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Eman E Hegazy,1 Marwa Gamal Bahey,1 Alaa Mohammed Abo Hagar,2 Amira Abdelgalil Elkholy,3 Esraa A Mohamed1 1Department of Medical Microbiology and Immunology, Faculty of Medicine, Tanta University, Tanta, Egypt; 2Department of Anesthesiology, Surgical Intensive Care and Pain Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt; 3Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta, EgyptCorrespondence: Eman E Hegazy, Tel +20 10 99008274, Email dr_emanhegazy2010@yahoo.comBackground: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant gram-negative bacteria has been proven to be an escalating public health challenge in Egypt owing to its high mortality rate and raised health care costs.Purpose: Detection of carbapenem-resistant gram-negative bacilli among VAP patients, genotypic identification of carbapenemase genes in the isolated strains with evaluation of their impact on patient outcome and detection of carbapenemase-producing enterobacterales by MASTDISCS combi Carba plus disc system.Methods: Broncho-alveolar lavage fluid (BALF) and endotracheal aspirate were collected aseptically from clinically suspected VAP patients. Pathogen identification and antibiotic sensitivity testing were done. Carbapenemase-encoding genes (blaKPC, blaNDM, and blaOXA-48) were tested by PCR in all carbapenem-resistant gram-negative isolates. Performance of MASTDISCS combi Carba plus in isolated Enterobacterales was assessed in relation to the PCR results.Results: Eighty-three carbapenem-resistant gram-negative isolates were detected. The most frequent pathogens were Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa representing 34.9%, 20.5% and 18.1%, respectively. blaKPC was the predominant gene. Patients with persistent mechanical ventilation less than 15 days and Pseudomonas aeruginosa infection were significantly associated with a higher death rate. MAST-Carba plus had the highest sensitivity, specificity, positive and negative predictive values for detecting OXA-48 carbapenemases representing 81.8%, 92.5%, 75% and 94.9%, respectively.Conclusion: Worse outcome in VAP patients was associated with carbapenem-resistant gram-negative bacilli. MASTDISCS combi Carba plus is an efficient simple method for identification of different carbapenemases among enterobacterales.Keywords: Mast DISCS, carbapenemase, enterobacterales, ventilator-associated pneumonia, VAP

Aims/hypothesis: Dipeptidyl peptidase-4 (DPP-4) inhibition has beneficial effects on various metabolic indicators in diabetes. Stromal cell-derived factor-1 (SDF-1) is expressed in diverse organs including the kidneys and is cleaved and inactivated by DPP-4 enzyme. The aim of this study was to conduct a randomised controlled trial to assess the effect of sitagliptin on diabetic nephropathy when used as an add-on therapy to the advanced hybrid closed-loop (AHCL) system in adolescents with type 1 diabetes and nephropathy., Methods: This open-label, parallel-group, randomised controlled trial took place at the Pediatric Diabetes Clinic, Ain Shams University, Egypt. Forty-six adolescents aged 14.13 ± 2.43 years on the MiniMed 780G system for at least 6 months before study, with HbA 1c ≤69 mmol/mol (8.5%) and diabetic nephropathy in the form of microalbuminuria, were randomly assigned to two groups (n=23 for each) based on a computer-generated randomisation sequence. The intervention group received oral sitagliptin 50 mg for 3 months. The other group used AHCL only and served as a control group. The primary outcome measure was the change in urinary albumin/creatinine ratio (UACR) after 3 months of administration of sitagliptin. The key secondary outcome measure was the change from baseline in SDF-1 levels after treatment., Results: Data for all participants were analysed. No significant difference was found between the groups as regards baseline clinical and laboratory characteristics as well as AHCL system settings (p>0.05). Serum SDF-1 levels were higher in all individuals with type 1 diabetes vs healthy control individuals (p<0.001). After 3 months, sitagliptin resulted in a significant decrease of SDF-1 levels from 3.58 ± 0.73 to 1.99 ± 0.76 ng/ml (p<0.001), together with improvement of UACR from 7.27 ± 2.41 to 1.32 ± 0.31 mg/mmol (p<0.001). In addition, sitagliptin reduced postprandial glucose, sensor glucose, coefficient of variation and total daily dose of insulin, while time in range 3.9-10.0 mmol/l (70-180 mg/dl) and insulin-to-carbohydrate ratio were significantly increased. Sitagliptin was safe and well-tolerated without severe hypoglycaemia or diabetic ketoacidosis., Conclusions/interpretation: Sitagliptin as an add-on therapy to AHCL had a reno-protective effect for individuals with type 1 diabetes and diabetic nephropathy, in addition to the improvement of time in range while reducing glycaemic variability and without compromising safety., Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors., Trial Registration: ClinicalTrials.gov NCT06115460., Competing Interests: Declarations. Acknowledgements: The authors thank all the participants and their families for their collaboration during the study. Data availability: The data are available on reasonable request from the authors. Funding: Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: All authors (NSE, EAI, MHE-H, MZI, AAE) contributed substantially to the study design, analysis or interpretation of data; critically reviewed, drafted or edited the manuscript; and approved the final work for submission. NSE is responsible for the integrity of the work as a whole., (© 2024. The Author(s).)

