Dear Madam/Sir,
We read with great interest the article by Vidhale and colleagues.1 They provide a detailed description of a man presenting with a relatively rapidly progressing neurodegenerative disease including his neuroimaging findings.
After testing for a few DNA repeat expansion diseases, the authors arrived at the conclusion that their patient’s diagnosis was Friedreich ataxia (FRDA). FRDA is a recessive neurodegenerative disease caused by bi-allelic expansion of an intronic GAA repeat in the frataxin (FXN) gene. Their patient had 5 and 37 GAA repeats. The lower limit for full penetrance alleles is > 66 GAA repeats.2 Thus, it is not apparent how their patient meets diagnostic criteria for FRDA.
The 37 GAA repeat allele falls at the lower end of premutation alleles (range 34-65), so named as these alleles do not cause disease, but can rarely expand to the disease range during meiosis. In rare cases, somatic expansion of pre-mutations in cell populations has been postulated to cause disease, but this occurs only in the setting of the 2nd allele in the clear pathogenic range of expansion.
The authors alternatively postulate that the patient could represent a compound heterozygous state based on his clinical presentation. Comparison with cases of very late-onset FRDA (vLOFA), however, clearly shows that the patient’s course is too rapid and severe for vLOFA. Even if the patient were to carry a pathogenic point mutation in one of the allel...
Dear Madam/Sir,
We read with great interest the article by Vidhale and colleagues.1 They provide a detailed description of a man presenting with a relatively rapidly progressing neurodegenerative disease including his neuroimaging findings.
After testing for a few DNA repeat expansion diseases, the authors arrived at the conclusion that their patient’s diagnosis was Friedreich ataxia (FRDA). FRDA is a recessive neurodegenerative disease caused by bi-allelic expansion of an intronic GAA repeat in the frataxin (FXN) gene. Their patient had 5 and 37 GAA repeats. The lower limit for full penetrance alleles is > 66 GAA repeats.2 Thus, it is not apparent how their patient meets diagnostic criteria for FRDA.
The 37 GAA repeat allele falls at the lower end of premutation alleles (range 34-65), so named as these alleles do not cause disease, but can rarely expand to the disease range during meiosis. In rare cases, somatic expansion of pre-mutations in cell populations has been postulated to cause disease, but this occurs only in the setting of the 2nd allele in the clear pathogenic range of expansion.
The authors alternatively postulate that the patient could represent a compound heterozygous state based on his clinical presentation. Comparison with cases of very late-onset FRDA (vLOFA), however, clearly shows that the patient’s course is too rapid and severe for vLOFA. Even if the patient were to carry a pathogenic point mutation in one of the alleles, the second allele would still not be pathogenic at 37 GAA repeats.
In summary, the case report points to the fact that interpretation of genetic tests needs subspecialty expertise provided by medical geneticists, genetic counsellors or neurogeneticists. The neurologist can play an important role in classifying the neurologic phenotype and guide further evaluations. I sincerely doubt that the official report of the genetic testing laboratory suggested a diagnosis of FRDA. Errors of overinterpreting genetic test results and, even more so, erroneous interpretation can be harmful to patients and their relatives.
References
1. Vidhale TA, Gupta HR, Pj R, Gandhi C. Very late-onset Friedreich's ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type. BMJ Case Rep. 2021 Jul 23;14(7):e242073. doi: 10.1136/bcr-2021-242073.
A taser is a weapon used by police in order to provide a safe means of subduing an uncooperative person via an “electric shock”. This handheld device features two small barbed darts designed to puncture the skin. These darts are connected via copper wires to a main unit which delivers an electric current to the individual causing neuromuscular incapacitation by disrupting the voluntary control of muscles(1). A number of studies have raised concern over the health risks of tasers, including ventricular arrhythmias and cardiac arrest(2). Something I have come across during my training was a case of complete heart block provoked by a taser discharge. This phenomenon is not frequently described in the literature.
The patient in question had cardiac arrest immediately after receiving a discharge from a taser during an altercation with police. Thankfully, he was given bystander CPR and had return of spontaneous circulation after 3 minutes. On presentation to the Emergency Department the patient was found to be in complete heart block. He was admitted acutely to the coronary care unit for monitoring and had a permanent pacemaker inserted three days later.
The taser is considered a non-lethal weapon but can it truly be considered such?
Since it is not thought of as a firearm, taser use is not regulated by the Bureau of Alcohol, Tobacco, Firearms and Explosives. The main objective of this article is not to comment on the propriety of taser...
A taser is a weapon used by police in order to provide a safe means of subduing an uncooperative person via an “electric shock”. This handheld device features two small barbed darts designed to puncture the skin. These darts are connected via copper wires to a main unit which delivers an electric current to the individual causing neuromuscular incapacitation by disrupting the voluntary control of muscles(1). A number of studies have raised concern over the health risks of tasers, including ventricular arrhythmias and cardiac arrest(2). Something I have come across during my training was a case of complete heart block provoked by a taser discharge. This phenomenon is not frequently described in the literature.
