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Background: BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients. Methods: One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls. Results: Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers. Conclusions: In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency and antibiotic susceptibility of bacteria isolated in patients with blepharitis. StudyDesign: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Ophthalmology, Rawalpindi Pakistan, from Oct 2019 to Oct 2021. Methdology: 160 cases of blepharitis, during a period of 2 years, who were not using topical or systemic antibiotics were recruited in this cross-sectional study. After detailed history and slit-lamp examination of eyelids and tears film each patient underwent sample collection under aseptic conditions, from the eyelid margin. The samples were inoculated in a culture of blood agar and chocolate agar (Biomeriux), Then the susceptibility of the identified bacteria to common systemic and topical antibiotics were tested using the disc diffusion method (Rosco Neo-Sensitab). Results: In 160 patients, 118(73.7%) were males and 42(26.3%) were females. According to type of blepharitis, 98(61.3%) had posterior blepharitis and 62(38.7%) had anterior blepharitis. Culture of eyelid sample of 77(48.1%) patients showed growth of coagulase-negative staphylococcus Coagulase-negative staphylococcus (CoNS) show greater resistance towards Penicillin 77(100%), Ciprofloxacin 55(72.5%) and Erythromycin 33(42.8%) however more susceptibility was shown towards Linezolid (CoNS). 71(45%) had Staphylococcus aureus isolated from their culture. 77(100%), Vancomycin 77(100%), Gentamycin 66(85.8%), Chloramphenicol 56(74.5%) and Cotrimoxazole 55(72.5%). Staphylococcus aureus show greater resistance towards Penicillin 72(100%), Ciprofloxacin 41(56.9%) and Tetracyclins 30(41.6%) however more susceptibility was found towards Gentamycin 72(100%), Linezolid 72(100%), Vancomycin 72(100%) and Chloramphenicol 61(84.7%). Conclusion: Coagulase-negative staphylococcus (CoNS) and Staphylococcus aureus have been the main isolated organisms in blepharitis. These bacteria have been shown to be resistant to Penicillin, Ciprofloxacain Erythromycin and Tetracyclins However both are highly Sensitive to Vancomycin and Linezolid along with Significant Sensitivity towards Chloamphenicol, Gentamycin, Amoxicillin-Clavulanate and Cotrimoxazole. [ABSTRACT FROM AUTHOR]

Introduction: Members of Enterobacterales are very common pathogens, which continue to show resistance to many antibiotics. Carbapenem performed well for some time. Colistin was the final hope for the carbapenem-resistant Enterobacterales, but resistance against it has virtually tied the clinician's hands, especially when it comes to treating critically ill patients. Purpose: Detection of colistin resistance by the agar method as well as by the polymerase chain reaction (mobilized colistin resistance-1 gene) in carbapenem-resistant Enterobacterales. Materials and Methods: A cross-sectional study from Dec 2019 to Dec 2020 was conducted at the Department of Microbiology, Army Medical College, National University of Medical Sciences Rawalpindi Pakistan. Antimicrobial susceptibility of Enterobacterales was determined according to the Kirby–Bauer disc diffusion method except for colistin. Colistin agar was used, in concentrations of 2 μg/mL and 4 μg/mL. Results were interpreted according to Clinical and Laboratory Standards Institute guidelines 2020. Mobilized colistin-resistant-1 gene in the carbapenem resistant Enterobacterales was detected by performing real-time polymerase chain reaction assay. Results: Among the 172 carbapenem-resistant Enterobacterales 18 isolates were resistant using the colistin agar test. Whereas by molecular method colistin resistance was detected among 10 isolates that carried mobilized colistin resistance 1 gene, making the frequency of the MCR-1 gene 5.81%. Seventy percent of isolates were from paired blood samples. Eight patients, from whom the colistin resistant gene was isolated expired. Conclusion: Colistin resistance is a very serious issue and should not be missed in a clinical microbiology laboratory. The phenotypic agar test method is an excellent option for routine use, as it combines ease of performance with affordable cost. However, molecular methods are essential for the detection of mobilized colistin resistance gene (1– 9) for epidemiological purposes. [ABSTRACT FROM AUTHOR]

