28 e-Letters

  • What category does a K-cup fall into? (Keurig coffeemaker pod)

    Is a k-cup pod considered French press? Was a k-cup studied?

  • The index of clinical suspicion is equally important

    Dear Sir,
    The article is interesting. We in the UAE are using high-sensitivity Troponin I for the last 8 years in all patients suspected of the acute coronary syndrome and all cardiovascular emergencies (for risk stratification) presenting in the emergency units. We observed many patients who presented after 3-hour of symptoms-onset with negative first high-sensitivity Troponin I (<5ng/L) showed positive second or a third repeat test, when we had high-index of suspicion clinically, largely because of chronic comorbidities like diabetes mellitus and expatriates from Bangaldesh. Therefore the message must be evaluated in light of overall picture and value of Troponin should be used only as one of the important markers.

  • Treatment with PCSK9-inhibitors - a questionable measure

    According to Steffens et al.,1 patients with cardiovascular disease (CVD) whose cholesterol is too high despite ongoing cholesterol-lowering treatment should be treated with the PCSK9-inhibitor alirocumab. They base their conclusion on twelve weeks of treating 244 middle-aged and elderly patients (half of whom had familial hypercholesterolemia), where the LDL-cholesterol (LDL-C) was lowered by around 50% without any serious side effects. A relevant question is whether or not such treatment provide clinic benefit.
    The optimal way to demonstrate the benefits of any drug is through the use of double-blinded placebo-controlled trials. More than 30 PCSK9-inhibitor-trials have now been published,2,3 and none of them has demonstrated a reduction in overall or CV mortality. Only three, which included 73 936 patients with CVD, were performed correctly.2 Although LDL-cholesterol was lowered by more than 50%, none of them achieved a statistically significant reduction in either total or CVD mortality. In the longest trial (the 2.8 year long ODYSSEY-trial), which included almost 19,000 statin-treated patients, total mortality was a little lower in the alirocumab-group (3.5% vs 4.1%),2 which means that to save one life per year, it is necessary to treat more than 550 patients at a cost of more than five million US dollars.
    That such a strong cholesterol-lowering is ineffective is not unexpected, because there is much evidence that CVD is not caused by elevated...

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  • Ivermectin May Prevent and Reverse Immunosenescence By Antagonizing Alpha-fetoprotein and Downmodulating PI3K/Akt/mTOR Hyperactivity

    In their recent discussion on the anti-inflammatory activity of ivermectin in sepsis, DiNicolantonio et al. [1] left open the question on how ivermectin may protect against COVID-19 initial symptoms and progression.

    Insight was published by Li et al. [2] in their derivation of an ivermectin host protein and SARS-CoV-2 host protein interaction network (PPI). For this they metabolically labelled proteins in an ovarian cancer cell line and determined which proteins were upregulated and downregulated related to a 24 hour exposure to ivermectin versus no exposure. There were 4,447 identified proteins differentially regulated by ivermectin. When compared with the 284 host proteins known to be affected by SARS-CoV-2, this left 52 proteins in common, 50 of which were downmodulated. Only two proteins, HMOX1 and IL1F10 were upregulated by ivermectin.

    This protein-protein interaction (PPI) network revealed EGFR at the center of the pathway with connections to mTOR/APOE, NFKB1/APP, AKT, MAPK1, and CASP3 through TGFB1 interacting with the protein ALB (albumin). BSG, recently shown to be absolutely essential for foam cell formation in macrophages [3] was also captured in the PPI network. Moreover, foam cell formation has been shown in macrophages to be mediated under the direction of EGFR [4] as well as for the foamy sebocytes of sebaceous glands which line the mucosal surfaces and may be an important site of viral entry [5]. Foam cell formation is important in ho...

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  • High dose melatonin monotherapy for COVID

    The use of high dose melatonin early and aggressively for those infected with COVID-19 was the subject of an international symposium held in December 2020 (1). Dr Richard Neel reported on over 1000 cases that have responded to monotherapy with melatonin.
    Why this works, as speculated upon in this article, is open to debate. What is most important is that people can benefit from this treatment modality. Thank you for the opportunity to raise awareness of this underappreciated therapeutic option.
    (1) https://www.youtube.com/watch?v=p_4JeOj1JLc

  • Maintain sharp vigilance on adverse reactions of ivermectin

    To the Editor:
    We read with great interest the editorial by Dr. James J DiNicolantonio and colleagues.1 In their editorial, the authors have expressed their opinions that ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19. However, we want to highlight some concerns about the use of ivermectin for late-stage COVID-19.
    First, we do agree with the authors that ivermectin can be a potential drug for late-stage COVID-19 considering its anti-inflammatory effects. The authors stated that it is reasonable to suspect that, in doses at or modestly above the standard clinical dose, ivermectin may have important clinical potential for managing disorders associated with life-threatening respiratory distress and cytokine storm—such as advanced COVID-19.
    Second, a usual dose or modestly above the standard clinical dose of ivermectin may induce neurologic disorders, which can be fatal.2 Encephalopathy and coma are well-known side effects of ivermectin treatment in animals. But few cases of neurologic disorders after ivermectin treatment have been reported in humans.3 Neurologic disorders may include coma, ataxia, pyramidal signs, and binocular diplopia. Thus, the seriousness of the adverse reaction in humans implies that caution is warranted regarding medical prescriptions of ivermectin.
    We declare no competing interests.
    Contributors: All authors contributed to the final manuscript.

