Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.     

Carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with and without coronary artery disease

BACKGROUND: Carotid intima-media thickness and pulse wave velocity are non-invasive markers of atherosclerosis and have been shown to reliably predict presence and extent of atherosclerotic vascular disease. However, studies examining their association with each other have shown inconsistent results. Hence it was sought to assess correlation between carotid intima-media thickness and pulse wave velocity in patients with and without coronary artery disease. METHODS AND RESULTS: Sixty-four patients with angiographically proven coronary artery disease and 84 age-matched individuals without coronary artery disease but having one or more conventional cardiovascular risk factors were included in the study. Individuals with established cerebrovascular disease and peripheral vascular disease were excluded from the study. Carotid intima-media thickness of far wall was measured at three predefined sites (distal common carotid, carotid bifurcation and proximal internal carotid artery) on each side. Brachial-ankle pulse wave velocity was measured non-invasively using VP 1000 (Colin Corporation) automated ABI/ PWV analyzer. There was no significant difference in gender and presence of cardiovascular risk factors in the two groups. Mean and maximum carotid intima-media thickness and brachial-ankle pulse wave velocity were all significantly higher in coronary artery disease patients as compared to patients without coronary artery disease (0.842 v. ( 0.657 mm, p <0.0001; 1.076 v. 0.795 mm, p <0.0001; 1708.63 v. 1547.26 cm/s, p <0.0004 respectively). There was a significant correlation between brachial-ankle pulse wave velocity and both mean and maximum carotid intima-media thickness in patients with coronary artery disease (r = 0.47, p <0.0001 and r=0.41, p < 0.0008 respectively) but not in individuals without coronary artery disease (r=0.01 and -0.1 respectively). CONCLUSIONS: Presence of significant correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with coronary artery disease but absence of the same in individuals without major atherosclerotic vascular disease suggests that the correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity becomes stronger with increasing extent of atherosclerosis.     

Gunshot-induced fractures of the extremities: a review of antibiotic and debridement practices

The use of antibiotic prophylaxis and debridement is controversial when treating low- and high-velocity gunshot-induced fractures, and established treatment guidelines are currently unavailable. The purpose of this review was to evaluate the literature for the prophylactic antibiotic and debridement policies for (1) low-velocity gunshot fractures of the extremities, joints, and pelvis and (2) high-velocity gunshot fractures of the extremities. Low-velocity gunshot fractures of the extremities were subcategorized into operative and non-operative cases, whereas low-velocity gunshot fractures of the joints and pelvis were evaluated based on the presence or absence of concomitant bowel injury. In the absence of surgical necessity for fracture care such as concomitant absence of gross wound contamination, vascular injury, large soft-tissue defect, or associated compartment syndrome, the literature suggests that superficial debridement for low-velocity ballistic fractures with administration of antibiotics is a satisfactory alternative to extensive operative irrigation and debridement. In operative cases or those involving bowel injuries secondary to pelvic fractures, the literature provides support for and against extensive debridement but does suggest the use of intravenous antibiotics. For high-velocity ballistic injuries, the literature points towards the practice of extensive immediate debridement with prophylactic intravenous antibiotics. Our systematic review demonstrates weak evidence for superficial debridement of low-velocity ballistic fractures, extensive debridement for high-velocity ballistic injuries, and antibiotic use for both types of injury. Intra-articular fractures seem to warrant debridement, while pelvic fractures with bowel injury have conflicting evidence for debridement but stronger evidence for antibiotic use. Given a relatively low number of studies on this subject, we recommend that further high-quality research on the debridement and antibiotic use for gunshot-induced fractures of the extremities should be conducted before definitive recommendations and guidelines are developed.

Electronic supplementary material

The online version of this article (doi:10.1007/s12178-015-9284-9) contains supplementary material, which is available to authorized users.     

Relationship between the Charlson Comorbidity Index and cost of treating hip fractures: implications for bundled payment

BackgroundThe aim of this study is to investigate how the Charlson Comorbidity Index (CCI) scores contribute to increased length of stay (LOS) and healthcare costs in hip fracture patients.ResultsMultivariate linear regression analysis modeled the length of stay as a function of CCI score. Each unit increase in the CCI score corresponded to an increase in length of hospital stay and hospital costs incurred [effect size = 0.21; (0.0434–0.381); p = 0.014]. Patients with a CCI score of 2 (compared to a baseline CCI score of 0), on average, stayed 1.92 extra days in the hospital, and incurred $8,697.60 extra costs.ConclusionsThe CCI score is associated with length of stay and hospital costs incurred following treatment for hip fracture. The CCI score may be a useful tool for risk assessment in bundled payment plans.

Level of evidence

Level III.     

Advances in the management of diabetic macular oedema based on evidence from the Diabetic Retinopathy Clinical Research Network

The Diabetic Retinopathy Clinical Research Network (DRCR.net) performs studies on new treatments for diabetic retinopathy. This review aims to summarise recent findings from DRCR.net studies on the treatment of diabetic macular oedema. We performed a PubMed search of articles from the DRCR.net, which included all studies pertaining to the treatment of diabetic maculopathy. The main outcome measures were retinal thickening as assessed by central subfield thickness on optical coherence tomography and improvement of visual acuity on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Findings from each study were divided into modalities of treatment, namely photocoagulation, bevacizumab, triamcinolone, ranibizumab and vitrectomy. While modified ETDRS focal/grid laser remains the standard of care, intravitreal corticosteroids or anti-vascular endothelial growth factor agents have also proven to be effective, although they come with associated side effects. The choice of treatment modality for diabetic macular oedema is a clinical judgement call, and depends on the patient’s clinical history and assessment.     

Gross and microscopic study of insertion of levator palpebrae superioris and its anatomical correlation in superior palpebral crease formation and its clinical relevance

Background

To study insertion of LPS and correlate anatomically the formation of superior palpebral crease and its clinical relevance in section of Indian population.

Methods

Twenty-five human eyelids from cadavers ranging from 15–80 years were studied by dissection and histology.

Results

The levator aponeurosis traverses through interfascicular space of orbicularis oculi with twenty four inserting into subcutaneous tissue. Low septo aponeurotic sling or preaponeurotic fat was not observed. Lower one third tarsal insertion seen in twenty four specimens. Fibres become denser as it reaches the connective tissue anterior to tarsal plate. The crease was at different levels in relation to the tarsal insertion.

Conclusion

The aponeurosis insertion is either to the skin, the subcutaneous tissue or into the interfascicular space of the orbicularis. The present study reaffirms the insertion of LPS to the subcutaneous tissue of the eyelid with an extension reaching lower one third of the tarsal plate. The tissues in the anterior tarsal plate are closely packed but to act as a single complex to form a dynamic crease has not been confirmed in the study. No gross or histological difference was observed in the skin of the eyelid in the vicinity of the crease. The pattern of insertion of LPS aponeurosis plays a direct role in the formation of superior palpebral crease an important role in surgeries for Ptosis. The eyelids studied were of Indian origin with crease, and further comparative studies needs to be done for the precise anatomical explanation of single fold eyelids.