eLetters

12 e-Letters

published between 2018 and 2021

  • Comment on Kir et al article: "High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Beckton Dickinson (BD) Onclarity assay"

    Dear Editor,

    We read with interest the recently published manuscript by Kir et al. entitled “High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Becton Dickinson (BD) Onclarity assay” [1]. The study evaluates the off-label use of commercial HPV assays on formalin-fixed paraffin-embedded (FFPE) specimens. The authors detail the performance of the Hologic Aptima RNA test and the BD Onclarity DNA test in a study of 189 cases (46 SCC, 107 HSIL and 36 benign/normal). They report that, while the specificity and positive predictive value (PPV) were 100% for both assays, the Aptima assay was more sensitive, detecting 99.4% (95% CI 96.46% to 99.98%) of CIN2+ cases, versus the BD Onclarity assay with a sensitivity of 75.9% (95% CI 65.27% to 84.62%) [1]. The authors conclude that “both assays are reliable methods for high-risk HPV detection and genotype determination in FFPE specimens” and that the “Aptima assay has the advantage of higher sensitivity”.

    We believe that there are a number of deficiencies in the study design (not addressed in the discussion section) which call into question the validity of the conclusions. Firstly, this is not a split sample study, nor a true head to head comparison since the samples were not randomly assigned to each assay for testing. All 189 cases were first tested with the Aptima assay and only approximately half (n = 97) were subsequently tes...

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  • No indication of cross-reactivity between SARS-CoV-2 infection and Architect HIV Combo assay

    To address the concern of potential cross-reactivity of SARS-CoV-2 with Architect HIV Combo assay (Abbott Laboratories, Abbott Park, Illinois, USA) reported in this article, we evaluated 846 COVID-19 convalescent plasma samples obtained from New York Blood Center (New York, New York, USA) using the Architect HIV Combo assay. Although all 846 samples were reactive in Architect SARS-Cov-2 IgG assay (Abbott Laboratories, Abbott Park, Illinois, USA), none of the samples were reactive in the Architect HIV Combo assay with average signal < 0.14 S/CO and standard deviation < 0.058 S/CO. Thus, the data shows no indication of cross-reactivity between SARS-CoV-2 infection and Architect HIV Combo assay.

    Furthermore, it is well known that HIV-1 gp41 protein also shows striking structural similarity to the fusion pH-induced conformation of influenza virus HA2 protein (Weissenhorn et. al. Nature 1997, 387:426). However, to our knowledge, no cross-reactivity case from flu vaccinated samples has been reported with the Architect HIV Combo assay since its launch in 2004. Collectively, the cross-reactivity of SARS-CoV-2 infection with Architect HIV Combo assay should be extremely low.

  • ultrasound BBB disruption as the cause of a fatigue syndrome

    Dear Dr Kaushik, JCP, BMJ et al,
    I hope this note finds You well
    Years after this most excellent Article was composed regarding gene activation in Patients with the CFS (chronic fatigue syndrome), was surprised to see this discussion on how ultrasound would adversely effect, ie disrupt, the BBB (Blood Brain Barrier) causing nausea, fatigue and headaches
    This might explain, at least partially, the events (Havana syndrome) at the US Embassy 2016 of unusual disease processes which occurred after presumed ultrasound exposure to Personnel

    https://en.wikipedia.org/wiki/Havana_syndrome

    https://www.researchgate.net/publication/235923211_A_review_of_current_a...

    A Review of Current Ultrasound Exposure Limits

    Anthony C. Zander et al
    University of Adelaide,
    Australia
    September 8, 2004

    Research has shown that airborne ultrasound has the potential to cause nausea,
    fatigue, and headaches [3–8]

    Apparently would be difficult to detect ultrasound presence but mismatched ultrasound devices of several types could present as audio frequency noise, possibly thought to be tinnitus

    Best wishes always
    Thank you for your assistance with this matter...

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  • mobEVID: A Smartphone-based COVID-19 Test Recording and Monitoring System

    Dear Sir,

    We read with great interest the article by Marietjie Venter and Karin Richter on the diagnostic assay for COVID-19 [1]. We agree with the authors about delays in diagnoses, a severe shortage of tests and laboratory capacity for performing RT-PCR tests. This is especially true for many developing countries such as Bangladesh, which is faced with current health care crises to provide healthcare for more than 165 million population. A large number of people are being tested for COVID-19 and confirmed with the disease every day in Bangladesh, and many more remain undetected due to the lack of testing. Further, the delay to receive test results and lack of medical records cause COVID-19 patients to transmit the disease in the community and hamper proper treatments.

