Risk factors of progression of chronic kidney disease patients under conservative treatment

Background: Chronic kidney disease (CKD) is recognized as a major health problem affecting approximately 13% of the US population. Early identification and treatment of risk factors of progression of chronic kidney disease can provide marked benefits later in the term of delaying progression to renal replacement therapy.Methods: The medical chart for 92 CKD patients on regular follow up in low clearance clinic with GFR below 20 ml/min were retrospectively reviewed annually for 4 years regular follow up period. The following variables were recorded for each patient: non-modifiable variables (Age, sex, nationality, BMI, systolic and diastolic blood pressure, smoking status, causes of kidney disease, diabetes status, hepatitis status, medication used (like ACEi/ARBs and Sodium bicarbonate) and modifiable variables which includes: Serum albumin, potassium level, serum bicarbonate level, level of proteinuria, rate of GFR decline (Delta GFR) /year, total cholesterol level and hemoglobin level. Then they were divided into 2 groups according to the endpoint during the follow up period. Group 1 include patients did not start dialysis yet and group 2 which include patients who started dialysis during their regular follow up period.Results: There is no statistically significant differences between the two groups regarding Age , sex, systolic and diastolic blood pressure and Body Mass Index( BMI), serum albumin and haemoglobin levels (p 0.295, 0.317, 0.220, 0.181,0.805, 0.884 and 0.451 respectively). There is no statistically a difference between the two groups regarding serum potassium level and serum total cholesterol level (p 0.515 and 0.517 respectively). Diabetic patients started dialysis earlier than non-diabetics with statistically significant difference between the two groups (p 0.029). The patients who weren’t taking ACEi or ARBs started dialysis earlier than those who were taking (p 0.005), while there was no significant differences between the two groups regarding sodium bicarbonate intake (p 0.256). Low sodium bicarbonate level and severity of proteinuria are of significantly important risk factors for progression of CKD disease (p 0.006 and 0.029 respectively).Conclusions: The most important risk factors for rapid progression are presence of diabetes, severity of proteinuria and low serum bicarbonate level in advanced stages of chronic kidney disease. Early recognition of these risk factors and their correction may retard the progression of CKD, which will delay the need for renal replacement therapy. In addition, ACEI or ARBs intake are almost renoprotective and may delay the rapid progression of chronic kidney disease especially in proteinuric patients.

Knowledge and Practice of PHC Physicians toward the Detection and Management of Hypertension and Other CVD Risk Factors in Egypt

Aim. To assess the knowledge and practice of PHC physicians toward the detection and management of hypertension (HTN) and other CVD risk factors. Methods. A cross-sectional study of all primary health care physicians of the FHU of three rural districts of Egypt was conducted. Each physician was subjected to a prevalidated interview questionnaire on the WHO-CVD risk management package for low and medium resources, and a checklist of observation of daily practices. Results. Hypertension was a priority problem in about two-thirds (62.9%) of physicians, yet only 19% have guidelines for HTN patients. Clinical history recording system for HNT was available for 50% of physicians. Levels of knowledge varied with regard to definition of HTN (61.3%, fair), procedures for BP measurement (43.5%, poor), indications for referral (43.5%, poor), patient counseling (61.3%, fair), patient treatment (59.8%, fair). Availability of clinical history recording system for HNT was a significant predictor for physician's level of knowledge (P = 0.001). Overall level of practice was fair (68.5%). Conclusion. PHC physicians have unsatisfactory knowledge and practice on hypertension. There is a need of more continuing medical education. Local and international manuals, workshops, and seminars on how to make use of these guidelines would improve doctors' performance

Evaluation of hepatitis B vaccine responsiveness in ‎hemodialysis and peritoneal dialysis patients