The patient in question had cardiac arrest immediately after receiving a discharge from a taser during an altercation with police. Thankfully, he was given bystander CPR and had return of spontaneous circulation after 3 minutes. On presentation to the Emergency Department the patient was found to be in complete heart block. He was admitted acutely to the coronary care unit for monitoring and had a permanent pacemaker inserted three days later.
The taser is considered a non-lethal weapon but can it truly be considered such?
Since it is not thought of as a firearm, taser use is not regulated by the Bureau of Alcohol, Tobacco, Firearms and Explosives. The main objective of this article is not to comment on the propriety of tasers, since it is the law enforcement authorities who must make a judgement call on that. However, I do believe that authorities should be judicious in its application. It is my opinion that a taser should be given equal consideration to a firearm since the consequences of discharging a taser can indeed be lethal.
References-
1. Ideker RE, Dosdall DJ. Can the direct cardiac effects of the electric pulses generated by the TASER X26 cause immediate or delayed sudden cardiac arrest in normal adults?. The American journal of forensic medicine and pathology. 2007 Sep 1;28(3):195-201.
2. Zipes DP. Sudden cardiac arrest and death following application of shocks from a TASER electronic control device. Circulation. 2012 May 22;125(20):2417-22.
Active TB globally affects over 10 million people each year and accounts for approximately 1.6 million deaths. Since publishing this case report we since have learned that IGRA blood tests are not entirely useful in diagnosing active TB, as IGRA will also pick up cases of latent TB.
Presently, the most useful microbiological method of diagnosis is now widely recognised as the Gene Xpert or Gene Xpert MTB/RIF Ultra, a rapid molecular test for Mycobacterium tuberculosis and rifampicin resistance which can be performed on sputum, pleural fluid or CSF. Access to this technology has been widely scaled up in recent years as part of the WHO End TB Strategy and most countries are switching from traditional AFB smears to rapid molecular testing due to reduced costs and demand on laboratory facilities. However, the COVID-19 pandemic has also redirected human, diagnostic and financial resources elsewhere and modelling predicts a regression in TB control and increase in mortality from 13% in 2020 to 20% in 2025.
Thank you very much for your letter on our published case report of a pregnant woman that was diagnosed with a left parietal glioma in the 28th gestational week after a first generalised seizure, and for your opinion and thorough review of the literature.
In our patient we performed a two-stage approach with first a tumour resection under general anaesthesia and preservation of the pregnancy and after caesarean section performed in the 37th gestational week an awake craniotomy for resection of residual tumour under neuropsychological monitoring and mapping.
We decided to do a two-stage approach after a round table where obstetricians, neurosurgeons, anesthetists, neonatologists, and midwives were involved and after several long conversations with the patient and her husband. For the patient clearly the health of her unborn child was the most important aspect of her treatment and therefore she wanted to prolong the pregnancy until term. The tumor of our patient was located with a broad base to the surface and seemed to have a plane to the underlying white matter. There was no, in this location possible eloquent, unaffected cortex overlying the tumor. Moreover, our patient was already in the 28th gestational week of her pregnancy, the uterine fundus was high and the abdomen extended. The use of cortical or subcortical electric stimulation does increase the seizure risk1-4. Because of all these reasons we decided aga...
Thank you very much for your letter on our published case report of a pregnant woman that was diagnosed with a left parietal glioma in the 28th gestational week after a first generalised seizure, and for your opinion and thorough review of the literature.
In our patient we performed a two-stage approach with first a tumour resection under general anaesthesia and preservation of the pregnancy and after caesarean section performed in the 37th gestational week an awake craniotomy for resection of residual tumour under neuropsychological monitoring and mapping.
We decided to do a two-stage approach after a round table where obstetricians, neurosurgeons, anesthetists, neonatologists, and midwives were involved and after several long conversations with the patient and her husband. For the patient clearly the health of her unborn child was the most important aspect of her treatment and therefore she wanted to prolong the pregnancy until term. The tumor of our patient was located with a broad base to the surface and seemed to have a plane to the underlying white matter. There was no, in this location possible eloquent, unaffected cortex overlying the tumor. Moreover, our patient was already in the 28th gestational week of her pregnancy, the uterine fundus was high and the abdomen extended. The use of cortical or subcortical electric stimulation does increase the seizure risk1-4. Because of all these reasons we decided against an awake craniotomy and an operation under general anesthesia was performed. During the first procedure we did not use electrophysiological monitoring or functional mapping at all to keep the seizure risk as low as possible.
We acknowledge that there are reports in the literature emerging that awake craniotomy during pregnancy seem to be a safe and feasible option and the authors of this letter provide a well-managed example from their own experience5. However, their patient was having a glioma with clear high-grade features present, leaving less time for multi staged procedures as these are aggressive tumors with limited prognosis. The tumor of our patient did radiologically not have high grade features, although preoperative imaging was obtained without administration of contrast. Histology of the tumor did show diffuse IDH-mutant astrocytoma classified between WHO grade II and III. The tumor exhibited methylation of the O-6 methylguanine DNA methyltransferase (MGMT) promotor and no complete deletion of cyclin-dependent kinase inhibitor 2a/b (CDKN2a/b) that are both positive prognostic and IDH mutation is a positive predictive marker. Morphologically it did show some anaplastic features and that is why it was finally treated like an anaplastic tumor.
