Saba Noor

Diabetic foot ulcer--A review on pathophysiology, classification and microbial etiology.

As the prevalence of diabetes is increasing globally, secondary complications associated to this endocrinal disorder are also ascending. Diabetic foot ulcers are potentially modifying complications. Disruption of harmony in glucose homeostasis causes hyperglycemic status, results in activation of certain metabolic pathways which in their abnormal state subsequently leads to development of vascular insufficiency, nerve damages headed by ulceration in lower extremity due to plantar pressures and foot deformity. Insult to foot caused by trauma at the affected site goes unnoticeable to patient due to loss of sensation. Among the above mention causes, resistance to infection is also considered as chief modulator of pathophysiological image of diabetic foot lesions. Healing as well as non-healing nature of ulcer relies upon the wound microbial communities and the extent of their pathogenicity. A validated classification system of foot ulcer is primarily necessary for clinicians in management of diabetic foot problems. Another aspect which needs management is proper identification of causative pathogen causing infection. The way of approaches presently employed in the diagnosis for treatment of foot ulcer colonized by different microbes is conventional techniques. Conventional diagnostic methods are widely acceptable since decades. But in recent years newly invented molecular techniques are exploring the use of 16S ribosomal regions specific to prokaryotes in bacterial identification and quantification. Molecular techniques would be a better choice if engaged, in finding the specific species harboring the wound.

Understanding Diabetic Foot Infection and its Management.

Diabetic Foot Ulcers (DFUs), a dreadful micro-vascular complication is liable for substantial increase in morbidity and mortality. DFU is a complicated amalgam of neuropathy, peripheral arterial diseases, foot deformities and infection. Spanning the spectrum from superficial cellulitis, microbial flora leads to chronic ostemyelitis and gangrenous extremity lower limb amputations. Wounds without affirmation of soft tissue or bone infection do not require antibiotic therapy. Treatment of mild and moderate infection requires empiric therapy covering gram-positive cocci, whereas severe or infection caused by drug resistant organisms needs broad spectrum anti-microbial targeting aggressive gram-negative aerobes and obligate anaerobes. Definitive therapy employed should be based on culture reports and clinical response. Evaluation of bone infection requires imaging by plain radiographs or MRI to increase sensitivity and specificity. Surgical interventions are must and may range from minor debridement to resections or revascularization and major amputations depending upon wound severity. On time and forceful management of diabetic foot ulcers by employing multidisciplinary management approaches focusing on prevention, learning, regular foot assessment, aggressive intervention, and optimal use of therapeutic footwear can often prevent exacerbation of the difficulty and eliminate the potential for amputation. Here, we review recent studies addressing diabetic foot infections with emphasis on pathophysiology, exclusive risk factors; evaluation including physical inspection, laboratory investigations, relevant treatment strategies and assessment of infection severity.

Culture-based screening of aerobic microbiome in diabetic foot subjects and developing non-healing ulcers

The study was carried on diabetic foot patients to deduce clinical attributes, the occurrence of the range of aerobic microbial flora and to assess their comparative in vitro susceptibility to the customarily used antimicrobials. We also studied the potential risk factors involved in the development of non-healing ulcers. A total of 87 organisms were isolated from 70 specimens, including Escherichia coli (19.5%) among the Gram-negative and Staphylococcus aureus (18.4%) among the Gram-positive as the predominant aerobes explored. Pseudomonas aeruginosa and E. coli were predominant isolates of non-healing ulcers. The antimicrobial sensitivity pattern revealed that vancomycin (100%) and amikacin (90.4%) exhibited highest sensitivity to Gram-positive cocci, while all strains of P. aeruginosa were sensitive toward imipenem (100%). The prevalent uncontrolled glycemic status, altered lipid spectra, the existence of neuropathy, and peripheral vascular disease, suggested predisposition toward the development of non-healing lesions. The study has underlined the need for continuous surveillance of bacteria and their antimicrobial sensitivity blueprints to provide the basis for empirical therapy and to minimize the risk of complications. Further, stringent clinical evaluation, and medical history will help in revealing the risk of developing non-healing status in diabetic foot ulcers.

