Epidemiology of cruciate ligament reconstruction in the Australian Defence Force and predictors of outcome.

BACKGROUND: The ability to predict the risk of poor outcome following knee cruciate ligament reconstruction in the Australian Defence Force (ADF) population would help direct individual rehabilitation programmes and workforce planning. This study describes the epidemiology of cruciate ligament reconstruction in the ADF and demonstrates the use of Bayesian networks (BN) to predict the likelihood of fitness for ongoing service under different scenarios. METHODS: Members who had knee cruciate ligament reconstruction through ADF were identified from billing data and matched to electronic medical records to extract demographic and clinical data. Outcome measure was medical fitness for ADF service up to 24 months after reconstruction. BN models were used to compare outcomes between (1) age groups according to military service, and (2) sexes according to body mass index (BMI). RESULTS: From November 2012 to June 2019, a total of 1199 individuals had knee cruciate ligament reconstruction (average 169 reconstructions/year). Following reconstruction and rehabilitation, 89 (7.4%) were medically unfit for service. Scenario analysis using a tree-augmented naïve BN model showed that, compared with Navy and Air Force, Army members had a higher probability of being unfit in those aged <35 years and a lower probability in those aged ≥35 years. In both sexes, those with obese BMI had the greatest probability of being unfit. CONCLUSION: While most ADF members were fit for ongoing military service following cruciate ligament reconstruction, service type, age, sex and BMI influenced outcome. BNs provided an interactive and intuitive method to demonstrate the impact of different variables on the outcome.

The risk factors for complications and survival outcomes of Klebsiella pneumoniae Bacteraemia in Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia.

INTRODUCTION: Mortality of Klebsiella pneumoniae (K. pneumoniae) bacteraemia was reported to be on the rise globally. The 30-day mortality rate of K. pneumoniae bacteraemia ranges from 16% to 55% in Beijing, Shanghai, and Taiwan. However, there is a lack of research on the survival outcomes of K. pneumoniae bacteraemia in Malaysia. The objectives of this study were to determine the poor prognostic factors and predictors of 14-day in-hospital mortality from K. pneumoniae bacteraemia. METHODS: This was a retrospective cohort study of patients with K. pneumoniae bacteraemia in Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM). We included adult patients with blood cultures positive for K. pneumoniae between 1 January 2016 and 31 December 2019. Those with polymicrobial bacteraemia were excluded. Medical records were reviewed to obtain the sociodemographic data, gender, underlying comorbidities, invasive procedures at presentation, sources of bacteraemia, and whether appropriate empirical and definitive antibiotics was given on time. Data regarding complications of K. pneumoniae bacteraemia, including liver abscess, endopthalmitis, septic shock, Quick Pitt (qPitt) bacteraemia score defined as hypothermia, hypotension, respiratory failure, cardiac arrest, and altered mental status and stay in intensive care unit (ICU) were also recorded. The main outcome measure used was the survival in 14 days. Summary of statistical analysis was done. RESULTS: A total of 260 patients with K. pneumoniae bacteraemia were included. All patients received appropriate empirical and definitive antibiotics within 24 h of the time that the sample for index blood cultures was obtained. Respiratory infection, septic shock, qPitt bacteraemia score ≥2, solid organ malignancy, stay in ICU, central venous line insertion at presentation, urinary catheterisation at presentation, and in-patient mechanical ventilation were identified as independent predictors of mortality in K. pneumoniae bacteraemia. The rate of complications such as liver abscess, endophthalmitis, ICU admission, and septic shock was not significantly different between survivors and non-survivors. The 14-day in-hospital mortality rate was 12.3%. The median length of hospitalisation was 11 days (IQR 6 - 19) . The predictors of poor prognosis for 14 days in-hospital mortality for K. pneumoniae bacteraemia were as follows: qPitt bacteraemia score ≥2, central venous line insertion, indwelling urinary catheter at presentation, and in-patient mechanical ventilation. Timing from K. pneumoniae bacteraemia event to death among those qPitt bacteraemia scores ≥2 was only for 9 days or less. CONCLUSIONS: The 14-day in-hospital mortality of patients with K. pneumoniae bacteraemia in our setting was low. The qPitt bacteraemia score ≥2 was the strongest predictor of poor prognosis for 14-day in-hospital mortality in patients with K. pneumoniae bacteraemia. The qPitt bacteraemia score should be proposed to be used as a bedside screening tool for gram negative bacteraemia in our daily clinical practice, which is also useful for predicting mortality in critically ill patients.

Hong Kong needs a territory-wide registry for out-of-hospital cardiac arrest.

Out-of-hospital cardiac arrest (OHCA) is an urgent disease entity, and the outcomes of OHCA are poor. This causes a significant public health burden, with loss of life and productivity throughout society. Internationally, successful programmes have adopted various survival enhancement measures to improve outcomes of OHCA. A territory-wide organised survival enhancement campaign is required in Hong Kong to maintain OHCA survival rates that are comparable to those of other large cities. One key component is to establish an OHCA registry, such as those in Asia, the United States, Europe, Australia, and New Zealand. An OHCA registry can provide benchmarking, auditing, and surveillance for identification of weak points within the chain of survival and evaluation of the effectiveness of survival enhancement measures. In Hong Kong, digitisation of records in prehospital and in-hospital care provides the infrastructure for an OHCA registry. Resources and governance to maintain a sustainable OHCA registry are necessary in Hong Kong as the first step to improve survival and outcomes of OHCA.

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives.

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.

The impact of Livestock Manure Control Policy on human leptospirosis in Republic of Korea using interrupted time series analysis.

Leptospirosis is a zoonotic disease that the pathogen can be transmitted to humans through the excretions of infected animals. In the Republic of Korea, the Livestock Manure Control Act was enforced in September 2007 to improve underground water hygiene. The objective of this study was to evaluate the impact of Livestock Manure Control Policy on the incidence and the trend of human leptospirosis. An interrupted time series analysis using the monthly incidence of leptospirosis was conducted based on data derived from the Korean National Surveillance System between January 1999 and January 2015. We used a Spearman correlation method to compare the level of leptospirosis incidence decrease between the metropolitan cities and rural provinces. The annual incidence of leptospirosis in South Korea decreased by 33% after policy enforcement of the policy. A significant change in the slope of human leptospirosis cases was observed after the policy enforcement (ß = -0·09, P < 0·001). Moreover, we detected a clear association between the size of the rice paddy fields and the decrease in leptospirosis incidence in provinces (r = 0·817, P = 0·01). This study shows that the Livestock Manure Control Policy had significantly reduced human leptospirosis incidence in the Republic of Korea, in particular, in rural regions.

Links between L-glutamate transporters, Na+/K+-ATPase and cytoskeleton in astrocytes: evidence following inhibition with rottlerin.

Astrocytes are plastic cells that play key roles in brain physiology and pathology, including via their glutamate transporters, excitatory amino acid transporter (EAAT)1 and EAAT2, maintaining low extracellular glutamate concentrations and protecting against excitotoxic neuronal injury. Alterations in cell surface expression of EAATs and astrocytic cytoskeleton are important for regulating transporter activity. This study employed the actions of rottlerin, to interrogate the regulation of EAAT activity, expression and localization, and interfaces with Na(+)/K(+)-ATPase and astrocytic morphology. EAAT activity and expression were determined in primary cultures of mouse astrocytes in the presence of and after rottlerin removal, with or without trafficking inhibitors, using uptake ([(3)H]d-aspartate, (86)Rb(+)) and molecular analyses. Astrocytic morphology and EAAT localization were investigated using Western blotting and immunocytochemistry, in concert with image analysis of glial fibrillary acidic protein, F-actin and EAAT1/2. Rottlerin induced a time-dependent inhibition of glutamate transport (Vmax). Rapid changes in cytoskeletal arrangement were observed and immunoblotting revealed increases in EAAT2 total and cell surface expression, despite reduced EAAT activity. Rottlerin-induced inhibition was reversible and its rate was increased by monensin co-treatment. Rottlerin inhibited, while monensin stimulated Na(+)/K(+)-ATPase. Removal of rottlerin rapidly elevated Na(+)/K(+)-ATPase activity beyond control levels, while co-treatment with monensin failed to stimulate the Na(+)/K(+)-ATPase. These data reveal inhibition of EAAT activity by rottlerin is not associated with loss of EAATs at the cell surface, but rather linked to cytoskeletal rearrangement, and inhibition of the Na(+)/K(+)-ATPase. Rapid recovery of Na(+)/K(+)-ATPase activity, and subsequent restoration of glutamate uptake indicates that astrocytic morphology and EAAT activity are co-regulated by a tightly coupled, homeostatic relationship between l-glutamate uptake, the electrochemical gradient and the activity of the Na(+)/K(+)-ATPase.