    Prior to the COVID-19 test, several pre-conditional medical records are required to support the results. In Bangladesh, these records are generally gathered by health workers in the testing centres manually and ignoring many important symptoms and conditions. However, this
    process is tedious and prone to omission, error and bias, leading to incomplete medical records. Further, participants are required to return to the centre the next day to collect test results which might increase community transmission. To mitigate such disadvantages, we developed a
    smartphone-based RT-PCR record and monitoring app ‘mobEVID’.

    This app has been built following Novel coronavirus RT-PCR app...

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  • Pathologists in the era of COVID-19: back to autopsy.

    Dear Editor,
    before COVID-19, in the era of targeted therapies, pathologists played a cornerstone role in providing information especially about cancer diagnoses.1 Therefore, scientific community felt that autopsies were out-dated. Now, in this emerging reality, we are assisting to the transformation of the pathologist’s role: instead of proceeding to the “future” of molecular diagnosis we are going back to the “past” of our “noir” connotation. This negative meaning was linked, in the popular culture, to frequent post-mortem examinations performed by pathologist forgetting the paramount value of this medical procedure in explaining pathogenetic mechanisms of all diseases.2 During COVID-19 pandemia, Italian Hospitals changed their usual health department strategy. Hospital Governments strengthened intensive care units and lung units and decreased surgical activities. Pathologists’ role shifted from microscopic diagnosis back to the original mortuary role, setting aside optical microscope, the principal pathologist’s tool, and leaving space to necropsy activity with management of dead bodies by mortuary staff and pathologists in the perspective of threat of transmission of SARS-CoV-2.2 For this reason, Government has promptly implemented extraordinary and detailed measures to restrict viral spread from this source.3 In Italy, pathologists fill in death certificate, a legal instrument and a permanent record of an individual’s death, that requires accuracy, promptness,...

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  • Hic est locus ubi mors gaudet succurrere vitae

    In the last few months, starting from the late 2019 in the area of Wuhan, China, an enormous increase in the number of infections due to SARS-coronavirus-2 (SARS-CoV-2) has been witnessed worldwide.[1-2] So far, 16 April 2020, the Situation report of the World Health Organization (WHO) has reported 1,914,916 confirmed cases and 123,010 deaths, of which 84,607 in the European Region.[2] This data could be itself sufficient to testify the importance of the on-going pandemic, which is further confirmed by the uncertainties regarding the possibility of gaining a natural or vaccine-mediated lifelong immunity. It is a matter of fact that, until the discovery of a vaccination, and maybe beyond that, it is likely that the world will have to deal with the virus and its long-time consequences for years. This necessarily imply that measures to deal with SARS-CoV-2 in all aspects, from life until death and post-mortem examination, have to be figured out and put in place.
    A growing issue regards the distinction between “died from” and died with” SARS-CoV-2, which would be fundamental in order to gain knowledge on several issues including lethality of the virus, trend of death rate, and to compare data from different countries and regions (e.g. higher SARS-CoV-2 death rate per 1,000 infections are reported for Italy, UK and Belgium, while it is very low in Germany, Turkey and South Korea.[3] A complete post-mortem examination is probably an irreplaceable mean of distinguishing bet...

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  • A report on the impact of the introduction of a centralised lymphoma review network in Ireland

    Dear Editor,

    Further to our 2019 paper entitled ‘Impact and importance of a centralised review panel for lymphoma diagnostics in the WHO era: a single centre experience’, we write to report on the impact of the subsequent introduction of a centralised lymphoma review network in Ireland.
    We previously described a discordance rate of 7.8% (14/179) between referral and review lymphoma diagnoses sent to St. James’s Hospital (SJH) Dublin for multi-disciplinary team (MDT) review between 2013-2016. Since then a formal lymphoma review network has been established in Ireland, resulting in a significant increase in lymphoma cases reviewed at SJH. 736 lymphoma cases were reviewed between 2017-2019, of which 0.007% had a discordant diagnosis (5/736). This rate is markedly lower than that previously reported in the published literature (6-48%) [1, 2].

