INTRODUCTION: Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes. METHODS: Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS). RESULTS: At a median follow-up duration of 102 (range 3-357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression. CONCLUSION Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.
Adjuvants, Immunologic/therapeutic use* ; Administration, Intravesical ; BCG Vaccine/therapeutic use* ; Diabetes Mellitus ; Disease Progression ; Humans ; Male ; Metformin/therapeutic use* ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; Urinary Bladder Neoplasms/drug therapy*

In the original publication the bands in Fig. 1J and Fig. 2B were not visible. The correct versions of Fig. 1J and Fig. 2B are provided in this correction.

Background: Venous thromboembolism (VTE) is a serious complication that may occur after total knee arthroplasty (TKA), leading to the recommendation of routine chemoprophylaxis by international guidelines. This study aims to determine if short-duration chemoprophylaxis after TKA reduces the incidence of VTE in an Asian population. Methods: A retrospective study of 316 patients who underwent unilateral primary TKA between 1 January 2011 and 31 December 2013 was conducted. All patients received mechanical prophylaxis. One hundred seventeen patients (37%) received additional chemoprophylaxis, whereas 199 patients (63%) did not. A Doppler ultrasound (DUS) of both lower limbs was conducted for all patients within 6 days after surgery (median = 3 days) to assess for both proximal and distal DVT. Chemoprophylaxis in the form of enoxaparin (low molecular weight heparin; LMWH), aspirin, or heparin was administered until patients had a normal DUS, for a median duration of 4 days. Patients were followed up clinically for a minimum of 6 months to monitor for delayed or recurrent VTE and at least 2 years for patient-reported outcome measures. Results: Overall, 24 patients (7.59%) developed deep vein thrombosis (DVT): three proximal and 21 distal DVTs.Twenty-three of the 24 patients were asymptomatic. Twenty of 199 patients (10.05%) with only mechanical prophylaxis developed DVT, whereas four of 117 patients (3.42%) with additional chemoprophylaxis developed DVT.Multivariate analysis showed that chemoprophylaxis use was associated with reduced incidence of DVT (odds ratio = 0.19, p value = 0.011). Other factors associated with increased DVT incidence include female gender (odds ratio = 5.45, p value = 0.034), positive history of cancer (odds ratio = 5.14, p value = 0.044), and increased length of stay in hospital (odds ratio = 1.19, p value < 0.001). Conclusions Our study has shown that despite the low incidence of DVT in Asian patients undergoing TKA, shortduration chemoprophylaxis might be effective in reducing the incidence of DVT. However, most DVTs observed in our study were distal and may be of limited clinical significance. Further studies are needed to investigate the impact of chemoprophylaxis use on the incidence of PE and overall mortality rates among Asian patients.

Background: Venous thromboembolism (VTE) is a serious complication that may occur after total knee arthroplasty (TKA), leading to the recommendation of routine chemoprophylaxis by international guidelines. This study aims to determine if short-duration chemoprophylaxis after TKA reduces the incidence of VTE in an Asian population. Methods: A retrospective study of 316 patients who underwent unilateral primary TKA between 1 January 2011 and 31 December 2013 was conducted. All patients received mechanical prophylaxis. One hundred seventeen patients (37%) received additional chemoprophylaxis, whereas 199 patients (63%) did not. A Doppler ultrasound (DUS) of both lower limbs was conducted for all patients within 6 days after surgery (median = 3 days) to assess for both proximal and distal DVT. Chemoprophylaxis in the form of enoxaparin (low molecular weight heparin; LMWH), aspirin, or heparin was administered until patients had a normal DUS, for a median duration of 4 days. Patients were followed up clinically for a minimum of 6 months to monitor for delayed or recurrent VTE and at least 2 years for patient-reported outcome measures. Results: Overall, 24 patients (7.59%) developed deep vein thrombosis (DVT): three proximal and 21 distal DVTs.Twenty-three of the 24 patients were asymptomatic. Twenty of 199 patients (10.05%) with only mechanical prophylaxis developed DVT, whereas four of 117 patients (3.42%) with additional chemoprophylaxis developed DVT.Multivariate analysis showed that chemoprophylaxis use was associated with reduced incidence of DVT (odds ratio = 0.19, p value = 0.011). Other factors associated with increased DVT incidence include female gender (odds ratio = 5.45, p value = 0.034), positive history of cancer (odds ratio = 5.14, p value = 0.044), and increased length of stay in hospital (odds ratio = 1.19, p value < 0.001). Conclusions Our study has shown that despite the low incidence of DVT in Asian patients undergoing TKA, shortduration chemoprophylaxis might be effective in reducing the incidence of DVT. However, most DVTs observed in our study were distal and may be of limited clinical significance. Further studies are needed to investigate the impact of chemoprophylaxis use on the incidence of PE and overall mortality rates among Asian patients.