Financial burden of diabetic foot ulcers to world: a progressive topic to discuss always:

Diabetic foot complications are the most common occurring problems throughout the globe, resulting in devastating economic crises for the patients, families and society. Diabetic foot ulcers (DFUs) have a neuropathic origin with a progressive prevalence rate in developing countries compared with developed countries among diabetes mellitus patients. Diabetic patients that are of greatest risk of ulcers may easily be diagnosed with foot examination. Economic burden may be carefully examined. The budget costing must include both the clinical and social impact of the patients.

Biofabrication of Zinc Oxide Nanoparticle from Ochradenus baccatus Leaves: Broad-Spectrum Antibiofilm Activity, Protein Binding Studies, and In Vivo Toxicity and Stress Studies

Biofilms are complex aggregation of cells that are embedded in EPS matrix. These microcolonies are highly resistant to drugs and are associated with various diseases. Biofilms have greatly affected the food safety by causing severe losses due to food contamination and spoilage. Therefore, novel antibiofilm agents are needed. This study investigates the antibiofilm and protein binding activity of zinc nanoparticles (ZnNPs) synthesized from leaf extract of Ochradenus baccatus. Standard physical techniques, including UV-visible spectroscopy Fourier transform infrared spectroscopy and X-ray diffraction and transmission electron microscopy, were used to characterize the synthesized OB-ZnNPs. Synthesized OB-ZnNPs demonstrated significant biofilm inhibition in human and food-borne pathogens (Chromobacterium violaceum, Escherichia coli, P. aeruginosa, Klebsiella pneumoniae, Serratia marcescens, and Listeria monocytogenes) at subinhibitory concentrations. OB-ZnNPs significantly reduced the virulence factors like violacein, prodigiosin, and alginate and impaired swarming migration and EPS production. OB-ZnNPs demonstrated efficient binding with HSA protein and no change in their structure or stability was observed. In addition, in vivo toxicity evaluation confirmed that OB-ZnNPs possessed no serious toxic effect even at higher doses. Moreover, they were found to have excellent antioxidant properties that can be employed in the fields of food safety and medicine. Hence, it is envisaged that the OB-ZnNPs can be used as potential nanomaterials to combat drug resistant bacterial infections and prevent contamination/spoilage of food.

Molecular and culture based assessment of bacterial pathogens in subjects with diabetic foot ulcer

INTRODUCTION Expeditious and precise discerning of bacterial pathogens is a fundamental grail, of clinical diagnostic microbiology. Genotypic detection is a budding substitute to recognize phenotypic culture based processes in bacterial identification. AIMS We report a comparative evaluation of biochemical and genomic-based assays for exploring the commonest bacterial flora of infected diabetic foot ulcers along with clinical variables of subjects enrolled. METHODS The pathogens selected (i) Staphylococcus aureus ii) Pseudomonas aeruginosa, iii) Escherichia coli and iv) Klebsiella pneumonia, stood for the most frequent isolates of diabetic foot infection in previous studies from Northern India. Identification of these pathogens were done by conventional assays and polymerase chain reaction. RESULTS Of 50 specimens obtained from infected DFUs, 74% of cases were affirmative by bacteriological assays and 90% showed positivity via polymerase chain reaction (PCR). Among processed samples 44 isolates were detectable through phenotypic analysis and 65 bacteria by species-specific PCR. Thirteen samples and 21 isolates could not be scrutinized by phenotypic identification systems. The most prevalent pathogens identifiable were Klebsiella pneumonia, followed by Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. CONCLUSIONS We have shown that PCR-based diagnostic methods improved the identification compared to conventional methods and highlight the incorporation of PCR due to shorten turnaround time translating into improved clinical outcomes.

Glycated albumin and the risk of chronic kidney disease in subjects with Type 2 Diabetes: A study in North Indian Population