Dengue surveillance by proxy: travellers as sentinels for outbreaks in the Pacific Islands.

Sensitive surveillance systems are crucial for effective control of infectious disease outbreaks, and regional surveillance could provide valuable data to supplement global systems, improve sensitivity and timeliness of reporting, or capture otherwise undetected outbreaks. In New Zealand (NZ), there are no endemic arboviral diseases in humans, and the majority of dengue cases are imported from neighbouring Pacific Islands where comprehensive surveillance systems are under development. From 1997 to 2009, 679 cases of dengue were reported in NZ (74·2% acquired from the Pacific Islands), and the patterns of reported incidence of dengue acquired from different islands closely reflected local reported incidence in those areas. NZ is therefore in a unique position to provide early alerts on dengue outbreaks in the Pacific Islands. Such a strategy would reduce disease burden in both the Pacific Islands and NZ, and provide a model for transnational collaboration in disease surveillance with regional as well as global benefits.

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients.

OBJECTIVES: The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in intensive care units in Malaysia is significant. Invasive MRSA infections are commonly treated with vancomycin. In clinical practice, the serum vancomycin trough concentration is used as a surrogate marker of vancomycin efficacy. A low concentration of vancomycin may result in less effective therapy and increase the risk of bacterial resistance. We evaluated the relationship between the resolution of MRSA infections and trough concentrations of vancomycin. METHODS: A total of 76 patients admitted between January 2005 and February 2011 were included in the study. Serum vancomycin trough concentration data were collected from the microbiology records. The clinical response was evaluated on the basis of clinical notes and culture test results. RESULTS: A total of 262 appropriate trough concentration data were included, with a median of 3 trough concentrations per patient. Fifty-four patients responded to vancomycin therapy. The initial trough concentration did not differ between responders and non-responders (p=0.135) but the corrected trough concentration was higher among responders than among non-responders (11.64±1.50 mg/l and 9.25±1.59 mg/l, respectively; p=0.036). The average total daily dose of vancomycin was significantly higher among the responders (p=0.008). CONCLUSION: In this critically ill population, a vancomycin dose of 15 mg/kg/day was found sufficient to produce optimal trough concentrations to eradicate the MRSA infection. This study demonstrated the significant relationship between response to treatment of MRSA infection and serum vancomycin trough concentrations.

Initial experience of cryoballoon catheter ablation for atrial fibrillation in Hong Kong.

OBJECTIVE. To report the initial experience in using cryoballoon catheter ablation in the treatment of atrial fibrillation in Hong Kong. DESIGN. Single-centre, prospective case series. SETTING. Regional hospital, Hong Kong. PATIENTS. Sixteen patients (mean age, 55 years; standard deviation, 14 years; 11 males) with paroxysmal (n=12) or persistent (n=4) atrial fibrillation. INTERVENTIONS. Pulmonary vein isolation by ablation with a 28-mm cryoballoon catheter. MAIN OUTCOME MEASURES. Safety, effectiveness, and learning curve of this procedure. RESULTS. Of 67 pulmonary veins, 61 (91%) could be successfully isolated with the cryoballoon alone. The remaining pulmonary veins were isolated with additional ablation using an 8-mm tip cryocatheter. One phrenic nerve palsy developed during right middle pulmonary vein ablation, which resolved. Another patient endured a minor guidewire dissection of the right inferior pulmonary vein. The mean (standard deviation) procedural and fluoroscopic times were 231 (32) and 62 (18) minutes, respectively. On comparing the first nine and last seven procedures, there was a significant improvement in procedural time (mean [standard deviation], 244 [32] vs 213 [24] minutes; P=0.04) and in the fluoroscopic time (70 [21] vs 51 [7] minutes; P=0.038). With a median follow-up of 21 months, nine (75%) of the 12 patients with paroxysmal atrial fibrillation and one (25%) of those four with persistent atrial fibrillation had no recurrence, without the use of anti-arrhythmic drugs. CONCLUSIONS. Pulmonary vein isolation by cryoballoon catheter ablation is safe and effective in treating patients with paroxysmal, but not for patients with persistent atrial fibrillation. A relatively short learning curve of around 10 cases was deemed appropriate.

