Distribution of Causative Microorganisms in Diabetic Foot Infections: A Ten-Year Retrospective Study in a Tertiary Care Hospital in Central Malaysia.

Diabetes mellitus is a global pandemic, especially in Southeast Asia. Diabetic foot infection (DFI) is a common complication of this condition and causes significant morbidity and mortality in those affected. There is a lack of locally published data on the types of microorganisms and empirical antibiotics being prescribed. This paper highlights the importance of local microorganism culture and antibiotic prescription trends among diabetic foot patients in a tertiary care hospital in central Malaysia. This is a retrospective, cross-sectional study of data taken from January 2010 to December 2019 among 434 patients admitted with diabetic foot infections (DFIs) using the Wagner classification. Patients between the ages of 58 and 68 years old had the highest rate of infection. Pseudomonas Aeruginosa, Proteus spp., and Proteus mirabilis appeared to be the most isolated Gram-negative microorganisms, and Staphylococcus aureus, Streptococcus agalactiae, and MRSA appeared to be the most common Gram-positive microorganisms. The most common empirical antibiotics prescribed were ampicillin/sulbactam, followed by ciprofloxacin and ceftazidime, and the most common therapeutic antibiotics prescribed were ampicillin/sulbactam, ciprofloxacin, and cefuroxime. This study could be immensely pertinent in facilitating future empirical therapy guidelines for treating diabetic foot infections.

Does obesity affect diaphyseal femoral fracture healing treated with intramedullary locking nail?

OBJECTIVES: This study aims to evaluate the effect of obesity on radiological fracture union in diaphyseal femoral fractures (DFFs) treated with intramedullary nailing (IMN). PATIENTS AND METHODS: Between January 2017 and December 2018, a total of 120 patients (101 males, 19 females; mean age: 35.1±3.0 years; range, 18 to 72 years) treated with IMN for closed DFFs were retrospectively analyzed. Data including age, sex, location, weight, height, comorbidities such as diabetes mellitus, hypertension or kidney injury, date of injury, mechanism of injury, type of femoral fractures (AO classification), date of surgery, duration of surgery, IMN length and diameter used, date of radiological fracture union and complications of surgery such as nonunion, delayed union, and infections were recorded. RESULTS: Of the patients, 63 had obesity and 57 did not have obesity. There was a statistically significant difference in fracture configuration among patients with obesity; they sustained type B (p=0.001) and type C (p=0.024), the most severe fracture configuration. The nonunion rate was 45%. Obesity had a significant relationship with fracture nonunion with patients with obesity having the highest number of nonunion rates (n=40, 74.1%) compared to those without obesity (n=14, 25.9%) (p=0.001). Fracture union was observed within the first 180 days in 78.9% of patients without obesity, while it developed in the same time interval in only 38.1% of patients with obesity (p=0.001). CONCLUSION: Fracture union time for the patients with obesity was longer, regardless of the fracture configuration. Obesity strongly affects fracture union time in DFFs treated with an IMN. Obesity should be considered a relative risk in decision-making in the choice of fixation while treating midshaft femoral fractures.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 transfection of guide RNA targeting on MMP9 as anti-cancer therapy in human cutaneous squamous cell carcinoma cell line A431.

Introduction: Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin malignancy, representing around 20% of all skin cancers. It is the main cause of death due to non-melanoma skin cancer every year. Metastatic cutaneous SCC is associated with poor prognosis in patients and warrants a more effective and specific approach such as disruption of genes associated with cancer metastasis. Material and methods: Matrix metalloproteinases (MMPs) are enzymes involved in cancer progression and are regarded as major oncotargets. Among others, MMP9 plays critical roles in tumour progression, angiogenesis, and invasion of cutaneous SCC. We aimed to determine whether the MMP9 gene is a suitable gene target for anti-cancer therapy for cutaneous SCC. We performed clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 transfection of guide RNA (gRNA) targeting the MMP9 gene into human cutaneous SCC cell line A431. Results: Following CRISPR transfection treatment, the viability (p < 0.01) and migratory activities (p < 0.0001) of in vitro cutaneous SCC cells were found to be reduced significantly. The use of quantitative polymerase chain reaction (qPCR) also revealed downregulation of the mRNA expression levels of cancer-promoting genes TGF-ß, FGF, PI3K, VEGF-A, and vimentin. Direct inhibition of the MMP9 gene was shown to decrease survivability and metastasis of cutaneous SCC cell line A431. Conclusions: Our findings provided direct evidence that MMP9 is important in the viability, proliferation, and metastasis of cutaneous SCC cells. It serves as a positive foundation for future CRISPR-based targeted anti-cancer therapies in treating skin cancer and other forms of malignancies that involve MMPs as the key determinants.

A review of the efficacy of intraarticular hip injection for patients with hip osteoarthritis: To inject or not to inject in hip osteoarthritis?