Background: Emergence of resistance among Escherichia coli (E.coli) isolates against therapeutic options for UTIs (Urinary tract infections) has led to renewed interest in older antibiotics like Fosfomycin. In this study we evaluated diagnostic accuracy of Rapid Fosfomycin NP test based on glucose metabolism for rapid Fosfomycin susceptibility testing among urinary E.coli isolates. Methods: In a cross-sectional validation study conducted in the Microbiology Department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan from 15th March to 15th September 2020, 149 consecutive urine specimens were included as per selection criteria. Rapid Fosfomycin NP test was performed as per protocol of Nordmann P et al on urinary E.coli isolates for detection of Fosfomycin resistance and results were compared with reference modified Kirby-Bauer disk diffusion method. Results: Out of total 149 E.coli isolates from 149 urine specimens, 80 were classified as Fosfomycin susceptible and 69 as Fosfomycin resistant by reference disk diffusion method. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of rapid Fosfomycin NP test was found to be 94.2%, 98.75%, 98.48%, 95.2% and 96.64%, respectively. In our study reliable results were achieved after 2.5 hours of incubation. Conclusion: The rapid Fosfomycin NP test is valid and user-friendly technique which can be performed with minimal technical expertise. It is less time consuming than disk diffusion and E- test strips and easy to perform as compared to agar dilution method. It can be useful as alternative to agar dilution in urinary E.coli isolates which would help in selecting appropriate therapeutic option for UTIs. [ABSTRACT FROM AUTHOR]

The aim of this study is to see the frequency, clinical presentation, and therapeutic response of extensively drug-resistant Salmonella enterica serovar Typhi and current susceptibility pattern of typhoidal Salmonella strains in our setup. This study was carried out at the Department of Medical Microbiology and Immunology and Department of Medicine, Pakistan Navy Ship (PNS) Shifa Hospital, Karachi, from January 1 to December 31, 2018. All the blood culture samples of patients (indoor and outdoor) with suspicion of enteric fever were processed. Isolates were cultured and identified using standard microbiological procedures. The antimicrobial sensitivity against the typhoidal Salmonellae was determined using Kirby-Bauer disc diffusion method as per the guidelines of Clinical and Laboratory Standards Institute (2018) and all the extensively drug-resistant (XDR) isolates were confirmed by Vitek 2 system. Clinical presentation and response to treatment of patients were followed. A total of 292 typhoidal Salmonella isolates were cultured. Resistance to ciprofloxacin against both Salmonella Typhi and Salmonella Paratyphi A was found to be very high (91%). Percentage of multidrug-resistant (MDR) isolates in Salmonella Typhi was 76% (182 isolates) and in Salmonella Paratyphi it was 34% (18 isolates). XDR isolates in Salmonella Typhi were significant that is 48% (115 isolates). Only 10 cases were given azithromycin who responded to treatment in mean 4.3 days. Out of 115 cases of XDR Salmonella Typhi, 103 patients were given parenteral meropenem and clinical response was seen in mean 5 days. The emergence and rapid spread of extensively drug-resistant Salmonella Typhi is alarming and highlights the significance of strict antimicrobial susceptibility surveillance programs with antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of various types and complications of Dengue fever in patients admitted to Medical 'E' Ward of Khyber Teaching Hospital Peshawar. Materials and Methods: This cross sectional study was conducted at Khyber Teaching Hospital Peshawar from July to September 2017.A sample of about 300(N=300) diagnosed dengue Patient were selected through non probability convenient sampling technique. Type and complications of dengue fever was determined by clinical examination and laboratory investigations. Data was analysed using SPSS version 20. Results: Mean age was 31.5 + 1.586 SD. 64% patients were male and 36% were female. 26.6% patients were having comorbidities of various categories i.e. diabetes, hypertension, pregnancy, asthma, fatty liver and chronic renal failure. 21% patients presented with dengue haemorrhagic fever. While no patients were found in dengue shock syndrome during the study. 36% patients presented with various complications like pleural effusions, UTI, bicytopenia, seizure, ARF and ascites. Conclusion: A vast majority of patients admitted in medical 'E' ward having high and more fever spikes were having low platelets and high haematocrit value. Also younger patients were having more complications interestingly as compared to old age patients which were only 6(02%) patients above age 70. Also Simple Dengue fever and DHF were more in male as compared to female. UTI was the most common complication which was in 30(10%) patients. [ABSTRACT FROM AUTHOR]

