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Functional dyspepsia (FD) is a prevalent global health concern increasing with years. Inspired by the Traditional Chinese Medicine (TCM) liver-stomach disharmony syndrome in order to find a quick natural alternative treatment, a Ferula asafoetida-Silybum marianum (Asdamarin™) combined extract has been developed and proved its rapid efficiency and its safety with a 7-day randomized, double-blind, placebo-controlled pilot study (CTRI/2018/05/013993 dated 21/05/2018) conducted on 70 healthy human volunteers (aged 18–60 years) supplemented with 250 mg / twice a day of either a placebo or Asdamarin™. Subjects were evaluated from baseline to the end of the study (EOS) through changes in Gastrointestinal Symptom Rating Scale (GSRS), changes in Glasgow Dyspepsia Severity Score (GDSS) and changes in the short form of Nepean Dyspepsia Index (NDI-SF) for Quality of Life. Compared to the baseline a significant reduction (p < 0.001) of GDSS questionnaire score was noted in the Asdamarin™ group (from 5.66 ± 3.1 at baseline to 5.09 ± 2.8 at the End Of Study (EOS)) compared to placebo group (from 2.77 ± 1.3 baseline to 2.69 ± 1.3 EOS), a significant decrease (p < 0.001) of GSRS score noted in the Asdamarin™ group (from 32.11 ± 8.6 baseline to 19.11 ± 5.4 EOS) compared to the placebo group (from 25.23 ± 3.6 baseline to 23.2 ± 4.9 EOS), and a significant reduction (p < 0.001) of NDI-SF scoring was noted in the Asdamarin™ group (from 15.74 ± 4.1 baseline to 11.54 ± 2.1 EOS) compared to placebo group (from 12.54 ± 3.2 baseline to 11.63 ± 2.6 EOS). Asdamarin™ has been found safe and very well tolerated during the study.

Acute severe Asthma is a common paediatric emergency managed according to the BTS and SIGN guidelines. They recommend that if initial β2 agonist treatment bears no response, frequent Ipratropium Bromide doses can be given every 20-30 minutes [1]. We present a case of paradoxical bronchospasm to Ipratropium, an observed but rare side effect.

A case of oncocytic papillary cystadenoma in a 72-year old woman, a rare tumor of laryngeal seromucinous glands of unclear nature is presented. The patient had a history of chronic inflammation of laryngeal mucosa and both her age and tumor location were typical. The lesion was resected transorally without complications. Histological findings are shown in the present study. The controversial status of oncocytic papillary cystadenoma as either a true neoplasm or a combination of metaplastic and hyperplastic changes, its resemblance to Warthin’s tumor and optimal approach to treatment are discussed.

We report a case of a right gluteal mass from the sacroiliac joint to the knee of an infant girl. Biopsy showed histopathological features similar to infantile fibrosarcoma (IFS). However, unlike most IFS, no ETV6-NTRK3 fusion gene abnormality was detected. Molecular analysis with TruSight RNA Pan-Cancer Panel detected the presence of KIAA1549-BRAF translocation and an oncogenic NF2p.Q459* SNV with potential clinical significance. A review revealed that the combination of this patient’s tumor site with the presence of a KIAA1549-BRAF translocation abnormality and an accompanying single nucleotide variant has not been previously described. The detection of this translocation abnormality raises the possibility that the spindle cell tumors in infants with an absence of the ETV6-NTRK3 fusion gene abnormality might have a distinct pathogenetic mechanism different from the previously known IFS and congenital mesoblastic nephroma. Furthermore, the discovery of BRAF translocation and its aberrant signaling of the mitogen-activated protein kinase (MAPK) pathway in this tumor contributes to the promise of clinical benefit of using the MEKi trametinib for the treatment of progressive disease that is refractory to conventional chemotherapy. 