Background: Zoonotic human tuberculosis (TB) caused by Mycobacterium bovis (M. bovis) is as vital as Mycobacterium tuberculosis, however with scarce available information. We aimed to use whole-genome sequencing (WGS) technology to take a deep insight into the circulating genotypes of human M. bovis and the genomic characteristics underlying virulence and drug resistance., Methods: The study included smear positive Ziehl-Neelsen samples from patients with suspected tuberculosis. Samples were cultured on Lowenstein-Jensen media and suspected colonies of M. bovis were selected to undergo DNA extraction and WGS. Data was analysed using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), and online bioinformatics tools. A phylogenetic tree was constructed for our sequenced strains, in addition to a set of 59 previously sequenced M. bovis genomes from different hosts and countries., Results: Out of total 112 mycobacterial positive cultures, five M. bovis were isolated and underwent WGS. All sequenced strains belonged to Mycobacterium tuberculosis var bovis, spoligotype BOV&#95;1; BOV&#95;11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA and rpsA), isoniazid (KatG and ahpC), ethambutol (embB, embC, embR and ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA and gyrB). Rifampin (rpoB and rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system. The phylogenetic analysis revealed close genetic relatedness of three sequenced M. bovis strains to previous reported cow strains from Egypt and human strains from France, as well as relatedness of one M. bovis strain to four human Algerian strains. One sequenced strain was related to one cow strain from Egypt and a human strain from South Africa., Conclusions: All sequenced M. bovis isolates showed the same spoligotype, but diverse phylogeny. Resistance gene mutations were detected for anti-TB drugs including pyrazinamide, isoniazid, streptomycin, ethambutol, fluoroquinolones, cycloserine, rifampin and delamanid. The virulence profile comprised genes assigned mainly to secretion system, cell surface components and regulation system. Phylogenetic analysis revealed genetic relatedness between our isolates and previously sequenced bovine strains from Egypt as well as human strains from other nearby countries in the region., (© 2024. The Author(s).)

Aim: To investigate the association between beta1-adrenergic receptor ( ADRB1 ) polymorphisms and response to bisoprolol treatment in beta-blocker naive patients with acute coronary syndrome (ACS)., Patients & Methods: Seventy-seven patients received bisoprolol for four weeks. Blood pressure and heart rate were measured at baseline and during treatment. TaqMan allelic discrimination method was utilized for ADRB1 Ser49Gly and Arg389Gly genotyping., Results: Arg389Arg carriers showed greater reductions in systolic and diastolic blood pressure (-8.5% ± 7.8% vs -0.76% ± 8.7%, p = 0.000218), and (-9.5% ± 9.7% vs -0.80% ± 11.5%, p = 0.000149), respectively, compared with Gly389 carriers. No statistical difference was found for study's outcomes based on codon 49., Conclusion: Arg389Gly polymorphism is a promising bisoprolol response predictor in ACS patients., Competing Interests: Competing interests disclosure The authors declare that there are no conflicts of interest present., (© 2023 The Authors.)