We present five patients with vibrio necrotising fasciitis, a lethal and disabling disease. Two of these patients had a history of exposure to either warm seawater or raw/live seafood, three had underlying chronic liver disease, and four presented with hypotension and fever. There were three deaths and four patients required intensive care unit stays. Among the two survivors, one had high morbidity. Only one patient met the criteria of Laboratory Risk Indicator for Necrotising Fasciitis score > 6. A clinician should suspect possible vibrio necrotising fasciitis if the following are present: contact with fresh seafood/warm seawater, a known history of chronic liver disease and pain that is out of proportion to cutaneous signs. All patients must be managed via intensive care in high dependency units. We recommend a two-step surgical protocol for patient management involving an initial local debridement, followed by a second-stage radical debridement and skin grafting.
Aged ; Aged, 80 and over ; Debridement ; End Stage Liver Disease ; complications ; Fasciitis, Necrotizing ; diagnosis ; microbiology ; surgery ; Female ; Fever ; complications ; Hepatitis B ; complications ; Humans ; Hypotension ; complications ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Seafood ; Seawater ; Severity of Illness Index ; Singapore ; Skin Transplantation ; Vibrio ; Vibrio Infections ; diagnosis ; surgery

Osteoarthritis of the knee is a common disease that causes significant disability. Most patients can be managed conservatively in the outpatient setting. A small minority require surgery. The cornerstones of treatment are weight loss, exercise and analgesia. Walking aids, medial patellar taping, acupuncture and transcutaneous electrical nerve stimulation are useful management adjuncts. Current evidence does not support routine prescription of glucosamine and chondroitin supplements. Early consultation with an orthopaedic surgeon should be made when conservative measures fail.

OBJECTIVETo estimate the value of blastocyst culture for preimplantation genetic diagnosis (PGD).

METHODSDay 3 embryos were biopsied and analyzed with fluorescence in situ hybridization (FISH) technique. Embryos with normal FISH results were cultured into blastocysts, and the ones with better morphology scores were transferred. Fourteen embryos with abnormal FISH results were cultured into blastocysts. Part of the cells taken from the blastocysts were amplified by whole genomic amplification (WGA) and assessed by array-based comparative genomic hybridization (array-CGH) analysis.

RESULTSSix blastocysts with normal FISH results were transferred in 5 cycles. Four healthy babies of 3 cycles were delivered. Another one was a singleton pregnancy but with embryo growth arrest, whose villus karyotype was normal. Fourteen embryos with abnormal FISH results were cultured into blastocysts and analyzed by array-CGH. Six blastocysts were normal by array-CGH.

CONCLUSIONFISH combined with blastocyst culture may further ensure the accuracy of PGD result. Detection at the blastocyst stage can avoid false positive results and mosaic interferences on Day 3 stage and are therefore more authentic.

