Contemporary approach to understand and manage COVID-19-related arrhythmia

Arrhythmia, one of the most common complications of COVID-19, was reported in nearly one-third of diagnosed COVID-19 patients, with higher prevalence rate among ICU admitted patients. The underlying etiology for arrhythmia in these cases are mostly multifactorial as those patients may suffer from one or more of the following predisposing mechanisms; catecholamine surge, hypoxia, myocarditis, cytokine storm, QTc prolongation, electrolyte disturbance, and pro-arrhythmic drugs usage. Obviously, the risk for arrhythmia and the associated lethal outcome would rise dramatically among patients with preexisting cardiac disease such as myocardial ischemia, heart failure, cardiomyopathy, and hereditary arrhythmias. Considering all of these variables, the management strategy of COVID-19 patients should expand from managing a viral infection and related host immune response to include the prevention of predictable causes for arrhythmia. This may necessitate the need to investigate the role of some drugs that modulate the pathway of arrhythmia generation. Of these drugs, we discuss the potential role of adrenergic antagonists, trimetazidine, ranolazine, and the debatable angiotensin converting enzyme inhibitors drugs. We also recommend monitoring the level of: unbound free fatty acids, serum electrolytes, troponin, and QTc (even in the absence of apparent pro-arrhythmic drug use) as these may be the only indicators for patients at risk for arrhythmic complications.

Essential clinical and diagnostic aspects in pediatric psoriasis

Psoriasis is a chronic, immune-mediated, inflammatory disease of the skin. The quality of life is significantly affected, being characterized by relapses, remissions and the presence of comorbidities associated with psoriasis. Several factors are implicated in the onset of psoriasis in children, including: genetic factors, environmental factors, psychosocial stress, obesity, trauma, skin irritation, use of certain drugs such as lithium, β-adrenergic antagonists and necrosis factor inhibitors. (TNF), the presence of Crohn's disease or juvenile rheumatoid arthritis. Psoriasis is a burden for the patient in the case of the adult, being even more difficult in the case of children. Atypical manifestations in pediatric psoriasis can be difficult to diagnose.

Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup

Background β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning. Methods We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. Results A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations. Conclusions BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.

Antifungal activity of Propranolol against Fusarium keratitis isolates from the Mycotic Ulcer Treatment Trial (MUTT) and the United States

SYNOPSISBackgroundFusarium keratitis is an infection of the cornea that often results in corneal perforation requiring corneal transplantation even with topical ocular antifungal therapy. The polyene natamycin remains the current antifungal of choice for Fusarium keratitis, but prompt sterilization of the cornea is often not achieved with contemporary therapy. Recently, natamycin synergy with the beta-adrenergic antagonist timolol against Fusarium species was reported.ObjectiveOur objective in this study was to characterize the in vitro antifungal effects of additional beta-adrenergic antagonists alone or in combination with natamycin on Fusarium keratitis isolates from the Mycotic Ulcer Treatment Trial (MUTT) and USA.MethodsMicrobroth dilution assays were used to determine the minimal inhibitory concentration (MIC) of beta-adrenergic antagonists against 18 Fusarium spp. keratitis (10 from MUTT, 8 from USA) and 3 Aspergillus fumigatus isolates. The fractional inhibitory concentration index (FICI) was calculated to assess interactions with natamycin.ResultsMost beta-blockers did not show antifungal activity or synergy with natamycin with the exception of propranolol. A racemic mix of propranolol had fungicidal activity with MIC between 31 and 83 μg/mL for the Fusarium isolates. The MIC of the less cardioactive R enantiomer was lower (27-83 μg/mL) than the MIC of the S enantiomer (42-104 μg/mL). The MICs of both propranolol and natamycin were lower in combination but were not synergistic. The MIC of propranolol was 156 μg/mL for the A. fumigatus isolates.ConclusionsPropranolol has intrinsic in vitro fungicidal activity and lowers the MIC of natamycin. Both the R and S enantiomers of propranolol had antifungal activity with the MIC modestly but significantly lower for R-propranolol. These findings have relevance both for the treatment of fungal keratitis and of glaucoma in the setting of fungal keratitis. Further study of propranolol’s antifungal activity may lead to a novel treatment for fungal keratitis and possibly other fungal infections.Trial RegistrationClinicalTrials.gov Identifier: NCT00997035 (MUTT Trial)

