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Althoughchronic hepatitis C (CHC) therapies based on direct-acting antiviral (DAA) agents safely improved treatment effectiveness, some cases do not obtain sustained virological response (SVR) and, thus, evaluating factors that may be related to treatment failure is very important. We aimed to evaluate the association of baseline serum collagen IV with DAA treatment failure in Egyptian patients with CHC. A total of 175 CHC patients (100 responders and 75non-responders tosofosbuvir/daclatasvir) were included. Collagen IV was assessed using sensitive chemiluminescent immunoassay. There was distinctly higher ( P  < 0.0001) collagen IV in non-responders compared to responder patients as the median (interquartile range) were 19.02 (13.4-25.2) vs .9.7 (7.2-12.3) µg/L, respectively. Collagen IV has a good ability for distinguishing nonresponders from responder patients (AUC = 0.890) with sensitivity of 92%, specificity 72%, PPV 71.1%, NPV 92.3% and accuracy of 80.6%. Collagen IV was correlated ( p  < 0.05) with decreased albumin ( r =-0.266), elevated APRI ( r  = 0.288), and elevated FIB-4 ( r  = 0.281) scores. In conclusion,these findings suggested the remarkable role of baseline collagen IV in the prediction of HCV DAAs treatment response. Thus, however further studies are needed, its measurement may improve treatment duration and the disease control.

Background: In addition to the great challenge of early diagnosis and prognosis in breast cancer (BC), the role of gene promoters in BC remains largely unexplored. This study aimed to evaluate aldo-keto reductase family 1 member B1 ( AKR1B1 ) methylation as noninvasive biomarker for early BC diagnosis., Methods: A total of 200 (120 with BC, 40 with benign breast diseases, 40 healthy) Egyptian women were enrolled. AKR1B1 methylation level was determined using EpiTect Methyl II QPCR assay quantitative polymerase chain reaction., Results: Findings revealed that hypermethylation AKR1B1 was reported to be associated ( P  < .0001) with BC cases (93.2 [75.4-98.6]) compared with benign (23.9 [22.6-48.3]) or healthy (15.5 [10.6-16]) controls. It had a great diagnostic power (area under the curve [AUC] = 0.909) that was superior to cancer antigen (CA) 15-3 (AUC = 0.681) and carcinoembryonic antigen (CEA) (AUC = 0.539). Interestingly, AKR1B1 hypermethylation was reported to be significant in identifying BC early stages (AUC = 0.899) and grades (AUC = 0.903). Independent to hormonal status and HER2neu expression, AKR1B1 hypermethylation was related to some tumor severity features, including advanced stages, high histological grades, and lymph node invasion. Also, AKR1B1 high degrees of methylation were significantly correlated with the increase in CEA ( r  = .195; P  = .027), CA-15.3 ( r  = .351; P  = .0001) and tumor stages ( r  = .274; P  = .014), grades ( r  = .253; P  = .024), and lymph node invasion ( r  = .275; P  = .014)., Conclusions: This study revealed that aberrant AKR1B1 methylation could facilitate early BC detection from benign br0east disorders. Hypermethylated AKR1B1 was related to BC aggressiveness suggesting its potential role as diagnostic and prognostic BC biomarker., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Chronic hepatitis C (CHC) infection is a major public health problem in many low- and middle-income countries. The study aimed to find out how interleukin IL-6 and IL-8 levels in the blood affect the virological response to directacting antivirals (DAAs) and to find useful clinical or immunological markers for the response to HCV treatment., Methods: CHC patients from a real Egyptian population (n = 4,300), who were treated during the Egyptian national initiative to eliminate HCV at the Sherbin Central Hospital, Dakahlia Governorate, Ministry of Health, Egypt, were enrolled in our study. They were all patients who did not obtain a sustained virological response (SVR) (n = 75; non-responder; the response rate was 98.26%), and a total of 100 patients were randomly selected from patients who obtained SVR (responder) and were age- and gender-matched (p > 0.05) with non-responder patients. Serum levels of IL-6 and IL-8 were measured by commercial ELISA kits., Results: Non-responder patients were associated with significantly high levels of ALT, AST, ALP, and total bilirubin. Non-responders had significantly (p < 0.05) higher baseline IL-6 (16.7 ± 4.92 pg/mL) and IL-8 (37.81 ± 10.55 pg/mL) levels compared to responders (12.68 ± 2.06, 29.06 ± 5.94 pg/mL, respectively). There was a substantial (p < 0.05) association between the combination of two cytokines and a high likelihood of treatment failure, as indicated by all parameters examined, with the highest correlation values seen., Conclusions: The present study showed that increased IL-6 and IL-8 were associated with HCV treatment failure. Also, IL8 was associated with hepatic fibrosis.

Purpose: To assess the frequency and the predictive factors of Acute Kidney injury (AKI) in patients undergoing percutaneous nephrolithotomy (PNL)., Methods: A prospective observational work. Demographic, preoperative laboratory data, stone characteristics, and intraoperative and postoperative data were gathered. Perioperative AKI had been defined as an elevation in serum creatinine by ≥ 0.3 mg/dl within 48 h, or ≥ 1.5 times baseline, or urine volume less than 0.5 ml/ kg/hour for 6 hours. A multivariate logistic regression analysis was performed to determine the predictive factors of AKI. ROC curves were utilized to determine the cutoff values of the risk variables. P-values were deemed statistically significant when they were less than 0.05., Results: A total of 418 participants had been involved. The frequency of AKI was 13.9, and 17.2% of patients with AKI developed CKD. The risk factors were age > 46.5 years, smoking, BMI > 28.5 kg/m 2 , hypertension, diabetes, utilization of angiotensin-converting enzyme inhibitors (ACEI), haemoglobin < 10.8 gm/dl, baseline creatinine > 1.41 mg/dl, eGFR < 65.2 ml/min./1.73 m 2 , serum uric acid > 5.2 mg/dl, stone volume > 1748 mm 3 , large tract size, long operative time, and intra-operative bleeding. Patients with AKI had a notably extended duration of hospitalization (3.2 days ± 0.45 vs 2.1 ± 0.42, p < 0.001)., Conclusions: Perioperative AKI occurred in 13.9% of individuals undergoing PNL. Identification and optimization of the risk factors and meticulous technique during PNL procedures should be attempted to decrease the risk of AKI., (© 2024. The Author(s).)