Background: Early assessment of cerebrovascular disease in chronic obstructive pulmonary disease (COPD) patients is an important issue for a favorable influence on the quality of life., Methodology: This cross-sectional case-control study was conducted on 38 eligible COPD patients (mean age 55.5 ± 11.5, 25 males, and 13 females) and 26 age-/sex-matched healthy controls. All participants were subjected to stroke risk screening instruments that included the Stroke Riskometer™, the Framingham 10-Year Risk Score, the stroke risk screening tool (the Department of Disease Control of Thailand), the My Risk Stroke Calculator, and Q Stroke. Radiologically, diffusion tensor imaging (DTI) and echo-gradient MRI (T2 star) T2 star imaging were done. Color-coded duplex sonography was done. Laboratory investigations included C-reactive protein (CRP), serum amyloid A, plasma fibrinogen level, serum IL6, 8-Isoprostane, vWF and urinary albumin creatinine ratio., Results: Stroke risk screening instruments revealed a significant increase in COPD patients. DTI showed a significant bilateral reduction in fractional isotropy and a significant bilateral increase in mean diffusivity of white matter through many areas in COPD patients. Patients also had a significant increase of intima-media thickness, presence of atherosclerotic focal thicknesses or plaques on duplex sonography. There was a significant elevation of CRP, serum amyloid A, plasma fibrinogen level, serum IL6, 8-isoprostane, von Willebrand factor (vWF), and urinary albumin creatinine ratio in COPD patients., Conclusion: COPD patients had an increased risk for stroke that could be assessed on stroke risk screening instruments, DTI, T2 star, duplex sonography, and laboratory investigation and could be correlated with the severity of the disease., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death., Methods: A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. We compared all secondary cases among healthcare workers with secondary cases among non-healthcare workers. Multivariable logistic regression identified risk factors for death., Results: Of the 2223 laboratory-confirmed MERS-CoV cases reported to WHO, 415 were healthcare workers and 1783 were non-healthcare workers. Compared with non-healthcare workers cases, healthcare workers cases were younger (P < 0.001), more likely to be female (P < 0.001), non-nationals (P < 0.001) and asymptomatic (P < 0.001), and have fewer comorbidities (P < 0.001) and higher rates of survival (P < 0.001). Year of infection (2013-2018) and having no comorbidities were independent protective factors against death among secondary healthcare workers cases., Conclusion: Being able to protect healthcare workers from high threat respiratory pathogens, such as MERS-CoV is important for being able to reduce secondary transmission of MERS-CoV in healthcare-associated outbreaks. By extension, reducing infection in healthcare workers improves continuity of care for all patients within healthcare facilities., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sildenafil enhances the nitric oxide-cGMP pathway of erection, which is claimed to have a role in nocturnal penile tumescence and rigidity (NPTR). This study aimed to find whether RigiScan can predict the response to sildenafil among erectile dysfunction (ED) patients and to find which RigiScan parameter produces the best prediction. Medical records of 172 ED patients were revised regarding their full sexual history, standard andrology examination, NPTR monitoring by the RigiScan device, and the degree of response to sildenafil. Of 172 ED patients, 94 patients (54.7%) were sildenafil responders. All RigiScan parameters were higher in the sildenafil responder group. The RigiScan parameters with the most differentiating power between both sildenafil responders and non-responders were base rigidity (AUC 0.860) and then tip rigidity (AUC 0.831). The cut-off value of base and tip rigidity with the highest diagnostic accuracy was 42.5%. This finding was found to be more specific than the sensitivity in predicting a positive response to sildenafil (85.9% vs . 70.2% and 92.3% vs . 59.6%, for base and tip rigidity, respectively). Sildenafil response in ED cases can be predicted through NPTR monitoring using the RigiScan device and ED patients with RigiScan base or tip rigidity less than 42% are not expected to respond well to sildenafil.

