A Comprehensive Clinical Outcome Analysis of Endoscopic Vessel Harvesting for Coronary Artery Bypass Surgery.

Background: The long saphenous vein is routinely used for coronary bypass graft (CABG) surgery, and two primary techniques are commonly utilized: endoscopic vessel harvesting (EVH) and open vessel harvesting (OVH). The aim of this study was to compare the clinical outcomes of the EVH and OVH techniques used for CABG within the confines of a tertiary hospital. Methods: The clinical data of all patients subjected to either EVH or OVH for CABG surgery between 2014 and 2018 were retrospectively analyzed. Statistical analysis was performed to discern variations in the rates of postoperative complications between EVH and OVH. Results: A cohort of 1884 individuals were included in this study, 75.3% of whom underwent EVH. Notably, the incidence of postoperative leg wound complications was significantly different between the patients who underwent OVH and the patients who underwent EVH, with incidence rates of 18.6% and 32%, respectively (p < 0.001). Leg wound complications (p < 0.001; OR 1.946; 95% CI 1.528-2.477) and leg wound infections (p = 0.050, OR 1.517, 95% CI 0.999-2.303) were significantly associated with OVH. Moreover, leg wound hematoma (p = 0.039, OR = 0.402, 95% CI = 0.169-0.957) and EVH were strongly associated. Conclusions: The large sample of patients and the inclusion of a range of Asian ethnic groups provided notable insights into postoperative complications related to different modalities. EVH was associated with a lower incidence of postoperative leg wound complications, which suggests that EVH is a better modality for those undergoing CABG surgery.

Traction-induced aneurysm of an accessory left hepatic artery: a potentially fatal but synchronously treatable complication of a large hiatus hernia.

A 59-year-old man presented to our surgical clinic with a long-standing history of heart burn, and upper abdominal pain. Gastroscopy showed a large sliding hiatus hernia associated with severe reflux oesophagitis. Oesophageal pH manometry revealed a high DeMeester score of 36.03. A computed tomography (CT) scan was performed for preoperative hiatal hernia repair planning. This showed the incidental finding of an accessory left hepatic artery (ALHA) and an aneurysm of this accessory artery. The aneurysm occurred at the point where the ALHA traversed the diaphragmatic crus and was only present in association with the hiatus hernia. These observations suggest that the aetiology of the aneurysm was due to traction during development of the hiatus hernia. The patient went onto have a laparoscopic hiatus hernia repair and Toupet fundoplication with ligation of the accessory left hepatic artery and made an excellent recovery. ALHAs are not uncommon, occurring in around 15% of the general population, with aneurysms of the hepatic arteries accounting for about 20% of cases of visceral artery aneurysms. The case presented herein highlights the importance of performing an arterial phase CT when planning surgery for large hiatus hernias to detect more cases like this one. This would allow early detection and concurrent treatment of an associated aneurysm with repair of the hiatus hernia, to prevent aneurysmal complications later on.

Can the measured angle ABC on the lateral projection of the knee be used to determine the tube angulation for an optimum skyline projection?

INTRODUCTION: The current technique of angulating for a skyline knee projection relies heavily on the radiographer's estimation of the patella tilt, rendering it subjective and prone to errors. This study therefore aims to (i) examine the correlation between angle ABC measured on the lateral X-ray image and skyline angulation (measured in degrees) and (ii) determine the inter-rater reliability of angle ABC measurements. METHODS: 145 sets of lateral and skyline X-ray images from patients aged 40-70 years old were retrospectively analysed. Angle ABC was measured using prominent landmarks such as the trochlear sulcus, tibial tuberosity and the anterior border of the patella on the lateral knee radiograph. It was then retrospectively compared with the skyline tube angulations to identify any correlation between the two. An inter-rater reliability test was also conducted using the intraclass correlation coefficient (ICC) to determine the reproducibility of the measurement method. RESULTS: A weak correlation was found between angle ABC and skyline angulation (r = 0.1, p = 0.25). The proposed method of measurement shows good inter-rater reliability (ICC = 0.81, 95% CI: 0.77 to 0.84). CONCLUSION: There is insufficient evidence to indicate a correlation between angle ABC and skyline angulation. However, angle ABC can be reliably measured, implying the replicability of the measurement method for other purposes. IMPLICATIONS FOR PRACTICE: The proposed measurement method of angle ABC on the lateral view could have future applications in other areas such as in the measurement of patellofemoral alignment and trochlear morphology.