5-aminolevulenic acid (5-ALA) in glioma surgery permits the intraoperative visualization of malignant glioma tissue and supports the neurosurgeon to reach a complete resection of the contrast-enhancing tumor. Some studies show a potential risk for the fetus if 5-ALA has been given together with irradiation in the first trimester6. To this date, there is no evidence about a possible teratogenic effect of 5-ALA in the third trimester7-9.
In our clinic we do not use the drug Gliolan® but a pharmaceutic product containing 5-ALA that is completely manufactured by our hospital pharmacy. Before application of this drug in our pregnant patient we had extensive consultation with our clinical pharmacologists and pharmacists. This counseling did not identify a risk to the pregnancy of our patient who was in the third trimester and therefore application was officially allowed. Before application of this medication we had a shared decision making conversation with the patient, where we informed her openly about studies showing possible risks for the fetus in the first trimester6 but that there was no evidence for risk to her pregnancy in the current stage. She then agreed to the use of 5-ALA for her surgery.
In the retrospect, we agree that administration of 5-ALA may not have been necessary since we considered a possible second operation already initially.
The authors of the e-letter took the statement that propofol would not be appropriate from two cases described from Sethuraman et al. where after very long procedures (11 and 10 hours respectively) the use propofol caused maternal mild metabolic acidosis10.
As our procedure did not last that long, the use of propofol during pregnancy in this case was reasonable as also confirmed by Wang et al. 11
Furthermore, during surgery we regularly performed ABGs in order to monitor the pH and avoid acidosis.
It will remain challenging to define standards of care for glioma patients in pregnancy. However, we agree with the authors of this letter that the single-stage strategy with awake craniotomy is a considerable alternative to our proposed strategy and that multidisciplinary discussion and careful perioperative planning are of upmost importance for these patients.
1. Jasper H. Electrocorticography. In. Boston: Little Brown1954:p. 692 - 738.
2. Blume WT, Jones DC, Pathak P. Properties of after-discharges from cortical electrical stimulation in focal epilepsies. Clin Neurophysiol. 2004;115(4):982-989.
3. Karakis I, Leeman-Markowski BA, Leveroni CL, et al. Intra-stimulation discharges: an overlooked cortical electrographic entity triggered by direct electrical stimulation. Clin Neurophysiol. 2015;126(5):882-888.
4. PINSKY C, BURNS BD. Production of epileptiform afterdischarges in cat's cerebral cortex. J Neurophysiol. 1962;25:359-379.
5. Kamata K, Fukushima R, Nomura M, Ozaki M. A case of left frontal high-grade glioma diagnosed during pregnancy. JA Clin Rep. 2017;3(1):18.
6. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7(5):392-401.
7. Hadjipanayis CG, Widhalm G, Stummer W. What is the Surgical Benefit of Utilizing 5-Aminolevulinic Acid for Fluorescence-Guided Surgery of Malignant Gliomas? Neurosurgery. 2015;77(5):663-673.
8. Yang JZ, Van Vugt DA, Melchior MF, Hahn PM, Reid RL. Photodynamic ablation of early pregnancy in the rat with 5-aminolevulinic acid: a potential new therapy for tubal ectopic pregnancy in the human. Fertil Steril. 1994;62(5):1060-1065.
9. Olzowy B, Hundt CS, Stocker S, Bise K, Reulen HJ, Stummer W. Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid. J Neurosurg. 2002;97(4):970-976.
10. Sethuraman M, Neema PK, Rathod RC. Prolonged propofol infusion in pregnant neurosurgical patients. J Neurosurg Anesthesiol. 2007;19:67-8.
11. Wang, Lars Peter MD (Cph), FANZCA*; Paech, Michael James MBBS, DRCOG, FRCA, FANZCA, FFPMANZCA, FRANZCOG (Hon), DM† Neuroanesthesia for the Pregnant Woman, Anesthesia & Analgesia: July 2008 - Volume 107 - Issue 1 - p 193-200
Dear Editor,
This case report presents a very important accompaniment of COVID-19 illness which has currently raised up to epidemic scale in India (1). There is sound empirical evidence that unsupervised use of steroids, uncontrolled blood sugar and existing immunosuppression in COVID-19 may predispose the patients to the opportunistic mucormycosis infection (2,3). Surprisingly, co-infection with mucormycosis were rarely reported during the first wave in India, although the pandemic had spread extensively in the country. There is a possibility that sudden and massive increase in the number of cases and consequently collapsing of the health system in the country may have contributed in the rise of mucormycosis cases in various ways, including multiple iatrogenic causes, such as no proper sterilization of the medical equipment and the hospital wards. Wearing unclean face masks carrying fungal spores and other unhygienic practices might have also contributed in rise of the cases (4). However, no significant reporting of mucormycosis cases during the first wave of COVID-19 pandemic poses some valid questions, whether the newer SARS-CoV-2 variants, particularly that of B.1.617 lineage which are being suggested as the driver of the second wave in India (5), are causing greater and/or early immunosuppression than the wild strain. Emerging evidence suggest that the new SARS-CoV-2 strains, including that of B.1.617 lineage, may have increased virulence (6,7). Although, certai...