Objective: This study aims to investigate the association of neonatal indirect hyperbilirubinemia in exclusively breast-fed infants with UGT1A1 (Uridine Diphosphate-Glucuronyl transferase 1A1) polymorphism., Methods: 50 neonates were classified into 2 groups: 1) 30 full term neonates with indirect hyperbilirubinemia (gestational age (GA) 39.5 ± 1.2 weeks); 2) 20 apparently healthy full-term neonates. Group 1 was further subdivided based on percentage of body weight lost: (A) less than 10%; (B) 10% or more., Results: There was a statistically significant decrease in weight at sample collection and significant increase in indirect bilirubin level in patients group compared to control group, there was statistically significant difference as regard to genotype frequency [G/G, G/A, A/A], and allele frequency (A,G) between patients and control group. There was statistically significant increase in indirect bilirubin level in G/A - A/A genotypes. By comparing subgroup (A) and subgroup (B), there was statistically significant increase in total bilirubin level in subgroup (B). There was statistically high significant difference regarding genotype frequency (G/G, G/A, A/A) and allele frequency (G, A) between subgroup A and B. Multiple stepwise regression analysis was done using hyperbilirubinemia as a dependent factor and body weight loss, genotype (G/A) and allele (A) as independent factors. Body weight loss, genotype (G/A) and allele (A) was found to be significant independent predictors for hyperbilirubinemia., Conclusion: The results of the present study revealed that UGT1A1 polymorphism can be used as a novel predictor for neonatal hyperbilirubinemia in breast fed full term neonates.

A literature review of publically available information was undertaken to summarize current understanding and gaps in knowledge about Middle East respiratory syndrome coronavirus (MERS-CoV), including its origin, transmission, effective control measures and management. Major databases were searched and relevant published papers and reports during 2012-2015 were reviewed. Of the 2520 publications initially retrieved, 164 were deemed relevant. The collected results suggest that much remains to be discovered about MERS-CoV. Improved surveillance, epidemiological research and development of new therapies and vaccines are important, and the momentum of recent gains in terms of better understanding of disease patterns should be maintained to enable the global community to answer the remaining questions about this disease.

There are gaps in the knowledge about the burden of severe respiratory disease in the Eastern Mediterranean Region (EMR). This literature review was therefore conducted to describe the burden of epidemicand pandemic-prone acute respiratory infections (ARI) in the Region which may help in the development of evidence-based disease prevention and control policies. Relevant published and unpublished reports were identified from searches of various databases; 83 documents fulfilled the search criteria. The infections identified included: ARI, avian influenza A(H5N1), influenza A(H1N1)pdm09 and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Pneumonia and ARIs were leading causes of disease and death in the Region. Influenza A(H1N1) was an important cause of morbidity during the 2009 pandemic. This review provides a descriptive summary of the burden of acute respiratory diseases in the Region, but there still remains a lack of necessary data.

This study aimed to identify seminal Corynebacterium strains in infertile men with and without leucocytospermia. Semen samples from 60 infertile men were allocated into two equal groups: semen samples with leucocytospermia and semen samples without leucocytospermia. Semen culture for Corynebacterium species was carried out on Columbia agar medium confirmed by Gram-stained film and biochemical tests followed by analytical profile index biotyping and antibiotic susceptibility. Bacterial isolates were detected in 20/60 semen cultures (33.3%) as Corynebacteria, Staphylococci, Alpha haemolytic streptococci and E. coli. In all, 12/60 (20%) had Corynebacterium positive semen culture, whereas C. seminal was the major isolated species followed by C. amycolatum, C. jekium and C. urealyticum. There was nonsignificant difference between patients with/without Corynebacterium positive culture regarding sperm concentration and normal sperm morphology; however, in positive cultures sperm motility was significantly lower compared with negative cultures. Antimicrobial sensitivity among Corynebacteria strains was highest for vancomycin, rifampicin then imipenem, ampicillin + sulbactam, ciprofloxacin. It is concluded that positive semen cultures for different Corynebacteria species were demonstrated in infertile men, whereas Corynebacterium seminale was the most common isolated species. Vancomycin, rifampicin then imipenem and ampicillin + sulbactam are recommended as sensitive antibiotics., (© 2015 Blackwell Verlag GmbH.)