Elevated serum thyroglobulin levels at the time of ablative radioactive iodine therapy indicate a worse prognosis in thyroid cancer: an Australian retrospective cohort study.

BACKGROUND: Serum thyroglobulin is used as a surrogate marker for well-differentiated thyroid carcinoma recurrence. This study investigates whether thyroglobulin measured at the time of ablative radioactive iodine therapy predicts disease-free survival. METHODS: A retrospective review was conducted of patients with well-differentiated thyroid carcinoma presenting from 1989 to 2010 at the Royal Prince Alfred Hospital, New South Wales, Australia. Disease-free survival of patients with a significantly elevated stimulated thyroglobulin level (27.5 µg/l or higher) at the time of ablative radioactive iodine therapy was compared to that of patients without a significantly elevated thyroglobulin level using univariate analysis. RESULTS: Patients with a thyroglobulin level of 27.5 µg/l or higher had an increased relative risk of disease recurrence of 4.50 (95 per cent confidence interval = 1.35-15.04). If lateral neck dissection was required at the time of surgery, patients also had an increased relative risk of macroscopic disease recurrence of 4.94 (95 per cent confidence interval = 1.47-16.55). CONCLUSION: An elevated thyroglobulin level of 27.5 µg/l or higher at the time of ablative radioactive iodine therapy is a prognostic indicator for macroscopic disease recurrence in well-differentiated thyroid carcinoma.

Acute adrenal insufficiency: an aide-memoire of the critical importance of its recognition and prevention.

Adrenal crisis is a life-threatening emergency that causes significant excess mortality in patients with adrenal insufficiency. Delayed recognition by medical staff of an impending adrenal crisis and failure to give timely hydrocortisone therapy within the emergency department continue to be commonly encountered, even in metropolitan teaching hospitals. Within the authors' institutions, several cases of poorly handled adrenal crises have occurred over the last 2 years. Anecdotal accounts from members of the Addison's support group suggest that these issues are common in Australia. This manuscript is a timely reminder for clinical staff on the critical importance of the recognition, treatment and prevention of adrenal crisis. The manuscript: (i) outlines a case and the clinical outcome of sub-optimally managed adrenal crisis, (ii) summarises the clinical features and acute management of adrenal crisis, (iii) provides recommendations on the prevention of adrenal crisis and (iv) provides guidance on the management of 'sick days' in patients with adrenal insufficiency.

Double-burden of malnutrition among the indigenous peoples (Orang Asli) of Peninsular Malaysia.

BACKGROUND: Double-burden of malnutrition (DBM) is an emerging public health concern among the Orang Asli (indigenous peoples) of Peninsular Malaysia. This study aimed to identify the presence of DBM at the community and household levels in Orang Asli population and its associated demographic and socio-economic factors. METHODS: This cross-sectional study was conducted in 11 Orang Asli villages surrounding the Krau Wildlife Reserve, Peninsular of Malaysia from October 2011 to January 2012. Of 438 households, a total of 981 adults and 304 children who met the study criteria agreed to participate. About 160 households were further selected with pairs of children aged 3-59 months and non-pregnant mothers aged 15-55 years. Demographic and socio-economic data were obtained using interviewer-administered questionnaire while weight and height were measured using standard procedures. Double-burden of malnutrition was defined as overweight/obese mother-underweight child (OWOBM/UWC), overweight/obese mother-stunted child (OWOBM/STC) or overweight/obese mother-underweight or/and stunted child (OWOBM/UWSTC). Binary logistic regression identified the demographic and socio-economic factors associated with double-burden households. RESULTS: About 26 % of overweight and obese adults coexisting with high proportions of underweight (49%) and stunted (64%) children in these Orang Asli villages. There was a higher prevalence of households with OWOBM/UWSTC (20%) and OWOBM/STC (19.4%) than households with OWOBM/UWC (12.5%). Boys (P < 0.05), older age mothers (P < 0.05), mothers with higher education (P < 0.05) and households with income per capita less than USD 29.01 (RM 97.00) (P < 0.01) were associated with higher odds of OWOBM/STC. Jah Hut (P < 0.05) and higher number of children (P < 0.05) were significantly associated with lower odds of OWOBM/UWC. CONCLUSIONS: The occurrence of double-burden of malnutrition in Orang Asli population deserves attention. Poverty reduction, access to quality diet and improved health and nutrition literacy are among strategies that could address the coexistence of DBM in this population.