The Rho kinase inhibitor Fasudil up-regulates astrocytic glutamate transport subsequent to actin remodelling in murine cultured astrocytes.

BACKGROUND AND PURPOSE: Glutamate transporters play a major role in maintaining brain homeostasis and the astrocytic transporters, EAAT1 and EAAT2, are functionally dominant. Astrocytic excitatory amino acid transporters (EAATs) play important roles in various neuropathologies wherein astrocytes undergo cytoskeletal changes. Astrocytic plasticity is well documented, but the interface between EAAT function, actin and the astrocytic cytoskeleton is poorly understood. Because Rho kinase (ROCK) is a key determinant of actin polymerization, we investigated the effects of ROCK inhibitors on EAAT activity and astrocytic morphology. EXPERIMENTAL APPROACH: The functional activity of glutamate transport was determined in murine cultured astrocytes after exposure to the ROCK inhibitors Fasudil (HA-1077) and Y27632 using biochemical, molecular and morphological approaches. Cytochemical analyses assessed changes in astrocytic morphology, F-/G-actin, and localizations of EAAT1/2. RESULTS: Fasudil and Y27632 increased [(3)H]-D-aspartate (D-Asp) uptake into astrocytes, and the action of Fasudil was time-dependent and concentration-related. The rapid stellation of astrocytes (glial fibrillary acidic protein immunocytochemistry) induced by Fasudil was accompanied by reduced phalloidin staining of F-actin and increased V(max) for [(3)H]-D-Asp uptake. Immunoblotting after biotinylation demonstrated that Fasudil increased the expression of EAAT1 and EAAT2 on the cell surface. Immunocytochemistry indicated that Fasudil induced prominent labelling of astrocytic processes by EAAT1/2. CONCLUSION AND IMPLICATIONS: These data show for the first time that ROCK plays a major role in determining the cell surface expression of EAAT1/2, providing new evidence for an association between transporter function and astrocytic phenotype. ROCK inhibitors, via the actin cytoskeleton, effect a consequent elevation of glutamate transporter function - this activity profile may contribute to their beneficial actions in neuropathologies.

Emerging tropical diseases in Australia. Part 1. Leptospirosis.

Human leptospirosis is a zoonotic disease of global importance that causes significant morbidity and mortality, particularly in developing nations. In this review, the history, epidemiology, transmission, clinical presentation and treatment of this disease, and its impact in Australia, are discussed. Central to this review is the delineation of diagnostic methods for the disease and the challenges that this disease presents for both the clinician and diagnostic laboratory. This information should furnish clinicians with an updated tool to help overcome a number of problems associated with the diagnosis of leptospirosis.

Successful living donor liver transplantation in portomesenteric thrombosis.

Chronic portal vein thrombosis (PVT) is often considered a relative contraindication for living donor liver transplantation due to the risks involved and higher morbidity. In this report, we describe a surgical strategy for living donor liver transplant in patient with complete PVT using venovenous bypass from the inferior mesenteric vein (IMV) and then using a jump graft from the IMV for portal inflow into the graft. IMV is a potential source for portal inflow in orthotopic liver transplant.