Background: Hepatitis B Virus (HBV) infection is considered as a major cause of liver ‎cirrhosis and hepatocellular carcinoma. Patients with End Stage Renal Disease (ESRD) are a risk group for HBV infection. The vaccine of hepatitis B has ‎been recommended for prevention of HBV infection in ESRD patient ‎especially on renal replacement therapy.  Methods: Eighty seven patients with ESRD on peritoneal ‎dialysis and hemodialysis requiring primary hepatitis B vaccination were ‎enrolled in the study. Each of them received 40 µg of recombinant hepatitis B ‎vaccine in a four-dose schedule. Antibody response was determined by the ‎levels of antibodies to the hepatitis B surface antigen (anti-HBs) after last ‎doses of the vaccination schedule.  Results: We observed three response patterns to the ‎immunizations in all patients after vaccination, the nonresponders (24.7%) ‎never reached the minimum protective titer of 10 mIU/mL, the poor responders (18.5%) had titers between 10 and 100 mIU/mL, and the good responders (56.8%) had antibody titers above 100 mIU/mL. Despite a reduction in anti-‎HBs over time, the good responders did not become unprotected during the ‎observation period, especially those participants who had titers above 1000 ‎mIU/mL after the initial immunization.  Conclusions: We concluded that the immune ‎response of the HBV vaccine was reduced in the HD and PD patients, which ‎need yearly re-evaluation of seroconversion with booster doses of HBV ‎vaccination if needed‎.

Reduced glomerular filtration rate as a predictor of coronary artery disease events in elderly patients

Background: Chronic kidney disease is independently associated with cardiovascular disease (CVD) events in high-risk populations according to several studies. However, findings from community-based population studies are insufficient. We studied the relationship between estimated glomerular filtration rate (eGFR) and risk of coronary artery disease (CAD) events in patients attending Zagazig University Hospital, Sharqiya governorate, Egypt.Methods: A total of 800 subjects aged ≥ 60 years admitted to Internal Medicine Department or attended medicine outpatient clinic were included in this study. Careful history and full clinical examinations were done to assess the risk factors of CAD. Serum creatinine, lipid profile and serum glucose were measured. Estimated eGFR was evaluated by creatinine based MDRD formula. According to eGFR, patients were divided into 2 groups: group 1 with eGFR ≥ 60 mL/min/1.73 m2 and Group 2 with eGFR < 60 mL/min/1.73 m (between 40 and 60 mL/min/1.73 m).Results: 410 patients were found to have eGFR P 60 mL/min/1.73 m2, while 390 patients were found to have eGFR < 60 mL/min/1.73 m2. eGFR was lower in patients with CAD (62 ± 13 mL/min/1.73 m2) in comparison with patients without CAD (76 ± 11 mL/min/1.73 m2) (P  ≤ 0.001). Older age, hypertension, Diabetes and Low HDL are highly significant risk factors for CAD in those patients (P 0.001).Conclusions: Reduced eGFR is a significant risk factor for CAD events in older patients. Monitoring of eGFR may have a pivotal role in early detection and management of CAD in those types of patients.Keywords: Coronary artery disease; Glomerular filtration rate; Elderl

Design, synthesis, and potent anticancer activity of novel indole-based Bcl-2 inhibitors

The Bcl-2 family plays a crucial role in regulating cell apoptosis, making it an attractive target for cancer therapy. In this study, a series of indole-based compounds, U1–6, were designed, synthesized, and evaluated for their anticancer activity against Bcl-2-expressing cancer cell lines. The binding affinity, safety profile, cell cycle arrest, and apoptosis effects of the compounds were tested. The designed compounds exhibited potent inhibitory activity at sub-micromolar IC50 concentrations against MCF-7, MDA-MB-231, and A549 cell lines. Notably, U2 and U3 demonstrated the highest activity, particularly against MCF-7 cells. Respectively, both U2 and U3 showed potential BCL-2 inhibition activity with IC50 values of 1.2 ± 0.02 and 11.10 ± 0.07 µM using an ELISA binding assay compared with 0.62 ± 0.01 µM for gossypol, employed as a positive control. Molecular docking analysis suggested stable interactions of compound U2 at the Bcl-2 binding site through hydrogen bonding, pi-pi stacking, and hydrophobic interactions. Furthermore, U2 demonstrated significant induction of apoptosis and cell cycle arrest at the G1/S phase. Importantly, U2 displayed a favourable safety profile on HDF human dermal normal fibroblast cells at 10-fold greater IC50 values compared with MDA-MB-231 cells. These findings underscore the therapeutic potential of compound U2 as a Bcl-2 inhibitor and provide insights into its molecular mechanisms of action