Invasive salmonellosis caused by Salmonella typhi and Salmonella paratyphi is a serious life-threatening complication in immunocompromised patients. Since blood cultures have only 40-80% sensitivity, very limited diagnostic modalities are left. Here, authors present a case of a 24-year-old pregnant lady who develops a unilateral breast abscess harbouring Salmonella typhi. The isolate was Extremely Drug Resistant (XDR), that is resistant to first line drugs, ciprofloxacin and ceftriaxone. She was successfully treated with combination of injection meropenem and tablet azithromycin and continued for 14 days. To the best of authors knowledge, this was the first reported case of Salmonella enterica serovar Typhi in a pregnant lady from Pakistan. [ABSTRACT FROM AUTHOR]

Partner and localizer of BRCA2 (PALB2) is a pancreatic cancer (PC) susceptibility gene reported in Caucasians. However, limited data are available among Asians. We investigated the contribution of PALB2 germline variants to Pakistani PC patients. 150 unselected and prospectively enrolled PC patients were comprehensively screened for PALB2 variants, using denaturing high-performance liquid chromatography and DNA sequencing. Novel variants were investigated for their pathogenic effect using in-silico tools. Potentially functional variants were screened in 200 controls. Twenty-two different PALB2 variants were identified. A missense variant (p.Arg37His) was identified in a 48-years-old male patient with a family history of breast cancer. Another missense variant (p.Trp898Arg) was identified in a 48-years-old male patient with a family history of esophageal cancer. A novel 3′ downstream variant (c.∗480A>G) was detected in a 34-years-old female patient with family history of lung cancer. Another novel 3′ downstream variant (c.∗417A>C) was identified in a 41-years-old male patient. All these variants were absent in 200 controls. p.Arg37His and p.Trp898Arg were predicted as likely pathogenic. c.∗417A>C and c.∗480A>G were classified as variants of uncertain significance. This is the first study that suggests a minimal contribution of PALB2 variants to PC risk in Pakistani population. [ABSTRACT FROM AUTHOR]

Objective: To see the efficacy of rapid colour test for the sensitivity of ceftriaxone against clinical isolates of salmonella typhi., Methods: The cross-sectional validation study was conducted at the Department of Microbiology, Pakistan Navy Ship Shifa Hospital, Karachi, from Nov 2018 to April 2019, and comprised clinical isolates of salmonella typhi that were obtained from five different hospitals in Karachi and Hyderabad. The isolates were tested using the rapid colour test. All the isolates were also tested using the conventional disc diffusion method and minimum inhibitory concentrations on the Vitek-2 version 8.01., Results: Of the 97 isolates, 83(85.5%) were ceftriaxone-resistant and 14(14.4%) were ceftriaxone-sensitive. Sensitivity and specificity of the rapid colour test were 100% when compared with the results of the other methods. All the results were readable within 2 hours on the colour test., Conclusions: The colour test was found to be a rapid, accurate and inexpensive tool to screen for ceftriaxone resistance in typhoid-endemic areas.

Objective: To determine whether routine preoperative hepatic venous pressure gradient measurements are necessary in child's-A cirrhotic patients undergoing liver resection for hepatocellular carcinoma, and to assess immediate post-operative liver dysfunction and 30-day mortality in such cases., Methods: The 3-year audit was done at Shuakat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data from January 1, 2015, to December 31, 2017, of all Child's class "A" patients with hepatocellular carcinoma without any clinical signs of portal hypertension who had preoperative hepatic venous pressure gradient measurements done. A proforma was used to collect the required data from patient files. Data was analysed using SPSS 21., Results: Of the 20 patients, 11(55%) were males. The overall mean age was 60.6±7.4 years. Only 2(10%) patients had raised hepatic venous pressure gradient. Of the total, 14(70%) patients underwent surgery. Mean duration of surgery was 222±82.5 minutes and mean hospital stay was 6.8±3.2 days. None of the patients had deranged prothrombin-time or bilirubin on postoperative day 5., Conclusions: The incidence of subclinical portal hypertension was very low. Hepatic venous pressure gradient measurement can be avoided in early stage hepatocellular carcinoma for child's A cirrhotic patients undergoing liver resection.

