IV Sodium Ferric Gluconate Complex in Patients Hospitalized Due to Acute Decompensated Heart Failure and Iron Deficiency

Background: Patients suffering from heart failure (HF) and iron deficiency (ID) have worse outcomes. Treatment with intra-venous (IV) ferric carboxymaltose has been shown to reduce HF rehospitalizations and to improve functional capacity and symptoms in patients with HF and reduced ejection fraction (HFrEF). However, IV ferric carboxymaltose is significantly more expensive than IV sodium ferric gluconate complex (SFGC) limiting its availability to most HF patients around the globe. Methods: A retrospective analysis comparing patients admitted to internal medicine or cardiology departments between January 2013 to December 2018 due to acute decompensated HF (ADHF) and treated with or without IV SFGC on top of standard medical therapy. Results: During the study period, a total of 1863 patients were hospitalized due to ADHF with either HFrEF or HF with preserved ejection fraction (HFpEF). Among them, 840 patients had laboratory evidence of iron deficiency (absolute or functional) and met the inclusion criteria. One hundred twenty-two of them (14.5%) were treated with IV SFGC during the index hospitalization. Patients treated with IV iron were more likely to have history of ischemic heart disease, atrial fibrillation, and chronic kidney disease. The rate of readmissions due to ADHF was similar between the groups at 30 days, 3 months, and 1 year. Conclusion: High risk patient hospitalized to ADHF and treated with IV SFGC showed comparable ADHF readmission rates, compared to those who did not receive iron supplementation.

A Narrative Review of Contemporary Global Perspectives into Epidemiology, Treatment, and Prognosis of Vertebrobasilar Strokes

Blood flow interruptions to the posterior cerebral circulation hallmark vertebrobasilar strokes (VBS), leading to mortality and significant disabilities, yet optimal therapy prevails unpublished. Recent epidemiological evidence indicates that VBS account for nearly 1/5 of all ischemic strokes globally, with acute basilar artery occlusion (BAO) contributing significant disabilities in nearly 1/3 of the victims. The prevalence of VBS in Africa is close to 5%, majorly in large intracranial vessels. Etiologically, Stenosis accounts for 20% of all VBS, while aneurysms face up to a 3% rupture rate. Furthermore, intravenous alteplase is the gold standard medical therapy for the cases presenting within 3 to 4.5 hours post-baseline regarding management options. Nevertheless, there is no consensus for BAO beyond 4.5 hours post-onset. Stent retrievers are the first-line endovascular reperfusion therapy device proposed. However, an 18% risk of in-stent restenosis is a significant drawback. Comprehensive prognostic factors are addressed in this review. However, prospective, multicenter, controlled studies are needed to clarify the time window dilemmas facing posterior circulation strokes. This narrative review explores recent VBS epidemiology, management advances, and prognosis.Rwanda J Med Health Sci 2021;4(3):418-429

Post-VX exposure treatment of rats with engineered phosphotriesterases

The biologically stable and highly toxic organophosphorus nerve agent (OP) VX poses a major health threat. Standard medical therapy, consisting of reactivators and competitive muscarinic receptor antagonists, is insufficient. Recently, two engineered mutants of the Brevundimonas diminuta phosphotriesterase (PTE) with enhanced catalytic efficiency (kcat/KM = 21 to 38 × 106 M−1 min−1) towards VX and a preferential hydrolysis of the more toxic P(−) enantiomer were described: PTE-C23(R152E)-PAS(100)-10-2-C3(I106A/C59V/C227V/E71K)-PAS(200) (PTE-2), a single-chain bispecific enzyme with a PAS linker and tag having enlarged substrate spectrum, and 10-2-C3(C59V/C227V)-PAS(200) (PTE-3), a stabilized homodimeric enzyme with a double PASylation tag (PAS-tag) to reduce plasma clearance. To assess in vivo efficacy, these engineered enzymes were tested in an anesthetized rat model post-VX exposure (~ 2LD50) in comparison with the recombinant wild-type PTE (PTE-1), dosed at 1.0 mg kg−1 i.v.: PTE-2 dosed at 1.3 mg kg−1 i.v. (PTE-2.1) and 2.6 mg kg−1 i.v. (PTE-2.2) and PTE-3 at 1.4 mg kg−1 i.v. Injection of the mutants PTE-2.2 and PTE-3, 5 min after s.c. VX exposure, ensured survival and prevented severe signs of a cholinergic crisis. Inhibition of erythrocyte acetylcholinesterase (AChE) could not be prevented. However, medulla oblongata and diaphragm AChE activity was partially preserved. All animals treated with the wild-type enzyme, PTE-1, showed severe cholinergic signs and died during the observation period of 180 min. PTE-2.1 resulted in the survival of all animals, yet accompanied by severe signs of OP poisoning. This study demonstrates for the first time efficient detoxification in vivo achieved with low doses of heterodimeric PTE-2 as well as PTE-3 and indicates the suitability of these engineered enzymes for the development of highly effective catalytic scavengers directed against VX.