Screening for pineal trilateral retinoblastoma revisited: a meta-analysis

Topic To determine until what age children are at risk for pineal trilateral retinoblastoma (TRb), whether its onset is linked to the age at which intraocular retinoblastomas develop, and the lead time from a detectable pineal TRb to symptoms. Clinical relevance About 45% of patients with retinoblastoma – those with a germline RB1 pathogenic variant – are at risk for pineal TRb. Early detection and treatment is essential for survival. Current evidence is unclear on the usefulness of screening for pineal TRb and, if useful, until what age screening should be continued. Methods We conducted a study according to the MOOSE guideline for reporting meta-analyses of observational studies. We searched PubMed and Embase between January 1, 1966, and February 27, 2019, for published literature. We considered articles reporting patients with TRb with survival and follow-up data. Inclusion of articles was performed separately and independently by two authors, and two authors also independently extracted the relevant data. They resolved discrepancies by consensus. Results One hundred thirty-eight patients with pineal TRb were included. Of 22 asymptomatic patients, 21 (95%) were diagnosed before the age of 40 months (median 16, interquartile range 9–29). Age at diagnosis of pineal TRb in patients diagnosed with retinoblastoma at ≤6 months versus >6 months of age were comparable (P=0.44), suggesting independency between the ages at diagnosis of intraocular retinoblastoma and pineal TRb. The laterality of intraocular retinoblastoma and its treatment were unassociated with the age when the pineal TRb was diagnosed. The lead time from an asymptomatic to a symptomatic pineal TRb was approximately 1 year. By performing a screening magnetic resonance imaging scan every 6 months after the diagnosis of heritable retinoblastoma (median age 6 months) until the age of 36 months, at least 311 and 776 scans would be required to detect one asymptomatic pineal TRb and to save one life, respectively. Conclusion Patients with retinoblastoma are at risk for pineal trilateral retinoblastoma for a shorter period than previously assumed and the age at diagnosis of pineal trilateral retinoblastoma is independent of the age at diagnosis of retinoblastoma. The GRADE level of evidence for these conclusions remains low.Peer reviewe

Molecular pathogenicity of 1-nonadecene and l-lactic acid, unique metabolites in radicular cysts and periapical granulomas

Recently, 1-nonadecene and l-lactic acid were identified as unique metabolites in radicular cysts and periapical granuloma, respectively. However, the biological roles of these metabolites were unknown. Therefore, we aimed to investigate the inflammatory and mesenchymal-epithelial transition (MET) effects of 1-nonadecene, and the inflammatory and collagen precipitation effects of l-lactic acid on both periodontal ligament fibroblasts (PdLFs) and peripheral blood mononuclear cells (PBMCs). PdLFs and PBMCs were treated with 1-nonadecene and l-lactic acid. Cytokines’ expression was measured using quantitative real-time polymerase chain reaction (qRT-PCR). E-cadherin, N-cadherin, and macrophage polarization markers were measured using flow cytometry. The collagen, matrix metalloproteinase (MMP)-1, and released cytokines were measured using collagen assay, western blot, and Luminex assay, respectively. In PdLFs, 1-nonadecene enhances inflammation through the upregulation of some inflammatory cytokines including IL-1β, IL-6, IL-12A, monocyte chemoattractant protein (MCP)-1, and platelet-derived growth factor (PDGF) α. 1-Nonadecene also induced MET through the upregulation of E-cadherin and the downregulation of N-cadherin in PdLFs. 1-Nonadecene polarized macrophages to a pro-inflammatory phenotype and suppressed their cytokines’ release. l-lactic acid exerted a differential impact on the inflammation and proliferation markers. Intriguingly, l-lactic acid induced fibrosis-like effects by enhancing collagen synthesis, while inhibiting MMP-1 release in PdLFs. These results provide a deeper understanding of 1-nonadecene and l-lactic acid’s roles in modulating the microenvironment of the periapical area. Consequently, further clinical investigation can be employed for target therapy

Asynchronous pineoblastoma is more likely after early diagnosis of retinoblastoma : a meta-analysis

Purpose To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening. Methods We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta-analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis. Results Seventy-nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs. Conclusions An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma.Peer reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London