Hip injection (HI) for osteoarthritis (OA) are in vogue nowadays. Corticosteroids (CSs) and hyaluronic acid (HA) gel are the two most common agents injected into the hip. Off late, platelet-rich plasma (PRP), mesenchymal stem cell (MSC), bone marrow aspirate concentrate (BMAC), local anesthetic (LA) agents, non-steroidal anti-inflammatory drugs (NSAIDs) and their different combinations have also been injected in hips to provide desired pain relief. However, there is a group of clinicians who vary of these injections. A search of the literature was performed on PubMed, Cochrane Library, and DOAJ using the keywords "hip osteoarthritis injection". Data were analyzed and compiled. Intraarticular CSs are effective in providing the desired pain relief in OA hip, but repeated injections should be avoided and the interval between HI and hip arthroplasty must be kept for more than three months. Methylprednisolone or triamcinolone are combined with 1% lidocaine or 0.5% bupivacaine. Chondrotoxic effects of LA is a concern. Although national guidelines do not favor the use of HA for hip OA, numerous publications have favored its usage for a moderate grade of OA. The PRP, MSC, and BMAC are treatment options with great potential; however, currently, the evidence is conflicting on their role in hip OA. There is always a risk of septic arthritis, particularly when aseptic precautions are not followed, and clinicians must vary of this complication.

Literature review and case report of bilateral extensive psoas abscess: A rare case of spondylomyelitis with infection spread to Hunter's canal with a rare causative microorganism.

A 43-year-old male patient with underlying diabetes mellitus presented with lower abdominal pain radiating to left thigh. He was hemodynamically stable, but appeared lethargic. Both iliac fossae were tender, and crepitus appreciated along the anteromedial aspect of the left thigh. The patient initially responded well to treatment and was discharged; however, he was re-admitted several months later due to recurrent collection showing the growth of Klebsiella pneumoniae in the culture and succumbed to sepsis due to deep-seated intramuscular abscess and lung empyema. In conclusion, psoas abscess is a condition that can mimic various pathologies related to the lower abdomen and, therefore, clinicians should always have a high index of suspicion to prevent a missed diagnosis. Early detection may yield good outcomes, if managed with adequate surgical drainage and appropriate antibiotics.

Common musculoskeletal disorders in chronic liver disease patients.

Chronic liver disease (CLD) is the commonest ailment affecting the hepatobiliary system. Six significant pathologies related to CLD include hepatic osteodystrophy (HO), increased infection susceptibility, sarcopenia, osteonecrosis of the femoral head (OFH), increased risk of periprosthetic complications and fracture. Hepatic osteodystrophy, which comprises osteopenia, osteoporosis, and osteomalacia, refers to alterations in bone mineral metabolism found in patients with CLD. The HO prevalence ranges from 13 to 95%. Low complement levels, poor opsonization capacity, portosystemic shunting, decreased albumin levels, and impaired reticuloendothelial system make the cirrhotic patients more susceptible to developing infectious diseases. Septic arthritis, osteomyelitis, prosthetic joint infection, and cellulitis were common types of CLD-associated infectious conditions. The incidence of septic arthritis is 1.5 to 2-fold higher in patients with cirrhosis. Sarcopenia, also known as muscle wasting, is one of the frequently overlooked manifestations of CLD. Sarcopenia has been shown to be independent predictor of longer mechanical ventilation, hospital stay, and 12-month mortality of post-transplantation. Alcohol and steroid abuse commonly associated with CLD are the two most important contributory factors for non-traumatic osteonecrosis. However, many studies have identified cirrhosis alone to be an independent cause of atraumatic osteonecrosis. The risk of developing OFH in cirrhosis patients increases by 2.4 folds and the need for total hip arthroplasty increases by 10 folds. Liver disease has been associated with worse outcomes and higher costs after arthroplasty. Cirrhosis is a risk factor for arthroplasty complications and is associated with a prolonged hospital stay, higher costs, readmission rates, and increased mortality after arthroplasty. Greater physician awareness of risk factors associated with musculoskeletal complications of CLD patients would yield earlier interventions, lower healthcare costs, and better overall clinical outcomes for this group of patients.

Local Trends of Antibiotic Prescriptions for Necrotizing Fasciitis Patients in Two Tertiary Care Hospitals in Central Malaysia.