Safety and Efficacy of Endovascular Treatment for Progressive Stroke in Patients With Acute Basilar Artery Occlusion

Background and Purpose: It is unknown the benefit of endovascular therapy (EVT) for progressive stroke in patients with basilar artery occlusion (BAO). The aim of this study was to compare the efficacy and safety of EVT with standard medical therapy (SMT) in a population of BAO patients with progressive stroke.Methods: The EVT for Acute Basilar Artery Occlusion Study (BASILAR) is a national prospective registry of consecutive patients with acute BAO within 24 h of symptom onset. According to the applied therapy, all patients were divided into SMT and EVT groups. Subsequently, the EVT group was divided into early (≤6 h) and late groups (>6 h) according to the time window. The efficacy outcome was favorable functional outcomes (modified Rankin Scale score ≤ 3) at 90 days. The safety outcomes included mortality within 90 days and symptomatic intracerebral hemorrhage (sICH) after EVT.Results: The EVT cohort presented more frequently with a favorable functional outcome (adjusted odds ratio, 5.49; 95% confidence interval, 2.06–14.61, p = 0.01) and with a decreased mortality (adjusted odds ratio, 0.3; 95% confidence interval, 0.17–0.54, p < 0.001). What's more, EVT still safe (P = 0.584, P = 0.492, respectively) and effective (P = 0.05) in patients with progressive stroke when the treatment time window exceeds 6 h.Conclusions: EVT was more effective and safer than SMT for progressive stroke in patients with BAO. Besides, EVT remains safe and effective in patients with progressive stroke when the treatment time window exceeds 6 h. Predictors of desirable outcome in progressive stroke patients undergoing EVT included lower baseline NIHSS score, higher baseline pc-ASPECTs, successful recanalization and shorter puncture to recanalization time.

COMPARATIVE ANALYSIS OF SURFACE ELECTROMYOGRAPHY DATA IN PATIENTS WITH CHRONIC DAILY HEADACHE AFTER BOTULOTOXIN INJECTION TYPE A AND STANDARD MEDICAL THERAPY

Goal. The aim of the study was to compare the results of surface electromyography after injection of Botulinum toxin type A and standard medical therapy. Material and methods. The study encompassed 62 participants with chronic daily headaches (CDH). Group I included 26 patients with chronic migraine (15 treated with BTX-A injection and 11 treated with standard medical therapy), whilst, Group II comprised of 36 patients with chronic tension type headache (20 treated with BTX-A injection and 16 treated with standard medical therapy) with an average age of 32.1 ± 10.3 (M ± SD) years. Before and after therapy, clinical questionnaires, instrumental data, and headache episode characteristics were collected from all patients. To examine the differences between BTX - A injection and standard medical therapy, we measured muscle activity with surface EMG in patients with chronic daily headache before and after 3 months of treatment. On days when the patients had no headache attacks, the surface EMG was measured. Results. After treatment, surface electromyography data revealed a statistically significant difference in outcomes between the patients who received BTX-A injection and those who received standard medical therapy. Before treatment on surface EMG, all patients with chronic daily headache had high amplitude and velocity in the muscles under study, and there was no statistically significant difference between these groups, where p => 0.05. In this study, it was discovered that there was no statistically significant difference in pericranial and neck muscles dysfunction (before treatment between patients receiving BTX-A injection and standard medical therapy in Group I, patients with CM 95% CI -0.9087 - 0.4887; t = -0.607, df = 40, p = 0.5470 and Group II, patients with CTTH 95 % CI -0.5756 - 0.4356, t = -0.27, After treatment, there was a statistically significant difference between groups treated by BTX- A injection and standard medical therapy, with CM 95% CI 0.3258 - 1.4142, t = 3.231, df = 40, p = 0.0025 and CTTH 95 % CI 0.1020 - 1.1780, t = 2.381, df = 58, p = 0.0206, where p = <0.05. Conclusion. The obtained results testify the effectiveness of BTX-A injections compared to standard medical therapy in patients with CDH.

Malignant Vascular Tumors of the Head and Neck—Which Type of Therapy Works Best?

Malignant vascular tumors of the head and neck are rare neoplasms with variable clinical presentation, wide age distribution, and variable clinical courses. The heterogeneous presentation of angiosarcomas and epithelioid hemangioendothelioma often leads to misdiagnosis and unsuitable treatment. While risk factors for angiosarcomas are previous radiation, chronic lymphedema, and exposure to arsenic, thorium oxide, or vinyl chloride, there are only limited and retrospective data available on prognostic factors in EHE. In both angiosarcomas and EHE, surgery is the mainstay of treatment. There is limited evidence regarding the role of radiotherapy in EHE, although EHE is considered relatively radiosensitive. In angiosarcomas, adjuvant radiotherapy is recommended according to retrospective case series. A standard medical therapy for metastasized malignant vascular tumors is lacking. Chemotherapy, which is effective in angiosarcoma, is mostly ineffective in EHE. Targeted therapy, antiangiogenetic drugs and immunotherapy have been studied as new treatment options. The goal of this review is to summarize the current data regarding malignant vascular tumors along with their diagnosis and management.

