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The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study investigates the effects of SCG embedded into biodegradable polymer blends and aimed to formulate and characterise biomass-reinforced biocomposites using spent coffee ground (SCG) as reinforcement in PHB/PLA polymer blend. The effect of SCG filler loading and varying PHB/PLA ratios on the tensile properties and morphological characteristics of the biocomposites were examined. The results indicated that tensile properties reduction could be due to its incompatibility with the PHB/PLA matrixSCG aggregation at 40 wt% content resulted in higher void formation compared to lower content at 10 wt%. A PHB/PLA ratio of 50/50 with SCG loading 20 wt% was chosen for biocomposites with treated SCG. Biological treatment of SCG using Phanerochaete chrysosporium CK01 and Aspergillus niger DWA8 indicated P. chrysosporium CK01 necessitated a higher moisture content for optimum growth and enzyme production, whereas the optimal conditions for enzyme production (50-55 %, w/w) differed from those promoting A. niger DWA8 growth (40 %, w/w). SEM micrographs highlighted uniform distribution and effective wetting of treated SCG, resulting in improvements of tensile strength and modulus of biocomposites, respectively. The study demonstrated the effectiveness of sustainable fungal treatment in enhancing the interfacial adhesion between treated SCG and the PHB/PLA matrix., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tay Guan Seng reports financial support was provided by Universiti Sains Malaysia. Tay Guan Seng reports financial support and equipment, drugs, or supplies were provided by PMI Packaging Sdn. Bhd. Tay Guan Seng reports financial support and equipment, drugs, or supplies were provided by CY Enterprise Sdn. Bhd. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Management of outbreaks of the newly emerging pathogen Candida auris may include use of antimicrobial wash-mitts for decolonization. However, currently there is little clinical evidence to support the wide adoption of 'whole-body decolonization' as part of the protocol to effectively manage C. auris outbreaks. The aim of this study was to investigate the chemical tolerance of C. auris compared with the surrogate test organism Candida albicans as established in the European Standards (EN)., Methods: Two commercially available antiseptic-impregnated wash-mitts based on either chlorhexidine digluconate (CHG) or octenidine dihydrochloride (OCT) were studied. Comparison of susceptibility of C. auris and C. albicans was investigated based on the standardized test protocol EN 13624. Experiments were conducted using the impregnation liquid squeezed from the wash-mitts at a contact time of 30 s at different concentrations between 0.5% and 97% in the presence of low organic soiling., Findings: Yeasticidal efficacy according to EN 13624 was found for the OCT wash-mitts at 30 s at ≥10% concentration with C. albicans. In comparison, reduction ≥4 log 10 was found at a much lower concentration of ≥1% for both C. auris strains. For the CHG wash-mitts, efficacy against C. albicans was below 2 log 10 reduction at 97% concentration within 30 s. Efficacy against the two C. auris strains was around 3 log 10 reduction., Conclusion: Both C. auris strains were found to be significantly more susceptible when compared with C. albicans. Data also demonstrate that not all antiseptic-impregnated wash-mitts are equally effective against C. auris with OCT having a higher efficacy compared with CHG., (Copyright © 2023. Published by Elsevier Ltd.)