AIM Glycated albumin (GA) suggested being alternative glycemic marker than haemoglobin A1C (HbA1c) in patients with chronic kidney diseases (CKD). We investigated the association between GA and the progression of diabetic nephropathy (DN) in T2DM subjects. METHODS We recruited T2DM subjects with different stages of CKD who had regularly measured serum creatinine and estimated glomerular filtration rates (eGFR) according to Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, HbA1c consecutively every 3 months along with GA levels and other anthropometric and demographic measurements. We grouped age and sex matched subjects into the CKD progression, Group I healthy subjects (n = 100, M: F;50:50). Group II T2DM subjects with eGFR ≥90 mL/min (n = 167, M:F; 76:91). Group III of T2DM patients with eGFR 60-89 mL/min (n = 91, M:F; 44:47). Group IV T2DM subjects with eGFR 30-59 mL/min (n = 68, M:F;31:37). Group V T2DM with eGFR ≤ 29 mL/min (n = 21, M:F; 13:8). RESULTS Pearsons correlation analysis between glycated albumin and biochemical parameters were established in all subjects. GA/HbA1c ratio increases with poor glycemic control except for nephrosis state. CONCLUSION Mean GA levels were more closely associated with DN progression than mean HbA1c in subjects with T2DM and can be implemented as an alternative diagnostic marker in nephropathy.

Inflammatory markers as risk factors for infection with multidrug-resistant microbes in diabetic foot subjects

BACKGROUND Diabetic foot ulcers (DFUs), a dreadful microvascular complication of diabetes is responsible for substantial increase in morbidity and mortality. Infection, not a cause, but a consequence in DFUs that accounts for minor or major limb loss. The current study aimed to evaluate the microbial etiology of infected diabetic foot ulcers in northern tertiary care hospital, assessment of risk factors and role of inflammatory markers involved in colonization of multidrug-resistant organisms (MDROs) and their impact on the outcome. METHODS Pus aspirates and soft tissue samples from 65 patients with infected DFUs were collected and processed for aerobic culture analysis. Serum concentrations of IL-6 and TNF-α were determined by enzyme linked immuno-sorbent assay. RESULTS Aerobic gram-negative isolates were more commonly present (74.7%), followed by gram-positive aerobes (25.2%). Fifty-seven percent patients were positive for MDROs. IL-6 (pg/mL) was significantly lower in diabetic patients with MDROs infected foot ulcers than without (47.0±17.2 vs. 78.3±22.1 vs. p=<0.001) and TNF-α (pg/mL) was also significantly diminished in MDROs infected subjects than without (144.2±25.8 vs. 168.7±20.9, p<0.001) respectively. CONCLUSIONS In this study diabetic foot wounds harbored by MDROs were associated with longer duration of ulcer and increased ulcer size. Poor glycemic control was also a confounding factor in mounting MDROs infected ulcers. The declined levels WBCs and neutrophils as well as of cytokines IL-6 and TNF-alpha explains compromised immune responses of host in multi drug resistant infections.

Prevalence of thyroid disorders in North Indian Type 2 diabetic subjects: A cross sectional study

BACKGROUND Type 2 diabetes mellitus (T2DM) is a major health burden worldwide with many patients encountering thyroid dysfunction later in their life. Various studies have found that diabetes and thyroid disorders mutually influence each other and both disorders tend to coexists. However, the prevalence of thyroid dysfunction and associated clinical variables in these patients has not been investigated. OBJECTIVES The study aimed at determining the incidence and prevalence of thyroid dysfunction in patients with T2DM in relation to age, sex, metabolic syndrome and other co-morbid conditions. RESEARCH DESIGNS & METHODS In this cross-sectional study, 250 Type 2 DM patients were enrolled aged between 40 and 75 years. All the patients were evaluated for thyroid dysfunction by testing thyroid profile (T3, T4 and TSH. These subjects were also investigated for fasting blood sugar (FBS), post prandial glucose (PPG) glycosylated hemoglobin (HbA1c), serum cholesterol, serum triglycerides, high density lipoprotein (HDL), low density lipoprotein(LDL), very low density lipoprotein(VLDL), blood urea, serum creatinine and presence of other co-morbid conditions. The observations and interpretations were recorded and results obtained were statistically analyzed. RESULTS A high prevalence of thyroid dysfunction (28%) was observed in type 2 diabetic patients with subclinical hypothyroidism (18.8%) as the commonest thyroid disorder. Thyroid dysfunction was more prevalent in females, with presence of dyslipidemia, retinopathy, poor glycemic state (HbA1c ≥7) and longer duration of diabetes as significant contributing factors associated. CONCLUSIONS In addition to glycemic status, screening of thyroid disorder should be routinely done in type 2 diabetic subjects along with other comorbid conditions.