    This dramatic reduction in the level of discordant lymphoma diagnoses demonstrates the positive impact of centralized review networks with specialist haematopathologist input upon lymphoma diagnostics in Ireland. This trend is most likely attributable to the fact that cases are now referred directly to SJH for Specialist Haematopathologist opinion pre-diagnosis, where the necessary ancillary tests required for accurate diagnosis are available on site. Additionally, as previously discussed by Bowen et al, rates of diagnostic discrepancies tend to be higher in non-academic institutions compared to academic institutions...

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  • COVID-19 infection: "high risk to an individual but a low risk to the community"?

    Dear Editor,

    given the spread of Covid-19 infection with its serious consequences and given that the phenomenon has taken on partly unexpected epidemic dimensions which have required drastic Italian government restrictive measures to counteract its spread, in Our opinion it is legitimate to think of a reclassification of the risk category to which the pathogen Covid-19 belongs.

    As it is known, Covid-19 is a viral pathogen of relatively recent acquisition in the human species which in its changed forms has presented over time health problems of growing social impact in different parts of the world and currently in Italy.

    The SARS-1 (SARS-CoV, 2002, China) and MERS (2012, Saudi Arabia) forms have relatively little interest in Europe while the SARS-CoV-2 (China, Wuhan, 2019; Covid-19) has importantly spread in Italy.

    So far beta-coronaviruses capable of causing disease in humans have been classified by WHO in the Risk Group (RG) 3: ”viral agent with high individual risk, but with a risk of collective spread assessed as low-moderate”.

    So, the probability of propagation in the community of this virus was assessed as "moderate".

    Also the NIH Guidelines defines the risk groups 3 as “high risk to an individual but a low risk to the community”

    Furthermore, RG3 (NIH and WHO) is defined as to have efficient therapeutic approaches .

    However, the present experience has led us to realize that Covid-19 has a very hig...

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  • Fy2 Doctor

    As a interested candidate for histopathology speciality training, I had the opportunity to attend a lung MDT in which roughly 25 cases were discussed. The case load was huge and some cases were rushed. The rushed cases were to be rediscussed which is a good form of safety netting although not ideal. The histopathology consultant requested reminders so immunohistology or second readings do not get missed. It would truely revolutionise MDT meetings if standard double reading could become a routine practice although already done in majority of cases.

    The author has shed light on the importance of double reading of slides along with impressive figures.

    A second review of slides could be a way to not only reduce error, but also improve quality of care in terms of management and immunohistology.

    Thank you so much for highlighting the importance of a routine second review prior to MDT meetings. During the taster session, I asked the Histopathology consultants if they encourage second reviews and was informed that wherever there is the slightest doubt, another consultant or sub-specialist would be consulted. It was reassuring to know that histopathologists can always benefit from their colleagues expertise.

    This practice safeguards patients in the sense that a correct diagnosis can be made in all cases minimising potential errors.

  • (In)appropriate JAK2 V617F mutation testing

    It is essential to remember that the goal of clinical pathology laboratory testing is not the acquisition of information itself, but to improve patient outcome through the promotion of proper laboratory test utilization, namely an appropriate test request and result utilization [1]. Given that pathology laboratory testing is reported to play a crucial role in 70% of clinical decisions and that the overall mean rate of inappropriate over-utilization is around 20% [2], innovations that rationalise and guide appropriate testing are welcome. Mahe et al are to be commended on defining an algorithm to determine which patients to test for the myeloproliferative neoplasm (MPN)-associated JAK2 V617F mutation [3]. Such an approach is particularly pertinent given that identification of this mutation has shifted from a confirmatory test for a relatively uncommon group of diseases to an advance screening test in the initial work up of patients in whom the numerous secondary causes that result in haematological indices similar to that of MPN have not been excluded. Also, the recent revision of World Health Organization classification of myeloid neoplasms lowered the threshold of haemoglobin level for considering a diagnosis of the MPN polycythaemia vera (PV) with a subsequent perceived and real impact on the level of JAK2 V617F testing [4, 5]. Using simple complete blood count (CBC) indices, Mahe et al found that application of their JAK2-tree algorithm to a historical dataset would hav...

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