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Effective disinfection strategies are essential to prevent the spread of Mycobacterium tuberculosis. Tuberculocidal efficacy of disinfectants can be demonstrated by testing disinfectants in in-vitro tests, such as the well-established quantitative suspension test EN 14348 using Mycobacterium terrae as a surrogate organism in European disinfectant testing. In other European standard tests, such as EN 13727 and EN 13624, use of the pour plate technique is well established; however, in EN 14348, the spread plate technique alone is considered. Comparative experiments according to EN 14348 with M. terrae were conducted using a peracetic-acid-based disinfectant. Either the pour plate technique or the spread plate technique was used for cultivation. Differences in colony size and morphology were observed when comparing the growth of M. terrae on pour plates compared with spread plates. However, no significant differences in biocidal efficacy data were obtained when applying either spread plates or pour plates in the quantitative suspension test described in EN 14348 under both clean and dirty conditions., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Invasive pulmonary aspergillosis is increasingly identified as a complication of influenza, termed 'influenza-associated pulmonary aspergillosis' (IAPA)., Aims: To assess the morbidity and mortality of critically ill influenza patients with and without IAPA., Methods: PubMed, Cochrane Library, Scopus and Embase databases were searched for studies containing comparative data of critically ill influenza patients with IAPA. Primary outcomes were all-cause in-hospital and intensive care unit (ICU) mortality. Secondary outcomes were clinical characteristics; duration of invasive mechanical ventilation (IMV); ICU and hospital length of stay (LOS); and requirement for vasopressor, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO)., Findings: The incidence of IAPA was 28.8% in 853 critically ill influenza patients, with an overall mortality rate of 33.4%. No differences in age and comorbidities were observed. Patients with IAPA were predominantly male and received chronic corticosteroids. In-hospital (49.2% vs 27.0%; P=0.002) and ICU (46.8% vs 20.8%; P<0.001) mortality rates were higher among patients with IAPA than in patients without IAPA. A greater proportion of patients with IAPA required IMV, and had a prolonged IMV duration (mean 17.3 vs 10.5 days; P<0.001), ICU LOS (mean 26.8 vs 12.8 days; P=0.001) and hospital LOS (mean 38.7 vs 27.0 days; P=0.003). Patients with IAPA had greater disease severity and were significantly more likely to require vasopressor (76.4% vs 57.9%; P<0.001), RRT (45.7% vs 19.1%; P<0.001) and ECMO (25.9% vs 12.8%; P=0.004) support compared with patients without IAPA., Conclusions: A diagnosis of IAPA in critically ill patients is associated with greater morbidity and mortality. Early recognition and more research are needed to determine better diagnostic and treatment strategies., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Since the first appearance of Candida auris in 2009, this yeast has become a relevant pathogen in the clinical field. C. auris has been detected on various surfaces in health facilities, and is therefore a target for appropriate disinfection procedures. Preventive measures have to be implemented based on disinfectants with proven efficacy against C. auris., Aim: The chemical tolerance of C. auris was compared with the surrogate test organism Candida albicans as established in the European standards (EN). In this way, conclusions will be drawn as to whether the disinfectants tested according to EN 13624 and EN 16615 are at least equally effective against C. auris., Methods: The chemical susceptibility of C. auris and C. albicans was investigated using standardized EN test protocols. EN 13624 and EN 16615 were used in this study to examine two commercially available surface disinfectants based on alcohol and quaternary ammonium compounds (QACs), respectively. In addition, the survival rates of the two yeast species were studied on a defined test surface simulating practical conditions., Findings: In comparison with C. albicans, C. auris was found to be significantly more susceptible to the alcohol- and QAC-based disinfectants used in this study. C. albicans was found to be more tolerant to drying on the test surface in EN 16615, yielding higher recovery rates., Conclusion: C. albicans is a suitable surrogate test organism when targeting yeasticidal efficacy, which, based on EN 13624 and EN 16615, includes efficacy against the human pathogen C. auris., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Lesion length is a major predictor of adverse outcomes after percutaneous coronary intervention. Long lesions often require multiple stents with variable overlap, which increases the probability of geographical miss and the incidence of mechanical complications, such as side-branch occlusion, restenosis, and stent thrombosis. These pitfalls may be avoided by use of an ultra-long device., Methods: We retrospectively assessed the performance of the 48-mm Xience Xpedition everolimus-eluting stent (EES) at our institution., Results: A total of 123 patients (mean age: 60.94 years, n = 93 [76%] male) with 129 lesions were identified. Lesions (n = 69, 53.5%) were located in the left anterior descending artery, the right coronary artery (n = 47, 36.4%), and the circumflex artery (n = 8, 6.2%); 83 lesions involved a major side branch. The majority were treated with a provisional single-stent strategy. Other characteristics included significant tortuosity in 15 lesions (11.6%) and moderate-to-heavy calcification in 46 lesions (35.7%). In all cases, balloon pre-dilatation was performed before stent insertion. Successful delivery and deployment of the 48-mm EES device was achieved in 100% of the patients. The mean number of stents per lesion was 1.4, while the mean total stent length was 58 ± 17.3 mm and mean stent diameter, 3.00 ± 0.67 mm. The procedural success rate was 99.2%. The 30-day major cardiac adverse event (MACE) rate was 0.8%, while the 12-month MACE was 3.3%., Conclusion: The Xience 48-mm EES device appears to be safe and efficacious with a low clinical event rate at the 12-month follow-up. Where feasible, this would support the use of the ultra-long 48-mm platform in lieu of multiple overlapping shorter devices.

Background: Organ scarcity continues to be the main problem limiting the number of liver transplants performed. Outcomes of patients waitlisted for an organ in an Asian country with low organ donation rate have not been well evaluated. Our current policy of allocating 15 exception points to patients with hepatocellular carcinoma (HCC) to render them competitive for a transplant also requires review., Methods: The waiting list registry and the organ transplant registry of a single institution in Asia were reviewed from December 2005 to June 2016 for all patients who underwent liver transplantation. Patient characteristics and outcomes of waitlist dropouts were evaluated. Statistical analyses were performed using SPSS version 20.0., Results: One hundred seventy-three patients were waitlisted for a deceased donor liver-only transplant. The most common etiology of liver disease was hepatitis B, followed by cholestatic diseases. Approximately half of the patients had HCC (45.6%). Priority listing for transplant comprised 15.6% of cases. Median Model for End-Stage Liver Disease (MELD) at listing was 15, and median waiting time to transplant was 17 weeks (interquartile range = 6.5-43.5). Overall, 89 (51.4%) patients underwent liver transplantation and 68 (39.3%) dropped out. For patients with HCC, the most common cause of dropout was progression beyond University of California San Francisco transplant criteria (62.5%). The cumulative incidence of dropout at 3 months among patients with HCC who received exception MELD scores was 11%. This was higher than those listed with physiologic MELD of 14-16 points (7%) but lower than those with 17-19 points (16%)., Conclusions: Hepatitis B-related liver disease and HCC comprise the majority of patients listed for liver transplant. Dropout rates are high and this is due to the lack of donor organs. The current policy of allocating 15 exception MELD points to patients with HCC within transplant criteria may underestimate the dropout risk of patients with HCC in our population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The transmission of fungi via transplant, although well-known, has not often been molecularly proven. We describe a case of donor-derived candidiasis verified by whole genome sequencing., Case Description: The multiorgan donor was a 42-year-old woman with subdural hemorrhage. Procurement of the thoracic organs was performed followed by the abdominal organs. Tissue from the left bronchus grew Candida dubliniensis. The liver recipient was a 63-year-old woman with cryptogenic liver cirrhosis. She was noted to have worsening leukocytosis on postoperative day (POD) 9. Computed tomography of the abdomen and pelvis showed multiple rim-enhancing collections around the graft. Percutaneous drainage was performed. Fluid cultures grew C dubliniensis. C dubliniensis isolated from the donor's left bronchus and the liver recipient's abscesses were verified to be related by whole genome sequencing. We postulate that C dubliniensis colonizing the donor's transected trachea could have contaminated the inferior vena cava when the former was left open after explant of the donor's lungs. A portion of the donor's contaminated inferior vena cava was transplanted along with the liver graft, resulting in the infected collections in the recipient., Conclusions: Our case report highlights the importance of maintaining a sterile field during organ procurement, especially in a multiorgan donor whose organs are explanted in succession., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Calcinosis is a well-recognized manifestation of systemic sclerosis. Paraspinal or intraspinal calcinosis is rare, with reports of calcinosis involving the cervical, thoracic and lumbar separately, but not together. We now report a case of limited cutaneous scleroderma with extensive paraspinal calcinosis of the cervical and lumbar spine.

