Twelve-year trend of Escherichia coli antibiotic resistance in the Islamabad population.

Objective: Increasing rates of antimicrobial resistance among E. coli is a growing concern worldwide. We aimed to assess the changing antibiotic sensitivity pattern in Uropathogenic E. coli over a period of 12 years with special emphasis on ESBL-producing E. coli. Methods: A retrospective study was done on the population of Islamabad from 1st Jan 2005 to Dec 2010 and then continued from 1st Jan 2016 to 31st May 2021. A total of 12000 samples were analyzed for isolation and identification of bacteria and antimicrobial susceptibility testing, from patients having uncomplicated urinary tract infections. Our primary was to find the antibiotics with the highest sensitivity against E. Coli in 2021, while our secondary outcome was to find the overall sensitivity pattern of E. Coli to antibiotics from 2005 to 2021. Results: There was a decrease in susceptibility rates of E. coli to Amoxicillin-Clavulanic Acid 47%, Trimethoprim-Sulfamethoxazole (TMP-SMX) 27%, Fluoroquinolones 24% & Cephalosporins 38%. There was a significant increase in the use of Nitrofurantoin and Fosfomycin. High resistance rates to Fluoroquinolones (76%), TMP-SMX (73%), Cephalosporins (62%), and Amoxicillin (53%) were documented. However, significantly high degree of sensitivity rates to Fosfomycin (92%), Aminoglycosides (90%) & Nitrofurantoin (80%) were recorded. Conclusions: Uropathogenic E. coli shows the highest sensitivity to Fosfomycin and Aminoglycosides in the year 2021, followed by Nitrofurantoin and Sulbactam. Cephalosporins, Amoxicillin/Cluvalanic acid, TMP-SMX, and Fluoroquinolones show a declining sensitivity pattern. UTIs can be prevented well by lifestyle changes, taking vitamins, trace elements, and carbohydrates.

A 3' untranslated region polymorphism rs2304277 in the DNA repair pathway gene OGG1 is a novel risk modulator for urothelial bladder carcinoma.

Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 200 UBC cases and 200 controls. We found association of OGG1 rs2304277 [odds ratio (OR)GG = 3.55, 95% confidence interval (CI) = 1.79-7.06] and XPC rs2228001 (ORAC = 2.38, 95% CI = 1.43-3.94) with UBC. In stratified analysis with respect to smoking status, OGG1 rs2304277 and XPC rs2228001 exhibited increased risk in smokers [(rs2304277 ORGG = 4.96, 95% CI = 1.51-16.30) (rs2228001 ORAC = 2.19, 95% CI = 1.02-4.72)] as well as nonsmokers [(rs2304277 ORGG = 2.95, 95% CI = 1.26-6.90) (rs2228001 ORAC = 2.57, 95% CI = 1.31-5.04)]. These polymorphisms were also associated with both low-grade [(rs2304277 ORGG = 3.73, 95% CI = 1.72-8.09) (rs2228001 ORAC = 2.18, 95% CI = 1.21-3.92)] and high-grade tumors [(rs2304277 ORGG = 3.45, 95% CI = 1.52-7.80) (rs2228001 ORAC = 2.81, 95% CI = 1.48-5.33)] as well as with non-muscle-invasive bladder cancer [(rs2304277 ORGG = 4.03, 95% CI = 1.87-8.67) (rs2228001 ORAC = 2.14, 95% CI = 1.20-3.81)] and muscle-invasive bladder cancer [(rs2304277 ORGG = 3.06, 95%CI = 1.31-7.13) (rs2228001 ORAC = 2.95, 95%CI = 1.51-5.75)]. This is the first study on DNA repair gene polymorphisms and UBC in the Pakistani population. It identifies OGG1 rs2304277 and replicates XPC rs2228001 as significant modulators of UBC susceptibility.

Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population.

Urothelial bladder carcinoma (UBC) is the most common among urinary bladder neoplasms. We carried out a preliminary study to determine the genetic etiology of UBC in Pakistani population, for this 25 sequence variants from 17 candidate genes were studied in 400 individuals by using polymerase chain reaction-based techniques. Multivariate logistic regression analysis was performed for association analysis of the overall data as well as the data stratified by smoking status, tumor grade and tumor stage. Variants of GSTM1, IGFBP3, LEPR and ACE were found to be associated with altered UBC risk in the overall comparison. CYP1B1 and CDKN1A variants displayed a risk modulation among smokers; IGFBP3 and LEPR variants among non-smokers while GSTM1 polymorphism exhibited association with both. GSTM1 and LEPR variants conferred an altered susceptibility to low grade UBC; GSTT1, IGFBP3 and PPARG variants to high grade UBC while ACE polymorphism to both grades. GSTM1 and LEPR variants exhibited risk modulation for non-muscle-invasive bladder cancer (NMIBC); GSTT1 and PPARG variants for muscle-invasive bladder cancer (MIBC), and ACE variant for NMIBC as well as MIBC. In general, the susceptibility markers were common for low grade and NMIBC; and distinct from those for high grade and MIBC indicating the distinct pathologies of both groups. In brief, our results conform to reports of previously associated variants in addition to identifying novel potential genetic predictors of UBC susceptibility.

THE KNOCKED-OUT UNILATERAL KIDNEY! CAUSES AND PRESENTATION.

BACKGROUND: Due to lack of awareness and non-availability of proper medical facilities in Pakistan, patients with kidney problems tend to seek urological consultation very late when their kidney has already knocked-out. The aim of the study was to find the various presenting complaints of patients having unilateral loss of kidney function and their aetiologies. The study also targeted the patient's awareness regarding their disease. METHODS: This descriptive case-series of 103 consecutive patients who were diagnosed as having less than 20% of function on DTPA Renal Scan were evaluated. The aetiology of the non-functioning kidney (NFK) was made on either imaging findings or during the exploration, and/or on histopathology if necessary. The results were analysed using SPSS 16.0. Results: The aetiology of the unilateral renal failure included those that were secondary to nephro-pelvic stones in 39.8% and ureteric stones in 14.6%. Of the other aetiologies culminating in a unilateral NFK, 7.8% of the patients had chronic pyelonephritis, 20.4% had PUJO and 5.8% were Genito-urinary Tuberculosis; 3.9% had VUR and were found incidentally, 3.9% developed non-functioning kidney iatrogenically. About 39.8% of the patients knew about their primary disease causing destruction of renal function since long. The remaining 60.2% were unaware that they had developed NFK already when they presented. CONCLUSION: Proper education through awareness program both for the public and general practitioners can detect early threats to the kidney and hence decrease the loss of a kidney. This will also decrease the number of nephrectomies carried out for the benign condition.