Background: Sudden cardiac death is a major healthcare issue in reduced ejection fraction heart failure (HFrEF) patients. Recently, the new association of sacubitril/valsartan showed a reduction of both ventricular arrhythmias (VA) and mortality even at low dose compared to enalapril in HF patients. The purpose of our study was to assess whether the highest dose of sacubitril/valsartan compared to lower doses may improve the rate of death and VA in a population of patients with HFrEF and with an implantable cardiac defibrillator (ICD). Methods: 104 HF patients with reduced EF under sacubitril/valsartan with an ICD were divided in 2 groups: the first one with the lower doses of sacubitril/valsartan (24/26 mg or 49 mg/51 mg twice daily) and the second with the maximal dose (97mg/103mg twice daily). The primary outcome was a composite of death or appropriate ICD therapy for VA. Results: After a median follow-up of 14 months, 39 patients were treated with lower doses and 65 patients with the highest dose. Patients from the lower doses group were older (70 [60-80] vs. 66 [60-70]; p = 0,03), more symptomatic at initiation (NYHA 3: 44% vs. 19%; p < 0,01) and more often in atrial fibrillation (31% vs. 12%; p = 0,04). The primary composite endpoint occurred in 14 patients (36%) in the low doses group versus 7 patients (11%) in high dose group (p < 0,01). This difference was particularly observed in the subgroup of patients with ischemic cardiomyopathy. In a multivariable analysis, the higher dose was independently associated with the primary outcome with an HR = 2,934 [IC 95% 1,147 – 7,504]; p = 0,03. Kaplan-Meier curve showed an early effect of the highest dose of sacubitril/valsartan association. Conclusion: Patients with HFrEF under the highest dose of sacubitril/valsartan showed better clinical outcomes with a decrease of both mortality or appropriated ICD therapies related to ventricular arrhythmias.

Objective: The long-term outcome of percutaneous transluminal angioplasties is mainly determined by restenoses, either by progression of the underlying disease or by intimal hyperplasia. Pharmacological substances on the one hand and the implantation of stents on the other have been developed with the intention of preventing precisely this complication. While patients are treated after PTA of peripheral vessels with different low-molecular-weight heparins, the indication for stent implantation is determined individually rather by experience. The aim of this study was to determine gender-specific risk factors of long-term outcome after percutaneous transluminal angioplasty (PTA) of peripheral vessels with or without stentimplantation. Methods: In the present study, we examined the long-term results of percutaneous transluminal angioplasty (PTA) of peripheral vessels. Between 2007 and 2017, in total, 3,276 patients underwent PTA with or without stent implantation in our clinic. All patients were treated postinterventionally for 48 hours with 25,000 IU heparin (Unfractionated Heparin (UFH), heparinsodium-Braun, 25,000 I.E./5 ml, 2 ml/h) monitored by the partial thromboplastin time and subsequently underwent a control investigation every 6 months. The endpoint of the study was determination of symptomatic stenosis larger than 50% that required reintervention. Results: 239 (68.2% with mean age 68.02 years) male patients and 111 female patients (31.71% with mean age 62.92 years) were evaluated with complete follow-up. A total of 470 PTAs were performed on male patients and 213 on female patients in multiple interventions. The majority of patients at the time of treatment were in stage IIb according to the classification of Fontaine (81.6% of male patients and 68% of females). In our sample, peripheral arterial disease stage III and IV according to Fontaine classification occurred twice as frequently in female patients as in male patients (stage III in 12.6% in female versus 6.1% in male, and stage IV in 18% in female versus 8.9% in males). In both groups, the femoral superficialis artery was most frequently dilated (64 cases, 30% in female and 155 cases, 32.9% in male), followed by the iliacal communis artery (46 cases in female and 99 cases in male, both with 21.5%). A balloon angioplasty of the tibialis anterior and posterior arteries was performed twice as frequently in female patients as in male patients (28 cases with 13.1% of tibialis ant. artery in female versus 32 cases with 6.8% in male patients, and in 17 cases with 7.9% of tibialis post. artery in female versus 16 cases with 3.4% in male patients). In this study, without consideration of gender, patency rates of 79% after 2.5 years, 67% after 5 years, 49% after 7.5 years and 37% after 10 years were determined for PTA without stent implantation. Between the 7th and 10th year in follow-up, the cumulative patency rates for stent implantation was 49%, whereas it was 31% for PTA alone. The results of this study show that the stent assisted PTA`s of comm. artery and external iliacal artery are significantly independent of risk factors better than the femoral vessels, and these in female patients better than in male patients. Male patients do not benefit significantly from stent implantation in the long term. As the COXI and II regression analyses show, gender-linked results are most evident for renal insufficiency and diabetes mellitus, and less pronounced also for the number of open lower leg vessels. Conclusion: Under consideration of gender and risk factors, while male patients with diabetes mellitus, renal insufficiency and/or poor run-off did not benefit from stent implantation in the long-term, female patients with similar risk factors showed higher patency rates after stent therapy. In addition, the long-term results after PTA of femoral superficialis artery and poplitea artery are significantly worse than PTA of the pelvic vessels in both genders.