Background: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient., Objective: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting., Methods: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed., Results: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized β = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized β = -0.14, p = 0.028) in a linear regression model., Conclusions: PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Zivadinov has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Janssen, Protembis, Filterlex and Novartis for speaking and consultant fees. He received financial support for research activities from Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Protembis, CorEvitas and V-WAVE Medical. Niels Bergsland and Dejan Jakimovski have nothing to disclose. Myassar Zarif, Samuel Hunter, Stephen Newman, Tom Fuchs and Mary Ann Picone have not declared any conflict of interest. Bianca Weinstock-Guttman received honoraria as a speaker and/or as a consultant for Biogen Idec, Sanofi &Genzyme, Genentech, Novartis, BMS, Bayer, Horizon and Janssen. Dr Weinstock-Guttman received research funds from Biogen Idec, Genentech and Novartis. Lorena Lorefice received honoraria for consultancy and speaking from Biogen, Novartis, Sanofi, Genzyme, Merck and Bristol Myers Squibb. Menno Schoonheim: Serves on the editorial board of Neurology and Frontiers in Neurology, receives research support from the Dutch MS Research Foundation, Eurostars-EUREKA, ARSEP, Amsterdam Neuroscience, MAGNIMS and ZonMW (Vidi grant, project number 09150172010056) and has served as a consultant for or received research support from Atara Biotherapeutics, Biogen, Celgene/Bristol Meyers Squibb, EIP, Sanofi, MedDay and Merck. Sarah A. Morrow, in the last 3 years, has served as an advisory board member or received consulting fees from Biogen Idec; BMS/Celgene; EMDSerono; Novartis; Roche; Sanofi. She has participated in a speaker’s bureau for Biogen Idec; BMS/Celgene; EMDSerono; Novartis; Roche; Sanofi. She has received research support from Biogen Idec; EMDSerono, Novartis, Roche; Sanofi Genzyme. She has participated as a site investigator in clinical trials sponsored by Bristol Myers Squibb/Celgene; EMDSerono; Novartis; Roche; Sanofi. Gabriel Pardo received grants (to the institution) from Biogen, EMD Serono, Roche/Genentech, Sanofi Genzyme, Novartis, Abbvie, and BMS; consultant and/or speaker bureau for Biogen, EMD Serono, Roche/Genentech, Sanofi Genzyme, Novartis, Janssen, BMS, TG Therapeutics, PRIME Education, and MSAA. Mark Gudesblatt received honoraria from Biogen and Genentech. Jacqueline Nicholas received research grants from Biogen, Novartis, PCORI, Genentech, University of Buffalo, EMD Serono; Consulting for EMD Serono, Genentech, Greenwich Biosciences, Novartis, TG Therapeutics and Sanofi; Speaking honoraria for BMS, EMD Serono, Horizon, TG Therapeutics. Andrew Smith received honorariums from EMD Serono and Sanofi Genzyme for speaking bureau and combination for Genzyme for an advisory board. Mahmoud A. AbdelRazek received consultant fees from Bristol Myers Squibb. Wachy Vongchucherd, Jon Riolo and Diego Silva are employees of Bristol Myers Squibb. Michael G. Dwyer has received personal compensation from Bristol Myers Squibb and Filterlex for consultant fees. He received financial support for research activities from Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Protembis, CorEvitas and V-WAVE Medical. Ralph HB. Benedict has received consultation or speaking fees from Bristol Myer Squibb, Biogen, Merck, EMD Serono, Roche, Immune Therapeutics, Novartis, and Sanofi-Genzyme., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hepatitis C virus (HCV) was reported to relate to polymorphous and frequent extrahepatic manifestation. Despite the limited studies, HCV viral oncoproteins may be implicated in breast cancer (BC) tumor aggressiveness. In a trial to elucidate a mechanistic link, this study aimed to investigate a mutant p53 and c-Myc oncoprotein expression levels in BC patients with and without HCV infection., Methods: A total of 215 BC patients (119 infected and 96 non-infected with HCV) were collected. ELISA was used for detection of anti-HCV antibodies, mutant p53, c-Myc, HCV-NS4, CEA, CA 125, and CA-15.3., Results: HCV infection was related to BC late stages, lymph-node invasion, distant metastasis, high grades, and large size. HCV-infected patients had a significantly (P < 0.05) higher WBCs, ALT and AST activity, bilirubin CEA, CA125 and CA15.3 levels, and reduced hemoglobin, albumin, and RBCs count. Regardless of tumor severity, HCV infection was associated with significant elevated levels of mutant p53 (22.5 ± 3.5 µg/mL; 1.9-fold increase) and c-Myc (21.4 ± 1.8 µg/mL; 1.5-fold increase). Among HCV-infected patients, elevated levels of p53 and c-Myc were significantly correlated with elevated tumor markers (CEA, CA 125, and CA15.3) and HCV-NS4 levels., Conclusions: This study concluded that HCV infection may be accompanied with BC severity behavior and this may be owing to elevated expression of mutant p53 and c-Myc oncoproteins., (© 2023. The Author(s).)

Computed tomography (CT) total-airway-count (TAC) and airway wall-thickness differ across chronic obstructive pulmonary disease (COPD) severities, but longitudinal insights are lacking. The aim of this study was to evaluate longitudinal CT airway measurements over three-years in ex-smokers. In this prospective convenience sample study, ex-smokers with ( n  = 50; 13 female; age = 70 ± 9 years; pack-years = 43 ± 26) and without ( n  = 40; 17 female; age = 69 ± 10 years; pack-years = 31 ± 17) COPD completed CT, 3 He magnetic resonance imaging (MRI), and pulmonary function tests at baseline and three-year follow-up. CT TAC, airway wall-area (WA), lumen-area (LA), and wall-area percent (WA%) were generated. Emphysema was quantified as the relative-area-of-the-lung with attenuation < -950 Hounsfield-units (RA 950 ). MRI ventilation-defect-percent (VDP) was also quantified. Differences over time were evaluated using paired-samples t tests. Multivariable prediction models using the backwards approach were generated. After three-years, forced-expiratory-volume in 1-second (FEV 1 ) was not different in ex-smokers with ( p  = 0.4) and without ( p  = 0.5) COPD, whereas RA 950 was ( p  < 0.001, p  = 0.02, respectively). In ex-smokers without COPD, there was no change in TAC ( p  = 0.2); however, LA ( p  = 0.009) and WA% ( p  = 0.01) were significantly different. In ex-smokers with COPD, TAC ( p  < 0.001), WA ( p  = 0.04), LA ( p  < 0.001), and WA% ( p  < 0.001) were significantly different. In all ex-smokers, TAC was related to VDP (baseline: ρ = -0.30, p  = 0.005; follow-up: ρ = -0.33, p  = 0.002). In significant multivariable models, baseline airway wall-thickness was predictive of TAC worsening. After three-years, in the absence of FEV 1 worsening, TAC diminished only in ex-smokers with COPD and airway walls were thinner in all ex-smokers. These longitudinal findings suggest that the evaluation of CT airway remodeling may be a useful clinical tool for predicting disease progression and managing COPD. Clinical trial registration: www.clinicaltrials.gov NCT02279329.

