Attenuation of Ethanol Withdrawal by Ceftriaxone-Induced Upregulation of Glutamate Transporter EAAT2

Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a 2-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 h for 3–5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats vs Wistar rats, with withdrawal manifestations occurring >12 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/kg per injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS.     

The Safety of The Directly Acting Antiviral Treatment For Hepatitis C Virus According To The Egyptian National Program Protocol In Patients With Midrange Ejection Fraction

Background:The Egyptian National Committee of Viral Hepatitis program is the leading national hepatitis C virus (HCV) management program globally. However, limited data is available about the effect of the new directly acting antiviral agents on the cardiovascular system.Objectives:Our study aimed to assess the safety of the relatively new directly acting antiviral agents approved by the National Health Committee in Egypt to treat patients infected with hepatitis C virus who have midrange left ventricular ejection fraction.Methods:This multicenter study included 400 successive patients with an ejection fraction (40–49%) from May 2017 to December 2019. We classified them into two groups: Group I (Child A), who received Sofosbuvir and Daclatasvir for twelve weeks, and Group II (Child B), who received Sofosbuvir, Daclatasvir, and Ribavirin for twelve weeks. Patients were evaluated for their symptoms, ejection fraction, brain natriuretic peptide, lipid profile, fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance levels, and Holter monitoring (just before the start of treatment and within three days after completing therapy).Results:We found New York Heart Association Class, ejection fraction, brain natriuretic peptide, premature ventricular contractions burden, as well as highest and lowest heart rate did not show a statistically significant difference in both groups after treatment. The treatment did not cause bradycardia or non-sustained ventricular tachycardia. Fasting blood glucose and fasting insulin levels declined, with improved insulin resistance after treatment in both groups. Both low and high-density lipoprotein cholesterol increased after treatment in Group II.Conclusions:Both regimens of directly acting antiviral agents used in Egypt to treat chronic hepatitis C virus infection are safe in patients with New York Heart Association Class I and II with midrange left ventricular ejection fraction (40–49%). There are beneficial metabolic changes following HCV clearance as an improvement of insulin resistance.     

Failure Mechanism of Hybrid Steel Beams with Trapezoidal Corrugated-Web Non-Welded Inclined Folds

Literature of Steel Beams with a thin-walled trapezoidal Corrugated Web (SBCWs) shows that the capacity of SBCWs is affected by both the fatigue cracks initiated along the inclined folds (IFs) and the maximal additional stress located in the middle of the IFs. An experimental investigation on the behaviour of hybrid SBCWs under flexure is presented in this paper. This study focuses on the effect of the welding IF between the web and flanges (IFs welded or non-welded), the horizontal-fold length (200, 260, and 350 mm), and transversal flange stiffeners on the failure mechanism of the SBCW under three line load. Accordingly, six hybrid specimens were fabricated, instrumented, and tested (five SBCW specimens and one specimen with a flat web). The test setup was designed to generate shear and a moment in the testing zone via three-point bending. The results indicated that non-welded IFs specimens with or without flange stiffeners failed owing to web tearing after web and flange local buckling. The failure mode of the specimen with continuous welding between the web and flanges was local flange buckling. Finally, the paper presents a comparison between the experimental results and the European Code to predict the capacity of the flange towards local buckling. It was concluded that the non-welding the IFs affected the inelastic behaviour and the capacity of the SBCWs. In addition, the bending resistance equations presented by EN 1993-1-5 can safely predict the test results of the non-welded inclined fold and yield a high safe variation.     

Paradox in the cubital tunnel syndrome—frequent involvement of left elbow: first report

Objective

Cubital tunnel syndrome (CuTS) is the second most common compression neuropathy in the arm, but the existence of a compressive cause has not been determined conclusively and the majority of the cases are idiopathic. In this paper, involvement sides of limbs of patients with cubital tunnel syndrome were studied.

Material and methods

Between October 2008 and December 2011, the clinical assessment of consecutive operated patients with cubital tunnel syndrome in Rize Education and Research Hospital were analysed. The diagnosis and severity of syndrome was based on electro-diagnostic study.

Results

This study included 57 consecutive patients with cubital tunnel syndrome (39 men, 18 women; mean age, 44,7 years; range, 23–79 years; mean age, 44,7 years; range, 23–79 years); 31 patients underwent surgical treatment. Involvement was on the right side in 18 and on the left in 39 patients. Severity scores and MCV were statistically significant between sides.

Conclusion

Profound involvement with cubital tunnel was found in left elbow. According to the finding of non-dominant elbow involvement in our study, the exact etiology and ideal management of cubital tunnel syndrome continues to be heavily debated.     

Results of ACDF using Alexandria Modular Cage-Plate Construct in cervical canal stenosis

Background

The purpose of this study was to assess prospectively operative results and complications of treatment of cervical spinal canal stenosis (CCS) by anterior cervical discectomy and fusion (ACDF) using a newly introduced Alexandria Modular Cage-Plate Construct (AMCPC).

Methods

Fifteen patients (eight males, seven females) with symptomatic CCS were treated by ACDF, with a mean age of 51.2 years. Post-operative assessment depended upon clinical and radiological results.