Fibrinolytic therapy has become synonymous with tissue plasminogen activator (tPA) based on the belief that tPA alone was responsible for natural fibrinolysis. Although this assumption was belied from the outset by disappointing clinical results, it persisted, eventually causing fibrinolysis to be discredited and replaced by an endovascular procedure. Since time to reperfusion is the critical determinant of outcome, which in acute myocardial infarction (AMI) means within two hours, a time-consuming hospital procedure is ill-suited as first line treatment. For this purpose, fibrinolysis is more fitting. The assumption that tPA is responsible for fibrinolysis is contradicted by published findings. Instead, tPA ‘s function is limited to the initiation of fibrinolysis, which is continued by urokinase plasminogen activator (uPA) and that has the dominant effect. tPA and uPA gene deletion and clot lysis studies showed the activators have complementary functions, requiring both for a full effect at fibrin-specific doses. They are also synergistic in combination thereby requiring lower doses for efficacy. A clinical proof of concept study in 101 AMI patients who were treated with a 5 mg bolus of tPA followed by a 90 minute infusion of prouPA, the native form of uPA. A near doubling of the 24 h TIMI-3 infarct artery patency rate was obtained compared to that in the best of the tPA trials (GUSTO). In further contrast to tPA, there were no reocclusions and the mortality was only 1% [1]. A sequential combination of both activators, mimicking natural fibrinolysis, holds promise to significantly improve the efficacy and safety of therapeutic fibrinolysis.

Pulmonary hypertension (PH) in sickle cell disease (SCD) is associated with a mortality rate of 37%. There is an upregulation of adhesion molecules which leads to the expression of endothelin-1, a potent vasoconstrictor. A prospective, descriptive study was done to determine the safety and efficacy of macitentan in patients with SCD and PH. Continuous variables were reported as mean ± SEM or percentage where appropriate. We screened 13 patients and recruited five. All five patients were adults. Data were analyzed as appropriate by student t - test. Statistical significance was assumed at p < 0.05. Baseline pulmonary hemodynamics obtained by right heart catheterization and systemic hemodynamics were (± SEM): mean pulmonary artery pressure (MPAP) 32 ± 8 mmHg, right atrial pressure (RAP) 9 ± 4 mmHg, pulmonary vascular resistance (PVR) 257 dynes-sec/cm5 and CI 3·7 ± 0.39 l/m2. Of all parameters, only PVR and 6-min walk distance changed significantly. For the group, MPAP decreased by 15.6%, PVR by 22.5% and RAP by 25.5%. The 6-minute walk distance increased over sixteen weeks except in Patient 4 who had a 3% decrease. The mean walk distance increased in the total distance, from 464 ± 158 meters to 477 ± 190 meters (p .123). In four patients, the adverse events were mild to moderate and did not lead to study drug discontinuation. Significant improvement in pulmonary hemodynamics and exercise capacity in patients with SCD-related pulmonary arterial hypertension. We found that macitentan was safe and well tolerated.

Morbidity and mortality of the infected patients by multidrug-resistant bacteria have increased, emphasizing the urgency of fight for the discovery of new innovative antibiotics. In this sense, natural products emerge as valuable sources of bioactive compounds. Among the biodiversity, Eryngium pristis Cham. & Schltdl. (Apiaceae Lindl.) is traditionally used to treat thrush and ulcers of throat and mouth, as diuretic and emmenagogue, but scarcely known as an antimicrobial agent. With this context in mind, the goals of this study were to investigate the metabolic profile and the antibacterial activity of ethanolic extract (EE-Ep) and hexane (HF-Ep), dichloromethane (DF-Ep), ethyl acetate (EAF-Ep) and butanol (BF-Ep) fractions from E. pristis leaves. Gas Chromatography-Mass Spectrometry (GC-MS) was performed to stablish the metabolic profile and revealed the presence of 12 and 14 compounds in EAF-Ep and HF-Ep, respectively. β-selinene, spathulenol, globulol, 2-methoxy-4-vinylphenol, α-amyrin, β-amyrin, and lupeol derivative were some of phytochemicals identified. The antibacterial activity was determined by Minimal Inhibitory Concentration (MIC) using the broth micro-dilution against eight ATCC® and five methicillin-resistant Staphylococcus aureus (MRSA) clinical strains. HF-Ep was the most effective (MIC ≤ 5,000 µg/µL), being active against the largest part of tested Gram-positive and Gram-negative bacterial strains, including MRSA, with exception of Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 9027) and (ATCC 27853). These results suggest that E. pristis is a natural source of bioactive compounds for the search of new antibiotics which can be an interesting therapeutic approach to recover patients mainly infected by MRSA strains.

Video objective: To demonstrate that surgical technique of vaginal cervicoisthmic cerclage must be performed in women with history of cervical incompetence with more than two late miscarriages before 24 weeks or premature deliveries before 28 weeks and after prior failure of preventive Mc Donald cerclage. In this video, the authors describe the complete procedure in 8 steps to standardize and facilitate the procedure in a simple and safe way during pregnancy. Design: Step-by-step video demonstration of the surgical technique.Setting: Tertiary Center for University Hospital.