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
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...
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
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
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...
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 developed by the Indian Council of Medical Research [2]. After developing a beta version of the app, we consulted with a group of national experts (including people engaged with RT-PCR testing, health policymakers,
hospital administrators, researchers and clinicians). We demonstrated the contents and designs of the app to the experts. The app was further modified based on expert recommendations. We translated the materials of the app into Bangla following a rigorous process of translation and
back-translation by two bilingual researchers. This app allows users and laboratory personals to record COVID-19 test results and individual
medical records in the app and transmit them to a secure server for storage and use by clinicians. The user account contains four parts such including: (i) add new entry, (ii) repeat test, (iii) view personal details, and (iv) incomplete records. The 'new entry' part allows to create a new patient ID and is split into two sections, A and B. In section A, test participants provide their contact information such as name, address, email, phone number etc. and select information related to collected samples. In section B, the exposure history and medical records of the test participant are entered, for example, if the participants have recently travelled abroad or had contact with COVID-19 cases/suspected cases. In addition, clinical symptoms and conditions are presented as a drop-down menu to enter the participant's medical history. Finally, the details of the participant's hospitalization information are entered. On the other hand, the app allows any participants in Bangladesh to download the app and self-register as a user freely.
If a participant is tested for COVID-19, they can receive their RT-PCR test results rapidly through this app. Data from the app are stored securely in a central repository and can be exported in different formats (excel/pdf) to the local authority. This app can be used either in Bangla or English, which makes it more user friendly and interpretable to the users.
The mobEVID is a flexible option for both test providers and users to share primary information and test results rapidly. The app also contains up to date information on COVID-19 following national recommendations and medical records of the participants. These records are also helpful for clinicians treating the cases and inform the participants about their condition immediately for contact tracing, taking necessary action and monitoring progress. This app might be useful for government and policymaker to record COVID-19 cases, maintain a patient database and help prevent rapid community transmission of COVID-19 in Bangladesh.
Acknowledgement: We are thankful to Dr. Newaz Mohammed Bahadur, Dr. Firoz Ahmed, and Koushik Chandra Howlader to support us to build this apps.
References
[1] Venter M, Richter K. Towards effective diagnostic assays for COVID-19: a review. Journal of Clinical Pathology 2020;73:370-377.
[2] NIC EGov Mobile Apps “RT-PCR - Apps on Google Play.” Google, Google, 3 June 2020, play.google.com/store/apps/details?id=nic.hp.niv_reporting&hl=en.
*Correspondence
Dr Sheikh Mohammed Shariful Islam, MBBS, MPH, PhD, FESC
NHMRC Emerging Leader and National Heart Foundation Senior Research Fellow
Institute for Physical Activity and Nutrition, Deakin University,
221 Burwood Highway, Burwood 3125, Melbourne, Australia
Telephone: +61451733373, Email: shariful.islam@deakin.edu.au
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,...
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, and completeness and therefore they must take care of this delicate and sad situation having contact with infectious dead bodies. As well as other sanitary staff working with SARS-CoV-2 infected people, pathologists must wear personal protective equipment, like a clean protective outer garment, disposable gloves, a disposable surgical mask and appropriate eye protection. Since SARS-CoV-2 has been categorized as a hazard group 3 pathogen, autopsies of suspected COVID-19 deceased have been centralized in specific Hospitals with adequate autopsy rooms (equipped with negative pressure).4 As it happened in past with the explanation of pathogenetic mechanisms of several diseases, results of COVID-19 autopsies are thought to elucidate the biological bases of this new infectious disease. The aim of this report is to underline that the pandemia of COVID-19 represents a step back to past for pathologists, confirming the gold standard role of post-mortem examination in the progress of medicine and health care, as it happened till the seventies of the 20th century. The occurrence of an emerging, new pathology like COVID-19 restored the dignity of autopsies that will remain an essential tool to learn physiopathological mechanisms of diseases.
References
1. Masood S. The changing role of pathologists from morphologists to molecular pathologists in the era of precision medicine. Breast J 2020;26(1):27-34. doi: 10.1111/tbj.13728. Epub
2. Diebold J. Clinical autopsy—its role in modern medicine. Praxis (Bern 1994) 2007;96(43):1667-71.
3. Regione Lombardia Nota Direzione Generale Welfare 12/03/2020“Emergenza da COVID-19. Indicazioni in materia di attività funebre”
4. Hanley B, Lucas SB, Youd E, Swift B, Osborn M.Autopsy in suspected COVID-19 cases. J Clin Pathol 2020 doi: 10.1136/jclinpath-2020-206522. [Epub ahead of print]
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...
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 between these classes of deceased, by providing a multidisciplinary study of all organs and an extensive sampling of tissues, and of lowering the risks of misdiagnosis.
Legal medicine is the field where “mors gaudet succurrere vitae” (literally, death founds pleasure in helping life), or “the dead can speak to livings”.[4] Post-mortem examinations might suggest a mechanism of health harm, prevent the spread of a novel disease, control medical quality, arise suspicion toward a sign and even hint for a specific treatment and a preventive role of post-mortem examinations has been long declared.[5-7]
For example, the identification of pulmonary thromboemboli at post-mortem examination of patients who died from SARS, together with occlusions and microthrombosis of lung vessels in SARS-CoV-2 lung dissection and D-dimer elevation in patients now suggest the possibility of a therapeutic role of anticoagulant, heparin and low molecular weight heparin (LMWH) against SARS-CoV-2 infection.[8-11] Data regarding the true mechanism leading to death with SARS-CoV-2 are lacking, and it is unknown if a major role is played by respiratory acute insufficiency, multi-organ failure, cytokine release syndrome or hyper-response of the immune system, by haematological abnormalities, triggered within a disseminated intravascular coagulation (CID) syndrome or by all these mechanisms, in a different time from the contagion.[12-14]
So far, clinical criteria, e.g. onset of relevant symptoms before the death, have been applied, limiting the postmortem examination to the only collection of tissues (e.g. lung biopsies) and biological fluids to confirm the occurred infection by SARS-CoV-2. [15] Indeed, it is fundamental to limit the risks for health care professionals. [15] However, this could be a bit limitative, since the mere presence of a SARS-CoV-2 in the body does not prove that the deceased actually died because of it, even though a certified infection is surely a strong hint. Additionally, it is not clear whether the sensitivity of swabs might be affected in the post-mortem period, if false negatives could occur, due to a death of SARS-CoV-2 when the host succumbs and the timing of this negativity with respect to the time of death.
Finally, post-mortem examination of patients affected by SARS-CoV-2, healed and later died might provide an opportunity to ass long-time effects of the virus on lungs, hearts and other tissues.
For the above-mentioned reason, we would like to remark the importance of performing post-mortem examinations in this era of SARS-CoV-2 pandemic spread, provided that guidance to limit the risks for workers are respected and appropriate precautions put in place.[16]
Given the importance of a homogenization process regarding the death numbers due to SARS-CoV-2, borrowing a concept used in forensic toxicology for novel psychoactive substances (the scientific knowledge of which, as in the case of SARS-CoV-2 is still limited),[17] we would also like to suggest the adoption of a shared scale in the evaluation of the role of SARS-CoV-2.
In the evaluation the following factors are suggested:
1. Presence and severity of the infection by SARS-CoV-2, as assessed by in vivo data, including swabs, clinical records, radiological imaging, and post-mortem samples, including once again swabs, blood lower respiratory tract or any other sample.[15] When available, in vivo data are useful to assess if the victim has been infected, possessed risk factors for mortality and was suffering from symptoms suggestive of SARS-CoV-2 or not.[18] Post-mortem examinations on the other hand might provide insights on tissues not accessible in livings and multiple samples. [15, 19]
2. Presence and severity of previous diseases. These could have a role in facilitating the accidental contact between SARS-CoV-2 and the victim, as in the case of a hospitalized person who came in tight contact with an infected patient and acquired the infection in this setting, or of an immune-depressed patient. The latter is not only characterized by a facilitated contagion, in comparison with a healthy subject, but also a different natural history of the SARS-CoV-2 infection, been on one hand less prone to an abnormal physiological response, on the other extremely more exposed to the direct harm caused by the pathogen.
