balloon endoscopy, we analysed the endoscopic findings and calculated the prevalence of anaemia secondary to gastrointestinal disease. Haemoglobin, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), mean cell haemoglobin (MCH), iron panels, and immuno-faecal occult blood test (iFOBT) were evaluated to predict the diagnostic utility of each parameter in relation to gastrointestinal disorder in the elderly CKD population. RESULTS: Abnormal endoscopic findings were obtained by upper and lower endoscopy in 98 individuals (57.3%). Upper endoscopy revealed the most prevalent lesions to be gastritis, gastric ulcer, and duodenal ulcer. The upper and lower endoscopies revealed a total of 14.0% malignant and pre-malignant lesions. T-test and receiver-operating characteristic (ROC) curve were performed on all haematological parameters and iron panels. Low ferritin level (less than 100 ng/mL) and combination with low transferrin saturation (less than 20%) have a significant p value less than 0.05. None of these variables had a significant area under the curve (AUC) of more than 0.75. CONCLUSION: Positive endoscopic findings of anaemia are common in the older population at various stages of CKD, regardless of age, gender, or race. Malignant and premalignant lesions are not uncommon in older CKD patients. In the older CKD population, GI inflammation and ulceration are common lesions. Serum ferritin and TSAT levels are useful indicators of GI disorder in this population. Endoscopic evaluation as part of anaemia workup in the older people with CKD should not be ruled out.

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BACKGROUND: The SINgapore GERiatric intervention study to reduce cognitive decline and physical frailty (SINGER) randomised controlled trial (RCT) uses a multidomain lifestyle interventions approach, shown to be effective by the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial, to delay cognitive decline. OBJECTIVE: To investigate the efficacy and safety of the SINGER multidomain lifestyle interventions in older adults at risk for dementia to delay cognitive decline. PARTICIPANTS: 1200 participants between 60-77 years old, with Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score ≥6, fulfilling at least one of the following LIBRA index for diet, cognitive activity, physical activity and a Montreal Cognitive Assessment (MoCA) score ≥18, ≤27 points, will be recruited across Singapore. METHODS: SINGER is a 2-year multi-site RCT consisting of multidomain interventions: dietary advice, exercise, cognitive training, and vascular risk factors management. Participants will be randomised into either the Self-Guided Intervention (SGI; general lifestyle and health information and resources) or Structured Lifestyle Intervention (SLI) group. The SLI comprises diet training (6 group and 3 individual sessions over 12 months); exercise (supervised: 1-hour twice weekly for 6 months, unsupervised: 2-3/week for the rest of the study duration); cognitive sessions (15-30 minutes/session, 3/week for 6 months, together with 10 workshops in 24 months). Vascular management takes place every 3-6 months or otherwise as specified by study physicians. The primary outcome is global cognition measured using the modified Neuropsychological Battery assessing performance in various domains, such as episodic memory, executive function and processing speed. Secondary outcome measures include: domain-specific cognition and function, imaging evidence of brain and retinal changes, incidence and progression of chronic diseases, blood biomarkers, quality of life, mental health and cost-benefit analysis. CONCLUSIONS: SINGER is part of the Worldwide-FINGERS international network, which is at the forefront of harmonizing approaches to effective non-pharmacological interventions in delaying cognitive decline in older adults at risk of dementia. By establishing the efficacy of multidomain interventions in preventing cognitive decline, SINGER aims to implement the findings into public health and clinical practices by informing policy makers, and guiding the design of community- and individual-level health promotion initiatives.

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INTRODUCTION: Hepatocellular carcinoma (HCC) is among the common death-causing cancers worldwide. This liver malignancy is primarily diagnosed using radiological imaging techniques. Most of the patients in Malaysia present late and were diagnosed at an intermediate or advanced stage of Barcelona Clinic of Liver Cancer (BCLC). This causes a limitation on the treatment options for the patients. MATERIALS AND METHODS: We performed a retrospective crosssectional study of HCC cases within a five-year period in our center with data collected from Hospital Canselor Tunku Mukhriz (HCTM). This study examines the HCC risk factors, the pattern of diagnosis, treatment options and overall survival. RESULTS: The findings from this study showed that viral hepatitis was the highest risk factor in which most of the patients were elderly males who presented with abdominal distension. In addition, given the high prevalence of metabolic diseases Malaysia, it is predicted that the number of non-alcoholic steatohepatosis (NASH)-related HCC cases might increase. Alpha-fetoprotein (AFP) proved to have no significant role in the detection of the disease. The number of patients detected at early BCLC was minimal, resulting in limited options of treatment. Overall survival of our HCC patients was poor at 17 months. CONCLUSION: We conclude that HCC patients in HCTM mostly presented at late stage to hospital, hence limiting the treatment options and resulted in poor survival rate. Disease awareness should be implemented at primary care level to detect HCC at its early stage. Subsequently, a multidisciplinary hospital team is required to manage the disease at its different stages of presentation.

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Distal oesophageal spasm is a rare condition that affects the motility of the oesophagus. It can be diagnosed by highresolution oesophageal manometry and the diagnosis is supported by other modalities such as barium swallow and esophagogastroduodenoscopy examinations. Treatment options include pharmacological therapy, endoscopy and surgical interventions. We described a case of distal oesophageal spasm in an elderly patient who presented with chronic dyspepsia.

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Neuroendocrine neoplasm is an epithelial neoplasm with predominant neuroendocrine differentiation that can arise from many organs in the body. We reported a rare case of gastric neuroendocrine carcinoma which accounts for less than 1% of all gastric tumours that is associated with poor prognosis. The recognition of this rare tumour in early stage is challenging and high suspicious into it might bring to early detection and so forth might improve the prognostication.

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Computational studies using correlated wave function methods and density functional theory were carried out on a series of acetylene-linked bimane oligomers with particular emphasis on their excitonic properties and implications for intra-chain excitation energy transfer (EET). The low energy barriers found for the rotation of bimane subunits about the longitudinal axis are such that the π-conjugation is easily disrupted. Nevertheless, a distinctive feature of the oligomer lies in the parallel alignment of the S1 transition dipole along the longitudinal axis, which sustains electronic coupling between adjacent bimane subunits over a range of torsional angles and is crucial for driving intra-chain EET. Using a model that comprises hexameric donor and acceptor fragments, we evaluated electronic couplings and spectral overlaps, and applied Fermi's golden rule (in the weak electronic coupling regime) to approximate the lower limit of intra-chain EET in an acetylene-linked bimane photonic wire.

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Hepatic haemangioma is a solitary liver lesion and prevalent among the female patients. We report a case of diffuse hepatic haemangiomatosis in a 62-year-old man, who was referred for an incidental finding of multiple liver nodules. History and physical examinations were unremarkable. Computed tomography and magnetic resonance imaging of the liver were performed and showed multiple haemangiomatosis. In view of the rarity of this condition in men, a liver biopsy was done and confirmed haemangiomas. Available published literature on diffuse hepatic haemangiomatosis was reviewed.

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Fluorescence lifetimes were evaluated using TD-DFT under different approximations for the emitting molecule and various exchange-correlation functionals, such as B3LYP, BMK, CAM-B3LYP, LC-BLYP, M06, M06-2X, M11, PBE0, ωB97, ωB97X, LC-BLYP*, and ωB97X* where the range-separation parameters in the last two functionals were tuned in a non-empirical fashion. Changes in the optimised molecular geometries between the ground and electronically excited states were found to affect the quality of the calculated lifetimes significantly, while the inclusion of vibronic features led to further improvements over the assumption of a vertical electronic transition. The LC-BLYP* functional was found to return the most accurate fluorescence lifetimes with unsigned errors that are mostly within 1.5 ns of experimental values.

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Phenomenological and mechanistic models are widely used to assist resource planning for pandemics and emerging infections. We conducted a systematic review, to compare methods and outputs of published phenomenological and mechanistic modelling studies pertaining to the 2013-2016 Ebola virus disease (EVD) epidemics in four West African countries - Sierra Leone, Liberia, Guinea and Nigeria. We searched Pubmed, Embase and Scopus databases for relevant English language publications up to December 2015. Of the 874 articles identified, 41 met our inclusion criteria. We evaluated these selected studies based on: the sources of the case data used, and modelling approaches, compartments used, population mixing assumptions, model fitting and calibration approaches, sensitivity analysis used and data bias considerations. We synthesised results of the estimated epidemiological parameters: basic reproductive number (R 0), serial interval, latent period, infectious period and case fatality rate, and examined their relationships. The median of the estimated mean R 0 values were between 1·30 and 1·84 in Sierra Leone, Liberia and Guinea. Much higher R 0 value of 9·01 was described for Nigeria. We investigated several issues with uncertainty around EVD modes of transmission, and unknown observation biases from early reported case data. We found that epidemic models offered R 0 mean estimates which are country-specific, but these estimates are not associating with the use of several key disease parameters within the plausible ranges. We find simple models generally yielded similar estimates of R 0 compared with more complex models. Models that accounted for data uncertainty issues have offered a higher case forecast compared with actual case observation. Simple model which offers transparency to public health policy makers could play a critical role for advising rapid policy decisions under an epidemic emergency.

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This study investigated the impact of ABCB5, ABCC5 and RLIP76 polymorphisms on doxorubicin pharmacokinetics in Asian breast cancer patients (N=62). Direct sequencing was performed to screen for previously identified ABCC5 polymorphisms as well as polymorphisms in the exons and exon-intron boundaries of ABCB5 and RLIP76 genes. Genotype-phenotype correlations were analyzed using Mann-Whitney U-test. The homozygous variant allele at the ABCC5 g.+7161G>A (rs1533682) locus was significantly associated with higher doxorubicin clearance (g.+7161AA vs g.+7161GG, CL/BSA (Lh-1m-2): 30.34 (25.41-33.60) vs 22.46 (15.04-49.4), P=0.04). Homozygosity for the reference allele at the ABCC5 g.-1679T>A locus was associated with significantly higher doxorubicinol exposure (g.-1679TT vs g.-1679TA, AUC0-∞/dose/BSA (hm-5): 15.48 (6.18-67.17) vs 8.88 (3.68-21.71), P=0.0001). No significant influence of the three newly identified ABCB5 polymorphisms (c.2T>C, c.343A>G and c.1573G>A) on doxorubicin pharmacokinetics was observed. No polymorphisms were identified in the RLIP76 gene. These findings suggest that ABCC5 polymorphisms may explain partially the interpatient variability in doxorubicin disposition.

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BACKGROUND: Hyperkalemia, defined as a serum potassium level higher than 5 mEq/L, is common in the liver transplantation setting. Severe hyperkalemia may induce fatal cardiac arrhythmias; therefore, it should be monitored and treated accordingly. The aim of the current retrospective study is to evaluate and indentify the predictive risk factors of hyperkalemia during living-donor liver transplantation (LDLT). METHODS AND PATIENTS: Four hundred eighty-seven adult LDLT patients were included in the study. Intraoperative serum potassium levels were monitored at least five times during LDLT; patients with a potassium level higher than 5 mEq/L were included in group 1, and the others with normokalemia in group 2. Patients' categorical characteristics and intraoperative numeric variables with a P value <.1 were selected into a multiple binary logistic regression model. In multivariate analysis, a P value of <.05 is regarded as a risk factor in the development of hyperkalemia. RESULTS: Fifty-one of 487 (10.4%) patients had hyperkalemia with a serum potassium level higher than 5.0 mEq/L during LDLT. Predictive factors with P < .1 in univariate analysis (Table 1), such as anesthesia time, preoperative albumin level, Model for End-stage Liver Disease score, preoperative bilirubin level, amount of blood loss, red blood cell (RBC) and fresh frozen plasma transfused, 5% albumin administered, hemoglobin at the end of surgery, and the amount of furosemide used, were further analyzed by multivariate binary regression. Results show that the anesthesia time, preoperative serum albumin level, and RBC count are determinant risk factors in the development of the hyperkalemia in our LDLT serials. CONCLUSION: Prolonged anesthesia time, preoperative serum albumin level, and intraoperative RBC transfusion are three determinant factors in the development of intraoperative hyperkalemia, and close monitoring of serum potassium levels in patients with abovementioned risk factors are recommended.

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BACKGROUND: Whether the history of esophageal variceal bleeding (EVB) can be used clinically to predict the tolerability or hemodynamic instability during clamping of the inferior vena cava (IVC) and portal vein in liver transplantation is unknown and, therefore, needs to be elucidated. PATIENTS AND METHODS: A total of 50 anesthesia charts of patients who underwent living donor liver transplantation were reviewed, analyzed and compared retrospectively. Patients without a history of EVB were classified as group 1 and patients with a history of EVB were classified as group 2. The numbers of patients with a decrease in cardiac index (CI) of ≥20%, ≥30%, or ≥40% from their preclamping values after IVC clamping were compared with a χ(2), and a P value of .05 was regarded as statistically significant. RESULTS: The measured hemodynamic parameters before and 5 minutes after clamping of the IVC and portal vein were all significantly different in comparison with the patient's preclamping values. The incidence of a decrease in CI of ≥20%, ≥30%, or ≥40% 5 minutes after clamping of the IVC and portal vein were not significantly different between groups. CONCLUSIONS: Clamping of the portal vein and IVC without performing veno-venous bypass in living donor liver transplantation had a significant negative impact on CI in both groups due to the drastic reduction in the venous return. Statistical analysis revealed that a history of EVB affects hemodynamics in a manner similar to that in patients without history of EVB during IVC clamping.

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OBJECTIVE: Dual graft living donor liver transplantation (LDLT) is an alternative way to overcome small-for-size syndrome in LDLT. Surgical technique and outcome of using dual grafts have been reported, but there are no reports regarding anesthetic management. The aim of the current study is to compare the anesthetic management of single graft and dual graft liver transplantation. METHODS AND PATIENTS: Anesthesia records of 24 single graft liver transplantation recipients (GI) and 6 dual graft recipients (GII) were reviewed, analyzed, and compared retrospectively. Patient characteristics and intraoperative data between groups were compared with Mann-Whitney t test and Fisher's exact test where appropriate. P value less than .05 was regarded as significant. RESULTS: Patient characteristics and most of the intraoperative data were similar between groups. Significant difference was noted in the total anesthesia time and the anhepatic time. Both times were significantly longer in GII compared to GI. CONCLUSION: Dual graft living donor liver transplantation is surely a technically more challenging and demanding procedure. Therefore the total anesthesia time is longer, especially the anhepatic phase, because there are more graft vessels to be reconstructed before reperfusion. Overall the anesthetic management in terms of blood transfusion, fluid administration, sodium bicarbonate, calcium supplement, and the number of patients requiring fractional diluted noradrenaline support for maintenance of acceptable hemodynamic were not much different between the 2 groups.

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BACKGROUND: To test the hypothesis that low end-tidal carbon dioxide tension encountered during anhepatic phase in liver transplantation is related to hemodynamic status rather than ventilatory status, and can be used to predict the change in cardiac output during anhepatic phase. METHODS: We retrospectively analyzed and compared data, included end-tidal carbon dioxide tension (ETCO2), arterial blood pressure, heart rate, central venous pressure, cardiac output, cardiac index, and stroke volume, before and after inferior vena cava clamping, and 0, 5, 10, 30 minutes during the anhepatic, and 5 minutes after the release of IVC cross clamp during the reperfusion phase, with paired Student t test, repeated measurement, and linear regression. P < .05 was regarded as significant. RESULTS: The cardiac output and ETCO2 decrease significantly after clamping the inferior vena cava and increase concomitantly after unclamping. There is a positive correlation between the changes in % in cardiac output and ETCO2 (Pearson coefficient r = 0.741). CONCLUSION: The changes in ETCO2 can be used to predict the changes of the cardiac output in % when cardiac output monitoring is not available. Before unclamping of the IVC, mild hyperventilation is suggested to prevent excessive increase in PaCO2.

