Ain Shams University Hospital

Reddy D., Peters M., Shah T.T., van Son M., Tanaka M.B., Huber P.M., Lomas D., Rakauskas A., Miah S., Eldred-Evans D., Guillaumier S., Hosking-Jervis F., Engle R., Dudderidge T., Hindley R.G., et. al.

Focal high-intensity focused ultrasound is a safe alternative treatment option for patients with intermediate- to high-risk localised prostate cancer, which confers good medium-term cancer control. Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005–2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer–specific mortality. Differences in FFS between D’Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. The median (interquartile range) age was 66 (60–71) yr and prostate-specific antigen was 6.9 (4.9–9.4) ng/ml with D’Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17–58) mo; for those with ≥5 yr of follow-up, it was 82 (72–94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64–74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62–75%) and 65% (95% CI 56–74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

Cif L., Demailly D., Lin J., Barwick K.E., Sa M., Abela L., Malhotra S., Chong W.K., Steel D., Sanchis-Juan A., Ngoh A., Trump N., Meyer E., Vasques X., Rankin J., et. al.

Abstract Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5–37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden’s Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 16.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution.

Kotb S., Lyman M., Ismail G., Abd El Fattah M., Girgis S.A., Etman A., Hafez S., El-Kholy J., Zaki M.E., Rashed H.G., Khalil G.M., Sayyouh O., Talaat M.

To describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) healthcare-associated infections (HAI) in Egyptian hospitals reporting to the national HAI surveillance system. Design: Descriptive analysis of CRE HAIs and retrospective observational cohort study using national HAI surveillance data. Setting: Egyptian hospitals participating in the HAI surveillance system. The patient population included patients admitted to the intensive care unit (ICU) in participating hospitals. Enterobacteriaceae HAI cases were Klebsiella, Escherichia coli, and Enterobacter isolates from blood, urine, wound or respiratory specimen collected on or after day 3 of ICU admission. CRE HAI cases were those resistant to at least one carbapenem. For CRE HAI cases reported during 2011–2017, a hospital-level and patient-level analysis were conducted using only the first CRE isolate by pathogen and specimen type for each patient. For facility, microbiology, and clinical characteristics, frequencies and means were calculated among CRE HAI cases and compared with carbapenem-susceptible Enterobacteriaceae HAI cases through univariate and multivariate logistic regression using STATA 13. There were 1598 Enterobacteriaceae HAI cases, of which 871 (54.1%) were carbapenem resistant. The multivariate regression analysis demonstrated that carbapenem resistance was associated with specimen type, pathogen, location prior to admission, and length of ICU stay. Between 2011 and 2017, there was an increase in the proportion of Enterobacteriaceae HAI cases due to CRE (p-value = 0.003) and the incidence of CRE HAIs (p-value = 0.09). This analysis demonstrated a high and increasing burden of CRE in Egyptian hospitals, highlighting the importance of enhancing infection prevention and control (IPC) programs and antimicrobial stewardship activities and guiding the implementation of targeted IPC measures to contain CRE in Egyptian ICU’s .

Fouad Y.A., Abdelaziz T.T., Askoura A., Saleh M.I., Mahmoud M.S., Ashour D.M., Ashour M.M.

Objective: To determine if there was an increase in the rate of cases presenting with rhino-orbital-cerebral mucormycosis (ROCM) to a tertiary care center during the first wave of the coronavirus disease 2019 (COVID-19) pandemic and the characteristics of the presenting cases.Methods: Retrospective observational study reviewing ROCM cases presenting from March 25 until September 25, 2020. Cases fulfilling the clinical, radiological, and pathological/microbiological criteria for diagnosis with ROCM were included. The number of cases presenting during the designated interval, their COVID-19 status, comorbidities, and clinical presentation were analyzed. The number of cases during the corresponding interval in the previous 3 years was used as reference to detect if there was a recent spike.Results: Of the 12 ROCM cases identified, 5 had a concurrent positive reverse transcription PCR (RT-PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 1 had a prior positive result, and 6 did not have concurrent nor prior positive test results. Nine of the 12 cases had poorly controlled diabetes mellitus, and 2 cases had a hematological malignancy. All cases had orbital invasion, and eight cases had cerebral invasion. The number of cases identified during the interval is much higher than the numbers presenting in the prior 3 years during equivalent intervals (range, one to two cases) than those reported in the literature in different settings in the pre-pandemic era.Conclusions: There is an increased rate of ROCM cases presenting to our center during the first wave of the COVID-19 pandemic. This is a preliminary report, and further studies are needed to corroborate the findings and explain possible underlying links.