Background: The implementation and continuous improvement of patient safety learning systems (PSLS) is a principal strategy for mitigating preventable harm to patients. Although substantial efforts have sought to improve these systems, there is a need to more comprehensively understand critical success factors. This study aims to summarise the barriers and facilitators perceived by hospital staff and physicians to influence the reporting, analysis, learning and feedback within PSLS in hospitals., Methods: We performed a systematic review and meta-synthesis by searching MEDLINE (Ovid), EMBASE (Ovid), CINAHL, Scopus and Web of Science. We included English-language manuscripts of qualitative studies evaluating effectiveness of the PSLS and excluded studies evaluating specific individual adverse events, such as systems for tracking only medication side effects, for example. We followed the Joanna Briggs Institute methodology for qualitative systematic reviews., Results: We extracted data from 22 studies, after screening 2475 for inclusion/exclusion criteria. The included studies focused on reporting aspects of the PSLS, however, there were important barriers and facilitators across the analysis, learning and feedback phases. We identified the following barriers for effective use of PSLS: inadequate organisational support with shortage of resources, lack of training, weak safety culture, lack of accountability, defective policies, blame and a punitive environment, complex system, lack of experience and lack of feedback. We identified the following enabling factors: continuous training, a balance between accountability and responsibility, leaders as role models, anonymous reporting, user-friendly systems, well-structured analysis teams, tangible improvement., Conclusion: Multiple barriers and facilitators to uptake of PSLS exist. These factors should be considered by decision makers seeking to enhance the impact of PSLS., Ethics and Dissemination: No formal ethical approval or consent were required as no primary data were collected., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Cerebral gray matter (GM) atrophy is a proposed measure of neuroprotection in multiple sclerosis (MS). Glatiramer acetate (GA) limits clinical relapses, MRI lesions, and whole brain atrophy in relapsing-remitting MS (RRMS). The effect of GA on GM atrophy remains unclear. We assessed GM atrophy in patients with RRMS starting GA therapy in comparison to a cohort of patients with clinically benign RRMS (BMS)., Design/methods: We studied 14 patients at GA start [age (mean ± SD) 44.2 ± 7.0 years, disease duration (DD) 7.2 ± 6.4 years, Expanded Disability Status Scale score (EDSS) (median,IQR) 1.0,2.0] and 6 patients with BMS [age 43.0 ± 6.1 years, DD 18.1 ± 8.4 years, EDSS 0.5,1.0]. Brain MRI was obtained at baseline and one year later (both groups) and two years later in all patients in the GA group except one who was lost to follow-up. Semi-automated algorithms assessed cerebral T2 hyperintense lesion volume (T2LV), white matter fraction (WMF), GM fraction (GMF), and brain parenchymal fraction (BPF). The exact Wilcoxon-Mann-Whitney test compared the groups. The Wilcoxon signed rank test assessed longitudinal changes within groups., Results: During the first year, MRI changes did not differ significantly between groups (p > 0.15). Within the BMS group, WMF and BPF decreased during the first year (p = 0.03). Within the GA group, there was no significant change in MRI measures during each annual period (p > 0.05). Over two years, the GA group had a significant increase in T2LV and decrease in WMF (p < 0.05), while GMF and BPF remained stable (p > 0.05). MRI changes in brain volumes (GMF or WMF) in the first year in the GA group were not significantly different from those in the BMS group (p > 0.5)., Conclusions: In this pilot study with a small sample size, patients with RRMS started on GA did not show significant GM or whole brain atrophy over 2 years, resembling MS patients with a clinically benign disease course., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Weaning is the most crucial period associated with increased stress and susceptibility to diseases in rabbits. Methicillin-resistant Staphylococcus aureus (MRSA), a historic emergent pathogen related to post weaning stressors, adversely affects rabbit's growth rate and productive cycle. Since MRSA is rapidly evolving antibiotics resistance, natural products are desperately required to tackle the public health threats posed by antimicrobial resistance. Thus, this study aimed to screen the iin vitro antibacterial activity of Nigella sativa extract (NSE) and its interactions with antibiotics against MRSA isolates. Moreover, 200 weaned rabbits were divided into 4 groups to investigate the iin vivo superiority of NSE graded levels towards growth performance, tight junction integrity, immune responsiveness and resistance against MRSA. Herein, NSE showed promising antimicrobial activities against MRSA isolates from animal (77.8%) and human (64.3%) origins. Additionally, MRSA isolates exposed to NSE became sensitive to all antimicrobials to which they were previously resistant. Our results described that the growth-promoting functions of NSE, especially at higher levels, were supported by elevated activities of digestive linked enzymes. Post-NSE feeding, rabbits' sera mediated bactericidal activities against MRSA. Notably, upregulated expression of occludin, CLDN-1 , MUC-2 and JAM-2 genes was noted post NSE supplementation with maximum transcriptional levels in 500 mg/kg NSE fed group. Our data described that NSE constitutively motivated rabbits' immune responses and protected them against MRSA-induced experimental infection. Our results suggest the antimicrobial, growth stimulating and immunomodulation activities of NSE to maximize the capability of rabbits for disease response.

Some studies suggest that thyroid hormones and disorders can influence breast (BC) and ovarian (OC) cancers risks. However, studies regarding their effect on these tumors progression are limited. Thyroid-stimulating hormone (TSH), T4, free T4 (FT4), T3, and free T3 (FT3) were detected in patients with BC, OC, benign breast and ovary diseases, and healthy controls using highly sensitive chemiluminescence assay. In contrast to OC, hypothyroidism prevalence was associated with BC late stage (11/24 vs . 2/46), high grade (11/23 vs . 4/47), lymph node invasion (11/42 vs . 0/28), positive distant metastasis (11/25 vs . 1/45), and large tumor size (14/25 vs . 1/45) compared to tumor early stages, low grades, negative lymph node, and distant metastasis and small size, respectively. Patients with late stage, high grade, large tumor size, positive lymph nodes, or positive distant metastasis were significantly ( P < 0.05) associated with elevated levels of TSH and decreased levels of T4, FT4, T3, and FT3. There were both significant positive correlation of serum TSH and significant inverse correlation of T4, FT4, T3, and FT3 with these tumor worse outcomes. In conclusion, our results identify hypothyroidism as potentially important prognostic factor in BC not in OC that is associated with poor outcomes of BC patients.