BACKGROUND: Necrotizing fasciitis (NF) is a rapidly progressive inflammatory infection of the soft tissue (also known as the fascia) with a secondary necrosis of the subcutaneous tissues, leading to a systemic inflammatory response syndrome (SIRS), shock and eventually death despite the availability of current medical interventions. The clinical management of this condition is associated with a significant amount of morbidity with a high rate of mortality. The prognosis of the disease is affected by multiple factors, which include the virulence of the causative pathogen, local host immunity, local wound factors and empirical antibiotics used. The local trends in the prescription of empirical antibiotics are often based on clinical practice guidelines (CPG), the distribution of the causative microorganism and the cost-effectiveness of the drug. However, there appears to be a paucity of literature on the empirical antibiotic of choice when dealing with necrotizing fasciitis in the clinical setting. This paper will outline common causative microorganisms and current trends of prescription in two tertiary centres in Central Malaysia. METHODS: This was a cross-sectional study using retrospective data of patients treated for NF collected from two tertiary care hospitals (Hospital Seremban and Hospital Ampang) in Central Malaysia. A total of 420 NF patients were identified from the five years of retrospective data obtained from the two hospitals. RESULTS: The top three empirical antibiotics prescribed are ampicillin + sulbactam (n = 258; 61.4%), clindamycin (n = 55; 13.1%) and ceftazidime (n = 41; 9.8%). The selection of the antibiotic significantly impacts the outcome of NF. The top three causative pathogens for NF are Streptococcus spp. (n = 79; 18.8%), Pseudomonas aeruginosa (n = 61; 14.5%) and Staphylococcus spp. (n = 49; 11.7%). The patients who received antibiotics had 0.779 times lower chances of being amputated. Patients with a lower laboratory risk indicator for necrotizing fasciitis (LRINEC) score had 0.934 times lower chances of being amputated. CONCLUSIONS: In this study, the most common empirical antibiotic prescribed was ampicillin + sulbactam followed by clindamycin and ceftazidime. The antibiotics prescribed lower the risk of having an amputation and, hence, a better prognosis of the disease. Broad-spectrum empirical antibiotics following surgical debridement reduce the mortality rate of NF.

Hypoxia in Bone and Oxygen Releasing Biomaterials in Fracture Treatments Using Mesenchymal Stem Cell Therapy: A Review.

Bone fractures have a high degree of severity. This is usually a result of the physical trauma of diseases that affect bone tissues, such as osteoporosis. Due to its highly vascular nature, the bone is in a constant state of remodeling. Although those of younger ages possess bones with high regenerative potential, the impact of a disrupted vasculature can severely affect the recovery process and cause osteonecrosis. This is commonly seen in the neck of femur, scaphoid, and talus bone. In recent years, mesenchymal stem cell (MSC) therapy has been used to aid in the regeneration of afflicted bone. However, the cut-off in blood supply due to bone fractures can lead to hypoxia-induced changes in engrafted MSCs. Researchers have designed several oxygen-generating biomaterials and yielded varying degrees of success in enhancing tissue salvage and preserving cellular metabolism under ischemia. These can be utilized to further improve stem cell therapy for bone repair. In this review, we touch on the pathophysiology of these bone fractures and review the application of oxygen-generating biomaterials to further enhance MSC-mediated repair of fractures in the three aforementioned parts of the bone.

Necrotizing fasciitis, causative agents and management: a five-year retrospective study in two tertiary care hospitals in Central Malaysia.

PURPOSE: Necrotizing fasciitis (NF) is a rapidly progressive inflammatory infection of the fascia, with secondary necrosis of the subcutaneous tissues. The severity of the disease depends on the virulence of the organism and host immunity. There is a paucity of reports on the prevalence of NF causing pathogens and management. METHODS: Retrospective data of patients treated for NF were collected from two tertiary care hospitals in Central Malaysia between January 2014 and December 2018. RESULTS: A total of 469 NF patients were identified. More than half of the NF patients were males (n = 278; 59.28%). The highest number of cases was found among age groups between 30 and 79, with mean age of 56.17. The majority of the NF cases (n = 402; 85.72%) were monomicrobial. Streptococcus spp. (n = 89; 18.98%), Pseudomonas aeruginosa (n = 63; 13.44%) and Staphylococcus spp. (n = 61; 13.01%) were identified as the top three microorganisms isolated. Among the 469 NF cases, 173 (36.8%) were amputated or dead while 296 (63.1%) recovered. Proteus spp. (n = 19; 12.93%), Klebsiella pneumoniae (n = 18; 12.24%) and Escherichia coli (n = 14; 9.52%) were associated with all types of amputations. The most common antibiotic prescribed was unasyn (n = 284; 60.56%), followed by clindamycin (n = 56; 11.94%) and ceftazidime (n = 41; 8.74%). A total of 239 (61.8%) recovered while 148 (38.2%) were either amputated or dead when managed with the unasyn, clindamycin or ceftazidime. CONCLUSION: This study represents the largest NF cases series in Malaysia highlighting the causative agents and management.

Hypoxic-Mediated Oxidative Stress Condition and Hydroxyapatite-Inducing Osteogenic Differentiation of Human Mesenchymal Stem Cells: A Mathematical Modeling Study.