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series.

BACKGROUND: Ipilimumab (Yervoy; Bristol-Myers Squibb) is a novel fully humanised monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4, an immune checkpoint molecule, to augment anti-tumour T-cell responses. It is associated with significant immune-related side-effects including hypophysitis. AIM: We reviewed the clinical and biochemical characteristics of 10 patients with ipilimumab-induced hypophysitis (IH), and developed guidelines for the early detection and management of IH based on our experiences at three major teaching hospitals in Sydney. METHODS: All patients were evaluated at the Crown Princess Mary Cancer Centre and Department of Endocrinology, Westmead Hospital, Department of Endocrinology, Royal Prince Alfred Hospital, the Melanoma Institute Australia and Macarthur Cancer Therapy Centre, Campbelltown Hospital from 2010 to 2014. Relevant data were extracted by review of medical records. Main outcome measures included clinical features, hormone profile and radiological findings associated with IH, and presence of pituitary recovery. RESULTS: Ten patients were identified with IH. In four patients who underwent monitoring of plasma cortisol, there was a fall in levels in the weeks prior to presentation. The pituitary-adrenal and pituitary-thyroid axes were affected in the majority of patients, with the need for physiological hormone replacement. Imaging abnormalities were identified in five of 10 patients, and resolved without high-dose glucocorticoid therapy. To date, all patients remain on levothyroxine and hydrocortisone replacement, where appropriate. CONCLUSIONS: There is significant morbidity associated with development of IH. We suggest guidelines to assist with early recognition and therapeutic intervention.

Exome sequencing and array-based comparative genomic hybridisation analysis of preferential 6-methylmercaptopurine producers.

Preferential conversion of azathioprine or 6-mercaptopurine into methylated metabolites is a major cause of thiopurine resistance. To seek potentially Mendelian causes of thiopurine hypermethylation, we recruited 12 individuals who exhibited extreme therapeutic resistance while taking azathioprine or 6-mercaptopurine and performed whole-exome sequencing (WES) and copy-number variant analysis by array-based comparative genomic hybridisation (aCGH). Exome-wide variant filtering highlighted four genes potentially associated with thiopurine metabolism (ENOSF1 and NFS1), transport (SLC17A4) or therapeutic action (RCC2). However, variants of each gene were found only in two or three patients, and it is unclear whether these genes could influence thiopurine hypermethylation. Analysis by aCGH did not identify any unusual or pathogenic copy-number variants. This suggests that if causative mutations for the hypermethylation phenotype exist they may be heterogeneous, occurring in several different genes, or they may lie within regulatory regions not captured by WES. Alternatively, hypermethylation may arise from the involvement of multiple genes with small effects. To test this hypothesis would require recruitment of large patient samples and application of genome-wide association studies.

Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population.

BACKGROUND: High on-treatment platelet reactivity has been associated with poor outcomes following acute coronary syndromes (ACS). Both the loss of function CYP2C19*2 allele and the gain of function CYP2C19*17 allele along with a range of clinical characteristics have been associated with variation in the response to clopidogrel. AIM: The study aims to examine the frequency of CYP2C19 variants and understand the factors associated with on-treatment platelet reactivity in a New Zealand ACS population. METHODS: We prospectively enrolled 312 ACS patients. We collected clinical characteristics and measured on-treatment platelet reactivity using two validated point-of-care assays, VerifyNow and Multiplate. DNA was extracted and CYP2C19*2 and *17 alleles were identified using real-time polymerase chain reaction. RESULTS: CYP2C19*2 or CYP2C19*17 alleles were observed in 101 (32%) and 106 (34%) of patients, respectively, with significant differences in distribution by ethnicity. In Maori and Pacific Island patients, 47% (confidence interval (CI) 31-63%) had CYP2C19*2 and 11% (CI 4-19%) CYP2C19*17 compared with 26% (CI 19-32%) and 41% (CI 32-49%) in white people. Carriage of CYP2C19*2 alleles was associated with higher levels of platelet reactivity measured by either assay, but we observed no relationship between platelet reactivity and CYP2C19*17. In multivariate analysis diabetes, clopidogrel dose and CYP2C19*2 status were all significant independent predictors of platelet reactivity. CONCLUSIONS: Both CYP2C19*2 and *17 were common in a New Zealand ACS population, with CYP2C19*2 observed in almost half the Maori and Pacific Island patients. CYP2C19*2, diabetes and clopidogrel dose were independent contributors to on-treatment platelet reactivity.

Validation of a nomogram in the prediction of local recurrence risks after conserving surgery for Asian women with ductal carcinoma in situ of the breast.

AIMS: At our centre, ductal carcinoma in situ (DCIS) was commonly treated with breast-conservation therapy (BCT). Local recurrence after BCT is a major concern. The aims of our study were to review the outcomes of DCIS treatment in our patients and to evaluate a nomogram from Memorial Sloan Kettering Cancer Centre (MSKCC) for predicting ipsilateral breast tumour recurrence (IBTR) in our Asian population. MATERIALS AND METHODS: Chart reviews of 716 patients with pure DCIS treated from 1992 to 2011 were carried out. Univariable Cox regression analyses were used to evaluate the effects of the 10 prognostic factors of the MSKCC nomogram on IBTR. We constructed a separate National Cancer Centre Singapore (NCCS) nomogram based on multivariable Cox regression via reduced model selection by applying the stopping rule of Akaike's information criterion to predict IBTR-free survival. The abilities of the NCCS nomogram and the MSKCC nomogram to predict IBTR of individual patients were evaluated with bootstrapping of 200 sets of resamples and the NCCS dataset, respectively. Harrell's c-index was calculated for each nomogram to evaluate the concordance between predicted and observed responses of individual subjects. RESULTS: Study patients were followed up for a median of 70 months. Over 95% of patients received adjuvant radiotherapy. The 5 and 10 year actuarial IBTR-free survival rates for the cohort were 95.5 and 92.6%, respectively. In the multivariate analysis, independent prognostic factors for IBTR included use of adjuvant endocrine therapy, presence of comedonecrosis and younger age at diagnosis. These factors formed the basis of the NCCS nomogram, which had a similar c-index (NCCS: 0.696; MSKCC: 0.673) compared with the MSKCC nomogram. CONCLUSION: The MSKCC nomogram was validated in an Asian population. A simpler NCCS nomogram using a different combination of fewer prognostic factors may be sufficient for the prediction of IBTR in Asians, but requires external validation to compare for relative performance.

Critical analysis of valganciclovir dosing and renal function on the development of cytomegalovirus infection in kidney transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common and important opportunistic infections following kidney transplantation. It causes significant morbidity and mortality. Valganciclovir (VGCV) is the drug of choice for prophylaxis to prevent CMV infection. METHODS: We conducted a post-hoc analysis of a randomized controlled trial in 187 kidney transplant recipients to evaluate the impact of VGCV dosing and renal function on the development of CMV infection. RESULTS AND CONCLUSION: The results demonstrate that the following variables were independent risk factors for the development of CMV infection: high-risk CMV serostatus (donor positive/recipient negative; hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.46-5.28, P = 0.002); anti-thymocyte globulin induction therapy (HR 2.1, 95% CI 1.08-4.07, P = 0.028); higher mean tacrolimus trough concentration (HR 1.4, 95% CI 1.09-1.74, P = 0.007); creatinine clearance <60 mL/min (HR 3.4, 95% CI 1.64-6.85, P = 0.001); and body weight >80 kg (HR 2.1, 95% CI 1.05-4.37, P = 0.037). VGCV dosing was appropriate for most patients, in those who did and did not develop CMV infection. These results strongly suggest that the currently recommended dose adjustments of VGCV dosing based on estimated renal function calculated using ideal body weight may underestimate the renal function of overweight patients and indirectly result in underexposure of overweight patients to VGCV. Based on these findings, further VGCV pharmacokinetic analyses are warranted in kidney transplant recipients with moderate-to-severe renal dysfunction.

Management of incidental and non-incidental papillary thyroid microcarcinoma.

BACKGROUND: The incidence of papillary thyroid cancer is rising, with an increase in the number of microcarcinomas being discovered. There is controversy in the literature regarding the optimal management of these tumours. This study aimed to review our institution's experience with the presentation and management of papillary thyroid microcarcinoma. METHODS: Retrospective analysis from the Sydney Head and Neck Cancer Institute, from 1987 to 2009. RESULTS: A total of 228 patients were analysed. Papillary thyroid microcarcinomas were discovered incidentally in 116 (50.9 per cent) patients and non-incidentally in the remaining 112 (49.1 per cent) patients. Amongst the non-incidental group, 11.6 per cent of patients presented with lateral cervical lymph node involvement. Non-incidental microcarcinomas were significantly associated with younger age (<45 years) (p = 0.007) and larger tumours (5-10 mm) (p < 0.001). Only four patients in the incidental group suffered recurrent disease (locoregional). No patient developed distant metastatic disease or died during follow up. CONCLUSION: Papillary thyroid microcarcinomas present both incidentally and non-incidentally, with equal prevalence. Non-incidental tumours not infrequently present with cervical lymph node disease. The patient outcome is generally excellent.

Significant bacterial contamination risk reduction with the use of diversion pouch.

BACKGROUND: Significant efforts have been made towards bacterial risk minimization by limiting the chance of bacteria entering into collected blood, detecting its presence and eliminating them by pathogen reduction technology. Improved skin disinfection and the use of diversion pouch are effective upstream measures to reduce the risk of bacterial sepsis. Here we report on our experience with the use of blood bags with diversion pouch. MATERIALS AND METHODS: An observational study was performed to compare the bacterial contamination rate for two periods of time, i.e. before and after introduction of diversion pouch into blood bags. The incidence of bacterial contamination was monitored by the existing bacterial surveillance programme using pooled samples from 5 units of random donor platelets underwent aerobic culture in the BacT/ALERT 3D system. RESULTS: Between 1 June 2004 and 31 May 2006 (blood bag without diversion pouch), 50 (0·0213%) out of 234,252 units of random donor platelets were found to have bacteria on culture whereas 15 (0·0057%) isolates out of 262,156 units were found from 1 June 2007 to 31 May 2009 (after diversion pouch was introduced). Overall, there was an 85% reduction in bacterial contaminated risk due to skin flora (P < 0·0001) but an increasing trend of detection of non skin flora such as Streptococcus bovis was noted. CONCLUSION: Integration of diversion pouch into blood bags to divert the first 30 mL blood during blood collection on top of the current skin disinfection protocol can significantly reduce the risk of bacterial contamination.

Current State and Future Prospects of Direct-to-Consumer Pharmacogenetics.

Direct-to-consumer (DTC) DNA testing has grown from contentious beginnings into a global industry, by providing a wide range of personal genomic information directly to its clients. These companies, typified by the well-established 23andMe, generally carry out a gene-chip analysis of single-nucleotide polymorphisms (SNPs) using DNA extracted from a saliva sample. These genetic data are then assimilated and provided direct to the client, with varying degrees of interpretation. Although much debate has focused on the limitations and ethical aspects of providing genotypes for disease risk alleles, the provision of pharmacogenetic results by DTC companies is less studied. We set out to evaluate current DTC pharmacogenetics offerings, and then to consider how these services might best evolve and adapt in order to play a potentially useful future role in delivery of personalized medicine.

Dietary diversity is associated with nutritional status of Orang Asli children in Krau Wildlife Reserve, Pahang.