Soliman W.M., Sherif N.M., Ghanima I.M., EL-Badawy M.A.

To investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as activity markers in systemic lupus erythematosus (SLE) without nephritis and lupus nephritis (LN) patients. This study included 60 SLE patients with LN, 60 SLE patients without renal involvement and 30 healthy controls. We analyzed correlations between NLR and PLR and both disease activity and renal affection. The NLR of SLE patients was much higher than those of the controls. Both ratios showed significantly increased values in SLE patients with active disease. NLR and PLR were positively correlated with SLEDAI, ESR, and CRP and negatively correlated with C4. SLE patients with LN had higher levels of NLR than those without nephritis. NLR showed positive correlations with BUN, serum urea, serum creatinine and 24 h urinary protein. We found NLR to be related to anti-ds-DNA level and renal biopsy classes. While PLR was related only to anti ds-DNA. The best NLR to predict SLE active disease was 2.2 and the best PLR cut-off value was 132.9. NLR and PLR are useful inflammatory markers to evaluate disease activity in SLE patients. Also, NLR could reflect renal involvement in SLE patients and is associated with the different classes of its histological staging. Investigar el papel de la proporción de neutrófilos a linfocitos (NLR), y la relación de plaquetas a linfocitos (PLR) como marcadores de actividad en el lupus eritematoso sistémico (LES) sin nefritis, y pacientes con nefritis lúpica (NL). Este estudio incluyó a 60 pacientes con LES con NL, 60 pacientes con LES sin afectación renal y 30 controles sanos. Analizamos las correlaciones entre NLR y PLR con la actividad de la enfermedad y la afección renal. La NLR de los pacientes con LES fue mucho más alta que los de los controles. Ambas razones mostraron valores significativamente mayores en pacientes con LES con enfermedad activa. La NLR y la PLR se correlacionaron positivamente con SLEDAI, ESR y CRP y se correlacionaron negativamente con C4. Los pacientes con LES con LN tenían niveles más altos de NLR que aquellos sin nefritis. La NLR mostró correlaciones positivas con BUN, urea sérica, creatinina sérica y proteína urinaria de 24 h. Encontramos que la NLR está relacionada con el nivel de anti-dsDNA y las clases de biopsia renal. Mientras que la PLR estaba relacionada solo con anti-dsDNA. La mejor NLR para predecir la enfermedad activa del SLE fue de 2,2 y el mejor valor de corte de la PLR fue 132,9. La NLR y la PLR son marcadores inflamatorios útiles para evaluar la actividad de la enfermedad en pacientes con LES. Además, la NLR podría reflejar la afectación renal en pacientes con LES y se asocia con las diferentes clases de su estadificación histológica.

Abraham B., Megaly M., Sous M., Fransawyalkomos M., Saad M., Fraser R., Topf J., Goldsmith S., Simegn M., Bart B., Azzo Z., Mesiha N., Sharma R.

Although torsemide's oral bioavailability and half-life theoretically render it a more efficient diuretic than furosemide, the clinical outcomes of torsemide compared with furosemide remain unclear. We performed a systematic review and meta-analysis, including all published studies that compared torsemide and furosemide use in heart failure patients from January 1996 through August 2019. Nineteen studies (9 randomized control trials [RCTs] and 10 observational studies) with a total of 19,280 patients were included. During a mean follow-up duration of 15 months, torsemide was associated with a numerically lower risk of hospitalization due to heart failure (10.6% vs 18.4%; odds ratio [OR] 0.72, 95% confidence interval [CI] [0.51, 1.03], p = 0.07, I2 = 18%; number needed to treat [NNT] = 23) compared with furosemide. Torsemide was associated with statistically significant more improvement in functional status from New York Heart Association (NYHA) class III/IV to I/II (72.5% vs 58%; OR 2.32, 95% CI (1.32, 4.1), p = 0.004, I2 = 27%; NNT = 5) and lower risk of cardiac mortality (1.5% vs 4.4%; OR 0.37, 95% CI (0.20, 0.66), p

Khidr E.G., Abulsoud A.I., Doghish A.A., El-Mahdy H.A., Ismail A., Elballal M.S., Sarhan O.M., Abdel Mageed S.S., Elsakka E.G., Elkhawaga S.Y., El-Husseiny A.A., Abdelmaksoud N.M., El-Demerdash A.A., Shahin R.K., Midan H.M., et. al.

