Use of complement monoclonal antibody eculizumab in Shiga toxin producing Escherichia coli associated hemolytic uremic syndrome: A review of current evidence

Complement activation plays an important role in the pathogenesis of atypical hemolytic uremic syndrome. Eculizumab is a monoclonal antibody that blocks complement activity and has been approved for use in the treatment of atypical hemolytic uremic syndrome (HUS). Less well appreciated is the role of complement in Shiga toxin‐induced HUS (Shiga toxin producing Escherichia coli [STEC]‐HUS). To a limited extent, eculizumab has been used off label in patients with severe STEC‐HUS with neurological involvement. Through a systematic search of available databases, we identified 16 reports describing the use of eculizumab in STEC‐HUS (eight case reports/series, seven retrospective studies, and one prospective cohort study). All studies described its use in severe STEC‐HUS with neurological or multiorgan dysfunction; none were randomized or blinded. Four studies used the control groups. Although the overall quality of evidence is low, some published studies showed positive clinical improvement after treatment with eculizumab in severe STEC‐HUS with progressive neurological involvement.     

Spontaneous coronary artery dissection with pseudoaneurysm formation diagnosed by intravascular ultrasound: a case report

Spontaneous coronary artery dissection is a rare cause of myocardial ischemia. Coronary artery pseudoaneurysm may occur after percutaneous coronary interventions and rarely spontaneously. We present a patient who had spontaneous coronary artery dissection with formation of a pseudoaneurysm diagnosed by intravascular ultrasound.     

Abnormalities in nitric oxide and its derivatives in lung cancer

RATIONALE: A cellular prooxidant state promotes cells to neoplastic growth, in part because of modification of proteins and their functions. Reactive nitrogen species formed from nitric oxide (NO) or its metabolites, can lead to protein tyrosine nitration, which is elevated in lung cancer. OBJECTIVE: To determine the alteration in these NO derivatives and the role they may play in contributing to lung carcinogenesis. METHODS: We analyzed levels of NO, nitrite (NO2-), nitrate (NO3-), and the location of the protein nitration and identified the proteins that are modified. MEASUREMENTS AND MAIN RESULTS: Although exhaled NO and NO2- were increased, endothelial NO synthase or inducible NO synthase expression was similar in the tumor and tumor-free regions. However, immunohistochemistry showed that nitrotyrosine was increased in the tumor relative to non-tumor-bearing sections. We used proteomics to identify the modified proteins (two-dimensional polyacrylamide gel electrophoresis; mass spectrometry). Both the degree of nitration and the protein nitration profile were altered. We identified more than 25 nitrated proteins, including metabolic enzymes, structural proteins, and proteins involved in prevention of oxidative damage. Alterations of the biology of NO metabolites and nitration of proteins may contribute to the mutagenic processes and promote carcinogenesis. CONCLUSIONS: This study provides evidence in favor of a role for reactive nitrogen and oxygen species in lung cancer.     

Gastrointestinal perforation secondary to COVID-19: Case reports and literature review

Introduction:Corona virus disease-2019 (COVID-19) presents primarily with respiratory symptoms. However, extra respiratory manifestations are being frequently recognized including gastrointestinal involvement. The most common gastrointestinal symptoms are nausea, vomiting, diarrhoea and abdominal pain. Gastrointestinal perforation in association with COVID-19 is rarely reported in the literature.Patient concerns and diagnosis:In this series, we are reporting 3 cases with different presentations of gastrointestinal perforation in the setting of COVID-19. Two patients were admitted with critical COVID-19 pneumonia, both required intensive care, intubation and mechanical ventilation. The first one was an elderly gentleman who had difficult weaning from mechanical ventilation and required tracheostomy. During his stay in intensive care unit, he developed Candidemia without clear source. After transfer to the ward, he developed lower gastrointestinal bleeding and found by imaging to have sealed perforated cecal mass with radiological signs of peritonitis. The second one was an obese young gentleman who was found incidentally to have air under diaphragm. Computed tomography showed severe pneumoperitoneum with cecal and gastric wall perforation. The third case was an elderly gentleman who presented with severe COVID-19 pneumonia along with symptoms and signs of acute abdomen who was confirmed by imaging to have sigmoid diverticulitis with perforation and abscess collection.Interventions:The first 2 cases were treated conservatively. The third one was treated surgically.Outcome:Our cases had a variable hospital course but fortunately all were discharged in a good clinical condition.Conclusion:Our aim from this series is to highlight this fatal complication to clinicians in order to enrich our understanding of this pandemic and as a result improve patients’ outcome.     

