Interleukin (IL)-17A and IL-17F and asthma in Saudi Arabia: mRNA transcript levels and gene polymorphisms

Asthma is a multifactorial disorder and both genetic and environmental factors contribute to its development. The present study explored cytokines interleukin (IL)-17A and IL17F levels as usable parameters for the diagnosis of asthmatics Saudi patients. Blood samples were collected from 100 asthma patients and 100 matched controls. The transcript mRNA levels in whole blood were determined by real-time reverse-transcription polymerase chain reaction. Expression studies showed that levels of IL17A and IL17F were significantly higher in asthma patients compared to controls [IL17A: 1.112 (2.088) vs 0.938 (1.363)]; IL17F: 0.707 (1.33) vs 0.667 (0.590). The mRNA transcripts of IL17A and IL17F were positively and significantly correlated in all subjects examined in this study: controls as well as asthma patients (r = 0.455, P < 0.01 for controls and r = 0.644, P < 0.01 for patients). These findings suggest that asthma is characterized by an elevation of cytokines IL17A and IL17F and the measurement of their expression can be a valuable parameter for the diagnosis of asthma.Keywords: Asthma, interleukin-17F (IL17F), interleukin-17A (IL17A), gene expression, real time-polymerase chain reaction (RT-PCR), Saudi Arabia.African Journal of Biotechnology Vol. 12(23), pp. 3615-362

The EMT transcription factor ZEB1 governs a fitness-promoting but vulnerable DNA replication stress response

The DNA damage response (DDR) and epithelial-to-mesenchymal transition (EMT) are two crucial cellular programs in cancer biology. While the DDR orchestrates cell cycle progression, DNA repair and cell death, EMT promotes invasiveness, cellular plasticity and intratumor heterogeneity. Therapeutic targeting of EMT transcription factors, such as ZEB1, remains challenging, but tumor-promoting DDR alterations elicit specific vulnerabilities. Using multi-omics, inhibitors and high-content microscopy, we discover a chemoresistant ZEB1 high expressing sub-population (ZEB1hi) with co-rewired cell cycle progression and proficient DDR across tumor entities. ZEB1 stimulates accelerated S-phase entry via CDK6, inflicting endogenous DNA replication stress. However, DDR buildups involving constitutive MRE11-dependent fork resection allow homeostatic cycling and enrichment of ZEB1hi cells during TGFβ-induced EMT and chemotherapy. Thus, ZEB1 promotes G1/S transition to launch a progressive DDR benefitting stress tolerance, which concurrently manifests a targetable vulnerability in chemoresistant ZEB1hi cells. Our study thus highlights the translationally relevant intercept of the DDR and EMT

Identification of clinical phenotypes of peripheral involvement in patients with spondyloarthritis, including psoriatic arthritis: a cluster analysis in the worldwide ASAS-PerSpA study

OBJECTIVE: To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), and to evaluate whether these clusters correspond with the clinical diagnosis of a rheumatologist. METHODS: Cross-sectional study with 24 participating countries. Consecutive patients diagnosed by their rheumatologist as PsA, axial SpA or peripheral SpA were enrolled. Four different cluster analyses were conducted: one using information on the specific location from all the peripheral manifestations, and a cluster analysis for each peripheral manifestation, separately. Multiple correspondence analyses and k-means clustering methods were used. Distribution of peripheral manifestations and clinical characteristics were compared across the different clusters. RESULTS: The different cluster analyses performed in the 4465 patients clearly distinguished a predominantly axial phenotype (cluster 1) and a predominantly peripheral phenotype (cluster 2). In the predominantly axial phenotype, hip involvement and lower limb large joint arthritis, heel enthesitis and lack of dactylitis were more prevalent. In the predominantly peripheral phenotype, different subgroups were distinguished based on the type and location of peripheral involvement: a predominantly involvement of upper versus lower limbs joints, a predominantly axial enthesitis versus peripheral enthesitis, and predominantly finger versus toe involvement in dactylitis. A poor agreement between the clusters and the rheumatologist's diagnosis as well as with the classification criteria was found. CONCLUSION: These results suggest the presence of two main phenotypes (predominantly axial and predominantly peripheral) based on the presence and location of the peripheral manifestations

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

Background 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

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Prevalence and distribution of peripheral musculoskeletal manifestations in spondyloarthritis including psoriatic arthritis: results of the worldwide, cross-sectional ASAS-PerSpA study

Objectives To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world. Methods Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated. Results A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%). Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%). Conclusion These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.Pathophysiology and treatment of rheumatic disease

Identification of clinical phenotypes of peripheral involvement in patients with spondyloarthritis, including psoriatic arthritis: a cluster analysis in the worldwide ASAS-PerSpA study

Objective To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), and to evaluate whether these clusters correspond with the clinical diagnosis of a rheumatologist. Methods Cross-sectional study with 24 participating countries. Consecutive patients diagnosed by their rheumatologist as PsA, axial SpA or peripheral SpA were enrolled. Four different cluster analyses were conducted: one using information on the specific location from all the peripheral manifestations, and a cluster analysis for each peripheral manifestation, separately. Multiple correspondence analyses and k-means clustering methods were used. Distribution of peripheral manifestations and clinical characteristics were compared across the different clusters. Results The different cluster analyses performed in the 4465 patients clearly distinguished a predominantly axial phenotype (cluster 1) and a predominantly peripheral phenotype (cluster 2). In the predominantly axial phenotype, hip involvement and lower limb large joint arthritis, heel enthesitis and lack of dactylitis were more prevalent. In the predominantly peripheral phenotype, different subgroups were distinguished based on the type and location of peripheral involvement: a predominantly involvement of upper versus lower limbs joints, a predominantly axial enthesitis versus peripheral enthesitis, and predominantly finger versus toe involvement in dactylitis. A poor agreement between the clusters and the rheumatologist's diagnosis as well as with the classification criteria was found. Conclusion These results suggest the presence of two main phenotypes (predominantly axial and predominantly peripheral) based on the presence and location of the peripheral manifestations.Pathophysiology and treatment of rheumatic disease