Polymyxins play a significant role against carbapenem-resistant Enterobacteriaceae (CRE). A total of 121 clinical samples yielded growth of CRE that were included in the study. Rapid Polymyxin NP test was performed on all the isolates as described by Nordmann P et al. and results were compared with broth microdilution method. Majority of the isolates were Klebsiella pneumoniae (70.2%) followed by Escherichia coli (17.4%). A total of 71 isolates were found resistant and 50 as susceptible by broth microdilution. Sensitivity and specificity of rapid polymyxin NP test were found to be 97.2% and 100%, respectively. Our study concluded that rapid polymyxin NP test is reliable and can be used as an alternative to broth microdilution in resource limited settings.

Background: Pancreaticoduodenectomy (PD) plays an integral part in the management of pancreatic, periampullary and duodenal cancers, along with a few other pathologies of this region. Despite advances in surgery PD continues to have significant morbidity and noteworthy mortality. The aim of this study is to provide an in-depth report on the patient characteristics, indications and the outcomes of PD) in a tertiary cancer hospital in Pakistan., Materials and Methods: The study population included patients who underwent PD between January 1, 2014 and march 31, 2019, at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC) in Pakistan. The data was retrospectively analyzed from the Hospital Information System (HIS), which is a prospectively maintained patient electronic database of SKMCH&RC. Patient characteristics, procedural details and post-operative outcomes according to internationally accepted definitions were reported., Results: A total of 161 patients underwent PD at our hospital in the study period at a median age of 53 years, ranging from 19 to 78 years. 62% of the patients were males while 37% were females. Jaundice was the most common presenting symptom (64.6%), followed by abdominal pain (26.7%). PD with pancreaticogastrostomy was performed in 110 patients (68.3%), while pancreaticojejunostomy was performed in the rest of the cohort. Surgical site infection (SSI) was observed in 64 patients (40%). The incidence of Pancreatic Fistula grade C based on the International Study Group on Pancreatic Fistula (ISGPF) definition was 7.45% (n = 12). The 30 days mortality rate was 3.1%. Median survival of the cohort was 21 ±1.13 months and disease-free survival was 16±2.62 months., Conclusion: PD can be performed with acceptable morbidity and mortality in a resource constrained country, as long as it is undertaken in a high-volume center. This is in keeping with data published from other well-reputed international centers., Competing Interests: Declaration of competing interest None., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Acute respiratory illness caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) involved the whole globe within no time. Various studies published globally have shown variable severity of disease and mortality. The objective of our study was to describe clinical and epidemiological characteristics of the disease in our setup., Methods: in this descriptive case series, individuals with signs and symptoms of Coronavirus disease-19 (COVID-19) and asymptomatic patients with history of close contact to confirmed COVID-19 patients were considered for SARS-CoV-2 Polymerase chain reaction (PCR) assay. Epidemiological and clinical features of only PCR positive cases were recorded. Data regarding hospitalization status, exposure to known COVID-19 patients, clinical feature and clinical outcome of patients was collected and interpreted., Results: A total of 266 patients were found to be SARS-CoV 2 PCR positive which were included in the study. Mean age of patients was 39.45±31.9 years and majority of the patients in our study were male, i.e., 238 (89.5%). Most common clinical features among COVID-19 symptomatic patients were fever and dry cough followed by myalgias and sore throat. Eighteen (7%) out of 266 died in our setup. Time duration of viral shedding after initial positive PCR varied between 11 days to up to more than 55 days., Conclusion: Coronavirus disease-19 (COVID-19) can present with wide range of clinical spectrum and disease can be life threatening. Severity of disease, requirement of ICU care and mortality were directly related to age of the patient and underlying comorbidities. Rigorous precautionary measures are of utmost importance particularly in this high-risk population.

We present our experience of incidence and management of aberrant hepatic arterial anatomy encountered during pancreaticoduodenectomy (PD). Patients undergoing PD between December 2014 and November 2016 at the Shaukat Khanum Memorial Cancer Hospital, Lahore were included in this short report. Preoperative imaging and operative findings of these patients were reviewed to evaluate the hepatic arterial anatomy and classified according to Hiatt classification. Sixty-four PD were performed with aberrant arterial anatomy identified in 24 (37.5%) of the cases. Most common anomaly was replaced right hepatic artery (rRHA) arising from the superior mesenteric artery seen in seven (11%) of the patients. Aberrant vessels were recognised and preserved in 23 cases. In one patient, the rRHA was coursing through the pancreatic parenchyma needing resection and reconstruction with uneventful postoperative recovery. Hepatic arterial anomalies are common and it is possible to preserve these vessels with careful surgical dissection using artery first technique.