Toad glandular secretions and skin extractions contain many natural agents which may provide a unique resource for novel drug development. The dried secretion from the auricular and skin glands of Chinese toad (Bufo bufo gargarizans) is named Chansu, which has been used in Traditional Chinese Medicine (TCM) for treating infection and inflammation for hundreds of years. The sterilized hot water extraction of dried toad skin is named Huachansu (Cinobufacini) which was developed for treating hepatitis B virus (HBV) and several types of cancers. However, the mechanisms of action of Chansu, Huachansu, and their constituents within are not well reported. Existing studies have suggested that their anti-inflammation and anticancer potential were via targeting Nuclear Factor (NF)-κB and its signalling pathways which are crucial hallmarks of inflammation and cancer in various experimental models. Here, we review some current studies of Chansu, Huachansu, and their compounds in terms of their use as both anti-inflammatory and anticancer agents. We also explored the potential use of toad glandular secretions and skin extractions as alternate resources for treating human cancers in combinational therapies.

Vancomycin has been documented to cause various adverse cutaneous reactions. We present a case report of a man, who developed a large localized erythematous plaque in his forearm following parenteral vancomycin therapy. We believe this to be the first reported case of such cutaneous reaction associated with parenteral vancomycin therapy.

A study was conducted to investigate the influence of Asian monsoon on chlorophyll-a (Chl-a) content in Sabah waters and to identify the related oceanographic conditions that caused phytoplankton blooms at the eastern and western coasts of Sabah, Malaysia. A series of remote sensing measurements including surface Chl-a, sea surface temperature, sea surface height anomaly, wind speed, wind stress curl, and Ekman pumping were analyzed to study the oceanographic conditions that lead to large-scale nutrients enrichment in the surface layer. The results showed that the Chl-a content increased at the northwest coast from December to April due to strong northeasterly wind and coastal upwelling in Kota Kinabalu water. The southwest coast (Labuan water) maintained high concentrations throughout the year due to the effect of Padas River discharge during the rainy season and the changing direction of Baram River plume during the northeast monsoon (NEM). However, with the continuous supply of nutrients from the upwelling area, the high Chl-a batches were maintained at the offshore water off Labuan for a longer time during NEM. On the other side, the northeast coast illustrated a high Chl-a in Sandakan water during NEM, whereas the northern tip off Kudat did not show a pronounced change throughout the year. The southeast coast (Tawau water) was highly influenced by the direction of the surface water transport between the Sulu and Sulawesi Seas and the prevailing surface currents. The study demonstrates the presence of seasonal phytoplankton blooms in Sabah waters which will aid in forecasting the possible biological response and could further assist in marine resource managements.

Recent findings on the role of transforming growth factor (TGF)-β/Smad3 signaling in the pathogenesis of obesity and type 2 diabetes have underscored its importance in metabolism and adiposity. Indeed, elevated TGF-β has been previously reported in human adipose tissue during morbid obesity and diabetic neuropathy. In this review, we discuss the pleiotropic effects of TGF-β/Smad3 signaling on metabolism and energy homeostasis, all of which has an important part in the etiology and progression of obesity-linked diabetes; these include adipocyte differentiation, white to brown fat phenotypic transition, glucose and lipid metabolism, pancreatic function, insulin signaling, adipocytokine secretion, inflammation and reactive oxygen species production. We summarize the recent in vivo findings on the role of TGF-β/Smad3 signaling in metabolism based on the studies using Smad3(-/-) mice. Based on the presence of a dual regulatory effect of Smad3 on peroxisome proliferator-activated receptor (PPAR)β/δ and PPARγ2 promoters, we propose a unifying mechanism by which this signaling pathway contributes to obesity and its associated diabetes. We also discuss how the inhibition of this signaling pathway has been implicated in the amelioration of many facets of metabolic syndromes, thereby offering novel therapeutic avenues for these metabolic conditions.

In contrast to bacteraemic pneumococcal community-acquired pneumonia (CAP), there is a paucity of data on the clinical characteristics and outcomes of non-bacteraemic pneumococcal CAP. This retrospective study compared the outcome of hospitalized patients with bacteraemic and non-bacteraemic pneumococcal CAP treated at a medical centre from 2004 to 2008. Data on clinical outcomes including all-cause mortality, length of hospital stay, need for intensive-care unit admission and extrapulmonary involvement were analysed. In all, 221 patients with pneumococcal pneumonia (87 bacteraemic, 134 non-bacteraemic) were included. Patients with bacteraemic pneumococcal pneumonia (BPP) were older than those with non-BPP (46·2 ± 30·7 years vs. 21·7 ± 30·8 years, P<0·001) and were more likely to have underlying medical diseases (66·7% vs. 33·6%, P<0·001). The overall mortality rates at 7, 14, and 30 days were significantly higher in BPP than non-BPP patients (12·6% vs. 2·2%, 14·9% vs. 3·7%, 19·5% vs. 5·1%, all P<0·01). Multivariate logistic regression analysis showed that pneumococcal bacteraemia was correlated with extrapulmonary involvement (odds ratio 5·46, 95% confidence interval 1·97-15·16, P=0·001). In conclusion, S. pneumoniae bacteraemia increased the risk of mortality and extrapulmonary involvement in patients with pneumococcal CAP.