Background: Early accurate breast cancer (BC) diagnosis is critical in disease management. Mammography has been widely used. However, its radiation, and high false-negative and -positive results have always been a concern. We evaluated combined detection of human epididymal protein 4 (HE4) and trefoil factor 3 (TFF3) as substitute method to enhance BC diagnosis., Methods: HE4 and TFF3 blood levels were determined by ELISA in sera of 120 BC patients and 80 women (40 healthy and 40 benign breast disease) as controls. Receiver-operating characteristic curve was applied for evaluation diagnostic power of each biomarker and their combination., Results: In BC patients, serum HE4 [5 (2-11.9) vs. 3.1 (1.8-5.4) and 1 (1-3.5); P = 0.022] and TFF3 [5.3 (4.5-6.7) vs. 4.7 (4-4.8) and 3.9 (3-4.4); P = 0.027] were significantly higher than that in benign and healthy groups, respectively. Both HE4 (AUC = 0.783; P < 0.0001) and TFF3 (AUC = 0.759; P < 0.0001) had superior BC diagnostic ability compared to CEA and CA-15.3. Logistic regression analysis revealed simplified index BC-DETECT = HE4 + TFF3, and its values were significantly (P = 0.0132) elevated in BC (10.9 (8.4-17.2) compared to benign (7.2 (5.4-10.1)) and healthy (5.1 (4-6.3)) controls. AUC of BC-DETECT for BC prediction was (AUC = 0.850; P < 0.0001) with sensitivity, specificity, and positive and negative predictive values and accuracy of 84.2%, 70%, 80.8%, 74.7%, and 78.5%, respectively. High BC-DETECT levels were associated with tumor non-luminal subtypes, late stage, high grade, large size, lymph-node invasion, and multiple lesions., Conclusions: BC-DETECT is inexpensive, rapid, and easy to perform and reliably guides BC early detection. Moreover, the association between elevated BC-DETECT values and disease severity may propose its potential role as prognostic marker., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Objectives: To investigate the duration of B-cell depletion in a cohort of patients receiving ocrelizumab or rituximab for multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD)., Methods: We retrospectively searched our database for patients diagnosed with MS or NMOSD, who were receiving ocrelizumab or rituximab and had available CD19 measurements. We collected demographic data, infusion doses, infusion dates, CD19 absolute counts and percentages, and their collection dates. We paired each infusion with the subsequent CD19 measurements recorded before the next infusion, discarding measurements done during a washout period of 30 days after each infusion. We applied three definitions for B-cell depletion, the most stringent of which was an absolute B-cell count ≤20 cells/uL., Results: From 695 patients with demyelinating diseases in our database, over the period of January 1st 2010 to March 1st 2020, we identified 188 patients (178 with MS and 10 with NMOSD), who had received ocrelizumab or rituximab and had available CD19 measurements. 1054 CD19 measurements were captured. B-cell depletion, as defined above, was recorded as far out as 22.8 months after an ocrelizumab infusion, and 22.3 months after a rituximab infusion. Out of 90 B-cell measurements done ≥8 months (>210 days) after ocrelizumab infusion, 45(50%) measurements showed B-cell depletion. Similarly for rituximab, out of 113 measurements, 49(43%) showed B-cell depletion., Conclusions: This study demonstrates that B-cell depletion after ocrelizumab and rituximab continues beyond the traditional 6-month re-infusion interval in many patients. Our report provides data that can support clinical trials testing increasing the interval of re-infusion with ocrelizumab and rituximab beyond 6-months guided by B-cell measurements., (Copyright © 2022. Published by Elsevier B.V.)

In chronic hepatitis C (CHC), Toxoplasma gondii infection can lead to more severe diseases and is capable of changing the disease course. Former studies were concerning anti- T. gondii IgG/IgM seroprevalence in CHC patients regardless the antigenic proteins that are associated with active infection. Therefore, this study aimed to evaluate association between prevalence of 36-KDa T. gondii antigen (TAg) and both CHC progression and liver and viral biochemical parameters. One hundred-twenty five CHC patients (65 with fibrosis and 60 with cirrhosis) and forty healthy controls constituted this study. Demographics and clinical data were collected. Both TAg and HCV-NS4 were identified using ELISA. In contrast to healthy controls (0%), both seropositivity ( P  = 0.043) and mean serum level ( P  = 0.025) of TAg were higher in cirrhotic patients (43.3 %; 1.2 ± 0.2 ng/mL) compared to fibrotic patients (26.2 %; 0.7 ± 0.1 ng/mL). T. gondii infection was significantly ( P  < 0.05) associated with liver and viral biochemical parameters including increased ALT and AST activities, total bilirubin and AFP levels and decreased albumin and platelets count levels. Interestingly, TAg positivity were associated with elevated HCV-NS4 level compared to negative TAg patients (212.5 ± 25.3 vs. 133.9 ± 17.4 µg/mL ( P  = 0.026); r  = 0.559 ( P  < 0.0001)). In conclusion, this study highlighted association between T. gondii parasitemia and CHC progression since TAg was more prevalent among cirrhotic than fibrotic patients and healthy controls. The presence of TAg was associated with impaired liver functions and increased HCV-NS4 levels. Further studies are needed to define the mechanism of this association., (© Indian Society for Parasitology 2021.)

Chronic hepatitis C (CHC) leads eventually to liver fibrosis, advanced hepatic disease and related deaths. Therefore, it is very important to assess clinical risk factors associated with rapid CHC and hepatic fibrosis progression. Former studies reported diabetes mellitus synergistic interactions with other host factors to fibrosis progression. Here, we aimed to evaluate the association between elevated blood glucose levels and CHC progression according to METAVIR system in patients chronically infected with HCV-genotype 4 and to evaluate the correlation between elevated glucose levels and liver- and viral-related biochemical parameters. A total of 160 patients with CHC (80 with liver fibrosis and 80 with cirrhosis) and 40 healthy volunteers, negative for HCV, were included. Our results revealed that cirrhotic patients had high ( P = .0001) fasting (169.1 ± 50.2 mg/dL), postprandial (208 (123-320) mg/dL), and random (176.8 ± 51 mg/dL) glucose levels compared to patients with liver fibrosis (105.0 ± 32, 120 (105-135), and 113.5 ± 35 mg/dL, respectively). Mean serum fasting, postprandial and random glucose levels were significantly ( P = .0001) increased with an increase in fibrosis stages, F1< F2< F3< F4. Blood glucose levels were also significantly ( P < .05) correlated with liver disease related biological parameters and HCV-Ab titer. In conclusion, our results highlighted the fibrogenic impact of elevated glucose levels on CHC patients.

Background: Impact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis., Results: Three hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes., Conclusion: Absolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis., (© 2021. The Author(s).)