Effect of alcohol-induced septal ablation on left atrial volume and ejection fraction assessed by real time three-dimensional transthoracic echocardiography in patients with hypertrophic cardiomyopathy

Alcohol-induced septal ablation (AISA) is an accepted treatment for hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) outflow obstruction who are unresponsive to medical therapy. As left atrial (LA) enlargement has been correlated with increased morbidity and mortality in HCM, we assessed LA volumes and ejection fraction (EF) prior to and after AISA using real time three-dimensional (3D) transthoracic echocardiography (TTE) in 12 patients (9 women; mean age 52 ± 15 years; 11 Caucasian). All patients underwent successful AISA with no complications and their resting left ventricular outflow gradients decreased from 40.5 ± 22.2 to 9.1 ± 17.6 mmHg (P < 0.001) while their gradients with provocation decreased from 126.2 ± 31.7 to 21.8 ± 28.0 mmHg (P < 0.001). All patients showed improvements in their New York Heart Association (NYHA) functional class. Both the LA end-systolic (45.2 ± 12.9 to 37.2 ± 13.7 ml, P < 0.0001) and end-diastolic (79.6 ± 18.9 to 77.1 ± 18.6 ml, P = 0.001) volumes decreased after AISA. The LA EF increased from 43.1 ± 9.0 to 52.5 ± 8.8% (P = 0.001). The increase in LA EF correlated with the decrease in the resting left ventricular outflow gradient (R =−0.647, P = 0.03). In conclusion, 3D echocardiography can be utilized to follow LA function after AISA for HCM. AISA results in clinical improvement in patients with HCM and in improvement of LA EF that is correlated with the decrease in the left ventricular outflow gradient.     

Optimal asymmetric thread for orthodontic microimplants: Laboratory and clinical evaluation

Objectives:To investigate the performance of microimplants incorporating a newly designed asymmetric thread.Materials and Methods:Three microimplants were compared. The control group comprised microimplants with the original v-shaped thread. The two experimental groups (Taper 1.0 and Taper 1.25) comprised prototype microimplants constructed with the new asymmetric thread; the Taper 1.25 specimens had a 1.25-mm-long and sharper tip, while the Taper 1.0 and control groups had a less sharp 1-mm tip. Two specially designed artificial bone blocks mimicking soft (maxillary) and hard (mandibular) bone were used to evaluate the microimplant insertion characteristics and postinsertion lateral stability. The peak insertion torque, insertion time, Periotest value (PTV), and torsional strength were measured. Then the microimplants were evaluated clinically over a 3-month period.Results:Significant differences in peak insertion torque, insertion time, and PTV were observed and favored the experimental groups. Although statistically insignificant, the clinical success rate was also higher in the Taper 1.25 experimental group than in the control group (87.2% vs 75.6%).Conclusions:The better performances of the experimental microimplant, under both laboratory and clinical conditions (although statistically insignificant in the latter), demonstrate the superiority of the new asymmetric thread.     

Measurement of thrombin generation intra-operatively and its association with bleeding tendency after cardiac surgery

Introduction

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to haemostatic disturbances. Monitoring the haemostatic capacity by conventional clotting tests is challenging.

Materials and Methods

Thrombin generation (TG) by Calibrated Automated Thrombography, clotting tests and tissue factor pathway inhibitor (TFPI) measurements were performed to describe the relationship between haemostatic changes and alterations in these tests. Blood samples were collected before, during and after CPB. Furthermore, it was investigated whether TG measured intraoperatively, is associated with increased risk of bleeding postoperatively.

Results

TG diminished significantly (p < 0.01) after heparinization in the presence and absence of platelets (37% and 50%) compared to baseline. After the start of CPB, TG elevated and persisted till the end of surgery but remained lower than preoperatively. Activated clotting time increased after heparinization and after the start of bypass compared to baseline (400% and 500%). Anti-FXa activity reduced on the start of CPB compared to the level after heparinization, to almost the baseline value following protamine reversal of heparin. The plasma levels of total and free TFPI elevated 9 and 14 fold during bypass and remained after protamine administration higher than preoperatively. Plasma D-dimer levels reduced (p < 0.01) when bypass started. However, a marked elevation was observed in the following time points. TG in platelet-rich plasma measured after heparinization and after the start of CPB associated (p < 0.05) with postoperative blood loss.

Conclusions

TG can be determined during CPB despite the high heparinization level, it reflects the haemostatic capacity better than clotting-based assays and might better predict bleeding when performed intraoperatively.