The aim of this study was to evaluate the diagnostic performance of an enzyme-linked immunospot (ELISPOT) assay for interferon-γ in patients with suspected skeletal tuberculosis (TB). From March 2007 to June 2010, a total of 36 patients with suspected skeletal TB in a tertiary care hospital in Taiwan were enrolled. Twelve patients (35.3%) had culture-confirmed TB, three (8.8%) patients had probable TB, and the remaining 21 (58.3%) patients did not have TB. Fourteen patients with mycobacterial infection had available biopsy or surgical specimens for histopathological examination and 12 (85.7%) specimens had pathological features consistent with mycobacterial infection. Among the 12 patients with positive findings indicating mycobacterial infection, all seven patients with spinal TB and three of five patients with TB arthritis had positive ELISPOT assays. All nine patients with spinal TB had positive ELISPOT assays, but only four of six patients with TB arthritis had positive ELISPOT assays. The sensitivity, specificity, positive predictive value, and negative predictive value for skeletal TB diagnosis by the ELISPOT assay were 86.7%, 61.9%, 61.9%, and 86.7%, respectively. In conclusion, the ELISPOT assay can provide useful support in diagnosing skeletal TB, and spinal TB can be excluded based on a negative ELISPOT assay.

The aim of this study was to investigate the clinical significance of nontuberculous mycobacteria (NTM) isolates in elderly Taiwanese patients. From 2004 through 2008, patients >65 years old with NTM isolation were identified. The definitions of NTM disease followed the American Thoracic Society and Infectious Disease Society of America (ATS/IDSA) criteria. Among the 3,175 NTM isolates, Mycobacterium avium complex (MAC; n = 1,118, 35.2%) was the most prevalent species, followed by M. abscessus (n = 545, 17.2%). Among the 1,633 elderly patients with NTM isolates, the most prevalent NTM species were MAC (n = 592, 36.3%) and M. fortuitum complex (n = 311, 19.0%). NTM colonization was found in 1,339 (80.4%) patients and only 326 (19.6%) patients had NTM diseases. During the study period, the annual incidence rates (per 100,000 inpatients and outpatients) of NTM colonization and disease both increased significantly (p < 0.0001) from 10.5 to 15.8 and from 2.1 to 4.3, respectively. Isolated pulmonary NTM infections compromised 294 (90.2%) of the 326 elderly cases of NTM disease. In conclusion, this study found an increasing trend in the incidence of both NTM isolates and NTM diseases among elderly Taiwanese patients. MAC and M. abscessus were the most frequent species causing various types of NTM disease.

Background: Treatment with corticosteroids can reduce the incidence of postextubation stridor (PES) and reintubation in critically ill adult patients, but the mechanisms remain unknown., Methods: A randomized, controlled clinical trial was conducted in an adult medical and surgical Intensive Care Unit (ICU) of a teaching hospital. Seventy-one patients who had a cuff leak percentage <24% of tidal volume received either a bolus injection of methylprednisolone at 40 mg (treated group, n=38) or normal saline (placebo group, n=33) 4 h prior to a planned extubation. The cuff leak percentage was re-assessed 1 h and 4 h post-injection. Eighty patients who had a cuff leak percentage ≥ 24% served as a control group. Plasma concentrations of multiple cytokines and C-reactive protein (CRP) were measured at baseline, 4 h and 24 h after the intervention., Results: The incidences of PES (15.8% vs. 39.4%, P<0.05) and reintubation rate (7.9% vs. 30.3%, P<0.05) were lower in the treated group compared to the placebo group. The plasma concentrations of IL-4 and IL-10 increased while the levels of IL-6 and IL-8 decreased at 24 h in the treated group compared to the placebo group. No difference in CRP levels was observed between the treated and placebo groups., Conclusion: A single injection of methylprednisolone at the dose used 4 h prior to planned extubation effectively reduced the incidence of PES and the reintubation rate. These beneficial effects were associated with the up-regulation of IL-4 and IL-10 and the down-regulation of IL-6 and IL-8 in the critically ill adult patients.

We report a case of combined heart and liver transplantation for familial amyloid polyneuropathy. This is the first such combined transplant performed in Asia, and differs from previously described cases, in that cardiopulmonary bypass was continued at partial flow during liver transplantation in our case. This was done in order to provide haemodynamic support to the cardiac graft and to protect it from the impending reperfusion insult that frequently accompanies liver transplantation. The utility of this management course is discussed, along with its actual and potential complications. We also describe the impact of a lung-protective ventilation strategy employed during cardiac transplantation.

All patients with urine culture-confirmed genitourinary tuberculosis (GUTB) diagnosed between 1995 and 2007 at two medical centers in northern Taiwan were included in this retrospective study. Genotypes of 48 preserved Mycobacterium tuberculosis (MTB) isolates from these patients were determined by spoligotyping and double repetitive element PCR (DRE-PCR) analysis. Among the 64 patients, 38 (59.4%) were male with a mean ±SD age of 60.3 ± 16.1 years old. The overall mortality rate was 26.2%. Poor prognostic factors included age over 65 years (HR = 4.03; 95%; CI: 1.27-12.76), cardiovascular disease (HR = 5.96; 95% CI: 1.98-17.92), receiving steroids (HR = 10.16; 95% CI: 2.27-45.47), not being treated (HR 4.81; 95% CI 1.12-20.67). Spoligotyping and DRE-PCR of the 48 MTB isolates revealed that 20 (41.7%) belonged to the Beijing family and 40 (83.3%) had a clustering pattern. Identification of a Beijing family isolate was not correlated with drug resistance or mortality. Clustering strains were likely to be resistant to isoniazid (OR = 4.71; 95% CI: 1.10 to 23.53). In this study of patients with urine culture-confirmed GUTB, age and coexisting diseases were independently associated with an unfavorable outcome. The Beijing family was the dominant genotype of GUTB isolates, but did not correlate with drug resistance or outcome.

