Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding.MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days.ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; P_interaction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; P_interaction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant.ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.     

Accessibility to biologics and its impact on disease activity and quality of life in patients with rheumatoid arthritis in Kuwait

Clinical Rheumatology - Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or...     

Paediatric gastrointestinal disorders in SARS-CoV-2 infection: Epidemiological and clinical implications

The coronavirus disease 2019 (COVID-19) pandemic is a threat worldwide for individuals of all ages, including children. Gastrointestinal manifestations could be the initial presenting manifestation in many patients, especially in children. These symptoms are more common in patients with severe disease than in patients with non-severe disease. Approximately 48.1% of patients had a stool sample that was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA. Children typically form 1%-8% of all laboratory-confirmed cases of SARS-CoV-2. Gastrointestinal manifestations of COVID-19 in children are not rare, with a prevalence between 0 and 88%, and a wide variety of presentations, including diarrhoea, vomiting, and abdominal pain, can develop before, with or after the development of respiratory symptoms. Atypical manifestations such as appendicitis or liver injury could also appear, especially in the presence of multisystem inflammatory disease. In this review, we discussed the epidemiology of COVID-19 gastrointestinal diseases in children as well as their implications on the diagnosis, misdiagnosis, prognosis, and faecal-oral transmission route of COVID-19 and the impact of gastrointestinal diseases on the gut microbiome, child nutrition, and disease management.     

Adverse effects of nitroglycerin treatment on endothelial function,vascular nitrotyrosine levels and cGMP-dependent protein kinase activity in hyperlipidemic Watanabe rabbits

OBJECTIVE: With the present studies we sought to determine how treatment with nitroglycerin (NTG) affects endothelial function, oxidative stress and nitric oxide (NO)-downstream signaling in Watanabe heritable hyperlipidemic rabbits (WHHL). BACKGROUND: In vitro experiments have demonstrated potent antiatherosclerotic effects of NO suggesting that treatment with NO-donors such as NTG could compensate for the diminished availability of endothelial NO. Nitric oxide may, however, not only be scavenged by reaction with endothelium-derived superoxide but also form the potent oxidant and inhibitor of vascular function, peroxynitrite (ONOO(-)). METHODS: Watanabe heritable hyperlipidemic rabbits were treated for three days with NTG patches. Normolipidemic New Zealand White rabbits (NZWR) served as controls. Endothelial function was assessed ex vivo with organ chamber experiments and vascular superoxide was quantified using lucigenin (5 and 250 microM) and CLA-enhanced chemiluminescence. Vascular ONOO(-) formation was determined using nitrotyrosine antibodies. The activity of the cGMP-dependent kinase (cGK-I) was assessed by determining the phosphorylation of vasodilator-stimulated phosphoprotein VASP (P-VASP). RESULTS: Nitroglycerin treatment caused endothelial dysfunction in NZWR and WHHL, associated with an increase in superoxide and ONOO(-) production and a substantial drop in cGK-I activity. In vivo NTG-treatment decreased lipophilic antioxidants (alpha- and beta-carotene) in NZWR and WHHL. Treatment of NZWR with NTG also decreased plasma extracellular superoxide dismutase (EC-SOD)-activity. CONCLUSIONS: Nitroglycerin treatment of WHHL with exogenous NO worsens rather than improves endothelial dysfunction secondary to increased formation of superoxide and/or peroxynitrite leading to decreased cGK-I activity. The decrease in plasma levels of alpha- and beta-carotene may be at least in part due to a decrease in EC-SOD activity.     