Potential of Preoperative Voiding Efficiency in Predicting Postoperative Α-1 Adrenergic Antagonist Usage After Transurethral Resection of the Prostate

Background: Transurethral resection of the prostate (TURP) is the treatment of choice for patients with benign prostatic obstruction (BPO) who are refractory to medical treatment. Nevertheless, some patients still need α-1 adrenergic antagonists to control their post-TURP lower urinary tract symptoms (LUTS).Methods: In the present study, we developed a preoperative predictor of the continuous usage of α-1 adrenergic antagonists for post-TURP LUTS. We consecutively enrolled patients who underwent TURP at our hospital and divided them based on their use of α-1 adrenergic antagonists for more than 3 months postoperatively. Preoperative demographic data, including urodynamic parameters, were compared between the two groups. Forty-one patients were included in the study, with 17 patients (41%) receiving long-term α-1 adrenergic antagonists for their post-TURP LUTS.Results: Only lower pre-TURP voiding efficiency was significantly associated with long-term post-TURP α-1 adrenergic antagonist usage (63.3% vs. 75.1%, p = 0.03). A pre-TURP voiding efficiency of less than 75.48% had the greatest predictive ability, with a sensitivity of 88% and specificity of 50%.Conclusions: A preoperative voiding efficiency of less than 75.48% is a simple and noninvasive predictive factor for LUTS and would be helpful in preoperative evaluation and patient counseling.

Medical and non-medical interventions for post-operative urinary retention prevention: network meta-analysis and risk–benefit analysis

Aims: To assess the efficacy in lowering post-operative urinary retention, urinary tract infection and lower urinary tract symptoms and the incidence of adverse events among 12 interventions and to perform risk–benefit analysis. Methods: Previous randomized controlled trials were identified from MEDLINE, Scopus and CENTRAL database up to January 2020. The interventions of interest included early ambulation, fluid adjustment, neuromodulation, acupuncture, cholinergic drugs, benzodiazepine, antispasmodic agents, opioid antagonist agents, alpha-adrenergic antagonists, non-steroidal anti-inflammatory drugs (NSAIDs) and combination of any interventions. The comparators were placebo or standard care or any of these interventions. Network meta-analysis was performed. The probability of being the best intervention was estimated and ranked using rankogram and surface under the cumulative ranking curve. Risk–benefit analysis was done. Incremental risk–benefit ratio (IRBR) was calculated and risk–benefit acceptability curve was constructed. Results: A total of 45 randomized controlled trials with 5387 patients was included in the study. Network meta-analysis showed that early ambulation, acupuncture, alpha-blockers and NSAIDs significantly reduced the post-operative urinary retention. Regarding urinary tract infection and lower urinary tract symptoms, no statistical significance was found among interventions. Regarding the side effects, only alpha-adrenergic antagonists significantly increased the adverse events compared with acupuncture and opioid antagonist agents from the indirect comparison. According to the cluster ranking plot, acupuncture and early ambulation were considered high efficacy with low adverse events, corresponding to the IRBR. Conclusion: Early ambulation, acupuncture, opioid antagonist agents, alpha-adrenergic antagonists and NSAIDs significantly reduce the incidence of post-operative urinary retention with no difference in adverse events. Regarding the risk–benefit analysis of the medical treatment, alpha-adrenergic antagonists have the highest probability of net benefit at the acceptable threshold of side effect of 15%, followed by opioid antagonist agents, NSAIDs and cholinergic drugs.