Sindgikar et al. report a severe paradoxical reaction in a 15-year-old HIV-uninfected patient with stage III tuberculous meningitis, during her fifth month of treatment. After improving with re-initiation of corticosteroids, the paradoxical reaction worsened after the prednisolone was weaned over 8 weeks. The patient continued 4 months of corticosteroids in addition to 13 months anti-TB treatment (ATT) with significant morbidity at one year follow up, including permanent disability.
Whilst corticosteroids are the mainstay of treatment for paradoxical reactions, their effectiveness for this difficult-to-treat complication has not been assessed in randomised controlled trials (RCT)(1). TNF-alpha is a key cytokine implicated in the exaggerated inflammatory response underlying paradoxical reactions (2,3). We have used infliximab, a monoclonal antibody targeting TNF-alpha, in the management of severe paradoxical reactions in paediatric central nervous system TB with positive outcomes (4,5). Anti-TNFα monoclonal antibodies, including infliximab, have also been used with encouraging results in adults for this indication (6,7). Thalidomide, another anti-TNF-alpha therapy was evaluated in an RCT of children with stage II and III tuberculous meningitis (8), however, this trial was ceased early due to increased deaths and adverse outcomes with a thalidomide dose of 24 mg/kg/day. A subsequent case series of 38 children treated with low-dose thalidomide (3-5 mg/kg) with life-th...
Sindgikar et al. report a severe paradoxical reaction in a 15-year-old HIV-uninfected patient with stage III tuberculous meningitis, during her fifth month of treatment. After improving with re-initiation of corticosteroids, the paradoxical reaction worsened after the prednisolone was weaned over 8 weeks. The patient continued 4 months of corticosteroids in addition to 13 months anti-TB treatment (ATT) with significant morbidity at one year follow up, including permanent disability.
Whilst corticosteroids are the mainstay of treatment for paradoxical reactions, their effectiveness for this difficult-to-treat complication has not been assessed in randomised controlled trials (RCT)(1). TNF-alpha is a key cytokine implicated in the exaggerated inflammatory response underlying paradoxical reactions (2,3). We have used infliximab, a monoclonal antibody targeting TNF-alpha, in the management of severe paradoxical reactions in paediatric central nervous system TB with positive outcomes (4,5). Anti-TNFα monoclonal antibodies, including infliximab, have also been used with encouraging results in adults for this indication (6,7). Thalidomide, another anti-TNF-alpha therapy was evaluated in an RCT of children with stage II and III tuberculous meningitis (8), however, this trial was ceased early due to increased deaths and adverse outcomes with a thalidomide dose of 24 mg/kg/day. A subsequent case series of 38 children treated with low-dose thalidomide (3-5 mg/kg) with life-threatening TB mass lesions despite drug-susceptible anti-TB treatment and corticosteroids reported encouraging results (9), further supporting the role of anti-TNF-alpha agents in the treatment of paradoxical tuberculous reactions.
Future carefully designed trials are needed to evaluate the effectiveness of anti-TNF agents for paradoxical reactions. They could also establish risk factors and biomarkers to help determine which patients are likely to develop paradoxical reactions, and which would potentially benefit from anti-TNF-alpha therapy shortly after ATT initiation to prevent the long-term morbidity associated with this potentially devastating complication.
1. Marais S, Van Toorn R, Chow FC, et al. Management of intracranial tuberculous mass lesions: how long should we treat for? Wellcome Open Res. 2019;4:158.
2. Tsenova L, Sokol K, Freedman VH, Kaplan G. A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death. J Infect Dis. 1998;177(6):1563-1572.
3. Donald PR, Schoeman JF, Beyers N, et al. Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis. Clin Infect Dis. 1995;21(4):924-929.
4. Abo YN, Curtis N, Butters C, Rozen TH, Marais BJ, Gwee A. Successful Treatment of a Severe Vision-Threatening Paradoxical Tuberculous Reaction with Infliximab: First Pediatric Use. Pediatr Infect Dis J. 2020;39(4):e42-e45.
5. Abo YN, Curtis N, Osowicki J, et al. Iin press). Infliximab for paradoxical reactions in pediatric central nervous system tuberculosis. Journal of the Pediatric Infectious Diseases Societ. 2021.
6. Santin M, Escrich C, Majòs C, Llaberia M, Grijota MD, Grau I. Tumor necrosis factor antagonists for paradoxical inflammatory reactions in the central nervous system tuberculosis: Case report and review. Medicine. 2020;99(43):e22626-e22626.
7. Marais BJ, Cheong E, Fernando S, et al. Use of Infliximab to Treat Paradoxical Tuberculous Meningitis Reactions. Open Forum Infect Dis. 2021;8(1):ofaa604.
8. Schoeman JF, Springer P, van Rensburg AJ, et al. Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study. J Child Neurol. 2004;19(4):250-257.
9. van Toorn R, Solomons RS, Seddon JA, Schoeman JF. Thalidomide Use for Complicated Central Nervous System Tuberculosis in Children: Insights From an Observational Cohort. Clin Infect Dis. 2021;72(5):e136-e145.
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.
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.
Please see below for clarification to your queries:
1) What was Central Venous Pressure:
The CVP pressure was not measured as the patient was relatively well. Are you perhaps referring to JVP which was unremarkable.
2) If patient was, presumably Conscious, Oriented, able to take Food and Fluids by Mouth, could the Intravenous Administration of Fluids be avoided?
It is possible that IV fluids could have been avoided but in view of his AKI it was felt prudent to rehydrate with IV fluids. We appreciate that management in this scenario will differ.