3. Circumstances of the death. These are of paramount importance, especially for the exclusion of SARS-CoV-2 as a cause of death, as in road traffic fatal accidents, gunshot-wounds, asphyxia, burns etc. It is clear that an external traumatic event, occurred after the contraction of the virus, could break the chain of the even, or better substitute itself, leading to death in an independent manner with respect to CoV-2. Is this the extreme case of an infected asymptomatic patient which is struck by a vehicle or shot to dead by military forces, as recently occurred in Africa due to curfew violation.[20]
Suicides should be evaluated carefully, since they do not automatically exclude a contribution of SARS-CoV-2, even though in an indirect way. For examples, it has been reported by the news that suicides occurred due to the fear of having infected other people. Circumstances are also fundamental in order to ascertain the risk of contagion, as in the case of people in close contact with patients because co-inhabitants or due to professional setting, as for doctors. A high index of suspect should be always maintained in the latter case, given the likelihood of an infection.[21]
4. Post-mortem radiology. Especially when in vivo imaging is not disposable, chest X-ray or, even better, post-mortem computerized tomography (PMCT) or a “virtopsy” approach could facilitate the retrieval of typical features of SARS-CoV-2. Of course, the decision to submit a suspected CoV-2 victim to an expensive and time-consuming (considering the pre-scan and post-scan necessities, as to disinfect the room) PMCT should be evaluated case-by-case and is not mandatory. Most importantly, its execution should not negatively impact clinical routine and the necessities of living patients.
5. Pathologic macroscopic and microscopic findings. Lungs and respiratory airways appear as the primary target of the infection and certainly their analysis should be as accurate as possible. Some data has already been published on persons with certified infection and could be useful to assess a compatibility of cases to the described features. [15, 19, 22-24]. Though, iatrogenic damage due to medications or devices, as in the case of alveolar hyper-insufflation in the course of mechanical ventilation, is possible and should be considered carefully. Moreover, myocardial, liver and multi-organ failure has been described.[23, 25]
6. Toxicological evaluation. A toxicological screening of common drugs of abuse could be important to exclude acute intoxications. Moreover, in the cases of patients prescribed multiple drugs, an evaluation of concentrations could be useful to assess if levels were within therapeutic ranges or exceeded them, suggesting a potential overdose.
7. Additional analyses should be performed whenever suggested by circumstantial, clinical or necroscopic data.
A possible SARS-CoV-2 significance score or CSS could be classified in four-points, in order to provide a fast assessment tool, which could be used in order to help establishing the cause of death for the Judicial Authority, as follows:
• 0 when SARS-CoV-2 was merely an occasion, but does not upsurge to the role of cause of death. An occasion is classified by its insignificance with respect to the death, exchangeability, ineffectiveness, non-indispensability.[26] An example is that of a old victim, with multiple increasing episodes of acute pulmonary edema due to cardiac chronic decompensation in the last stage, whose conditions are so severe that he succumbed to the mere rhinitis manifestations of SARS-CoV-2 and would have died even in the presence of usually well-tolerated pathogens.
• 1, i.e. low, when SARS-CoV-2 was present and a causative role cannot be excluded, even though an alternative leading cause of death is likely. An example could be that of a victim with multi-organ failure due to failed transplant, who suffers of multiple opportunistic infections, including low symptomatic SARS-CoV-2.
• 2, i.e. medium SARS-CoV-2 has likely contributed to death, even if additional factors might have had a prominent role. An example could be that of a victim with past history of haemorrhages and a poor haemostatic balance, who receives LMWH or other similar medications due to massive SARS-CoV-2-induced CID and dies of cranial hemorrhage.
• 3, i.e. high: SARS-CoV-2 with all probability was the leading cause to death.
A CSS could remain U= unclassified/unclear, when not enough data is disposable, until the execution of additional analyses, e.g. of swabs or microscopical analysis, or even after that, when the role of SARS-CoV-2 is unclear.
The so-presented scale tends to over-aestimate the role of SARS-CoV-2, though this seems necessary at this historic moment due to its diffusion and to the lack of knowledge regarding time course, natural history and mechanisms of injury.
Moreover, CSS should not be intended as a mathematic simplification of the process of post-mortem evaluation, a self-explanatory and sufficient response to a complex issue. Though CSS contains several elements of judgement and could lower the inhomogeneities in forensic evaluation of SARS-CoV-2, it is to be considered as an additional concise tool to be placed side by side with full medico-legal evaluation and discussion.
6. Byard RW. Preventive pathology revisited. Forensic Sci Med Pathol 2014;10(2):155-6. doi: 10.1007/s12024-014-9534-y. Epub 2014 Jan 23.
7. Buschmann CT, Tsokos M, Kleber C. Preventive pathology: the interface of forensic medicine and trauma surgery for pre-hospital trauma management. Forensic Sci Med Pathol 2015;11(2):317-8. doi: 10.1007/s12024-014-9603-2.
8. Chong PY, Chui P, Ling AE, et al. Analysis of deaths during the severe acute respiratory syndrome (SARS) epidemic in Singapore: challenges in determining a SARS diagnosis. Arch Pathol Lab Med 2004;128(2):195-204.
9. Fox SE, Aibek A, Harbert JL, et al. Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans. medRxiv 2020.04.06.20050575. doi: https://doi.org/10.1101/2020.04.06.20050575
10. Luo W, Yu H, Gou J, et al. Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia (COVID-19). Preprints 2020, 2020020407.
11. Thachil J. The versatile heparin in COVID-19. J Thromb Haemost 2020. doi: 10.1111/jth.14821. [Epub ahead of print]
12. Henderson LA, Canna SW, Schulert GS, et al. On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis Rheumatol 2020. doi: 10.1002/art.41285. [Epub ahead of print]
13. Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020. doi: 10.1111/jth.14817. [Epub ahead of print]
14. Shi Y, Wang Y, Shao C, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ 2020. doi: 10.1038/s41418-020-0530-3. [Epub ahead of print]
15. Hanley B, Lucas SB, Youd E, et al. Autopsy in suspected COVID-19 cases. J Clin Pathol 2020. pii: jclinpath-2020-206522. doi: 10.1136/jclinpath-2020-206522.
16. Osborn M, Lucas S, Stewart R, et al. The Royal College of Pathologists. Briefing on COVID-19 Autopsy practice relating to possible cases of COVID-19 (2019-nCov, novel coronavirus from China 2019/2020). Available from: https://www.rcpath.org/uploads/assets/d5e28baf-5789-4b0f-acecfe370eee622... Access date: 18 April 2020
17. Elliott S, Sedefov R, Evans-Brown M. Assessing the toxicological significance of new psychoactive substances in fatalities. Drug Test Anal 2018;10(1):120-126. doi: 10.1002/dta.2225.
18. Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol 2020. pii: S0091-6749(20)30495-4. doi: 10.1016/j.jaci.2020.04.006. [Epub ahead of print]
19. Barton LM, Duval EJ, Stroberg E, et al. COVID-19 Autopsies, Oklahoma, USA. Am J Clin Pathol 2020;aqaa062. doi: 10.1093/ajcp/aqaa062
21. Zhan M, Qin Y, Xue X, et al. Death from Covid-19 of 23 Health Care Workers in China. N Engl J Med 2020. doi: 10.1056/NEJMc2005696. [Epub ahead of print]
22. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18.
23. Tian S, Xiong Y, Liu H, et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol 2020. doi: 10.1038/s41379-020-0536-x.