Results

Total number of operated levels was 25 levels, with a mean 1.67 levels/patient. Mean operative time was 69.6 min/level and 116 min/patient. Average blood loss was 78 mL/level and 130 mL/patient. Mean hospital stay was 2.8 days. Post-operative dysphagia/dysphonia persisted in one patient for 1 year. One patient developed C5 radiculopathy with grade 2 deltoid weakness that recovered after 3 months. According to Odom’s criteria, results were excellent in 13 patients (86.67 %), good in 1 (6.67 %), and fair in 1 patient. In 13 patients (23 cage-plates, 92 %), the implant showed to be completely contained until the end of follow-up (24 months). One patient had a broken screw and one had screw backing-out, both did not necessitate revision. The achieved sagittal profile was maintained without sinking-in of any cage.

Conclusion

AMCPC can be used safely for a variety of disorders requiring instrumentation and fusion. It is advantageous to stand-alone cage and to rigid cage-plates when intraoperative flexibility is needed. It overcomes the disadvantages of stand-alone cage, sinking-in, cage dislodgement and post-operative rekyphosis. In addition, it obviates the need for wearing post-operative neck collar.     

Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles

Liposomes are becoming increasingly important as drug delivery systems, to target a drug to specific cells and tissues and thereby protecting the recipient from toxic effects of the contained drug. Liposome preparations have been described to activate complement. In this study, we have investigated complement activation triggered by neutral dimyristoyl-phosphocholine (DMPC) liposomes in human plasma and whole-blood systems. Incubation in plasma led to the generation of complement activation products (C3a and sC5b-9). Unexpectedly, investigations of surface-bound C3 revealed contact activated, conformationally changed C3 molecules on the liposomes. These changes were characterized by Western blotting with C3 monoclonal antibodies, and by incubating liposomes with purified native C3 and factors I and H. Quartz crystal microbalance analysis confirmed binding of C3 to planar DMPC surfaces. In addition, we demonstrated that DMPC liposomes bound to or were phagocytized by granulocytes in a complement-dependent manner, as evidenced by the use of complement inhibitors. In summary, we have shown that C3 is activated both by convertase-dependent cleavage, preferentially in the fluid phase, by mechanisms which are not well elucidated, and also by contact activation into C3(H₂O) on the DMPC surface. In particular, this contact activation has implications for the therapeutic regulation of complement activation during liposome treatment.     

In-hospital outcomes of transapical versus surgical aortic valve replacement: from the U.S. national inpatient sample

OBJECTIVETo compare the outcomes of transapical transcatheter aortic valve replacement (TA-TAVR) and surgical aortic valve replacement (SAVR) using a large US population sample.METHODSThe U.S. National Inpatient Sample was queried for all patients who underwent TA-TAVR or SAVR during the years 2016−2017. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were in-hospital stroke, pericardiocentesis, pacemaker insertion, mechanical ventilation, vascular complications, major bleeding, acute kidney injury, length of stay, and cost of hospitalization. Outcomes were modeled using multi-variable logistic regression for binary outcomes and generalized linear models for continuous outcomes.RESULTSA total of 1560 TA-TAVR and 44,280 SAVR patients were included. Patients who underwent TA-TAVR were older and frailer. Compared to SAVR, TA-TAVR correlated with a higher mortality (4.5% vs. 2.7%, effect size (SMD) = 0.1) and higher periprocedural complications. Following multivariable analysis, both TA-TAVR and SAVR had a similar adjusted risk for in-hospital mortality. TA-TAVR correlated with lower odds of bleeding with (adjusted OR (aOR) = 0.26; 95% CI: 0.18−0.38;P < 0.001), and a shorter length of stay (adjusted mean ratio (aMR) = 0.77; 95% CI: 0.69−0.84; P < 0.001), but higher cost (aMR = 1.18; 95% CI: 1.10−1.28; P < 0.001). No significant differences in other study outcomes. In subgroup analysis, TA-TAVR in patients with chronic lung disease had higher odds for mortality (aOR = 3.11; 95%CI: 1.37−7.08; P = 0.007). CONCLUSIONThe risk-adjusted analysis showed that TA-TAVR has no advantage over SAVR except for patients with chronic lung disease where TA-TAVR has higher mortality.

Trans-apical aortic valve replacement (TA-TAVR) is typically reserved for patients who have unfavorable transfemoral approach.^[1] Several studies investigated the clinical outcomes of transfemoral-(TF) TAVR vs. surgical aortic valve replacement (SAVR); but there is paucity of data about the outcomes of TA-TAVR compared to SAVR. The STACCATO trial was the first randomized controlled trial to compare TA-TAVR versus SAVR. Though it was small trial (included only 70 operable patients) and was terminated prematurely (due to major adverse events in the TA-TAVR), it heralded a better outcome of SAVR when compared to TA-TAVR.^[2] Current trends in the U.S. show a steady decline in TA-TAVR procedures with a decrease in the rates of TAVR-related complications, such as stroke and need for pacemaker insertion. However, there has been no change in the risk of mortality or other peri-procedural complications.^[3]In this study, we aim to elucidate the applicability and safety of TA-TAVR when compared with SAVR. To our knowledge, this is the first retrospective cohort in the literature that compares the outcomes of TA-TAVR vs. SAVR in a national sample representative of the U.S. population.