We describe five patients with positive blood culture for Kocuria species. Three patients had catheter-related bacteraemia and one had infective endocarditis caused by Kocuria kristinae, and one had a K. marina isolate, which was considered to be a contaminant. Identification of the isolates was further confirmed by 16S rRNA gene sequence analysis. In conclusion, Kocuria species are an unusual cause of infection in immunocompromised patients. Accurate identification with molecular methods is imperative for the diagnosis of these unusual pathogens., (© 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases.)

This study investigated the correlation between antibiotic consumption and resistance among Staphylococcus aureus and enterococci causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009. Overall, the trend of total consumption (defined daily dose [DDD] per 1,000 patient-days) of glycopeptides, including vancomycin and teicoplanin, significantly increased during 2000 to 2003 and remained stable during 2004-2009. Vancomycin consumption significantly increased during 2003 and decreased after 2004. A significant decrease in the resistance rate with time was found for oxacillin- and gentamicin-resistant S. aureus. In contrast, the rates of vancomycin- and teicoplanin-resistant enterocci increased significantly. A significant correlation was found between the increased use of extended-spectrum cephalosporins, β-lactam-β-lactamase inhibitor combinations, carbapenems and the decreased prevalence of methicillin-resistant S. aureus (MRSA). In contrast, the increased use of teicoplanin, extended-spectrum cephalosporins, β-lactam-β-lactamase inhibitor combinations, and carbapenems was correlated with the increased prevalence of vancomycin-resistant enterococci (VRE). In conclusion, this 10-year study in a single institution identified different correlations between the prescription of antibiotics and the resistance rates of MRSA and VRE. Strict implementation of infection control policy based on these correlates would be helpful in decreasing the presence of these multidrug-resistant pathogens in hospitals.

The aim of this study was to investigate the clinical, microbiological, and pathological characteristics and the outcomes of skin and soft-tissue infection (SSTI) caused by non-tuberculous mycobacteria (NTM). Medical records of 50 patients with SSTI caused by NTM identified from 2005 to 2008 and 63 patients previously reported in a medical centre from 1997 to 2004 were reviewed. The annual incidence (per 100,000 outpatients and in-patients) ranged from 0·57 in 2005, 0·38 in 2007, to 1·1 in 2008, with an average of 0·62/100,000. From 1997 to 2008, the average incidence was 1·39/100,000 patients. The average annual incidence of SSTI caused by NTM was 0·62/100,000 outpatients and in-patients during 2005 and 2008. Of the total of 113 patients identified during the 12-year period, patients infected with Mycobacterium fortuitum and M. marinum were younger than those infected with M. avium-intracellulare complex (MAC) (36 and 44 years vs. 55 years, P=0·004 and P=0·056, respectively), and were more likely to have previous invasive procedures than those infected with MAC and M. abscessus (81·8% and 72·0% vs. 27·8% and 54·8%, P=0·007), and less likely to have associated immunosuppression (9·1% and 24% vs. 66·7% and 45·2%, P=0·006). Granuloma was more often observed in immunocompetent patients (60·1% vs. 40%, P=0·019), and in M. marinum-infected specimens (78·3%). There were significant differences in the demographic and clinical features of patients with NTM SSTI, including immunosuppression, trauma experience, and depth of tissue infections.

We have previously reported that microthrottle pumps (MTPs) display the capacity to pump solid phase suspensions such as polystyrene beads which prove challenging to most microfluidic pumps. In this paper we report employing a linear microthrottle pump (LMTP) to pump whole, undiluted, anticoagulated, human venous blood at 200 μl min(-1) with minimal erythrocyte lysis and no observed pump blockage. LMTPs are particularly well suited to particle suspension transport by virtue of their relatively unimpeded internal flow-path. Micropumping of whole blood represents a rigorous real-world test of cell suspension transport given blood's high cell content by volume and erythrocytes' relative fragility. A modification of the standard Drabkin method and its validation to spectrophotometrically quantify low levels of erythrocyte lysis by hemoglobin release is also reported. Erythrocyte lysis rates resulting from transport via LMTP are determined to be below one cell in 500 at a pumping rate of 102 μl min(-1).

This study analysed the clinical characteristics of bacteraemia due to unusual Citrobacter species. All non-freundii and non-koseri Citrobacter isolates were identified to species level by two commercial identification methods and 16S rRNA gene sequence analysis. A total of 306 patients with Citrobacter spp. bacteraemia were identified from January 2000 through December 2009. Four patients (1.3%) had C. braakii bacteraemia, and one had C. amalonaticus and C. sedlakii sepsis, respectively. Misidentification as non-freundii and non-koseri Citrobacter spp., which occurred in eight isolates with the Phoenix automated system PMIC/ID-30 and three with the Vitek II system, occurred in five of six infection episodes. Among the six patients with bacteraemia caused by non-freundii and non-koseri Citrobacter spp., five (83.3%) had healthcare-associated infection and five (83.3%) infections were secondary to intra-abdominal infection. Cancer and liver cirrhosis were the commonest underlying diseases. An attributable mortality was 33.3%. Antimicrobial susceptibility testing showed that the resistance patterns varied among different Citrobacter species. Non-freundii and non-koseri Citrobacter species are difficult to identify and are a rare cause of intra-abdominal infections with secondary healthcare-associated bacteraemia in immunocompromised patients., (Copyright © 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.)