24. Tian S, Hu W, Niu L, et al. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. J Thorac Oncol 2020. pii: S1556-0864(20)30132-5. doi: 10.1016/j.jtho.2020.02.010. [Epub ahead of print]
25. Yang F, Shi S, Zhu J, et al. Analysis of 92 deceased patients with COVID-19. J Med Virol 2020. doi: 10.1002/jmv.25891. [Epub ahead of print]
26. Puccini C. Istituzioni di Medicina Legale. Casa Editrice Ambrosiana 2003.
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...
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 such as SJH [3]. We believe that the ongoing educational component of the centralized review network, involving regular feedback and annual teaching sessions for pathologists in referring hospitals, has further improved the initial discordance rate.
We anticipate that this new low rate of discordance will be maintained in our institution, providing patients with an accurate diagnosis with which to best direct therapeutic considerations.
Kind regards,
Dr. Kate Dinneen
Specialist Registrar in Histopathology
St. James’s Hospital, Dublin, Ireland
Trinity College Dublin, Ireland
Dr Richard Flavin
Consultant Histopathologist
St. James’s Hospital, Dublin, Ireland
Trinity College Dublin, Ireland
References
1. Lester, J.F., et al., The clinical impact of expert pathological review on lymphoma management: a regional experience. Br J Haematol, 2003. 123(3): p. 463-8.
2. LaCasce, A.S., et al., Comparison of referring and final pathology for patients with non-Hodgkin's lymphoma in the National Comprehensive Cancer Network. J Clin Oncol, 2008. 26(31): p. 5107-12.
3. Bowen, J.M., et al., Lymphoma diagnosis at an academic centre: rate of revision and impact on patient care. Br J Haematol, 2014. 166(2): p. 202-8.
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...
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 high propagation ability in the community as it spreads very easily from one individual to another, this is also reflected into the containment measures issued urgently by a number of National European governments.
In addition, for Covid-19 effective and validated therapies are not currently known and there is no vaccine available against it.
It should also be considered that validated serological diagnostics for Covid-19 infection are currently unavailable.
It therefore seems necessary to review the classification of the risk associated with Covid-19 infection and with it, it seems necessary to review the consequent safety levels (bio-containment), for laboratories that have to handle potentially infected material (WHO Laboratory biosafety manual, 2004, III edition).
The topic is of considerable importance as regards the autopsy activity on subjects with Covid-19 infection or with suspected Covid-19 infection.
This activity, prudently, should be carried out in safe environments and with procedures corresponding to those relating to the safety levels suitable for the biocontainment of RG4 agents, rather than those corresponding to the containment level for RG3.
Guidelines are urgently needed to help pathologists operate in the safest way, also contributing to harmonizing approach at European level.
It is proposed to ensure that:
1. in case of an ascertained death for SARS-CoV-2 (i.e. with a positive test for Covid-19) post-mortem autopsy should be avoided, unless the procedure is performed in environment and in ways appropriate for diagnostic activities at RG4 level;
2. in each hospitalized patient, molecular assessment (nasopharyngeal swab test) should be performed to determine Covid-19 presence;
3. when this first test is negative, a second diagnostic test should be carried out in the following 24 hours as recommended by the WHO;
4. when a person dies (irrespective if hospitalized or not), in the absence of documented molecular verification on Covid-19 presence, a nasopharyngeal swab should be performed just after having ascertained the death with the usual procedures;
5. in any case, when a documented valid verification on Covid-19 presence in the subject is absent, post-mortem invasive assessments and procedures should be carried out only with the precautions indicated for RG4;
6. in any case, based on the available medical documentation, in the present Covid-19 epidemic context the pathologist should be free to decide unquestionably whether to perform a complete autopsy or to perform a minimally invasive autopsy on selected areas of the body.
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.
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...
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 have reduced testing for this mutation by 15%, a considerable impact on workload [3]. Co-incidentally, another group have reported a similar attempt to refine JAK2 V617F testing for suspected PV by incorporating the immature platelet fraction into a CBC-based algorithm [6]. These two studies from Canada and New Zealand suggest that JAK2 V617F over-requesting is a widespread issue.