Phosphodiestrase-5 inhibitors are an important line of treatment for erectile dysfunction (ED). To detect the clinical and hemodynamic predictors of sildenafil response, we conducted this study on 124 Egyptian men with ED. All patients were evaluated by thorough history and clinical assessment with measurement of the abridged international index of erectile function-5 (IIEF-5) score. All patients were then subjected to intracavernosal injection (ICI) of trimix and pharmaco-penile duplex ultrasonography (PPDU). Patients were then classified into sildenafil responders and non-responders after six consecutive doses of 100 mg sildenafil. On doing the binary logistic stepwise regression analysis, only ED duration, IIEF-5 score, and response to ICI were the significant independent predictors of sildenafil response. These three parameters together correctly predicted the sildenafil response by 81.5% (p value <0.001). With the receiver operator characteristic curve analysis, the cut-off value of ED duration was 2.5 years and it was 14 for the IIEF-5 score. These findings indicate that ED duration, the IIEF-5 score and response to ICI are more significant predictors of sildenafil response than the more expensive and time-consuming PPDU testing., (© 2015 American Society of Andrology and European Academy of Andrology.)

The CAG repeat and its association with infertility has been debatable. Therefore, this study was planned to assess the distribution of CAG repeat expansion in Egyptian patients and to investigate its association with male infertility. Forty-five infertile men were eligible for the study in addition to 20 aged-matched fertile males as control. Semen analysis, scrotal sonography, assay of serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH), and determination of the CAG repeat number within exon 1 of the androgen receptor (AR) gene were carried out. Statistically significant difference was found between infertile and control groups regarding sperm count, sperm motility, serum FSH level and CAG repeats (P < 0.05); statistically insignificant difference for the CAG repeats (P = 1.0) was found between oligozoospermic and asthenospermic groups; negative correlation was found between CAG repeat length and sperm count, and a positive correlation was found between CAG repeat length and serum FSH (P < 0.05). Our results validate the concept that long stretches of CAG repeat may be associated with lower AR function with derangement of sperm production, and this may contribute to male infertility in Egyptian men., (© 2011 Blackwell Verlag GmbH.)

Aim: To evaluate the effects of Lichtenstein tension-free inguinal hernioplasty on sexual function and generic quality of life, testicular volume, and perfusion., Patients and Methods: In a prospective study, testicular volume, testicular perfusion, sexual function, generic quality of life, chronic inguinal pain, and groin sepsis were investigated before and 3 and 9 months after surgical hernia repair., Results: Forty male patients completed this study. No differences in testicular volume or in peak systolic velocity were observed between the hernia and healthy sides of the body (P > 0.05). Preoperatively, there was a significantly higher end diastolic velocity (P < 0.04) and resistive index (P < 0.001) on the hernia side compared with the normal side; these elevations returned to normal postoperatively. Three months postoperative, the studied sexual function domains, except orgasm domain, and total sexual score presented significant improvement (P(s) < 0.05 and 0.001 respectively). By the end of the study, the mean total sexual score and the number of patients with enhanced total score had showed further clinical progress. The total generic quality-of-life score, general health perception and physical function, vitality, and social domains were statistically recovered at 3 months postoperative (P < 0.05), with further improvement in total score at 9 months. Two patients developed superficial groin sepsis, and seven (17.5%) experienced chronic inguinal pain., Conclusion: Inguinal hernia impaired testicular perfusion that improved postoperatively. Lichtenstein tension-free hernioplasty improved sexual function and generic quality of life without adverse mesh effects on testicular volume or perfusion.