We retrospectively investigated the prevalence of drug resistance in Mycobacterium tuberculosis (MTB) isolates recovered from elderly patients and compared the drug resistance patterns between the elderly (≥65 years old) and adult (15-64 years old) patients. Data on the prevalence of drug resistance in clinical and non-duplicate isolates of MTB recovered from 2000 to 2008 were evaluated. Among the 3,186 non-duplicate MTB isolates found during the study period, 1,497 isolates were recovered from elderly patients. Thirty-eight (2.54%) isolates were multidrug-resistant tuberculosis (MDRTB). The rates of resistance to isoniazid (INH), rifampicin (RIF), ethambutol (EMB), streptomycin (SM), ofloxacin, rifabutin, any one drug-resistant (ADR), and multidrug-resistant (MDR) were significantly lower in isolates from the elderly than from adults (p < 0.05). Significant decreasing trends in resistance rates to EMB, SM, at least any one of the four first-line agents (ADR), and MDRTB were observed (p < 0.05) . In conclusion, elderly patients had a lower rate of anti-TB drug resistance than adults and a decreasing overall trend of anti-TB drug resistance was found in the elderly in recent years, but the higher rate of MDRTB in Taiwan continues to present a challenge for the control of TB in the elderly.

The aim of this study was to evaluate the support to tuberculosis diagnosis of a new immunological tool, an enzyme-linked immunospot (ELISPOT) assay for interferon-γ, in diabetic patients. From March 2007 to January 2008, diabetic patients with suspected pulmonary tuberculosis were enrolled in a tertiary care hospital. Data on clinical characteristics of the patients and conventional laboratory results were collected and blood samples were obtained for ELISPOT assay (T SPOT-TB; Oxford Immunotec Ltd, Oxford, UK). A total of 84 patients with suspected pulmonary tuberculosis were recruited. Fifty-one (60.7%) of these patients were considered to have pulmonary tuberculosis, including 42 (50%) with confirmed tuberculosis and 9 (10.7%) with probable tuberculosis. The overall (confirmed and probable tuberculosis) sensitivity, specificity, positive predictive value and negative predictive value of the ELISPOT assay were 84.3%, 66.7%, 79.6%, and 73.3%, respectively. The negative predictive value of the ELISPOT assay was significantly higher in patients with adequate glycaemic control (90% vs 56.3%). In conclusion, the ELISPOT assay can provide useful support in diagnosing pulmonary tuberculosis in diabetic patients, especially those with adequate glycaemic control.

The inability of conventional identification systems to accurately identify Gordonia spp. often results in the misdiagnosis of infections by these rare pathogens, which require genomic sequencing for precise identification. In the present study, we describe nine cases of the various types of infection caused by Gordonia spp. From 1997 to 2008, 66 isolates (from 30 patients) initially identified as Rhodoccus spp. by conventional biochemical methods, by the Bacteriology Laboratory of National Taiwan University Hospital, were retrospectively analysed to assess the accuracy of species identification. Fifteen of these isolates (from nine patients) were later found to be Gordonia spp. by two molecular methods: PCR-restriction fragment length polymorphism for heat shock protein gene (hsp65) and the 16S rRNA gene sequencing analysis. Gordonia sputi (n = 8) was the most common species, followed by Gordonia terrae (n = 7). Most of the isolates were isolated from blood (n = 11), followed by soft tissue (n = 2) and eye (n = 2). Five patients presented with bacteraemia and two of these had catheter-related bloodstream infection. Two patients had soft tissue infections and another two patients had infective keratitis and conjunctivitis. The random amplified polymorphic DNA patterns for isolates from different patients were different, indicating that they were genetically unrelated. Accurate identification with molecular methods is required if the role of Gordonia spp. in causing infection is to be recognized., (© 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases.)

The genus of Nocardia is rapidly expanding and the species distribution varies with different geographical locations. We retrospectively reviewed the laboratory records of the bacteriology laboratory at National Taiwan University Hospital from January 1998 to June 2008 to identify patients with nocardiosis. During the study period, 164 isolates of Nocardia spp. were identified from 134 patients but only 113 patients had Nocardia infection. Nocardia brasiliensis (n = 54) was the most common pathogen, followed by N. asteroides (n = 36), N. farcinica (n = 7), N. flavorosea (n = 4), N. otitidiscaviarum (n = 3), N. nova (n = 3), N. beijingensis (n = 2) and one each of N. puris, N. jinanensis and N. takedensis. The major types of infection were cutaneous infection (56.6%), pulmonary infection (33.6%) and disseminated infection (7.1%). Eighty-eight patients received sulfonamide-containing antibiotic and eight of 100 patients with available data on outcomes died during the episode of nocardiosis. In conclusion, the clinical and microbiological manifestations of Nocardiosis vary with the different Nocardia species. Accurate identification of the species is crucial to make the diagnosis.

The clinical characteristics and outcomes of 71 patients with mycobacterial bacteraemia, infected with human immunodeficiency virus (HIV) (n = 47) and not infected with HIV (n = 24) are described. Mycobacterium avium complex (MAC) (54.9%) constituted the most frequently isolated mycobacterium, followed by Mycobacterium tuberculosis (MTB) (38.0%), Mycobacterium kansasii (4.2%), and Mycobacterium abscessus (2.8%). The Beijing family genotype was the most common type in MTB, and Mycobacterium intracellulare was the most common species in MAC. The overall mortality rate was 33.8%; it was lower in HIV-infected than in non-HIV-infected patients. HIV-infected patients were younger, had fewer underlying diseases and better nutritional status, and were more likely to have MAC bacteraemia than MTB bacteraemia.