Given the specificity of the JAK2 V617F mutation for the MPN and the distinct haematological and clinical characteristics of these malignancies, it is disappointing to realise that similar to previous studies [7], Mahe et al note that the majority of JAK2 V617F requests had no clinical details provided. While obtaining CBC data for 95% of their historical cohort it should be mentioned that not all laboratories performing JAK2 V617F mutation studies might have access to corresponding CBC results, e.g. centralised genetic or molecular diagnostic facilities. Other (uncommon) instances that preclude application of this algorithm are when a bone marrow aspirate is provided for molecular analysis or in the acknowledged clinical scenario where splanchnic vein thrombosis unveils a haematologically latent MPN [8].
For other providers of a similar molecular diagnostic service it would be valuable for the authors to discuss how they actually intend to implement this algorithm prospectively and to educate users of their service. A review after a period of operation would reveal any issues regarding barriers to adherence and provide welcome evidence for reducing unnecessary JAK2 V617F testing in a real-world setting.
REFERENCES
1. Salinas M, López-Garrigós M, Flores E, et al. Managing inappropriate requests of laboratory tests: from detection to monitoring. Am J Manag Care 2016;22:e311-6.
2. Zhi M, Ding EL, Theisen-Toupal J, et al. The landscape of inappropriate laboratory testing: a 15-year meta-analysis. PLoS One 2013;8:e78962.
3. Mahe E, Mønsted Pedersen K, Çolak Y, et al. JAK2-tree: a simple CBC-based decision rule to guide appropriate JAK2 V617F mutation testing. J Clin Pathol 2019;72:172-6.
4. Sandes AF, Gonçalves MV, Chauffaille ML. Frequency of polycythemia in individuals with normal complete blood cell counts according to the new 2016 WHO classification of myeloid neoplasms. Int J Lab Hematol 2017;39:528-31.
5. Langabeer SE. An increase in diagnostic JAK2 V617F mutation testing: is masked polycythaemia vera the explanation? Eur J Intern Med 2018;52:e37-8.
6. Johnson S, Baker B. A CBC algorithm combined with immature platelet fraction is able to identify JAK2 V617F mutation-positive polycythaemia vera patients. Int J Lab Hematol 2019, Epub ahead of print, doi: 10.1111/ijlh.12967.
7. Langabeer SE. Referral centre variation in requesting JAK2 V617F mutation analysis for the investigation of a myeloproliferative neoplasm. J Clin Pathol 2012;65:1149-50.
8. Goulding C, Uttenhal B, Foroni L, et al. The JAK2 (V617F) tyrosine kinase mutation identifies clinically latent myeloproliferative disorders in patients presenting with hepatic or portal vein thrombosis. Int J Lab Hematol 2008;30:415-9.
We found the paper ‘Long QT syndrome and sudden unexpected infant death’ by Van Niekerk and colleagues to be comprehensive and interesting. We would like to point out that there appears to be a misunderstanding as the authors state that in Australia and New Zealand all sudden and unexpected deaths are mandated to undergo targeted post-mortem genetic testing. Guidelines published by TRAGADY (Trans-Tasman Response AGAinst sudden Death in the Young) advocate that material suitable for DNA extraction must be obtained as part of the best practice guidelines for investigation of sudden death of a young person (1). However, subsequent genetic analysis is not mandated. A policy on the genetic investigation of cause of death in coronial autopsy cases has been recently released by the Royal College of Pathologists of Australasia (RCPA) (2). It is likely this policy document was not available at the time Van Niekerk and colleagues were writing their paper. The RPCA policy states that genetic testing of the deceased is not endorsed in the absence of engagement of the family of the deceased with a genetic counselling service and confirmation of a family history compatible with a heritable disorder. Ideally, there should be identification in the living relatives of a putative genetic defect (or defects) or phenotype for which testing is available. For a number of reasons, some of which are outlined in the RCPA policy document, mandatory post-mortem genetic testing may not be benefic...