Background: Dysphagia is a common complication seen in acute ischemic stroke patients, and can lead to morbidity and mortality. As such, quality measures have been instituted to track adherence to dysphagia screening in all stroke patients. In our 217-bed community hospital, we were faced with a low rate in successfully screening for dysphagia., Methods: Quality control interventions were implemented after an analysis of the reasons for dysphagia screening failures was performed. Interventions included online educational sessions for nurses, face-to-face sessions with medical residents, distribution of educational laminated cards, changing the method of documenting the dysphagia screen in our electronic record and others., Results: There was an increase of rates of screening for dysphagia from 67% to 91%., Conclusion: We conclude that failure analysis, implementation of quality control measures to address the cause of failures and re-evaluating success rates periodically was effective to address this problem., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Avian influenza (AI) has become a disease of great importance for human and animal health. Beside adverse side effects, there is resistance mutation for about all the conventional drugs that target viral proteins. This study aimed to evaluate antiviral activity of silver nanoparticles combined with epigallocatechingallate (EGCG-AgNPs) and co-administered with zinc sulphate (Zn+2) as alternative treatment strategy to control AI H9N2. EGCG conjugated silver nanoparticles (EGCG-AgNPs) were synthesized. Virus propagation was performed using embryonated Specific-Pathogen-Free (SPF) hen's eggs. Viral EID50 titers were determined before and after treatments. The antiviral activity was determined as Log virucidal reduction. A commercial tetrazolium MTS assay kit was used to determine cytotoxicity. Results showed that 50 μM EGCG was the most significant concentration reduced the logEID50/mL of AI H9N2. Co-treatment with zinc sulphate (1.3 mg/mL) increased the EGCG antiviral effect. The most effective antiviral activity was obtained when combined EGCG-AgNPs with zinc sulphate with the greatest virucidal log reduction. No cytotoxic effect in Vero cells was observed among all of these forms at concentrations of interest used in this study. In conclusion, the topical application of EGCG-AgNPs/ZnSO4 demands additional antiviral strategies against H9N2 AI. This combination may prevent virus transmission, inhibit virus replication within neighboring cells and inhibit microbial resistance by making microbial adaptability very difficult., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To determine whether studying patients with strictly unilateral relapsing primary angiitis of the CNS (UR-PACNS) can support hemispheric differences in immune response mechanisms, we reviewed characteristics of a group of such patients., Methods: We surveiled our institution for patients with UR-PACNS, after characterizing one such case. We defined UR-PACNS as PACNS with clinical and radiographic relapses strictly recurring in 1 brain hemisphere, with or without hemiatrophy. PACNS must have been biopsy proven. Three total cases were identified at our institution. A literature search for similar reports yielded 4 additional cases. The combined 7 cases were reviewed for demographic, clinical, imaging, and pathologic trends., Results: The median age at time of clinical onset among the 7 cases was 26 years (range 10-49 years); 5 were male (71%). All 7 patients presented with seizures. The mean follow-up duration was 7.5 years (4-14.1 years). The annualized relapse rate ranged between 0.2 and 1. UR-PACNS involved the left cerebral hemisphere in 5 of the 7 patients. There was no consistent relationship between the patient's dominant hand and the diseased side. When performed (5 cases), conventional angiogram was nondiagnostic. CSF examination showed nucleated cells and protein levels in normal range in 3 cases and ranged from 6 to 11 cells/μL and 49 to 110 mg/dL in 4 cases, respectively. All cases were diagnosed with lesional biopsy, showing lymphocytic type of vasculitis of the small- and medium-sized vessels. Patients treated with steroids alone showed progression. Induction therapy with cyclophosphamide or rituximab followed by a steroid sparing agent resulted in the most consistent disease remission., Conclusions: Combining our 3 cases with others reported in the literature allows better clinical understanding about this rare and extremely puzzling disease entity. We hypothesize that a functional difference in immune responses, caused by such discrepancies as basal levels of cytokines, asymmetric distribution of microglia, and differences in modulation of the systemic immune functions, rather than a structural antigenic difference, between the right and left brain may explain this phenomenon, but this is speculative., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Aims: Rheumatoid arthritis is an autoimmune systemic disorder causing pain, swelling, stiffness, and disability in various joints. This work was designed to evaluate the effect of sitagliptin and tofacitinib on Janus kinase (JAK)/signaling transducer and activator of transcription (STAT) and toll like receptor (TLR-4)/nuclear factor kappa B (NF-κB) signaling pathways in adjuvant induced arthritis in rats., Materials and Methods: Severity of arthritis was evaluated and serum was analyzed for inflammatory mediators. The mRNA and protein expression level of the most important members of the two signaling pathways were determined. Lipid profile, transaminases and renal function parameters were assessed., Key Findings: Sitagliptin and tofacitinib significantly decreased the level of inflammatory parameters, the mRNA and protein expression level of the members of JAK/STAT and TLR-4/NF-κB pathways with more prominent effect of sitagliptin on TLR-4/NF-κB pathway and more expected obvious effect of tofacitinib on JAK/STAT pathway. The combination offered additional anti-inflammatory effect by inhibiting the cross talk between these pathways as inhibition of NF-κB activation decreased the serum level of IL-6 preventing the activation of STAT-3 in tibiotarsal tissues., Significance: The combination of tofacitinib and sitagliptin normalized serum lipids and blood glucose level which could offer protection against cardiovascular diseases and caused partial reversal of serum transaminases and creatinine levels which can protect against tofacitinb's related hepato and nephrotoxicity. We could conclude that the combination of Sitagliptin with tofacitinib can offer synergistic anti-inflammatory effect and more protective action against side effects of tofacitinib., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction and Aim: The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease., Material and Methods: IL-28B rs12979860, liver stiffness and ECM proteins were assessed in 272 CHC patients., Results: Cirrhosis percentage increased to 10%, 52% and 96% with the increasing number of T alleles (CC, CT and TT, respectively). Also, elevated ECM proteins levels were correlated with the increasing number of T alleles. Interestingly, among cirrhotic patients, liver stiffness, MELD and ECM proteins were significantly (P &lt; 0.0001) higher in patients with TT more than CT genotype. FibroScan, hyaluronic acid, Laminin, Collagen IV and the N-terminal pro-peptide of collagen type III have high accuracy to differentiate liver status in CC from TT genotype. Area under receiver-operating characteristic curve (95% CI) were 1.0 (1.0-1.0), 0.97 (0.96- 1.0), 0.93 (0.85-1.0), 0.98 (0.97-1.0) and 0.93 (0.91-0.97), respectively., Conclusion: This study suggests that IL-28B T allele affects the natural course of CHC type 4 and also suggests that carriage of the IL-28B C allele protects from unfavorable clinical outcomes in CHC as coexistence of C allele with T allele reduced cirrhosis severity.

