Urinary and serum neutrophil gelatinase-associated lipocalin as a biomarker in Egyptian systemic lupus erythematosus patients: Relation to lupus nephritis and disease activity

AbstractBackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is an excellent structural biomarker for the early diagnosis of acute kidney injury, prognosis, dialysis requirement and mortality in several common clinical scenarios.Aim of the workThe aim of this work is to detect the levels of both urinary and serum NGAL in SLE patients with and without lupus nephritis (LN) and to correlate their levels with renal biopsy class and disease activity.Patients and methodsThe study included 35 SLE patients; 22 with LN and 13 without as well as 30 matched controls. The SLE Disease Activity Index (SLEDAI) was assessed and the renal biopsy class determined. Urinary and serum levels of NGAL were assessed by ELISA.ResultsThe 35 patients had a median age of 30years and disease duration of 4years. They were 31 females and 4 males. The SLE patients had an elevated urinary NGAL (UNGAL) (median 19ng/ml, IQR 8–87) as compared to controls (median 2ng/ml, IQR 1–18.3) (p<0.006). Levels of UNGAL were higher in patients with LN than those without (p<0.023). In patients with LN, serum levels of NGAL were not significantly different from controls (p=0.6). The UNGAL level significantly correlated with the renal score of SLEDAI (r=0.54, p=0.001) but serum NGAL level did not (r=0.25, p=0.15). UNGAL significantly correlated with grade III and IV of renal biopsy (r=0.67, p=0.009). The sensitivity of UNGAL levels for the diagnosis of LN was 85.7%, with a specificity of 80%.ConclusionUrinary NGAL is a sensitive marker of proliferative nephritis in SLE and disease activity

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Profiling of microRNAs by next-generation sequencing: Potential biomarkers for diffuse large B-cell lymphoma

الملخص: أهداف البحث: سرطان الغدد الليمفاوية يحتل المرتبة الخامسة بين أنواع السرطان الشائعة في جميع أنحاء العالم. سرطان الجهاز اللمفاوي هو الذي ينشأ من الخلايا التائية أو البائية. ترتبط الأورام اللمفاوية ذات الخلايا البائية الكبيرة المنتشرة بالغالبية العظمى من الأورام اللمفاوية اللاهودجكينية. يمكن أن تؤثر الرناوات الدقيقة غير المشفرة بشكل كبير على التعبير الجيني. يمكن استهداف العديد من الجينات بواسطة واحدة من الرناوات الدقيقة، وبالتالي، تؤثر بشكل كبير على شبكات التعبير الجيني. يمكن أن تعمل الرناوات الدقيقة كجينات مسرطنة أو مثبطات للورم للتحكم في تطور الأورام اللمفاوية في الخلايا البائية الكبيرة. بحثت هذه الدراسة في دور الرناوات الدقيقة في مرضى سرطان الغدد الليمفاوية في الخلايا البائية الكبيرة المنتشرة باستخدام تسلسل الجيل التالي، والذي أظهر الحساسية والدقة والمتانة. طريقة البحث: شملت الدراسة 7 مرضى و3 عناصر تحكم حضروا عيادة أمراض الدم والأورام. تم استخراج الرناوات الدقيقة من عينات الأنسجة الموجودة المضمنة بالفورمالين والمضمنة بالبرافين. تم استخدام تسلسل الجيل التالي (نظام إليومينا) لتسلسل العينات لتحديد ملامح الرناوات الدقيقة. النتائج: أظهرت عينات المرضى العديد من الرناوات الدقيقة مير-هسا (1248، 3607، 21، 142، 1244، 182، 6516، 766، 1291، 4449، و181أ)، في حين أظهرت العينات من الأفراد الأصحاء مير-هسا 14248، 3607، 21، 142 و 877. من المعروف أن مير-هسا-877-3ب يستهدف جينات متعددة، وتتفاعل الرناوات الدقيقة مثل مير-هسا-877-3ب و مير-هسا-1291 و مير-هسا-181أ-5ب في الغالب مع الجينات المستهدفة. الاستنتاجات: تشير ملفات تعريف الرناوات الدقيقة من الأنسجة المنتشرة التي تحتوي على الفورمالين والثابتة والمضمنة بالبرافين لمرضى سرطان الغدد الليمفاوية في الخلايا البائية الكبيرة إلى أن مستويات الرناوات الدقيقة يمكن أن تميز مرضى سرطان الغدد الليمفاوية في الخلايا البائية الكبيرة المنتشرة عند مقارنتها بالضوابط. لذلك يمكن أن تكون بمثابة علامة حيوية تشخيصية أو تنبؤية للأورام اللمفاوية ذات الخلايا البائية الكبيرة المنتشرة. يمكن أيضا أن تكون الجينات المتغيرة و الرناوات الدقيقة أهدافا علاجية محتملة. Abstract: Background: Lymphoma ranks fifth in prevalence among common cancer types worldwide. This lymphatic system cancer arises from T or B cells. Diffuse large B cell lymphomas (DLBCLs) are associated with most non-Hodgkin lymphomas. Non-coding microRNAs (miRNAs) greatly affect gene expression. A single miRNA can target numerous genes, thus largely influencing gene expression networks. MiRNAs can act as oncogenes or tumor suppressors in controlling DLBCL progression. This study investigated the roles of miRNAs in patients with DLBCL through next-generation sequencing, which was found to be sensitive, accurate, and robust. Methods: The study involved seven patients with DLBCLs and three controls at a hematology-oncology clinic. MiRNA was extracted from existing formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Illumina next-generation sequencing was used to sequence samples for miRNA profiling. Results: Samples from patients showed expression of various hsa-mir miRNAs (1248, 3607, 21, 142, 1244, 182, 6516, 766, 1291, 4449, and 181a), whereas those from healthy individuals showed expression of hsa-mir 1248, 3607, 21, 142, and 877. Hsa-mir-877-3p is known to target multiple genes, and miRNAs such as hsa-mir-877-3p, hsa-mir-1291, and hsa-mir-181a-5p interact primarily with target genes. Conclusions: MiRNA profiling in FFPE tissues from patients with DLBCL suggested that miRNA levels can distinguish patients with DLBCL from controls, and therefore may provide prognostic or diagnostic biomarkers for DLBCL. Altered genes and miRNAs may also be potential therapeutic targets