Effects of colchicine on major adverse cardiac events in next 6-month period after acute coronary syndrome occurrence; a randomized placebo-control trial

Background Cardiovascular disease in particular acute coronary syndrome (ACS) is remained one of the most cause of morbidity and mortality, annually. Considering inflammatory pathway of atherosclerosis, colchicine as an anti-inflammatory drug is introduced to be effective in pathogenesis, prognosis and mortality rate of these patients. So in order to find out the effects of this drug we conducted this trial to know whether it reduces major adverse cardiac events (MACE) in ACS patients or not. Methods In a prospective randomized double-blinded placebo-controlled trial, we enrolled ACS patients (40–70 years) with recent ST-segment elevation myocardial infarction (STEMI) or NSTE-ACS diagnosed by coronary angiography and managed with either medical therapy or percutaneous coronary intervention. Patients were assigned to two groups either receiving colchicine 0.5 mg daily or placebo for 6 months. Both groups simultaneously received standard medical therapy as accessible guidelines. MACE occurrence consists of decompensated heart failure, ACS, stroke and survival rate compared between two groups. Results A total of 249 patients were recruited between October 2019-March 2020 with mean age of 56.89 ± 7.54, 69.5% males; 120 assigned to the colchicine group and 129 assigned to the placebo group. Over the 6 months’ period, 36 MACE occurred that were 8 events in the colchicine group compared with 28 events in the placebo group experiencing the event (P = 0.001). All of four deaths in the colchicine group and two in the placebo group were due to cardiovascular events. Evaluating adverse effects, gastrointestinal symptom was the most with the rate of 15 (12.5%) in the colchicine group and 3 (2.5%) in the controls. (P = 0.002). Conclusion The addition of colchicine to standard medical therapy in ACS patients significantly reduces MACE occurrence and improves survival rate over the time.

Continuous Venovenous Hemodiafiltration Versus Standard Medical Therapy for the Prevention of Rhabdomyolysis-Induced Acute Kidney Injury: A Retrospective Cohort Study

Aim: To determine whether continuous venovenous hemodiafiltration (CVVHDF) plus standard medical therapy (SMT) vs. SMT alone prevents rhabdomyolysis (RM)-induced acute kidney injury (AKI) and to analyze the related health economics.Methods: This retrospective cohort study involved patients with RM without AKI, coronary heart disease, or chronic kidney disease treated with CVVHDF plus SMT (treatment group, n = 9). Matched patients with RM without AKI treated with SMT only served as controls (1:1 ratio). Baseline characteristics, biochemical indexes, renal survival data, and health economic data were compared between groups. In the treatment group, some biochemical data were compared at different time points.Results: At 2 and 7 days after admission, serum biochemical indices (e.g., myoglobin, creatine kinase, creatinine, and blood urea nitrogen) did not differ between the two groups. Total (P = 0.011) and daily hospitalization costs (P = 0.002) were higher in the treatment group than in the control group. After 53 months of follow-up, no patient developed increased serum creatinine, except for 1 treatment-group patient who died of acute myocardial infarction. In the treatment group, myoglobin levels significantly differed before and after the first CVVHDF treatment (P = 0.008), and serum myoglobin, serum creatinine, and blood urea nitrogen decreased significantly at different time points after CVVHDF.Conclusions: Although CVVHDF facilitated myoglobin elimination, its addition to SMT did not improve serum myoglobin or other biochemical indices or the long-term renal prognosis. Despite similar hospitalization durations, both total and daily hospitalization costs were higher in the treatment group.

Peripheral nerve stimulation for the management of acute and subacute post-amputation pain: a randomized, controlled feasibility trial

Introduction & aim: Temporary (60-day) percutaneous peripheral nerve stimulation (PNS) has demonstrated effectiveness for the treatment of chronic post-amputation pain, and this pilot study aims to evaluate the feasibility of temporary percutaneous PNS for the treatment of acute post-amputation pain. Patients & methods: Sixteen veterans undergoing lower extremity amputation received PNS and standard medical therapy or standard medical therapy alone. Results: The PNS group reported greater reductions in average phantom limb pain, residual limb pain and daily opioid consumption, and there were fewer participants taking opioids through 3 months post-amputation. Conclusion: This pilot study suggests that PNS is feasible in the acute postoperative period following lower limb amputation and may provide a non-pharmacologic analgesic therapy that lowers pain scores and reduces opioid consumption, and thus warrants further investigation.

Multi-Center Randomized Phase II Clinical Trial on Remote Ischemic Conditioning in Acute Ischemic Stroke Within 9 Hours of Onset in Patients Ineligible to Recanalization Therapies (TRICS-9): Study Design and Protocol

Aim: To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies.Sample Size Estimates: A sample size of 80 patients (40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at p = 0.05, two sided.Methods and Design: TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm.Study Outcomes: The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1α, and HSP27 at 24 h and 72 h.Discussion/Conclusion: RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04400981.