1700 Victims of intimate partner violence: characteristics and clinical outcomes.

OBJECTIVE: To investigate the demographics and clinical outcomes of intimate partner violence victims presenting to an emergency department. DESIGN: Retrospective, observational study. SETTING: Emergency department of a regional hospital in Hong Kong. PATIENTS: Adults presented with intimate partner violence during years 1999 to 2004. RESULTS: We assessed 1695 victims of intimate partner violence with a mean age of 39 (range, 18-84) years, of whom 87% were female. Most of the patients were in the age-group of 31 to 40 years and the overall male-to-female ratio was 1:7. In Tin Shui Wai and Yuen Long districts, such cases appeared to be on the increase. Nearly two thirds (65%) of all the victims presented to the emergency department outside the office hours of medical social workers. Approximately 10% had been abused once before, and 40% more than twice. The head (39%), face (30%), upper limbs (37%), and lower limbs (17%) were commonly the injured parts. The majority (73%) had mild injuries; severe injuries being relatively less common. The latter included lacerations or cuts (6.6%), nasal bone fractures (0.3%), limb fractures (0.8%), and ruptured tympanic membranes (0.9%). In-patient management was undertaken for 8% of the victims, due to physical injury in 68% of these individuals and psychological trauma in the remaining 32%. The hospital admission rate dropped from 12% in 2001 to 4% in 2004. CONCLUSIONS: Variations in demographic data had a significant impact on future service planning and management of intimate partner violence. Accident and Emergency Department and Emergency Medicine Ward services together with extended social worker support could provide timely, multidisciplinary care to meet the various needs of victims and subsequently reduce hospital admissions.

Current status of lung transplantation.

Two decades have passed since the first successful clinical lung transplant was performed in 1983, and, in the interim, lung transplantation has become the preferred treatment option for a variety of end-stage pulmonary diseases. Remarkable progress has been made in the field through refinement of technique and improved understanding of transplant immunology and microbiology. Unfortunately, donor shortages continue to limit the more widespread application of lung transplantation. In order to address this issue, marginal donors, living lobar and split lung donor techniques, and nonheartbeating donors have been used clinically to increase the number of donor lungs available. Chronic rejection of the lung allograft is currently the major hurdle limiting longterm survival. To date, prevention of known risk factors and treatment strategies have not lessened the devastating toll this process has on lung transplant survival. Better understanding of the cause of chronic rejection is needed in order to develop novel strategies for its treatment. Promotion of immune tolerance is a promising area that could potentially eliminate chronic rejection. The present article discusses recent advances in lung transplantation. It also details the major issues facing the field today. Only through continued clinical and experimental investigation will lung transplantation eventually reach its full potential.

Effects of pneumoperitoneum on hemodynamic and systemic immunologic responses to peritonitis in pigs.

BACKGROUND: Experimental evidence supporting the safety of laparoscopic intervention during sepsis is limited. The purpose of this study was to evaluate the effects of pneumoperitoneum on immunologic and hemodynamic responses to peritoneal sepsis. MATERIALS AND METHODS: A porcine model of peritonitis was created using an intraperitoneal autologous fecal inoculum. Pigs were then subjected to one of four procedures 24 h postinoculation (n = 6 per group): laparotomy, CO(2) laparoscopy, helium laparoscopy, and anesthesia only (1.5% isoflurane in 100% O(2), mechanical ventilation). Venous blood samples were obtained prior to inoculation, and at 24 (prior to procedure), 30, 48, 72, and 96 h postinoculation to determine white blood count (WBC) with differential, C-reactive protein (CRP), tumor necrosis factor, and bacteremia. Heart rate, end-tidal CO(2) (ETCO(2)), mean arterial blood pressure (MAP), and arterial blood gas variables were also measured at baseline and every 30 min throughout the procedure. RESULTS: Postoperative blood cultures confirmed systemic bacteremia in all groups at all time periods postinoculation. Following inoculation, WBC, band cell count, and CRP remained elevated above baseline in all groups throughout the study (P < 0.01). However, no significant differences in these parameters were observed among groups. In the CO(2) laparoscopy group, MAP, ETCO(2), and arterial pCO(2) were increased above baseline, while pH was decreased throughout the procedure (P < 0.01). CONCLUSIONS: In this animal model of peritonitis, CO(2) pneumoperitoneum induced hypercapnia, acidemia, and systemic hypertension intraoperatively, without a discernable effect on systemic immune function.