Background: Hepatitis C virus (HCV) has the lymphotropic feature that is supposed to be the reason of related extrahepatic manifestation. HCV viral oncoproteins may participate in the regulation of some gene expression that has been implicated in tumorigenesis. Our aim is to evaluate the HCV-NS4 circulating levels in breast cancer (BC) and to investigate its relation with BC tumor aggressiveness., Methods: This study was performed among 158 Egyptian women (120 with BC and 38 with benign breast diseases). ELISA was used for detection of anti-HCV antibodies, HCV-NS4, fibronectin, and CA 15-3., Results: No association between HCV detection in this group of BC patients (27.5% in BC vs. 23.7% in breast benign diseases, P = 0.687). Among HCV-infected patients, the mean HCV-NS4 serum level in BC was significantly higher than benign group (61.7 μg/mL vs. 33.9 μg/mL, P = 0.0005). Fibronectin levels were higher (P = 0.014) in patients infected with HCV than noninfected BC patients. Elevated HCV-NS4 levels were associated with tumor severity features like large size, late stages, high grades, and infiltrated lymph nodes. The elevated levels of HCV-NS4 (> 40 μg/mL) yielded an estimated odds ratio (95% confidence intervals) of 2.5 (0.98-6.36), 1.2 (0.44-3.33), 1.9 (0.53-7.00), and 2.5 (0.87-7.33) for developing large size, late stages, high grades, and infiltrated lymph nodes, respectively. Interestingly, HCV-NS4 levels significantly correlated with other BC tumor marker like CA15-3 (r = 0.535; P = 0.0009) and fibronectin (r = 0.432; P < 0.0001)., Conclusions: HCV-NS4 appears to be associated with BC progression features. Oncologists treating such BC patients should consider HCV screening to enable the early identification and to prevent progression of the disease.

IgG4-related disease can involve nearly any organ system, including the central and peripheral nervous systems. The pathology findings are consistent from organ to organ, but careful clinicopathological correlation is necessary to establish the diagnosis. Many non-neurological and neurological inflammatory conditions, previously regarded as idiopathic in nature, are now recognised to fall within the spectrum of IgG4-related disease. The condition is highly treatable, but probably remains substantially under-recognised. In this Review, we offer an important and timely update on the current and emerging aspects of this neurological disease. Following a short overview of IgG4-related disease, we describe the current understanding of neurological findings, pathophysiology, approaches to diagnosis, and treatment of IgG4-related disease affecting the central and peripheral nervous systems., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Purpose: Human immunodeficiency virus (HIV) infection has been shown to increase both ischemic and hemorrhagic stroke risks, but there are limited data on the safety and outcomes of intravenous thrombolysis with tPA (tissue-type plasminogen activator) for acute ischemic stroke in HIV-infected patients., Methods: A retrospective chart review of intravenous tPA-treated HIV patients who presented with acute stroke symptoms was performed in 7 large inner-city US academic centers (various search years between 2000 and 2017). We collected data on HIV, National Institutes of Health Stroke Scale score, ischemic stroke risk factors, opportunistic infections, intravenous drug abuse, neuroimaging findings, and modified Rankin Scale score at last follow-up., Results: We identified 33 HIV-infected patients treated with intravenous tPA (mean age, 51 years; 24 men), 10 of whom were stroke mimics. Sixteen of 33 (48%) patients had an HIV viral load less than the limit of detection while 10 of 33 (30%) had a CD4 count <200/mm 3 . The median National Institutes of Health Stroke Scale score at presentation was 9, and mean time from symptom onset to tPA was 144 minutes (median, 159). The median modified Rankin Scale score for the 33-patient cohort was 1 and for the 23-patient actual stroke cohort was 2, measured at a median of 90 days poststroke symptom onset. Two patients had nonfatal hemorrhagic transformation (6%; 95% confidence interval, 1%-20%), both in the actual stroke group. Two patients had varicella zoster virus vasculitis of the central nervous system, 1 had meningovascular syphilis, and 7 other patients were actively using intravenous drugs (3 cocaine, 1 heroin, and 3 unspecified), none of whom had hemorrhagic transformation., Conclusions: Most HIV-infected patients treated with intravenous tPA for presumed and actual acute ischemic stroke had no complications, and we observed no fatalities. Stroke mimics were common, and thrombolysis seems safe in this group. We found no data to suggest an increased risk of intravenous tPA-related complications because of concomitant opportunistic infections or intravenous drug abuse., (© 2017 American Heart Association, Inc.)

Background: Small-sized HCC can be effectively cured by surgery with good clinical outcomes. A highly sensitive HCC α-fetoprotein routine test (HCC-ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in the British Journal of Cancer. Here, we verified and studied the applicability of the HCC-ART to the detection of early-stage HCC., Methods: 341 cirrhotic patients and 318 HCC patients were included in this study. For each, the HCC-ART score was calculated, and then the sensitivity, specificity, and results of an ROC curve analysis were compared between the HCC-ART and AFP when these biomarkers were used to detect small-sized HCC., Results: Different HCC-ART cutoffs were set for the detection of different tumor sizes. The HCC-ART (AUC = 0.871, 70% sensitivity, 97% specificity) and the simplified HCC-ART (AUC = 0.934, 82% sensitivity, 100% specificity) were found to have high predictive power when attempting to separate cirrhotic patients from those with small-sized HCC. The simplified HCC-ART score was superior to AFP for determining stages according to the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), CLIP (0.945 AUC, 84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99% specificity) staging systems. The simplified HCC-ART score was more strongly correlated than AFP and other staging systems with HCC tumor size (P < 0.0001; r = 0.8)., Conclusion: The HCC-ART is superior to AFP for diagnosing early-stage HCC. Due to its advantages of minimal variability and a wide continuous scale for assessing HCC severity, the simplified HCC-ART has the potential to be more widely used than the original HCC-ART.

Purpose: To identify computational and qualitative features derived from dual-phase cone-beam CT that predict short-term response in patients undergoing transarterial chemoembolization for hepatocellular carcinoma (HCC)., Materials and Methods: This retrospective study included 43 patients with 59 HCCs. Six features were extracted, including intensity of tumor enhancement on both phases and characteristics of the corona on the washout phase. Short-term response was evaluated by modified Response Evaluation Criteria in Solid Tumors on follow-up imaging, and extracted features were correlated to response using univariate and multivariate analyses., Results: Univariate and multivariate analyses did not reveal a correlation between absolute and relative tumor enhancement characteristics on either phase with response (arterial P = .21; washout P = .40; ∆ P = .90). On multivariate analysis of qualitative characteristics, the presence of a diffuse corona was an independent predictor of incomplete response (P = .038) and decreased the odds ratio of objective response by half regardless of tumor size., Conclusions: Computational features extracted from contrast-enhanced dual-phase cone-beam CT are not prognostic of response to transarterial chemoembolization in patients with HCC. HCCs that demonstrate a diffuse, patchy corona have reduced odds of achieving complete response after transarterial chemoembolization and should be considered for additional treatment with an alternative modality., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed., Methods: A group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments., Results: The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of "no evidence of disease activity" (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity., Conclusion: BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.