For the past two decades since their discovery, scientists have linked microRNAs (miRNAs) to posttranscriptional regulation of gene expression in critical cardiac physiological and pathological processes. Multiple non-coding RNA species regulate cardiac muscle phenotypes to stabilize cardiac homeostasis. Different cardiac pathological conditions, including arrhythmia, myocardial infarction, and hypertrophy, are modulated by non-coding RNAs in response to stress or other pathological conditions. Besides, miRNAs are implicated in several modulatory signaling pathways of cardiovascular disorders including mitogen-activated protein kinase, nuclear factor kappa beta, protein kinase B (AKT), NOD-like receptor family pyrin domain-containing 3 (NLRP3), Jun N-terminal kinases (JNKs), Toll-like receptors (TLRs) and apoptotic protease-activating factor 1 (Apaf-1)/caspases. This review highlights the potential role of miRNAs as therapeutic targets and updates our understanding of their roles in the processes underlying pathogenic phenotypes of cardiac muscle.

Abdin M., El-Beltagy A.E., El-sayed M.E., Naeem M.A.

Biodegradable sodium alginate/gum Arabic (SG) films were obtained. The influence of Syzygium cumini seeds extract (SCSE) incorporation in SG films on morphological structure, polymer interaction, thermal behavior, antioxidant activity and physical characteristics were investigated. Moreover, the fabricated films were tested as wrapping materials to extend the shelf life of sunflower oil. Scanning electron microscopy micrographs showed heterogeneous and rough surface after incorporation by SCSE. Possible cross-linked interaction between alginate and gum Arabic and physical interaction between SCSE and SG films were assessed by FT-IR. Although, the addition of SCSE into SG films declined the thermal stability, elongation at break (EB), tensile strength (TS) and moisture content, films with better opacity, solubility and water vapor permeability were obtained. The SG-SCSE films showed obvious obstructing effects on the oil oxidation process during storage days. According to these results, it can be emphasized that edible films with the highest concentrations of added SCSE can serve as a good source of antioxidant compounds and physicochemical properties. Certainly, these properties can be usefully incorporated into the wrapped food commodity.

Rehman K.U., Gouda M., Zaman U., Tahir K., Khan S.U., Saeed S., Khojah E., El-Beltagy A., Zaky A.A., Naeem M., Khan M.I., Khattak N.S.

Noble metal nanoparticles (NMNPs) are viable alternative green sources compared to the chemical available methods in several approach like Food, medical, biotechnology, and textile industries. The biological synthesis of platinum nanoparticles (PtNPs), as a strong photocatalytic agent, has proved as more effective and safer method. In this study, PtNPs were synthesized at four different temperatures (25 °C, 50 °C, 70 °C, and 100 °C). PtNPs synthesized at 100 °C were smaller and exhibited spherical morphology with a high degree of dispersion. A series of physicochemical characterizations were applied to investigate the synthesis, particle size, crystalline nature, and surface morphology of PtNPs. The biosynthesized PtNPs were tested for the photodegradation of methylene blue (MB) under visible light irradiations. The results showed that PtNPs exhibited remarkable photocatalytic activity by degrading 98% of MB only in 40 min. The acid phosphatase mediated PtNPs showed strong bacterial inhibition efficiency against S. aureus and E. coli. Furthermore, it showed high antioxidant activity (88%) against 1,1-diphenyl-2-picryl-hydrazil (DPPH). In conclusion, this study provided an overview of the applications of PtNPs in food chemistry, biotechnology, and textile industries for the deterioration of the natural and synthetic dyes and its potential application in the suppression of pathogenic microbes of the biological systems. Thus, it could be used as a novel approach in the food microbiology, biomedical and environmental applications.

Elsakka E.G., Abulsoud A.I., El-Mahdy H.A., Ismail A., Elballal M.S., Mageed S.S., Khidr E.G., Mohammed O.A., Sarhan O.M., Elkhawaga S.Y., El-Husseiny A.A., Abdelmaksoud N.M., El-Demerdash A.A., Shahin R.K., Midan H.M., et. al.

MicroRNAs (miRNAs; miRs) are small non-coding ribonucleic acids sequences vital in regulating gene expression. They are significant in many biological and pathological processes and are even detectable in various body fluids such as serum, plasma, and urine. Research has demonstrated that the irregularity of miRNA in multiplying cardiac cells is linked to developmental deformities in the heart's structure. It has also shown that miRNAs are crucial in diagnosing and progressing several cardiovascular diseases (CVDs). The review covers the function of miRNAs in the pathophysiology of CVD. Additionally, the review provides an overview of the potential role of miRNAs as disease-specific diagnostic and prognostic biomarkers for human CVD, as well as their biological implications in CVD.