Dear Editor,
This case report presents a very important accompaniment of COVID-19 illness which has currently raised up to epidemic scale in India (1). There is sound empirical evidence that unsupervised use of steroids, uncontrolled blood sugar and existing immunosuppression in COVID-19 may predispose the patients to the opportunistic mucormycosis infection (2,3). Surprisingly, co-infection with mucormycosis were rarely reported during the first wave in India, although the pandemic had spread extensively in the country. There is a possibility that sudden and massive increase in the number of cases and consequently collapsing of the health system in the country may have contributed in the rise of mucormycosis cases in various ways, including multiple iatrogenic causes, such as no proper sterilization of the medical equipment and the hospital wards. Wearing unclean face masks carrying fungal spores and other unhygienic practices might have also contributed in rise of the cases (4). However, no significant reporting of mucormycosis cases during the first wave of COVID-19 pandemic poses some valid questions, whether the newer SARS-CoV-2 variants, particularly that of B.1.617 lineage which are being suggested as the driver of the second wave in India (5), are causing greater and/or early immunosuppression than the wild strain. Emerging evidence suggest that the new SARS-CoV-2 strains, including that of B.1.617 lineage, may have increased virulence (6,7). Although, certain degree of lymphocytopenia irrespective of the severity status has been a characteristic of COVID-19, any significant immunosuppression was observed in only severe cases (8). We need to study if there has been a change in this pattern with new variants. A comparative retrospective study of the count of the immune cells, primarily lymphocytes, in the blood samples of COVID-19 patients infected during the first and second waves, may potentially inform on this. Also, a selective study of the COVID-19 patients who have recently developed mucormycosis may substantiate this further.
References:
1. Declare mucormycosis an epidemic, Centre tells States - The Hindu [Internet]. [cited 2021 May 25]. Available from: https://www.thehindu.com/news/national/declare-mucormycosis-an-epidemic-...
2. Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis [Internet]. 2012 Feb 1 [cited 2021 May 25];54(SUPPL. 1):S16–22. Available from: http://www.broadinstitute.org/annotation/genome/
3. Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr Clin Res Rev [Internet]. 2021 May 21 [cited 2021 May 25]; Available from: https://linkinghub.elsevier.com/retrieve/pii/S1871402121001570
4. What is mucormycosis, the fungal infection affecting COVID patients in India? [Internet]. [cited 2021 May 25]. Available from: https://theconversation.com/what-is-mucormycosis-the-fungal-infection-af...
5. Vaidyanathan G. Coronavirus variants are spreading in India - what scientists know so far. Nature [Internet]. 2021 May 11 [cited 2021 May 25]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/33976409
6. Grint DJ, Wing K, Williamson E, McDonald HI, Bhaskaran K, Evans D, et al. Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February. Euro Surveill [Internet]. 2021 Mar 1 [cited 2021 May 25];26(11). Available from: https://pubmed.ncbi.nlm.nih.gov/33739254/
7. Yadav PD, Mohandas S, Shete AM, Nyayanit DA, Gupta N, Patil DY, et al. SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant. bioRxiv [Internet]. 2021 May 5 [cited 2021 May 25];2021.05.05.442760. Available from: https://doi.org/10.1101/2021.05.05.442760
8. Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z, et al. Viral and host factors related to the clinical outcome of COVID-19. Nature [Internet]. 2020 May 20 [cited 2020 May 27];1–7. Available from: http://www.nature.com/articles/s41586-020-2355-0
Do emerging SARS-CoV-2 variants cause early and greater immunosuppression which may contribute to co-infection with mucormycosis?
Dear Editor,
This case report presents a very important accompaniment of COVID-19 illness which has currently raised up to epidemic scale in India (1). There is sound empirical evidence that unsupervised use of steroids, uncontrolled blood sugar and existing immunosuppression in COVID-19 may predispose the patients to the opportunistic mucormycosis infection (2,3). Surprisingly, co-infection with mucormycosis were rarely reported during the first wave in India, although the pandemic had spread extensively in the country. There is a possibility that sudden and massive increase in the number of cases and consequently collapsing of the health system in the country may have contributed in the rise of mucormycosis cases in various ways, including multiple iatrogenic causes, such as no proper sterilization of the medical equipment and the hospital wards. Wearing unclean face masks carrying fungal spores and other unhygienic practices might have also contributed in rise of the cases (4). However, no significant reporting of mucormycosis cases during the first wave of COVID-19 pandemic poses some valid questions, whether the newer SARS-CoV-2 variants, particularly that of B.1.617 lineage which are being suggested as the driver of the second wave in India (5), are causing greater and/or early immunosuppression than the wild strain. Emerging...