Adult ; Blastocyst ; cytology ; Comparative Genomic Hybridization ; methods ; Embryo Transfer ; Female ; Genetic Diseases, Inborn ; diagnosis ; embryology ; genetics ; prevention & control ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Male ; Pregnancy ; Preimplantation Diagnosis ; methods

The Gram-negative bacilli Acinetobacter baumannii, Burkholderia cepacia, Ochrobactrum anthropi, Pseudomonas mendocina, Ralstonia spp., Serratia marcescens and Stenotrophomonas maltophilia are ubiquitous environmental organisms of low virulence, and do not usually cause illness in immunocompetent hosts. We report a case of multiple concurrent opportunistic Gram-negative bacilli causing septic arthritis in a healthy patient following trauma to the knee. Repeated operations, including arthroscopy, arthrotomy and debridement, were required before tissue cultures became negative. The patient also required an extended duration of intravenous and oral antibiotic treatment before he was discharged. Gram-negative bacillary septic arthritis is an uncommon but significant condition that requires repeated debridement and washouts in order to achieve bacterial eradication. This case report highlights the importance of an awareness of the external environment at the time of injury, as it impacts the type of organisms causing the infection, and consequently, the choice of empiric antibiotics required for successful treatment.
Adult ; Anti-Bacterial Agents ; therapeutic use ; Arthritis, Infectious ; microbiology ; therapy ; Arthroscopy ; Biopsy ; Combined Modality Therapy ; Debridement ; Gram-Negative Bacterial Infections ; microbiology ; therapy ; Humans ; Knee Injuries ; complications ; Male

Orthopaedic implant technology is heavily based on the development and use of biomaterials. These are non-living materials (e.g. metals, polymers and ceramics) that are introduced into the human body as constituents of implants that fulfill or replace some important function. Examples would be prosthetic joint replacements and fracture fixation implants. For orthopaedic biomaterials to succeed in their desired functions and outcomes in the body, a number of factors need to be considered. The most obvious mechanical properties of the implants are that they need to suit their intended function, and various classes and types of biomaterials have been developed and characterised for use in different implant components depending on their demands. Less well understood but no less important are the interactions that occur between the constituent biomaterials and the living cells and tissues, both of the human host as well as pathogens such as bacteria. Biomaterials used for orthopaedic applications are generally considered to be biocompatible. However, adverse effects arising from interactions at the implant interface can result in various modes of implant failure, such as aseptic loosening and implant infection. This review paper uses the illustrative example of total hip replacement (which has been called the operation of the century) to highlight key points in the evolution of orthopaedic biomaterials. It will also examine research strategies that seek to address some of the major problems that orthopaedic implant surgery are facing today.
Absorbable Implants ; Arthroplasty, Replacement, Hip ; instrumentation ; methods ; Biocompatible Materials ; Humans ; Orthopedic Procedures ; instrumentation ; methods ; trends ; Osteoblasts

INTRODUCTIONVascular endothelial growth factor (VEGF) is expressed in osteoarthritic articular cartilage. However, the pattern of VEGF expression throughout the whole life cycle of articular cartilage is not well elucidated. The aim of the study was to investigate the spatiotemporal expression of VEGF and its receptors, vascular endothelial growth factor receptor-1 (VEGFR1) and vascular endothelial growth factor receptor-2 (VEGFR2), in articular cartilage during growth, maturation and degeneration, using the guinea pig model of spontaneous osteoarthritis.

MATERIALS AND METHODSSections of tibial plateaus aged 2, 6 and 12 months were obtained, representing growing, mature and osteoarthritic cartilage respectively. Expression of VEGF and its receptors was determined by immunohistochemistry and in situ hybridisation.

RESULTSAt 2 months, VEGF and its receptors were expressed in chondrocytes within the superficial layer of the articular cartilage. At 6 months, no expression of VEGF and its receptors was noted. In the 12-month-old specimens, VEGF and its receptors were expressed in chondrocytes within articular cartilage that exhibited osteoarthritic changes (medial tibial plateaus), but not in the histologically normal lateral plateaus.

CONCLUSIONThis spatiotemporal distribution of VEGF and its receptors suggests that VEGF is expressed during articular cartilage growth, becomes quiescent at maturity, and is re-expressed in osteoarthritis.

Aging ; metabolism ; Animals ; Cartilage, Articular ; growth & development ; metabolism ; Chondrocytes ; metabolism ; Guinea Pigs ; Immunohistochemistry ; In Situ Hybridization ; Knee Joint ; metabolism ; Male ; Osteoarthritis, Knee ; metabolism ; Tibia ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism