Association of interleukin-23 receptor (IL-23R) gene polymorphisms (rs11209026, rs2201841 and rs10889677) with Egyptian rheumatoid arthritis patients

AbstractAim of the workTo analyse interleukin 23 receptors (IL23R) single-nucleotide polymorphism (SNPs) (rs11209026, rs2201841, and rs10889677) and to detect their association with Egyptian rheumatoid arthritis (RA) patients.Patients and methodsThe study included 120 Egyptian RA patients and 120 healthy controls that were genotyped for the three SNPs by real time/polymerase chain reaction for the first SNP and restriction fragment length polymorphism/PCR (RFLP/PCR) in the last two SNPs. The disease activity score (DAS28) was assessed in the patients.ResultsThe studied patients had a mean age of 42.5±13.4years, a disease duration of 5.2±3.5years and consisted of 22 males and 98 females. Joint deformities were present in 35 and 66 patients had swollen joints. The rheumatoid factor (RF) was positive in 78.3% and the DAS28 was 3.2±1.2. Our data emphasize that the AA genotype of rs11209026 was significantly associated with RA patients compared to the controls (p=0.001). We did not find any significant association between either rs2201841 or rs10889677 and the development of RA (p=1, p=0.56 respectively). The AA allele in the 3 SNPs were remarkable frequent in those with deformities and positive RF.ConclusionOur results suggest that IL23 receptor AA genotype variant of rs11209026 contributes to the aetiology of RA and may be considered a genetic marker and shared the susceptibility gene. We need to address the subgroup of patients who will benefit from the selective suppression of the IL-23 signalling which would represent new perspectives towards a personalized therapy of RA patients by further studies

Study of silent myocardial ischemia using exercise stress test among diabetic and non-diabetic patients with documented coronary artery disease

AbstractIntroductionProspective studies have documented an increased likelihood of sudden cardiac death and unrecognized myocardial infarction in patients with diabetes.Aim of the workTo study silent myocardial ischemia using exercise stress test among diabetic and non-diabetic patients with angiographically documented coronary artery disease.Patients and methodsPatients with contra-indications to exercise test were excluded.All patients were subjected to treadmill test using modified Bruce protocol & were considered to have silent ischemia if ECG shows ischemic changes without chest pain.StatisticsData were collected & analyzed statistically.ResultsThe study included 80 patients with CAD (40 diabetics & 40 non-diabetics).Their mean age was 58years old, including males (73.8%).According to stress test patients were classified:1-Group 1: 28 patients (35%), showed no ST depression no chest pain during exercise test, 10 patients of them (35.7%) were diabetic.2-Group 2: two patients (2.5%) who were diabetic showed chest pain without stress induced ST depression (only pain).3-Group 3: 26 patients (32.5%) showed stress ST depression without chest pain (silent ischemia), 18 patients of them (69.2%) were diabetic.4-Group 4: 24 patients (30%) showed ST depression and chest pain during exercise test (symptomatic ischemia), 10 patients of them (41.7%) were diabetic.All patients underwent coronary angiography (100%) and all of them had significant coronary artery disease (more than 50% stenosis).ConclusionDiabetics with coronary artery disease have a higher prevalence of silent myocardial ischemia than non-diabetics

The role of procalcitonin as a guide for the diagnosis, prognosis, and decision of antibiotic therapy for lower respiratory tract infections

AbstractObjectivesTo assess the value of PCT as a rapid and sensitive marker for diagnosis, prognosis, and therapy of lower respiratory tract bacterial infections necessitating antimicrobial treatment and comparing this marker with other markers of infections including C-reactive protein (CRP) and total white-blood cell counts (WBCs).Patients and methodsSixty Patients were enrolled in the study, they were subjected to complete history taking, physical examination, laboratory investigations including complete blood count, blood gases, blood chemistry, bacteriological culture for sputum and blood, serology for atypicals, and PCR for respiratory viruses, serum C-reactive protein (CRP) and PCT levels were measured. The patients were divided into two groups, group 1 included 26 patients who were culture negative for bacterial infection and group 2 included 34 patients who were culture positive. Group 2 patients were given antibiotic therapy according to the culture sensitivity.ResultThe results revealed that, there was no significant difference between group 1 and group 2 patients as regards age, sex, clinical manifestations, final diagnosis, white blood cell counts, blood gases, number of admitted patients, intensive care unit admission and length of hospital stay. A significant increase of PCT and CRP levels was detected in group 2 compared to group 1 at initial diagnosis. At cutoff value >0.5ng/ml, PCT gave a sensitivity of 94.1%, specificity of 88.4%, positive predictive value (PPV) of 91.4%, negative predictive value (NPV) of 92% and diagnostic efficiency of 91.6% for diagnosis of respiratory tract bacterial infections. However, at a cutoff value >8mg/L, CRP gave a sensitivity of 85.2%, specificity of 76.9%, PPV of 82.8%, NPV of 80% and diagnostic efficiency of 81.7%. After antibiotic therapy PCT and CRP levels dropped in group 2 patients as compared to their pre-treatment levels.ConclusionSerum PCT level could be used as a novel marker of lower respiratory tract bacterial infections for diagnosis, prognosis and follow up of therapy. This reduces side-effects of an unnecessary antibiotic use, lowers costs, and in the long-term, leads to diminishing drug resistance

Chemical Characterization of Taif Rose (<i>Rosa damascena</i> Mill var. <i>trigentipetala</i>) Waste Methanolic Extract and Its Hepatoprotective and Antioxidant Effects against Cadmium Chloride (CdCl₂)-Induced Hepatotoxicity and Potential Anticancer Activities against Liver Cancer Cells (HepG2)

Taif rose (Rosa damascena Mill) is one of the most important economic products of the Taif Governorate, Saudi Arabia. Cadmium chloride (CdCl2) is a common environmental pollutant that is widely used in industries and essentially induces many toxicities, including hepatotoxicity. In this study, the major compounds in the waste of Taif rose extract (WTR) were identified and chemically and biologically evaluated. GC–MS analysis of WTR indicated the presence of many saturated fatty acids, vitamin E, triterpene, dicarboxylic acid, terpene, linoleic acid, diterpenoid, monoterpenoid, flavonoids, phenylpyrazoles, and calcifediol (vitamin D derivative). The assessment of potential anticancer activity against HepG2 cells proved that WTR had a high cell killing effect with IC50 of 100–150 µg/mL. In addition, WTR successfully induced high cell cycle arrest at G0/G1, S, and G2 phases, significant apoptosis, necrosis, and increased autophagic cell death response in the HepG2 line. For the evaluation of its anti-CdCl2 toxicity, 32 male rats were allocated to four groups: control, CdCl2, WTR, and CdCl2 plus WTR. Hepatic functions and antioxidant biomarkers (SOD, CAT, GRx, GPx, and MDA) were examined. Histological changes and TEM variations in the liver were also investigated to indicate liver status. The results proved that WTR alleviated CdCl2 hepatotoxicity by improving all hepatic vitality markers. In conclusion, WTR could be used as a preventive and therapeutic natural agent for the inhibition of hepatic diseases and the improvement of redox status. Additional in vitro and in vivo studies are warranted

Evaluation of the Phytochemical and Pharmacological Potential of Taif&rsquo;s Rose (Rosa damascena Mill var. trigintipetala) for Possible Recycling of Pruning Wastes

This study investigated the phytochemical contents of Taif&rsquo;s rose pruning wastes and their potential application as phytomedicine, thereby practicing a waste-recycling perspective. In the Al-Shafa highland, four Taif rose farms of various ages were chosen for gathering the pruning wastes (leaves and stems) for phytochemical and pharmacological studies. The leaves and stems included significant amounts of carbohydrates, cardiac glycosides, alkaloids, flavonoids, and other phenolic compounds. The cardiac glycoside and flavonoid contents were higher in Taif rose stems, while the phenolic and alkaloid contents were higher in the plant leaves. Cardiovascular glycosides (2.98&ndash;5.69 mg g&minus;1), phenolics (3.14&ndash;12.41 mg GAE g&minus;1), flavonoids (5.09&ndash;9.33 mg RUE g &minus;1), and alkaloids (3.22&ndash;10.96 mg AE g&minus;1) were among the phytoconstituents found in rose tissues. According to the HPLC analysis of the phenolic compounds, Taif&rsquo;s rose contains flavonoid components such as luteolin, apigenin, quercetin, rutin, kaempferol, and chrysoeriol; phenolics such as ellagic acid, catechol, resorcinol, gallic acid, and phloroglucinol; alkaloids such as berbamine, jatrorrhizine, palmatine, reticuline, isocorydine, and boldine. Warm water extract was highly effective against Bacillus subtilis, Escherichia coli, and Proteus vulgaris, whereas methanol and cold water extracts were moderately effective against Aspergillus fumigatus and Candida albicans. The study&rsquo;s findings suggested that Taif&rsquo;s rose wastes could be used for varied medical purposes

miR-34a: Multiple Opposing Targets and One Destiny in Hepatocellular Carcinoma

Abstract Background and Aims: The role of miR-34a in hepatocellular carcinoma (HCC) is controversial and several unresolved issues remain, including its expression pattern and relevance to tumor etiology, tumor stage and prognosis, and finally, its impact on apoptosis. Methods: miR-34a expression was assessed in hepatitis C virus (HCV)-induced non-metastatic HCC tissues by RT-Q-PCR. Huh-7 cells were transfected with miR-34a mimics and the impact of miR-34a was examined on 84 pro-apoptotic/anti-apoptotic genes using PCR array; its net effect was tested on cell viability via MTT assay. Results: miR34a expression was up-regulated in HCC tissues. Moreover, miR-34a induced a large set of pro-apoptotic/anti-apoptotic genes, with a net result of triggering apoptosis and repressing cell viability. Conclusions: HCC-related differential expression of miR-34a could be etiology-based or stage-specific, and low expression of miR-34a may predict poor prognosis. This study&apos;s findings also emphasize the role of miR-34a in apoptosis

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research