Design,synthesis, antimicrobial,and DNA gyrase inhibitory properties of fluoroquinolone–dichloroacetic acid hybrids

A series of new fluoroquinolone conjugates 8a–g and 9a–f were synthesized via benzotriazole‐mediated synthetic approach with good yield and purity. Some of the synthesized analogs exhibited significant antibacterial properties against Escherichia coli and Staphylococcus aureus with potency higher than that of the parent drugs through in vitro standard bioassay procedure (conjugates 8c and 8d reveal antimicrobial properties with potency 1.9, 61.9, 20.7 and 2.4, 37.1, 8.3 folds relative to the parent antibiotic 6 against E. coli, S. aureus, and Enterococcus faecalis, respectively). The observed experimental data were supported by enzymatic DNA gyrase inhibitory property. Developed BMLR‐QSAR model validates the observed experimental data and recognizes the parameters responsible for the enhanced antibacterial properties.     

Short-term Effects of Alfacalcidol on Hospital Length of Stay in Patients Undergoing Valve Replacement Surgery: A Randomized Clinical Trial

PurposeVitamin D deficiency is highly prevalent in critically ill patients, and has been associated with more prolonged length of hospital stay and poor prognosis. Patients undergoing open-heart surgery are at higher risk due to the associated life-threatening postoperative complications. This study investigated the effect of alfacalcidol treatment on the length of hospital stay in patients undergoing valve-replacement surgery.MethodsThis single-center, randomized, open-label, controlled trial was conducted at El-Demerdash Cardiac Academy Hospital (Cairo, Egypt), from April 2017 to January 2018. This study included adult patients undergoing valve-replacement surgery who were randomized to the intervention group (n = 47; alfacalcidol 2 μg/d started 48 h before surgery and continued throughout the hospital stay) or to the control group (n = 42). The primary end points were lengths of stay (LOS) in the intensive care unit (ICU) and in the hospital. Secondary end points were the prevalence of postoperative hospital-acquired infections, cardiac complications, and in-hospital mortality.FindingsA total of 86 patients were included in the final analysis, with 51 (59.3%) being vitamin D deficient on hospital admission. Treatment with alfacalcidol was associated with a statistically significant decrease in ICU LOS (hazard ratio = 1.61; 95% CI, 1.77–2.81; P = 0.041) and hospital LOS (hazard ratio = 1.63; 95% CI, 1.04–2.55; P = 0.034). Treated patients had a significantly lower postoperative infection rate than did the control group (35.5% vs 56.1%; P = 0.017). The median epinephrine dose was lower in the intervention group compared to that in the control group (5.9 vs 8.2 mg; P = 0.019). The rate of in-hospital mortality was not significantly different between the 2 groups.ImplicationsEarly treatment with 2 μg of alfacalcidol in patients undergoing valve-replacement surgery is promising and well tolerated. This effect may be attributed to its immunomodulatory and cardioprotective mechanisms. ClinicalTrials.gov identifier: NCT04085770.     

Using specific synthetic peptide (p176) derived AgB 8/1-kDa accompanied by modified patient’s sera: A novel hypothesis to follow-up of Cystic echinococcosis after surgery