Conflicting results for circulating glypican-3 (GPC3) were reported in hepatocellular carcinoma (HCC) diagnosis. We aimed to improve the diagnostic power of GPC3 by developing a GPC-HCC model for diagnosing HCC. GPC3 was tested for HCC (138), liver cirrhosis (56), and fibrosis (62) patients by ELISA. Data from patient groups were retrospectively analyzed. A novel score, GPC-HCC, based on combination of GPC3 and routine laboratory tests, was developed for HCC diagnosis. The GPC-HCC model values produced a significant 1.7-fold increase in liver cirrhosis and 3.2-fold increase in HCC, in comparison with liver fibrosis. In contrast to GPC3 and alpha fetoprotein (AFP), the GPC-HCC model showed high HCC diagnostic power with area under the curve (AUC) of 0.939, sensitivity 93 %, specificity 93 %, positive predictive value 89 %, negative predictive value 95 %, and efficiency 93 %. GPC-HCC AUC in HCC with single tumor, absent vascular invasion, and tumor size ≤3 cm were 0.93, 0.92, and 0.92, respectively, compared with 0.63, 0.63, and 0.64, respectively, for GPC3 and 0.69, 0.70, 0.55, respectively, for AFP. In conclusion, owing to these promising findings, the combination of GPC3 with other laboratory simple routine tests (GPC-HCC model) could improve the diagnostic power of GPC3 in HCC screening and follow up of cirrhotic patients.

Background: Most spinal cord infarctions are due to aortic pathologies and aortic surgeries. Fibrocartilaginous Embolism (FCE) has been reported to represent 5.5% of spinal cord infarctions. Some believe that FCE is more common than presumed and is rather under-diagnosed due to vagueness surrounding its clinical presentation., Method: A literature search was conducted for case reports of FCE published before August 2014. PubMed, the Cochrane Central Register and Google Scholar were searched for different combinations of the key words "fibrocartilaginous, "nucleus pulposus", "embolism", "spinal cord", "inter-vertebral disc", "infarction", "stroke", "paraplegia", "quadriplegia", "myelopathy"., Result: Fifty-five case articles were reviewed, ten of which were translated from foreign languages. A total of 67 cases of FCE were found, 41 tissue-confirmed and 26 clinically suspected. A comprehensive summary of the clinical anatomy, patho-physiologic mechanisms, epidemiology, diagnosis and treatment of FCE is described, along with the conflicting opinions on its incidence and relevance after reviewing all of the related literature. The 41 tissue proven cases are summarized and a schematic approach to the clinical diagnosis of FCE, deducted from their clinical findings, is presented., Conclusion: FCE of the spinal cord, often mis-diagnosed as transverse myelitis, may be more common than presumed. Future research into FCE, including the development of a chondrolytic therapy that can be given empirically upon its clinical suspicion to acutely reverse its symptoms, may be of value.

The relation between interferon-gamma (IFN-γ) levels and the severity of liver diseases through fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) has not been fully clarified. Thus, we aimed to characterize IFN-γ levels in liver-diseased patients. IFN-γ levels were determined by Western-blot and ELISA in sera from 30 healthy individuals, 53 patients with non-significant fibrosis (F0-F1), 47 with moderate/severe fibrosis (F2-F3), 44 cirrhotic patients (F4), and 50 with HCC. Enhanced levels of IFN-γ were associated with the progression of liver disease. The differences were statistically significant (P < 0.0001) when patients with F2-F3, F4, or HCC were compared with F0-F1 or healthy controls. The increase in IFN-γ was associated with HCC (OR = 0.98, 95% CI 0.97-0.99, P = 0.002). There was no statistically significant association between IFN-γ levels and HCV-RNA (IU/ml) (r = 0.1, P = 0.43) or HCV-NS4 (µg/mL) (r = 0.1, P = 0.17). There was significant (P < 0.0001) association between IFN-γ levels and the fibrosis stages and activity, albumin, platelet count, total bilirubin, and international normalized ratio (INR). In conclusion, elevated concentrations of IFN-γ represent a characteristic feature of liver disease severity regardless of underlying disease. Significant correlations with indices of hepatic dysfunction suggest that enhanced IFN-γ levels represent a consequence of liver dysfunction rather than of inflammatory disease.

Background: The advent of noninvasive urine-based markers as well as other novel modalities has yielded improved diagnostic accuracy. However, the new markers failed to reach higher sensitivity and specificity. We therefore evaluated the potential role of epithelial membrane antigen (EMA) and nuclear matrix protein 52 (NMP-52) singly and combined as noninvasive biomarkers for the detection of bladder cancer (BC)., Methods: A total of 160 individuals including 66 patients with BC, 54 patients with benign urologic disorders and 40 healthy volunteers were investigated. Urinary EMA at 130 kDa and NMP at 52 kDa were identified, purified and quantified by Western blot, electroelution and enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of each biomarker and their combination were compared using area under receiver operating characteristic curves (AUC)., Results: Mean urinary EMA, 2.42 µg/mL, and NMP-52, 17.85 µg/mL, were significantly elevated in patients with BC compared to controls, 1.18 and 3.44 µg/mL, respectively (p&lt;0.0001). The combined use of these markers yielded values which were increased 4.4- and 13.7-fold in the benign and malignant disease groups, respectively, with respect to the normal group. The values of EMA and NMP-52 were significantly higher in patients with higher-grade tumors than those with lower-grade tumors (p&lt;0.0001). Moreover, this combination could predict all BC stages and grades with 0.91 AUC, 94% sensitivity and 80% specificity., Conclusions: EMA and NMP-52 in combination could be promising noninvasive biomarkers for BC detection.

Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy.