Do emerging SARS-CoV-2 variants cause early and greater immunosuppression which may contribute to co-infection with mucormycosis?
Dear Editor,
This case report presents a very important accompaniment of COVID-19 illness which has currently raised up to epidemic scale in India (1). There is sound empirical evidence that unsupervised use of steroids, uncontrolled blood sugar and existing immunosuppression in COVID-19 may predispose the patients to the opportunistic mucormycosis infection (2,3). Surprisingly, co-infection with mucormycosis were rarely reported during the first wave in India, although the pandemic had spread extensively in the country. There is a possibility that sudden and massive increase in the number of cases and consequently collapsing of the health system in the country may have contributed in the rise of mucormycosis cases in various ways, including multiple iatrogenic causes, such as no proper sterilization of the medical equipment and the hospital wards. Wearing unclean face masks carrying fungal spores and other unhygienic practices might have also contributed in rise of the cases (4). However, no significant reporting of mucormycosis cases during the first wave of COVID-19 pandemic poses some valid questions, whether the newer SARS-CoV-2 variants, particularly that of B.1.617 lineage which are being suggested as the driver of the second wave in India (5), are causing greater and/or early immunosuppression than the wild strain. Emerging evidence suggest that the new SARS-CoV-2 strains, including that of B.1.617 lineage, may have increased virulence (6,7). Although, certain degree of lymphocytopenia irrespective of the severity status has been a characteristic of COVID-19, any significant immunosuppression was observed in only severe cases (8). We need to study if there has been a change in this pattern with new variants. A comparative retrospective study of the count of the immune cells, primarily lymphocytes, in the blood samples of COVID-19 patients infected during the first and second waves, may potentially inform on this. Also, a selective study of the COVID-19 patients who have recently developed mucormycosis may substantiate this further.
References:
1. Declare mucormycosis an epidemic, Centre tells States - The Hindu [Internet]. [cited 2021 May 25]. Available from: https://www.thehindu.com/news/national/declare-mucormycosis-an-epidemic-...
2. Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis [Internet]. 2012 Feb 1 [cited 2021 May 25];54(SUPPL. 1):S16–22. Available from: http://www.broadinstitute.org/annotation/genome/
3. Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr Clin Res Rev [Internet]. 2021 May 21 [cited 2021 May 25]; Available from: https://linkinghub.elsevier.com/retrieve/pii/S1871402121001570
4. What is mucormycosis, the fungal infection affecting COVID patients in India? [Internet]. [cited 2021 May 25]. Available from: https://theconversation.com/what-is-mucormycosis-the-fungal-infection-af...
5. Vaidyanathan G. Coronavirus variants are spreading in India - what scientists know so far. Nature [Internet]. 2021 May 11 [cited 2021 May 25]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/33976409
6. Grint DJ, Wing K, Williamson E, McDonald HI, Bhaskaran K, Evans D, et al. Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February. Euro Surveill [Internet]. 2021 Mar 1 [cited 2021 May 25];26(11). Available from: https://pubmed.ncbi.nlm.nih.gov/33739254/
7. Yadav PD, Mohandas S, Shete AM, Nyayanit DA, Gupta N, Patil DY, et al. SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant. bioRxiv [Internet]. 2021 May 5 [cited 2021 May 25];2021.05.05.442760. Available from: https://doi.org/10.1101/2021.05.05.442760
8. Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z, et al. Viral and host factors related to the clinical outcome of COVID-19. Nature [Internet]. 2020 May 20 [cited 2020 May 27];1–7. Available from: http://www.nature.com/articles/s41586-020-2355-0
The data that is represented in footnote 21 (rate of 6 in 42,000 vs. the rate of .08 - 1.1 in 100,000) is significant. It represents approximately a 1 in 7,000 rate! I think that this is worth highlighting in a separate article.
Dear Editor,
Mucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with unconrolled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later part of treatment ....
Dear Editor,
Mucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with unconrolled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later part of treatment .