Colonoscopy screening for colorectal cancer in Egypt: a nationwide cross-sectional study

Abstract Background Current guidelines advocate for colorectal cancer (CRC) screening in adults who are at risk by using direct visualization methods such as colonoscopy. However, in Egypt, there is a paucity of data regarding the current practice of colonoscopy screening. Moreover, more information is needed about the knowledge and attitudes of potential participants regarding the procedure and possible barriers that can limit their participation. Methods We conducted a nationwide cross-sectional study using an interview-based survey of patients aged 45 years or above who presented to outpatient clinics of nine university hospitals throughout Egypt. Participants were surveyed to assess their compliance with CRC colonoscopy screening guidelines, their knowledge of and attitude towards colonoscopy screening, and their perspective on potential barriers to colonoscopy screening. Results A total of 1,453 participants responded to our survey in the nine study centers. Only a minority of participants (2.3%) were referred for CRC screening. Referral rates were higher among those who knew someone with a history of CRC (5.3% vs 1.5%, p < 0.001) or had a discussion with their physician about CRC (25.8% vs 0.7%, p < 0.001). Few responders (3.2%) had good knowledge regarding CRC screening. After introducing the concept of CRC screening to all participants, most patients (66.7%) showed a positive attitude towards having the procedure. Financial burden and fear of results were the two most frequently cited barriers to undergoing CRC screening (81.1%; and 60.1%, respecteively). Conclusions Despite the positive attitude, there is insufficient knowledge about CRC screening among eligible participants in Egypt. This has probably contributed to low compliance with current CRC screening guidelines and needs to be addressed at the national level

Additional file 1 of Colonoscopy screening for colorectal cancer in Egypt: a nationwide cross-sectional study

Additional file 1. Study centers overview

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally

Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Background and purpose: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). Methods: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. Results: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45–0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41–0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09–1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. Conclusions: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age

COS Ambassadors

A collection of materials and resources for COS ambassadors