The aims of this study were to compare the clinical features of patients with extensively drug-resistant tuberculosis (XDRTB) and multidrug-resistant tuberculosis (MDRTB) and the genotypic characteristics of these Mycobacterium tuberculosis isolates. A total of 90 non-HIV-infected patients having MDRTB (n = 80, not including XDRTB, 88.9%) and XDRTB (n = 10, 11.1%) were identified from 2000 to 2007. Genotypes of the 39 available isolates were evaluated by spoligotyping and the 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) scheme. Patients with XDRTB were more likely to have previous history of TB and cavitary lung lesions than patients with MDRTB (P < 0.05). Among the 39 isolates for spoligotyping analysis, the Beijing genotype was the most common (n = 21, 53.8%). Four (44.4%) isolates of XDRTB and 17 (56.7%) isolates of MDRTB belonged to Beijing family genotypes. There was no significant difference in the anti-tuberculosis drug resistance rates between Beijing and non-Beijing genotype isolates or in the clinical features of infected patients. In conclusion, significant differences in clinical manifestations existed among patients with XDRTB and MDRTB. The clinical features of patients infected with the Beijing genotype and the drug resistance profile of the Beijing genotype isolates were similar to those for the non-Beijing family genotype.

The Legionella species is an important cause of communityand hospital-acquired pneumonia. Bacteremic pneumonia caused by L. pneumophila is rarely reported. We describe the first reported case of hospital-acquired pneumonia and bacteremia caused by L. pneumophila from Taiwan in a patient with idiopathic thrombocytopenic purpura who received steroid treatment. The patient was successfully treated with ceftazidime and clindamycin initially, followed by ciprofloxacin for 14 days. The blood isolate was further confirmed by 16S rDNA sequence analysis.

In Taiwan, the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 7-valent pneumococcal conjugate vaccine (PCV7) have been available since January 2001 and October 2005, respectively. A hospital-based surveillance of invasive pneumococcal disease (IPD) in a medical center was conducted from 2000 to 2008 to evaluate the epidemiologic changes after pneumococcal vaccination. A total of 337 episodes in 328 patients were identified. The cumulative coverage rate of PPV23 among persons of age >or=75 years increased from 12% in 2007 to 41% in 2008, and that of PCV7 among children aged <5 years was 0.7% in 2005 and 25.2% in 2008. The annual incidence of IPD decreased from 6.2 cases per 10,000 hospitalizations in 2000-2005 to 3.8 cases in 2006-2008 (38.5% reduction, P < 0.001), but the fatality rate did not change significantly (24.4% and 21.8%, P = 0.74). The serotype coverage rates of PPV23 and PCV7 were not significantly different between 2000-2005 and 2006-2008 (both P > 0.05). A marked increase of serotype 19A from 2000-2005 (0.5%) to 2006-2008 (11.5%) was found (P < 0.001). In summary, a decline in IPD incidence but not in fatality rate occurred after the availability of PCV7 and the increased usage of PPV23. The rapid emergence of serotype 19A during this period is alarming.

Objectives: To evaluate diagnostic performance of an enzyme-linked immunospot assay for interferon-gamma (T SPOT-TB) in patients with suspected extrapulmonary tuberculosis (TB)., Methods: From January 2007 to December 2008, patients with suspected extrapulmonary TB were prospectively enrolled from 2 tertiary care hospitals., Results: A total of 138 patients with suspected extrapulmonary TB were enrolled; 50 patients had positive culture for Mycobacterium tuberculosis and 39 patients had probable TB. The sites of infection were lymph node (n = 20), pleura (n = 19), bone/joint (n = 15), urinary tract (n = 7), peritoneum (n = 7), meninges (n = 6), disseminated (n = 5), intestine (n = 3), pericardium (n = 2), skin (n = 2), throat (n = 1), neck (n = 1), and genitalia (n = 1). The overall sensitivity and specificity were 79.8% (71/89) and 81.6% (40/49). The sensitivity ranged from 100% for tuberculous meningitis, tuberculous pericarditis, and intestinal TB, 95% for lymphadenitis, to 42.9% for tuberculous peritonitis. The sensitivity of the T SPOT-TB assay was 70.6% in immunocompromised patients and 85.5% in immunocompetent patients (p = 0.09)., Conclusions: The T SPOT-TB assay can be a useful tool for diagnosing extra-pulmonary TB in immunocompetent and immunocompromised patients, particularly for tuberculous meningitis, pericarditis, lymphadenitis, and intestinal TB.

Thermoresponsive polymer-coated magnetic nanoparticles loaded with anti-cancer drugs are of considerable interest for novel multi-modal cancer therapies. Such nanoparticles can be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release. Gamma-Fe(2)O(3) iron oxide magnetic nanoparticles (MNP) with average sizes of 14, 19 and 43 nm were synthesized by high temperature decomposition. Composite magnetic nanoparticles (CNP) of 43 nm MNP coated with the thermoresponsive polymer poly-n-isopropylacrylamide (PNIPAM) were prepared by dispersion polymerization of n-isopropylacrylamide monomer in the presence of the MNP. In vitro drug release of doxorubicin-(dox) loaded dehydrated CNP at temperatures below and above the lower critical solution temperature of PNIPAM (34 degrees C) revealed a weak dependence of drug release on swelling behavior. The particles displayed Fickian diffusion release kinetics; the maximum dox release at 42 degrees C after 101 h was 41%. In vitro simultaneous hyperthermia and drug release of therapeutically relevant quantities of dox was achieved, 14.7% of loaded dox was released in 47 min at hyperthermia temperatures. In vivo magnetic targeting of dox-loaded CNP to hepatocellular carcinoma (HCC) in a buffalo rat model was studied by magnetic resonance imaging (MRI) and histology. In summary, the good in vitro and in vivo performance of the doxorubicin-loaded thermoresponsive polymer-coated magnetic nanoparticles suggests considerable promise for applications in multi-modal treatment of cancer.