Mucormycosis is a fatal fungal infections that mainly occurred during covid 19 pandemic in India. There have been multiple reports in news media's and in news papers across the country as termed it black fungus. Mucormycosis is not however a black fungus at all. Black fungus are rather different categories of fungus with melanin pigments. Mucormycosis fungi remain in the air and does not spread by contact or by oxygenation, humidifier,and water. The fungi remain in air indoor of wards or outdoor OPD system of hospital and in environment. The spores enters the respiratory tract via inhalation of air
Across the country india for last one month of very many incidence of mucormycosis against patients with covid -19 , especially who received dexamethasone with co morbidity diabetes mellitus and associated with high mortality and morbidities. The common presentation of covid 19 (active/recovering/or in post covid state) with mucormycosis are nasal blockade, nasal congestion, nasal discharge nasal bleeding ( bloody brown or black), local pain , facial pain, numbness,or swelling, head ache, orbital pain,tooth ache, loosening of maxillary tooth,jaw involvement,blurred or double vision with eye redness parasthesia, fever, skin rashes with eschar .When there is pulmonary involvement fever,cough, chest pain, pleural effusion,heamptosis, worsen respiratory symptoms.When HRCT lung is done may be confused with covid 19 related shadows ,reverse halo sign, cavity , multiple nodules,pleural effusion
The diagnosis is to be done either by pulmonary Bronchi alveolar lavage (BAL) ,mini BAL, nonbrochogenic lavage, sputum, larger transbronchial biopsy , CT guided biopsy from lung pleura by H&E stain followed by PAS stain and GMS or Grocot stain and culture in sabourdaud dextrose agar media. In GMS stain asptate or sparsely septate broad black hyphae found and in SDS agar media cottony rapid growth with or without black head. No serological or biochemical tests like galactomanan or beta D glycan tests will be positive. The treatment is control of blood sugar , diabetic ketoacidosis, in covid 19 patients, reduction of steroid with aim to sharp discontinue of steroid and other immunomodulators , if patients is receiving and use of liposomal amphotericin B promptly by IV infusion. There is no antifungal prophylaxis for mucormycosis
Acknowledgments 1)To Professor Dr Banya chakraborty , Prof and Head, microbiology of Calcutta School of Tropical Medicine ,108 Chittaranjan Avenue Kolkata 73 West Bengal India
2) To Prof . Dr Arunalok Chakraborty ,Prof and head microbiology at Post Graduate institutev of Medical Research ,Chandigarh India for discussion and formation of guidelines of diagnosis and treatment protocol for mucormycosis in covid 19 patients
References
1) RECOVERY Collaborative Group.
Dexamethasone in Hospitalized Patients with
Covid-19. N Engl J Med. 2021 Feb 25;384(8)
2). WHO Rapid Evidence Appraisal for COVID-19
Therapies (REACT) Working Group, . Association
Between Administration of Systemic
Corticosteroids and Mortality Among Critically
Ill Patients With COVID-19: A Meta-analysis.
JAMA. 2020 Oct 6;324(13):1330-1341
3.)https://www.mohfw.gov.in/pdf/ClinicalGuidanceonDiabetesManagementatCOVID... Facility.pdf
4.) Global guideline for the diagnosis &
management of mucormycosis. Lancet infectious disease
5) covid 19 associated mucormycosis (CAM) fungal infection study forum (FISF) recommendation http://www.fisttrust.org
Dear Editor,
Mucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with un controlled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during second wave of covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later pa...
Dear Editor,
Mucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with un controlled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during second wave of covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later part of treatment .
Mucormycosis is a fatal fungal infections that mainly occurred during covid 19 pandemic in India. There have been multiple reports in news media's and in news papers across the country as termed it black fungus. Mucormycosis is not however a black fungus at all. Black fungus are rather different categories of fungus with melanin pigments. Mucormycosis fungi remain in the air and does not spread by contact or by oxygenation, humidifier,and water. The fungi remain in air indoor of wards or outdoor OPD system of hospital and in environment. The spores enters the respiratory tract via inhalation of air
Across the country india for last one month of very many incidence of mucormycosis against patients with covid -19 , especially who received dexamethasone with co morbidity diabetes mellitus and associated with high mortality and morbidities. The common presentation of covid 19 (active/recovering/or in post covid state) with mucormycosis are nasal blockade, nasal congestion, nasal discharge nasal bleeding ( bloody brown or black), local pain , facial pain, numbness,or swelling, head ache, orbital pain,tooth ache, loosening of maxillary tooth,jaw involvement,blurred or double vision with eye redness parasthesia, fever, skin rashes with eschar .When there is pulmonary involvement fever,cough, chest pain, pleural effusion,heamptosis, worsen respiratory symptoms.When HRCT lung is done may be confused with covid 19 related shadows ,reverse halo sign, cavity , multiple nodules,pleural effusion
The diagnosis is to be done either by pulmonary Bronchi alveolar lavage (BAL) ,mini BAL, nonbrochogenic lavage, sputum, larger transbronchial biopsy , CT guided biopsy from lung pleura by H&E stain followed by PAS stain and GMS or Grocot stain and culture in sabourdaud dextrose agar media. In GMS stain asptate or sparsely septate broad black hyphae found and in SDS agar media cottony rapid growth with or without black head. No serological or biochemical tests like galactomanan or beta D glycan tests will be positive. The treatment is control of blood sugar , diabetic ketoacidosis, in covid 19 patients, reduction of steroid with aim to sharp discontinue of steroid and other immunomodulators , if patients is receiving and use of liposomal amphotericin B promptly by IV infusion. There is no antifungal prophylaxis for mucormycosis
Acknowledgments 1)To Professor Dr Banya chakraborty , Prof and Head, microbiology of Calcutta School of Tropical Medicine ,108 Chittaranjan Avenue Kolkata 73 West Bengal India
2) To Prof . Dr Arunalok Chakraborty ,Prof and head microbiology at Post Graduate institutev of Medical Research ,Chandigarh India for discussion and formation of guidelines of diagnosis and treatment protocol for mucormycosis in covid 19 patients
References
1) RECOVERY Collaborative Group.