    Funding: The authors have...

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  • The Impact of Daylight Savings Time Change on the Incidence of Percutaneous Coronary Intervention for Acute Myocardial Infarction

    Five years ago, our group at the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) published an analysis exploring the impact of day light saving time (DST) changes on the state -wide volume of percutaneous coronary intervention in patients presenting with acute myocardial infarction (AMI-PCI) in the weekdays following the time change.1 Using data from our clinical registry reflecting all PCIs performed at non-Federal hospitals throughout Michigan between 1/1/2010 and 9/15/2013, we identified a significant increase in AMI-PCI on Mondays following the Spring DST change (RR = 1.24, p = 0.011), and a significant reduction in cases on Tuesdays following fall DST changes (RR = 0.79, p = 0.044), adjusting for seasonal and weekday effects, and for an overall time trend. We have now repeated the analysis using registry data for the subsequent 5 ½ years, from 9/16/2013 – 3/31/2019 using the same methodology and obtained results inconsistent with our prior publication. In our analysis of more recent data, both of the previously reported effects were substantially attenuated and are no longer statistically significant (Spring Monday after change: RR = 1.095, p = 0.207; Fall Tuesday after change: RR = 0.96, p = 0.553). Our prior publication garnered a great deal of attention in the popular media2,3, often with alarming, sensational headlines. It has also been included in meta-analysis along with other publications identifying a similar Spring time change effect4...

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  • Aortic Inflammation and Calcification in Abdominal Aortic Aneurysmal Disease

    The prospective matched-cohort study by Joshi et al., investigated inflammation in both AAA and atherosclerosis using 18-FDG PET to generate non-invasive imaging biomarkers for aneurysm expansion and destabilization[1]. Such work is of great importance as atherosclerosis and AAA often co-exist and share many of the same underlying risk factors and pathologies including vascular inflammation and calcification. However, the magnitude and distribution of these processes both locally and globally were not previously investigated and could provide novel insight into AAA progression.

    It was shown that asymptomatic aortic aneurysms had greater inflammatory activity not only in the aneurysmal region but also throughout the entire aorta when compared to the atherosclerotic cohort. This diffuse inflammation of the aorta in AAA patients is supported by our ongoing work investigating the role of the aneurysm in affecting systemic endothelial change. This is assessed by measuring the flow-mediated dilatation (FMD) of the brachial artery [2, 3]. FMD decreases with increased maximum diameter of the aneurysmal sac and reverses following surgical intervention. This suggests that the local aneurysm itself to be a nidus of stimulus for inciting global change during the aneurysm’s natural history[4].

    Furthermore, they show that aneurysms with intra-luminal thrombi (ILT) demonstrated lower 18-FDG uptake both within the thrombus and in the adjacent aortic wall. Here, the authors...

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  • Final kissing balloon inflation and proximal optimization technique should be performed in true bifurcation lesions with large side branch

    Dear editor,
    I have read with great interest the results of nordic baltic bifurcation study-4 by Kumsar et al (1), in which study clinical outcomes after treatment of lesions in large bifurcations by simple or complex stent implantation were compared. In the 6-month results of this study, compared to the provisional method, a decrease in major adverse cardiac event (MACE) was observed in the complex group, although it was not statistically significant. Again, in the comparison of the 2-year results, no difference was observed between the two groups. The fact that complex stenting is not found to be superior to simple stenting for true bifurcation lesions with such a wide side branch can be due to several reasons:
    1- All patients did not receive a final kissing balloon inflation (FKBI). It is well known that the FKBI should be performed in two-stenting techniques for full treatment of the true bifurcation lesion. In addition, why was the high rate of FKBI application required in simple stenting? It is well known that in simple stenting, POT should be used instead of FKBI unless the there is a TIMI flow <3, and / or a dissection in the side branch (2).
    2- Interestingly, no proximal optimization technique (POT) was used in any patient. In any complex two-stent technique without POT, the lesion is not considered to be truly treated (3,4). I think this is the most important limitation of the study. POT provides optimal positioning of the main vascular ste...

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  • How negative results can become positive ones

    The authors of the metanalysis "Pharmacological interventions for the prevention of contrast-induced acute kidney injury in high-risk adult patients undergoing coronary angiography: a systematic review and meta-analysis of randomised controlled trials" conclude that "several drugs are renoprotective in patients with CKD [...] the evidence is strongest for NAC".
    This conclusion is at odds with previous research and metanalyses. The same authors report 10 papers (over a total of 27) which show potentially harmful effects of NAC (OR >1). Furthermore, the paper they cite with the largest sample size (by Weisbord et al, n>2000) does not show any beneficial effect of NAC. Notwithstanding these data, the authors "recommend that NAC should be used when a high dose of contrast is anticipated". I believe the readers should be aware about the poor evidence supporting this conclusion.
    NAC is a well-tolerated substance and, clearly, its use is unlikely to represent harm for patients (even though 1/3 of the studies reported by the authors would suggest that some negative effect might exist). Therefore, the main reason for its recommendation is its anxiolytic effect on physicians, who are convinced to use a "renoprotective" drug.