Background: Transient elastography (TE) is a reliable non-invasive predictor of hepatic fibrosis, but data on TE in Asians are limited., Aim: To evaluate prospectively the accuracy of TE for diagnosis of hepatic fibrosis in Asians compared with APRI (aspartate transaminase to platelet ratio index)., Methods: One hundred and twenty consecutive patients who underwent liver biopsy were enrolled. TE (Fibroscan) was performed by two independent operators. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) were used to evaluate the accuracy of TE and APRI in diagnosing significant fibrosis (F >or= 2) and cirrhosis (F4)., Results: Predominant aetiologies were hepatitis B (48%), non-alcoholic steatohepatitis (14%) and hepatitis C (8%). TE was unsuccessful in five patients (4.2%) because of small inter-costal space (three patients), obesity and ascites. There was good correlation between TE and fibrosis (r = 0.606). AUROC for diagnosis of significant fibrosis was 0.856 (95% CI 0.779-0.932) for TE and 0.673 (95% CI 0.568-0.777) for APRI. AUROC for diagnosis of cirrhosis was 0.924 (95% CI 0.857-0.990) for TE and 0.626 (95% CI 0.437-0.815) for APRI. Optimal TE value was 9.0 kPa for diagnosis of significant fibrosis and 16.0 kPa for cirrhosis with specificity/sensitivity/PPV/NPV/accuracy of 82.6%/85.2%/80.9%/86.7%/84.1% and 88.9%/82.7%/32.0%/98.8%/83.2%, respectively., Conclusions: Transient elastography is a reliable predictor of hepatic fibrosis in Asians. Failure of TE in Asians is commonly because of small inter-costal space. TE is superior to APRI for non-invasive diagnosis of hepatic fibrosis and cirrhosis.

Introduction: To characterise the anthropometrical and metabolic parameters of a group of non-diabetic and non-obese patients who had histologically-proven nonalcoholic steatohepatitis (NASH)., Methods: During September 1997 to November 1999, consent for liver biopsies were sought from a consecutive series of patients, whose body mass index (BMI) were equal to or less than 30 kg per square metres, and who had persistently elevated serum alanine transaminase (more than 2.5 times upper limit of normal for more than six months), with no associated viral hepatitis, alcohol or drug-induced liver disease, hereditary liver disease and diabetes mellitus. Patients who were found to have steatohepatitis histologically were further studied. Their body weight, height, waist and hip circumferences were taken, and fasting serum lipid and glucose measured. Serum insulin was measured in six patients and insulin resistance (IR) was calculated by homeostasis model assessment. Oral glucose tolerance tests were done if fasting glucose levels were greater than 6 mmol/L. All liver biopsies were reviewed by a single histopathologist. Three age- and sex-matched controls were randomly selected for each patient., Results: 11 of 12 patients who underwent liver biopsies were found to have NASH. All 11 were Chinese: eight males and three females. 73 percent of them had hepatic fibrosis. Overall, compared to controls, they had significantly higher body weight, BMI, IR and triglyceridaemia. The female patients also had a higher waist-hip ratio than controls. None had diabetes mellitus, and one had impaired glucose tolerance/fasting glycaemia. Nine out of 11 had BMI between 25 and 30 kg per square metres., Conclusion: Significant histological changes of NASH with hepatic fibrosis were found in Singaporean Chinese non-diabetic patients with BMI of less than 30 kg per square metres.

A 28-year-old Malay woman presented with recurrent abdominal pain for five years. She had delivered her child seven months earlier. She was found to have bicytopenia, with a haemoglobin level of 7.9 g/dL and a platelet count of 85 x 10(9)/L. Computed tomography revealed a wandering spleen. Complications of a wandering spleen, for which splenectomy is advocated, include functional asplenia (due to torsion of the splenic pedicle), splenic infarction or splenic vessel thrombosis. A splenectomy was performed and at operation, splenomegaly with a long mesentery was found. Splenic histology was negative for malignancy. The bicytopenia resolved postoperatively, and she remains well.

Visual disturbances in dengue infection are uncommon but may result in permanent visual impairment. We report a 32-year-old Chinese woman with dengue infection and she developed retinal haemorrhage, retinal vasculitis and macular detachment. Autoimmune screen revealed a low C4 complement level, possibly due to partial C4 complement deficiency. The patient was treated with steroids and there was significant improvement in her vision. Partial C4 deficiency predisposes to autoimmune disease, and patients with pre-existing low C4 levels may be susceptible to ocular complications in dengue infection. Interestingly, previous case reports of ophthalmic complications of dengue infection occurred in young female patients, who are likewise predisposed to autoimmune disease. In conclusion, in individuals predisposed to autoimmune disease (females and patients with partial C4 deficiency), dengue infection may provide the antigenic trigger for immune complex deposition and retinal vasculitis. Steroids may have an important role in the treatment of this condition.

Dynamic contrast-enhanced (DCE) imaging using MRI or CT is emerging as a promising tool for diagnostic imaging of cerebral disorders and the monitoring of tumor response to treatment. In this study, we present a robust and efficient deconvolution method based on a linearized model of the impulse residue function, which allows for the mapping of functional cerebral parameters such as cerebral blood flow, volume, mean transit time, and permeability. Monte Carlo simulation studies were performed to study the accuracy and stability of the proposed method, before applying it to clinical study cases of patients with cerebral tumors imaged using DCE CT. Functional parameter maps generated using the proposed method revealed the locations of the cerebral tumors and were found to be of sufficiently good clarity for marked regional differences in tissue vascularity and permeability to be assessed. In particular, tumor visualization and delineation were found to be better on the parameter maps that were indicative of the breakdown of the blood-brain barrier.