Dexamethasone in Hospitalized Patients with
Covid-19. N Engl J Med. 2021 Feb 25;384(8)
2). WHO Rapid Evidence Appraisal for COVID-19
Therapies (REACT) Working Group, . Association
Between Administration of Systemic
Corticosteroids and Mortality Among Critically
Ill Patients With COVID-19: A Meta-analysis.
JAMA. 2020 Oct 6;324(13):1330-1341
3.)https://www.mohfw.gov.in/pdf/ClinicalGuidanceonDiabetesManagementatCOVID... Facility.pdf
4.) Global guideline for the diagnosis &
management of mucormycosis. Lancet infectious disease
5) covid 19 associated mucormycosis (CAM) fungal infection study forum (FISF) recommendation http://www.fisttrust.org
The association between heart failure and energy drink consumption is based on the entire clinical course rather than the presentation alone. The patient remains in renal failure with renal biochemistry similar to presentation and has not received renal replacement therapy for some time. Despite this, the patient is no longer in heart failure with a significant improvement in cardiac function occurring prior to the introduction of heart failure medications - carvedilol, hydralazine and isosorbide dinitrite. The clinical course of spontaneous recovery was similar to the cited case report from Belzile and colleagues and hence our reason for bringing this to attention and contributing to greater awareness. We welcome the comments and debate as there is no test to confirm the relationship to energy drink intake and therefore extensive clinical characterisation is required to exclude alternative causes of severe heart failure. Severe heart failure which improves spontaneously to this magnitude - LVEF 9% to 51% is particularly rare.
Dear Madam/Sir,
We read with great interest the article by Vidhale and colleagues.1 They provide a detailed description of a man presenting with a relatively rapidly progressing neurodegenerative disease including his neuroimaging findings.
After testing for a few DNA repeat expansion diseases, the authors arrived at the conclusion that their patient’s diagnosis was Friedreich ataxia (FRDA). FRDA is a recessive neurodegenerative disease caused by bi-allelic expansion of an intronic GAA repeat in the frataxin (FXN) gene. Their patient had 5 and 37 GAA repeats. The lower limit for full penetrance alleles is > 66 GAA repeats.2 Thus, it is not apparent how their patient meets diagnostic criteria for FRDA.
The 37 GAA repeat allele falls at the lower end of premutation alleles (range 34-65), so named as these alleles do not cause disease, but can rarely expand to the disease range during meiosis. In rare cases, somatic expansion of pre-mutations in cell populations has been postulated to cause disease, but this occurs only in the setting of the 2nd allele in the clear pathogenic range of expansion.
The authors alternatively postulate that the patient could represent a compound heterozygous state based on his clinical presentation. Comparison with cases of very late-onset FRDA (vLOFA), however, clearly shows that the patient’s course is too rapid and severe for vLOFA. Even if the patient were to carry a pathogenic point mutation in one of the allel...
Show MoreDear Editor,
A taser is a weapon used by police in order to provide a safe means of subduing an uncooperative person via an “electric shock”. This handheld device features two small barbed darts designed to puncture the skin. These darts are connected via copper wires to a main unit which delivers an electric current to the individual causing neuromuscular incapacitation by disrupting the voluntary control of muscles(1). A number of studies have raised concern over the health risks of tasers, including ventricular arrhythmias and cardiac arrest(2). Something I have come across during my training was a case of complete heart block provoked by a taser discharge. This phenomenon is not frequently described in the literature.
The patient in question had cardiac arrest immediately after receiving a discharge from a taser during an altercation with police. Thankfully, he was given bystander CPR and had return of spontaneous circulation after 3 minutes. On presentation to the Emergency Department the patient was found to be in complete heart block. He was admitted acutely to the coronary care unit for monitoring and had a permanent pacemaker inserted three days later.
The taser is considered a non-lethal weapon but can it truly be considered such?
Since it is not thought of as a firearm, taser use is not regulated by the Bureau of Alcohol, Tobacco, Firearms and Explosives. The main objective of this article is not to comment on the propriety of taser...
Show MoreActive TB globally affects over 10 million people each year and accounts for approximately 1.6 million deaths. Since publishing this case report we since have learned that IGRA blood tests are not entirely useful in diagnosing active TB, as IGRA will also pick up cases of latent TB.
Presently, the most useful microbiological method of diagnosis is now widely recognised as the Gene Xpert or Gene Xpert MTB/RIF Ultra, a rapid molecular test for Mycobacterium tuberculosis and rifampicin resistance which can be performed on sputum, pleural fluid or CSF. Access to this technology has been widely scaled up in recent years as part of the WHO End TB Strategy and most countries are switching from traditional AFB smears to rapid molecular testing due to reduced costs and demand on laboratory facilities. However, the COVID-19 pandemic has also redirected human, diagnostic and financial resources elsewhere and modelling predicts a regression in TB control and increase in mortality from 13% in 2020 to 20% in 2025.