Cystic echinococcosis (CE) is caused by the larval stage of the tapeworm Echinococcus granulosus. Until now, CE does not have an effective follow-up after surgery. To date, CE follow-up is conducted based on either antibody or antigen detection assays by double antibody sandwich ELISA. Unlike antigen detection, antibodies to imply exposure to an Echinococcus infection while their titration could remain for a longer period (1–10 years) after surgery. Likewise, antibody respond may be related to the location of a mature hydatid cyst. Antigen detection shows presence of CE infection, it is extremely important and necessary in follow-up of CE after surgery. The circulating antigen (CAg) titration decrease faster than circulating antibody (during 1–3 weeks) after operation. Location of hydatid cyst in detecting antigen is affected less than antibody also. Regarding this subject, antigen detection has several limitations that lead to be used less in CE follow-up. Although, AgB 8/1-kDa subunit is considered as a principle and immunogenic CAg but sensitivity of CAg detection compared to with antibody has variable range, between 33% and 85% which owing to formation of circulating immune complexes (CICs) in result of antigen – antibody complex. The another problem is non using specific CAg (AgB 8/1-kDa subunit) for production of specific paratopes (rabbit hyper immune antiserum) against AgB 8/1-kDa which is used as capture (primary) antibody in double antibody sandwich ELISA assay. The designation of synthetic peptides from conserved regions of AgB 8/1-kDa can help to this problem. These regions (motifs) should be selected for allelic, dominant, immunogenic and conserved without any genetic variation. The first part of this hypothesis suggests which patient’s sera should be treated with acidic buffers such as boric acid, acetic acid, glycine/HCl, polyethylene glycol (PEG) or combination of each of them accompanied by boiling patient’s sera which causes breaking Ag-Ab complexes and in result of releasing AgB 8/1. These modifications are effective to releasing CAg from CIC. To date, the synthetic peptides have been widely used in CE serodiagnosis based on circulating antibody detection only. In second part of this hypothesis suggests the using synthetic peptide of p176 derived AgB 8/1-kDa subunit containing conserved specific epitopes for preparation of specific paratopes (rabbit hyper immune antiserum) based on CAg detection. So, there is no need any native antigens for preparation of non-specific rabbit hyper immune antiserum. These novel improvements can help to decrease the cross-reactivity with other parasitic diseases (specificity). Increasing antigen detection could make a chance in sensitivity of patient’s sera and in result of the best and suitable tool for CE follow-up.     

AM bundle controls the anterior–posterior and rotational stability to a greater extent than the PL bundle — A cadaver study

BackgroundThe purpose of this study was to evaluate the influence of both bundles of the anterior cruciate ligament (ACL) on knee stability, anterior–posterior translation (APT) and internal (IR) and external (ER) rotation in cadaveric knees using a computer navigation system.MethodsThe APT, IR, and ER of the knees were recorded in the intact condition, the anterolateral bundle (AM) or the posterolateral bundle (PL) deficit condition and in the ACL-deficient condition. The KT-1000 arthrometer was used for APT evaluation. The measurement of rotational movements was done using a rollimeter. All tests were performed at 30°, 60° and 90° of flexion.ResultsAt 30° of flexion: In the intact knee APT was 5.8 mm, IR 12.1°, ER 10.1°. After the AM was cut, the APT increased to 9.1 mm, IR to 13.9° and ER to 12.6°. After the PL was cut, the APT was 6.4 mm, IR 13.1° and ER 10.6°. After the AM and PL were cut, the APT was 10.8 mm, IR 15.7° and the ER was 12.9° on average.ConclusionsThe AM has a greater impact on the APT than the PL in all knee joint flexion angles. The PL does not resist the rotational stability more than the AM. The rotational stability is better controlled by both bundles of ACL as compared to one bundle of the ACL.Clinical RelevanceThis study acknowledges the fact that the both bundles of the ACL are importants for AP and rotational stability of the knee joint.     

Promoter Methylation of LEP and LEPR before and after Bariatric Surgery: A Cross-Sectional Study

IntroductionDNA methylation constitutes one important epigenetic mechanism that regulates gene expression in human cells. With regard to obesity, bariatric surgery-induced weight loss has been associated with promoter methylation changes in several genes. Hyperleptinemia is a characteristic feature of obesity. The underlying regulating mechanisms have not yet been completely elucidated.MethodsWe investigated the methylation of the promoters of the leptin gene (LEP) and the leptin receptor gene (LEPR) as well as leptin expression in pre- and postbariatric surgery patients using a comparative cross-sectional design.ResultsOur results revealed significantly higher LEP promoter methylation patterns in prebariatric surgery patients compared to postoperatively. DNA methylation of the LEPR promoter was significantly higher in the postoperative group. Moreover, we found significantly higher leptin serum levels in patients before the bariatric surgery than afterwards.DiscussionThese findings strengthen the suggestion that there is an association between LEP expression and LEP methylation in obesity. We suggest that the epigenetic profile of LEP might be influenced by leptin serum levels in the form of a regulating feedback mechanism.