We found the paper ‘Long QT syndrome and sudden unexpected infant death’ by Van Niekerk and colleagues to be comprehensive and interesting. We would like to point out that there appears to be a misunderstanding as the authors state that in Australia and New Zealand all sudden and unexpected deaths are mandated to undergo targeted post-mortem genetic testing. Guidelines published by TRAGADY (Trans-Tasman Response AGAinst sudden Death in the Young) advocate that material suitable for DNA extraction must be obtained as part of the best practice guidelines for investigation of sudden death of a young person (1). However, subsequent genetic analysis is not mandated. A policy on the genetic investigation of cause of death in coronial autopsy cases has been recently released by the Royal College of Pathologists of Australasia (RCPA) (2). It is likely this policy document was not available at the time Van Niekerk and colleagues were writing their paper. The RPCA policy states that genetic testing of the deceased is not endorsed in the absence of engagement of the family of the deceased with a genetic counselling service and confirmation of a family history compatible with a heritable disorder. Ideally, there should be identification in the living relatives of a putative genetic defect (or defects) or phenotype for which testing is available. For a number of reasons, some of which are outlined in the RCPA policy document, mandatory post-mortem genetic testing may not be beneficial.
References:
1. Skinner J, Duflou JA, Semsarian C. Reducing sudden death in young people in Australia and New Zealand: the TRAGADY initiative. Med J Aust. 2008;189:539 - 40.
2. Royal College of Pathologists of Australasia. Genetic investigation of cause of death in coronial autopsy cases. Sydney, Australia; 2017 [updated 2017; cited 2018 1 January]; Available from: https://www.rcpa.edu.au/getattachment/0b40e990-3778-4aca-aaeb-1ea1d42441....
Letter to the Editor – Journal of Clinical Pathology
We read with interest the invited editorial by Grealish et al. entitled “Standardisation of practice for Canadian pathologists' assistants.” First of all, we would like to congratulate the CAP-ACP Executive Committee on its accomplishments to date. Establishing a method for board certification of Canadian Pathologists’ Assistants (PAs) is an important achievement which promotes standardization and high quality anatomical pathology services.
However, our primary reason for writing is to address an error of omission. The editorial correctly notes that there are four two year long Master’s PA training programs in Canada; however, it should be also noted that these vary considerably in size with a ten-fold difference between the largest and the smallest based upon the number of students currently enrolled. The editorial then implies that Canadian training programmes are not accredited and are in need of some new mechanism to become accredited. The editorial states that “the pursuit of creating a ... Canadian accrediting body for PA training programme is ongoing.” We respectfully disagree. The two large Canadian training programmes, hosted by the University of Calgary and Western University, respectively have each been accredited by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS) (https://www.naacls.org/about.aspx ). NAACLS...
Letter to the Editor – Journal of Clinical Pathology
We read with interest the invited editorial by Grealish et al. entitled “Standardisation of practice for Canadian pathologists' assistants.” First of all, we would like to congratulate the CAP-ACP Executive Committee on its accomplishments to date. Establishing a method for board certification of Canadian Pathologists’ Assistants (PAs) is an important achievement which promotes standardization and high quality anatomical pathology services.
However, our primary reason for writing is to address an error of omission. The editorial correctly notes that there are four two year long Master’s PA training programs in Canada; however, it should be also noted that these vary considerably in size with a ten-fold difference between the largest and the smallest based upon the number of students currently enrolled. The editorial then implies that Canadian training programmes are not accredited and are in need of some new mechanism to become accredited. The editorial states that “the pursuit of creating a ... Canadian accrediting body for PA training programme is ongoing.” We respectfully disagree. The two large Canadian training programmes, hosted by the University of Calgary and Western University, respectively have each been accredited by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS) (https://www.naacls.org/about.aspx ). NAACLS is a highly coveted international standard that permits our graduates to write the American Society of Clinical Pathology (ASCP) board of certification (BOC) exam as well as the new Canadian Certification Council of Canada (CCCPA) exam and thus our graduates are able to practice on both sides of the border. Presently NAACLS accredits the eight PA training programs in the US (two more are in the final stages of approval) and the above named two in Canada (http://www.pathassist.org/?page=AboutUs_NAACLS); it also accredits training programs in a myriad of other technical arenas in the US and elsewhere. We would suggest that there is no need to create a redundant accreditation specific to Canada given that the two programs already represent the vast majority of Canadian trainees and given the undisputable standards of the NAACLS. Furthermore, nothing precludes other Canadian programmes from seeking and obtaining NAACLS accreditation. Grealish et al.’s suggestion that there should be a “Canadian accrediting body” to address four training programmes is not only unnecessary but would be costly and suffer from unavoidable conflicts of interest because of insufficient critical mass.