Avascular necrosis (AVN) of the bones remains a major clinical challenge. Fractures in the talus, the scaphoid, and the neck of the femur are especially challenging to heal due to the low blood vessel network and the lack of collateral blood supply. These fractures are associated with high rates of nonunion and increased infections that require repeated operations. Conventional treatments by autografting or allografting bone replacement and synthetic bone implants have limitations, including the invasiveness of operative procedures, tissue supply insufficiency, and the risk of host rejection. The advancement in tissue engineering has revealed the potential of stem cells as restorative agents for bone injuries. The administration of mesenchymal stem cells (MSCs) into the talus, the scaphoid, and the neck of the femur could produce enhanced osteogenesis via the manipulation of MSC culture conditions. In this study, we used hydroxyapatite as the nanomaterial, and hypoxic milieu to enhance MSC differentiation capacity into the osteogenic lineage, allowing for more rapid and efficient bone cell replacement treatment. Our results demonstrate 1% oxygen and 12.5 µg/mL of hydroxyapatite (HAP) as the optimal conditions to incorporate the osteogenic medium for the osteogenic induction of MSCs. We also established a proof of concept that the addition of HAP and hypoxic conditions could augment the osteoinductive capacity of MSCs. We also developed an accurate mathematical model to support future bone cell replacement therapy.

Colonization of Methicillin-Resistant Staphylococcus aureus (MRSA) among Medical Students in Tertiary Institution in Central Malaysia.

Methicillin-resistant Staphylococcus aureus or MRSA infection is virulent and presents with a broad spectrum of severity. Limited regional reports that specifically outlined the potential risk of medical students being part of the dissemination of MRSA in healthcare settings were noted. This study aims to assess the prevalence and contributory factors of colonization of MRSA on neckties, headscarves, and ID badges among medical students in a local medical university in Malaysia. A cross-sectional study was conducted involving 256 medical students. A validated questionnaire was used to collect the data, and sample swabs were collected between July and August 2013 by swabbing neckties, headscarves, or identification badges. The swabs were then streaked onto mannitol salt agar (MSA) and incubated at 37 °C overnight. Out of 433 samples taken, 40 swabs (9.24%) were positive for Staphylococcus aureus. Out of the 40 swabs, five (12.5%) isolates were MRSA (one culture was isolated from the headscarf of a preclinical student, one culture was isolated from the necktie of clinical students, while the remaining three were isolated from identification badges of clinical students. There was no significant association between age, gender, ethnicity, and phase of medical students with the colonization of MRSA (p > 0.05). There was a significant association between knowledge score on hand hygiene practice and phase of medical students. MRSA colonies were present on neckties, headscarves, and identification badges of medical students of all phases. The findings from this study suggest the need for improvement of hand hygiene knowledge and discontinuity of mandatory use of physical ID badges and neckties among medical students.

Superficial Femoral Artery Thrombosis After Midshaft Femoral Fracture Fixation With an Intramedullary Nail: A Case Report

@#Intramedullary nailing is the preferred method of closed shaft fracture fixation of long bones. One of the most dreaded complications to occur following internal fixation of a lower limb fracture is pseudo- or false aneurysm which can lead to the loss of the limb due to acute ischemia. This diagnosis is made by contrast angiogram of the limb. Pointers to the diagnosis include absent distal limb pulsation as well as other signs of acute ischemia post trauma or surgery. We present a case of development of pseudo-aneurysm in an elderly patient following open reduction and internal fixation of a femoral fracture. This case report outlines a prompt multidisciplinary approach of management in a rare case of pseudoaneurysm post fixation of long bone.

Imaging in peri-prosthetic assessment: an orthopaedic perspective.

As imaging techniques are ever-evolving, this article aims to provide a brief overview of the various modalities including their limitations. The ability of imaging for evaluation of implant osseo-integration will be addressed and also the role of imaging in assessing septic and aseptic loosening, with a particular focus on adverse tissue reactions, will be discussed. Specific features when imaging the big joints such as shoulder, hip, knee and ankle joint will also be outlined.Overall, a lack of standardisation and validity was noted and despite the gross variety of imaging modalities, there is no technique covering all aspects required for evaluation of implant fixation and septic and aseptic loosening. Each imaging modality has a role, depending on the information required and anticipated. The choice of imaging technique should not be primarily based on medical considerations but also on availability, accessibility, expertise and costs. Plain radiographs alone have been recommended in cases of suspected peri-prosthetic joint infections, given the lack of evidence for additional imaging techniques in this context. For aseptic loosening, ultrasound and plain radiographs may serve as initial screening tools. Metal artefact reducing sequences (MARS) MRI are advancing cross-sectional imaging and are likely to promote their role in patient evaluation.We conclude that imaging is one essential part in the work-up of patients with total joint replacements, within a specific clinical context. Close teamwork between experienced radiologists and orthopaedic surgeons is required for optimal patient care. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160058. Originally published online at www.efortopenreviews.org.