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We have carried out first principles electronic structure calculations on the ground and excited valence states of syn and anti bimanes. While syn bimanes fluoresce strongly after photoexcitation to the first excited singlet state (S1) and are commonly used as fluorophores in biological labeling studies, anti bimanes largely phosphoresce at low temperatures. We show that this is due to subtle differences in the energetic ordering of excited singlet and triplet states within the isomers. In particular, T2 in anti bimanes is characterized by a π→π* transition and large exchange interactions with the singlet counterpart cause it to lie below and energetically close to S1 at the Franck-Condon region. This opens up a pathway for very fast intersystem crossing (ca. 10(11) s(-1)) from the optically bright S1 state to the triplet manifold, which effectively quenches fluorescence. On the other hand, T2 is energetically inaccessible to S1 in syn bimanes and intersystem crossing via S1→ T1 cannot compete effectively with fluorescence to S0. We have also located minimum energy conical intersections between S0 and S1 in bimanes. However, these structures are significantly distorted from their equilibrium geometries as well as energetically much higher than S1 at the Franck-Condon region. They are therefore not expected to play a part in the photophysics of bimanes after excitation to S1.

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In 2011, our hospital started a new system of 100% procedural audit of anaesthesia work, in which we incorporated the reporting of critical incidents. This monitoring of critical incidents has enabled identification of the spectrum of incidents and risk factors and helped in the education of trainees and specialists. In this review, we analyse 379 incidents that had been reported among 44,915 anaesthetics administered in a two-year period. The risk of incidents was higher in patients of lower American Society of Anesthesiologists physical status, anaesthesia of long duration and anaesthesia carried out after-hours. The most common incidents were airway problems and drug administration problems. Fifty-nine percent of incidents were evaluated to be preventable and adverse outcomes occurred in 48% of cases. Human factors were the major contributors to incidents. We suggest that incorporating critical incident reporting as part of a 100% procedural audit facilitated, rather than discouraged, the reporting of critical incidents, even though reporting was not anonymous. The rate of incident reporting increased from 0.37% to 0.84%.

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BACKGROUND: Inorganic polyphosphates (polyP), which are secreted by activated platelets (short-chain polyP) and accumulate in some bacteria (long-chain polyP), support the contact activation of factor XII (FXII) and accelerate the activation of FXI. OBJECTIVES: The aim of the present study was to evaluate the role of FXI in polyP-mediated coagulation activation and experimental thrombus formation. METHODS AND RESULTS: Pretreatment of plasma with antibodies that selectively inhibit FXI activation by activated FXII (FXIIa) or FIX) activation by activated FXI (FXIa) were not able to inhibit the procoagulant effect of long or short-chain polyP in plasma. In contrast, the FXIIa inhibitor, corn trypsin inhibitor, blocked the procoagulant effect of long and short polyP in plasma. In a purified system, long polyP significantly enhanced the rate of FXII and prekallikrein activation and the activation of FXI by thrombin but not by FXIIa. In FXI-deficient plasma, long polyP promoted clotting of plasma in an FIX-dependent manner. In a purified system, the activation of FXII and prekallikrein by long polyP promoted FIX activation and prothombin activation. In an ex vivo model of occlusive thrombus formation, inhibition of FXIIa with corn trypsin inhibitor but not of FXI with a neutralizing antibodies abolished the prothrombotic effect of long polyP. CONCLUSIONS: We propose that long polyP promotes FXII-mediated blood coagulation bypassing FXI. Accordingly, some polyp-containing pathogens may have evolved strategies to exploit polyP-initiated FXII activation for virulence, and selective inhibition of FXII may improve the host response to pathogens.

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