INTRODUCTION: It is known that dietary diversity improves diet quality and nutritional status of young children. This study aimed to determine the relationship between dietary diversity and nutritional status of Orang Asli children in Krau Wildlife Reserve. METHODS: A total of 216 children from three Orang Asli sub-tribes (Jah Hut, Temuan and Che Wong) aged 1 to 6 years from 162 households in 16 villages participated in this cross-sectional study. Children and mothers were measured for body weight and height. Mothers were interviewed for household socio-demographic information and diet diversity of children in the last 7 days. Diet diversity score (DDS) was calculated based on 15 food groups. RESULTS: There was a high prevalence of underweight (50.9%) and stunting (61.6%) in Orang Asli children. For mothers, 11.1%, 27.8% and 7.4% were underweight, overweight and obese, respectively. Mean DDS of children was 6.38 [95% CI-6.10, 6.65] of the possible 15. Higher DDS of children was significantly related to older age (p < 0.05), the non Jahut sub-tribe (p < 0.01) and longer maternal years of schooling (p < 0.05). DDS was also positively related to weight-for-age z-scores (p < 0.001) and height-for-age z-scores (p < 0.05). CONCLUSION: Undernutrition remains a major nutrition problem among Orang Asli children living within the forest reserve. Efforts to promote dietary diversity should emphasise traditional and nutritious foods that could improve health and nutritional status of the Orang Asli children.

Load fatigue performance of conical implant-abutment connections.

PURPOSE: Conical implant-abutment connections for platform switching have been recently introduced in implant systems. This study investigated the load fatigue performance of three conical abutment systems and their corresponding titanium and zirconia abutments. MATERIALS AND METHODS: Regular-diameter implants of the Ankylos (AK), PrimaConnex (PC), and Straumann (ST) systems were tested with their corresponding titanium (Ti) and zirconia (Zr) abutments tightened to the recommended torque (n = 5 implant-abutment assemblies per group). A rotational load fatigue machine applied a sinusoidally varying tensile-compressive 21 N load to specimens at a 45-degree angle, producing an effective bending moment of 35 Ncm at a frequency of 10 Hz. The number of cycles to failure was recorded, with the upper limit set at 5 million cycles. Results were evaluated through analyses of variance. RESULTS: Except for the ST Zr group, which showed no failures in four samples and one failure just below the screw head, and the AK Ti group, in which one sample was preserved without fracture, all groups experienced failure of at least one of the components, whether the abutment screw only, the abutment, and/or the implant neck. There were significant differences between systems. There was no difference between systems for the Ti abutments, and the ST group was significantly different from the AK and PC groups for the Zr abutments. CONCLUSIONS: Ti conical abutments appear to have poorer load fatigue performance compared with earlier studies of external-hexagon connections. The load fatigue performance of Zr conical abutments varied and seemed to be highly system dependent. Many of the fractures in both the Ti and Zr abutment groups occurred within the implant, and retrieval would pose a significant clinical challenge. The clinician should weigh the mechanical, biologic, and esthetic considerations before selection of any implant system, connection type, or abutment material.

The danger of using inappropriate point-of-care glucose meters in patients on icodextrin dialysis.

AIMS: Icodextrin is a glucose polymer used to maintain an osmotic gradient in peritoneal dialysis. Metabolites of icodextrin are known to cause overestimation of blood glucose in glucose meters using glucose dehydrogenase/pyrroloquinolinequinone systems. The aim of this study is to determine the extent of icodextrin interference in glucose meters using the newer glucose dehydrogenase/NAD or glucose oxidase systems. This has not been established previously. METHODS: Fasting blood samples (n = 4) were spiked with either one icodextrin metabolite (maltose, maltotriose or maltotetraose) or a combination, at various blood concentrations expected during dialysis. Samples were tested in triplicate on: five glucose-meters, a Radiometer® (glucose oxidase/hydrogen peroxide) and laboratory (hexokinase) analysers. Each meter was also tested on blood from six patients undergoing dialysis. Accuracy was evaluated as % Bias = [(meter glucose - laboratory glucose)/laboratory glucose] × 100. RESULTS: A single icodextrin metabolite affected glucose measurements and, in combination, the interferences were additive in the two Accu-Chek® and Optium® Xceed meters by > 10%. Amongst these meters, the Optium Xceed 5-s machine was less affected. Meters using glucose oxidase were least affected by interference. A similar trend in interference was observed in vivo. CONCLUSION: While meters using glucose dehydrogenase/NAD are less affected by icodextrin metabolites, interference can still be demonstrated. The degree of interference can vary in different glucose meters using this enzyme/cofactor system, as seen in the Optium Xceed machines. Icodextrin is an important source of interference that sometimes even experienced professionals are unaware of and which leads to clinically significant errors in insulin dose adjustment. Awareness of this interference and selection of the most appropriate glucose meters are crucial to minimize this hazard.