Thank you very much for your letter on our published case report of a pregnant woman that was diagnosed with a left parietal glioma in the 28th gestational week after a first generalised seizure, and for your opinion and thorough review of the literature.
In our patient we performed a two-stage approach with first a tumour resection under general anaesthesia and preservation of the pregnancy and after caesarean section performed in the 37th gestational week an awake craniotomy for resection of residual tumour under neuropsychological monitoring and mapping.
We decided to do a two-stage approach after a round table where obstetricians, neurosurgeons, anesthetists, neonatologists, and midwives were involved and after several long conversations with the patient and her husband. For the patient clearly the health of her unborn child was the most important aspect of her treatment and therefore she wanted to prolong the pregnancy until term. The tumor of our patient was located with a broad base to the surface and seemed to have a plane to the underlying white matter. There was no, in this location possible eloquent, unaffected cortex overlying the tumor. Moreover, our patient was already in the 28th gestational week of her pregnancy, the uterine fundus was high and the abdomen extended. The use of cortical or subcortical electric stimulation does increase the seizure risk1-4. Because of all these reasons we decided aga...
Show MoreDear Editor,
Show MoreThis case report presents a very important accompaniment of COVID-19 illness which has currently raised up to epidemic scale in India (1). There is sound empirical evidence that unsupervised use of steroids, uncontrolled blood sugar and existing immunosuppression in COVID-19 may predispose the patients to the opportunistic mucormycosis infection (2,3). Surprisingly, co-infection with mucormycosis were rarely reported during the first wave in India, although the pandemic had spread extensively in the country. There is a possibility that sudden and massive increase in the number of cases and consequently collapsing of the health system in the country may have contributed in the rise of mucormycosis cases in various ways, including multiple iatrogenic causes, such as no proper sterilization of the medical equipment and the hospital wards. Wearing unclean face masks carrying fungal spores and other unhygienic practices might have also contributed in rise of the cases (4). However, no significant reporting of mucormycosis cases during the first wave of COVID-19 pandemic poses some valid questions, whether the newer SARS-CoV-2 variants, particularly that of B.1.617 lineage which are being suggested as the driver of the second wave in India (5), are causing greater and/or early immunosuppression than the wild strain. Emerging evidence suggest that the new SARS-CoV-2 strains, including that of B.1.617 lineage, may have increased virulence (6,7). Although, certai...
Do emerging SARS-CoV-2 variants cause early and greater immunosuppression which may contribute to co-infection with mucormycosis?
Dear Editor,
Show MoreThis case report presents a very important accompaniment of COVID-19 illness which has currently raised up to epidemic scale in India (1). There is sound empirical evidence that unsupervised use of steroids, uncontrolled blood sugar and existing immunosuppression in COVID-19 may predispose the patients to the opportunistic mucormycosis infection (2,3). Surprisingly, co-infection with mucormycosis were rarely reported during the first wave in India, although the pandemic had spread extensively in the country. There is a possibility that sudden and massive increase in the number of cases and consequently collapsing of the health system in the country may have contributed in the rise of mucormycosis cases in various ways, including multiple iatrogenic causes, such as no proper sterilization of the medical equipment and the hospital wards. Wearing unclean face masks carrying fungal spores and other unhygienic practices might have also contributed in rise of the cases (4). However, no significant reporting of mucormycosis cases during the first wave of COVID-19 pandemic poses some valid questions, whether the newer SARS-CoV-2 variants, particularly that of B.1.617 lineage which are being suggested as the driver of the second wave in India (5), are causing greater and/or early immunosuppression than the wild strain. Emerging...
The data that is represented in footnote 21 (rate of 6 in 42,000 vs. the rate of .08 - 1.1 in 100,000) is significant. It represents approximately a 1 in 7,000 rate! I think that this is worth highlighting in a separate article.
Dear Editor,
Show MoreMucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with unconrolled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later part of treatment ....
Dear Editor,
Show MoreMucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with un controlled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during second wave of covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later pa...
The association between heart failure and energy drink consumption is based on the entire clinical course rather than the presentation alone. The patient remains in renal failure with renal biochemistry similar to presentation and has not received renal replacement therapy for some time. Despite this, the patient is no longer in heart failure with a significant improvement in cardiac function occurring prior to the introduction of heart failure medications - carvedilol, hydralazine and isosorbide dinitrite. The clinical course of spontaneous recovery was similar to the cited case report from Belzile and colleagues and hence our reason for bringing this to attention and contributing to greater awareness. We welcome the comments and debate as there is no test to confirm the relationship to energy drink intake and therefore extensive clinical characterisation is required to exclude alternative causes of severe heart failure. Severe heart failure which improves spontaneously to this magnitude - LVEF 9% to 51% is particularly rare.
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