Background: Perinatal exposure to hepatitis C virus (HCV) antigens during pregnancy may affect the developing immune system in the fetus. We aimed to study the perinatal transmission of HCV structural and non-structural antigens., Methods: Sera from 402 pregnant mothers were tested for anti-HCV antibody and HCV RNA. HCV antigens were determined in sera from 101 HCV-infected mothers and their cord blood., Results: In both serum and cord blood samples, HCV NS4 (non-structural 4) at 27 kDa, E1 (envelope 1) at 38 kDa and E2 (envelope 2) at 40 kDa were identified, purified and quantified using western blotting, electroelution and ELISA. Maternal sera and neonate cord blood samples had similar detection rates for NS4 (94.1%), E1 (90.1%) and E2 (90.1%). The mean maternal serum levels (optical density, OD) of HCV NS4 (0.87 ± 0.01), E1 (0.86 ± 0.01) and E2 (0.85 ± 0.01) did not differ significantly (p > 0.05) from those of neonatal cord blood (0.83 ± 0.01, 0.87 ± 0.01 and 0.85 ± 0.01, respectively). Also, strong correlations (p < 0.0001) were shown between sera and cord blood sample levels of HCV NS4, r = 0.77; E1, r = 0.76 and E2, r = 0.80. The vertical transmission of these antigens in vaginal delivery did not differ significantly (p > 0.05) from those in caesarean section., Conclusions: These findings indicate that vertical transmission of HCV NS4, E1 and E2 antigens was very high. Thus, exposure to these antigens may influence the developing immune responses to natural infection or future vaccination.

Left ventricular noncompaction (LVNC) is a cardiomyopathy with hypertrabeculation of the LV, often complicated by heart failure, arrhythmia and thromboembolic events. The features of LVNC are still incompletely characterized due to its late recognition as clinically relevant condition. The aims of this study were to describe echocardiographic and electrophysiologic characteristics of LVNC patients and to assess the effects of chronic β-blocker treatment. Study patients (n = 20; 42.5 [36.3; 52.5] years; 12 men) exhibited reduced LV ejection fraction (median LVEF = 32 %) and an increased LV mass of 210 g. Sinus rhythm was present in 19 patients, whereas one patient was in atrial fibrillation. Baseline heart rate was 77.5 beats per minute. Left bundle branch block was detected in five cases. In a subgroup of patients receiving β-blocker therapy (n = 17), LV mass was reduced from 226 [178; 306] g to 220 [169; 254] g (p = 0.007) at 13 ± 6 months follow-up. By contrast, a subgroup of three patients that were not treated with an anti-β-adrenergic agent showed LV mass increase from 180 [169; 197] g to 199 [185; 213] g (p = 0.023). LVEF and electrocardiographic parameters were not significantly modulated during chronic β-blocker treatment. There was no sustained symptomatic ventricular tachyarrhythmia, thromboembolic event or death in either group. In conclusion, this study reveals reduction of LV mass among LVNC patients during β-blocker therapy. Effects of β-blocker treatment in LVNC require validation in prospective controlled studies.

Background: The NINDS trial demonstrated the efficacy of intravenous (IV) recombinant tissue plasminogen activator (rtPA) in improving the neurologic outcome in patients presenting with acute ischemic strokes. Patients who had a prior history of intracranial hemorrhage (ICH) were excluded from this trial, possibly due to a hypothetical increase in the subsequent bleeding risk. Thus, there is little data available, whether against or in favor of, the use of IV rtPA in patients with prior ICH. We aim to aid in determining the safety of IV rtPA in such patients through a retrospective hospital-based single center study., Methods: We reviewed the brain imaging of all patients who received IV rtPA at our comprehensive stroke center from January 2006 to April 2014 for evidence of prior ICH at the time of IV rtPA administration. Their outcomes were determined in terms of subsequent development of symptomatic ICH as defined by the NINDS trial., Results: Brain imaging for 640 patients was reviewed. A total of 27 patients showed evidence of prior ICH at the time of IV thrombolysis, all intra-parenchymal. Only 1 patient (3.7%) developed subsequent symptomatic ICH after the administration of IV rtPA. Of the remaining 613 patients who received IV rtPA, 25 patients (4.1%) developed symptomatic ICH., Conclusion: This retrospective study provides Level C evidence that patients with imaging evidence of prior asymptomatic intra-parenchymal hemorrhage presenting with an acute ischemic stroke do not show an increased risk of developing symptomatic ICH after IV thrombolysis., (© 2015 S. Karger AG, Basel.)

Immunohistochemical studies proved that the presence of breast cancer (BrCa) is accompanied by elevated levels of epithelial membrane antigen (EMA) and decreased levels of cytokeratin-1 (CK1). We, therefore, hypothesize that the serum EMA/CK1 ratio may serve as a promising biomarker for early diagnosis of breast cancer. The circulating levels of EMA and CK1 were determined by Western blot and enzyme-linked immunosorbent assay (ELISA) in sera from 102 women with BrCa and 90 women as controls (40 with benign breast disease and 50 healthy). EMA at 130 kDa and CK1 at 67 kDa were identified, purified, and quantified in sera of BrCa patients using ELISA. EMA/CK1 ratio values were found to discriminate BrCa patients from controls (P < 0.0001) with high diagnostic ability (area under the curve [AUC] = 0.901, sensitivity = 82, specificity = 76). The sensitivity and specificity for early-stage (≤ T2) BrCa were 72 and 76%, respectively. The ratio values of patients with late-stage (>T2) tumors were significantly higher than those of patients with early-stage (≤ T2) tumors. Moreover, higher grades (grades 2-3) were associated with higher values than grade 1 tumors. AUC values in different BrCa patients who had early stage, low grade, or size ≤ 2 cm were 0.855, 0.762, and 0.839, respectively. AUC values of patients with positive lymph node or positive distant metastasis were 0.907 and 0.913, respectively. We show for the first time the impact of serum EMA and CK1 ratio in BrCa detection. Differential EMA/CK1 values may serve as a diagnostic marker in early-stage breast cancer patients.

Hepatitis C virus (HCV)-RNA amplification is a costly procedure in terms of time and reagents. Consequently, the search for more a cost-effective specific HCV diagnostic method is of great interest. Capillary zone electrophoresis (CZE) methods that detect HCV in serum, plasma, whole blood, and ascites without the need for sample pretreatment are not currently available. Here, a CZE method was developed that detects a larger specific peak in serum and other body fluids of HCV-infected patients than that found in healthy or hepatitis B virus (HBV)-infected individuals. The nature of the HCV peak was investigated using biochemical treatments, including RNase, DNase, and chymotrypsin enzymes. Electroeluted HCV peak was applied to transmission electron microscopy; electron micrographs showed that the HCV peak was attributed to virus-like particles with diameter and morphological properties similar to non-enveloped HCV nucleocapsids. The determination of CZE-HCV and HCV-RNA levels using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) in 258 subjects revealed that these two tests were highly correlated (r = 0.92, p < 0.0001). One important issue of HCV testing is the storage conditions of serum to obtain reliable results. Serum samples at -20 °C showed the best preservation of the HCV peak up to one year. In conclusion, we detected HCV using CZE in a microliters volume from different body fluids. Besides the stability of samples in maintaining their peak height, the HCV-CZE test is rapid (<15 min) and a well-suited and low-cost technique. Thus, a major improvement in the quantitative diagnosis of HCV infection was established.