The appropriate ‘made in Canada’ solution was already found in the Canadian certification process. While there initially had been considerable enthusiasm in Canada for simply adopting the pre-existing American certification process, this approach did not address the needs of Canadian on-the-job trained (OJT) PAs, which as correctly noted in the editorial, began the profession in Canada and should be honoured. Therefore, separate certification examinations in Canada and the US were, unfortunately, unavoidable. However, having taken this approach to certification is not a good enough reason to start down the pathway of dual program accreditations. We would like to stress that North America-wide accreditation is the best solution for Canadian training programmes and their trainees. Quite simply, NAACLS accreditation is the gold standard and Canadians should not settle for anything less!
Reference:
Grealish M, Wolff A, Eastwood J, Lee D; PA Section of the CAP-ACP Executive Committee. Standardisation of practice for Canadian pathologists' assistants. J Clin Pathol. 2017 Dec;70(12):998-1000. Epub 2017 Sep 12.
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
Show MoreThank you for your assistance with this matter...
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...
Show MoreDear Editor,
Show Morebefore 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,...
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.
Show MoreA 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...
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...
Show MoreDear 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...
Show MoreAs 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.
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...
Show MoreWe found the paper ‘Long QT syndrome and sudden unexpected infant death’ by Van Niekerk and colleagues to be comprehensive and interesting. We would like to point out that there appears to be a misunderstanding as the authors state that in Australia and New Zealand all sudden and unexpected deaths are mandated to undergo targeted post-mortem genetic testing. Guidelines published by TRAGADY (Trans-Tasman Response AGAinst sudden Death in the Young) advocate that material suitable for DNA extraction must be obtained as part of the best practice guidelines for investigation of sudden death of a young person (1). However, subsequent genetic analysis is not mandated. A policy on the genetic investigation of cause of death in coronial autopsy cases has been recently released by the Royal College of Pathologists of Australasia (RCPA) (2). It is likely this policy document was not available at the time Van Niekerk and colleagues were writing their paper. The RPCA policy states that genetic testing of the deceased is not endorsed in the absence of engagement of the family of the deceased with a genetic counselling service and confirmation of a family history compatible with a heritable disorder. Ideally, there should be identification in the living relatives of a putative genetic defect (or defects) or phenotype for which testing is available. For a number of reasons, some of which are outlined in the RCPA policy document, mandatory post-mortem genetic testing may not be benefic...
Show MoreLetter to the Editor – Journal of Clinical Pathology
We read with interest the invited editorial by Grealish et al. entitled “Standardisation of practice for Canadian pathologists' assistants.” First of all, we would like to congratulate the CAP-ACP Executive Committee on its accomplishments to date. Establishing a method for board certification of Canadian Pathologists’ Assistants (PAs) is an important achievement which promotes standardization and high quality anatomical pathology services.
However, our primary reason for writing is to address an error of omission. The editorial correctly notes that there are four two year long Master’s PA training programs in Canada; however, it should be also noted that these vary considerably in size with a ten-fold difference between the largest and the smallest based upon the number of students currently enrolled. The editorial then implies that Canadian training programmes are not accredited and are in need of some new mechanism to become accredited. The editorial states that “the pursuit of creating a ... Canadian accrediting body for PA training programme is ongoing.” We respectfully disagree. The two large Canadian training programmes, hosted by the University of Calgary and Western University, respectively have each been accredited by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS) (https://www.naacls.org/about.aspx ). NAACLS...
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