3) How did the Elevated Blood Pressure evolved during Hospitalization, either with or without Medications.
He had only one dose of amlodipine as inpatient and didn’t require any further doses for BP control. On discharge his Blood pressure was within normal limits and his GP was advised to continue monitoring his blood pressure as he had previously been doing.
4) What was Patient's Diet and Fluid Intake Both Quantitative and Qualitative during the Hospitalization?
AKI resolved within 24 hours of admission so exact fluid intake, urinary output and diet were not documented.
5) Whether the Patient took any Formal or Alternative Medicines or Home Remedies for Coryza he had Two Weeks before Episode of Shortness of Breath, that could have caused Autoimmune Hemolysis?
Please see below for clarification to your queries:
1) What was Central Venous Pressure:
The CVP pressure was not measured as the patient was relatively well. Are you perhaps referring to JVP which was unremarkable.
2) If patient was, presumably Conscious, Oriented, able to take Food and Fluids by Mouth, could the Intravenous Administration of Fluids be avoided?
It is possible that IV fluids could have been avoided but in view of his AKI it was felt prudent to rehydrate with IV fluids. We appreciate that management in this scenario will differ.
3) How did the Elevated Blood Pressure evolved during Hospitalization, either with or without Medications.
He had only one dose of amlodipine as inpatient and didn’t require any further doses for BP control. On discharge his Blood pressure was within normal limits and his GP was advised to continue monitoring his blood pressure as he had previously been doing.
4) What was Patient's Diet and Fluid Intake Both Quantitative and Qualitative during the Hospitalization?
AKI resolved within 24 hours of admission so exact fluid intake, urinary output and diet were not documented.
5) Whether the Patient took any Formal or Alternative Medicines or Home Remedies for Coryza he had Two Weeks before Episode of Shortness of Breath, that could have caused Autoimmune Hemolysis?
The patient had not taken any over the counter medication/herbal medications for his symptoms. This was confirmed on patient’s records.
6) If the Patient's Blood Pressure before Present Illnesses was known and if he took any medications for it and any other conditions eg Bleeding per Rectum?
He had previously been started on antihypertensive medications. These were Bisoprolol and Ramipril. He stopped Bisoprolol himself, after discussion with the GP, because he felt tired and Ramipril was discontinued because of cough. His BP was monitored on further GP visits and was within normal limits without any medications.
He was reviewed by Gastroenterology team as inpatient and upper GI bleed was excluded.
For bleeding PR an outpatient colonoscopy was requested which subsequently showed first degree haemorrhoids and a few diverticulae in the sigmoid colon.
7) What were the instructions including those regarding medications diet and follow-up given to the Patient at the time of Discharge?
No specific advice was given regarding to diet. Repeat blood tests were advised which were kindly performed and followed up by the GP. These had returned to normal. It is an excellent point to comment on the role of diet in patients with high blood pressure. It is not current practice to discuss about diet as an inpatient unless there are compelling reasons to do so however discussions on healthy life style should be built into our regular practice.
Bisoprolol was restarted after discussion with patient because of an episode of SVT in the hospital.
We hope that these answer your queries and many thanks for bringing these to our attention.
Dear Dr. Biswas,
In their recent article ‘Anaplastic astrocytoma during pregnancy: the importance of an effective multidisciplinary approach’, Filippi and colleagues described the therapeutic strategy for a pregnant patient whose left parietal glioma was discovered after a new-onset generalized seizure [1]. Following the multidisciplinary conference, they planned to attain a full-term pregnancy with staged tumor resection. First, the mass reduction was performed with neuronavigation and fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) under general anesthesia. Then awake craniotomy was planned for the residual tumor removal after delivery. Although the authors have provided excellent perioperative care for this complicated case, we have some reservations about the therapeutic strategy for malignant glioma in a pregnant patient.
The guidelines for the diagnosis and treatment of gliomas, released by the European Association for Neuro-Oncology, present the following management options for newly diagnosed malignant glioma: resection or biopsy, followed by radiotherapy or chemotherapy (or combined modality treatment) [2]. In pregnant patients, the neurosurgical intervention for a malignant tumor is recommended regardless of gestational age, although the 32 week gestation point is generally used as the cutoff [3]. The extent of glioma resection is a decisive prognosis factor irrespective of tumor subtype [4]. In view of the absence of information on th...
Dear Dr. Biswas,
In their recent article ‘Anaplastic astrocytoma during pregnancy: the importance of an effective multidisciplinary approach’, Filippi and colleagues described the therapeutic strategy for a pregnant patient whose left parietal glioma was discovered after a new-onset generalized seizure [1]. Following the multidisciplinary conference, they planned to attain a full-term pregnancy with staged tumor resection. First, the mass reduction was performed with neuronavigation and fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) under general anesthesia. Then awake craniotomy was planned for the residual tumor removal after delivery. Although the authors have provided excellent perioperative care for this complicated case, we have some reservations about the therapeutic strategy for malignant glioma in a pregnant patient.
The guidelines for the diagnosis and treatment of gliomas, released by the European Association for Neuro-Oncology, present the following management options for newly diagnosed malignant glioma: resection or biopsy, followed by radiotherapy or chemotherapy (or combined modality treatment) [2]. In pregnant patients, the neurosurgical intervention for a malignant tumor is recommended regardless of gestational age, although the 32 week gestation point is generally used as the cutoff [3]. The extent of glioma resection is a decisive prognosis factor irrespective of tumor subtype [4]. In view of the absence of information on the long-term effects on newborns of mothers that received anticonvulsants, chemotherapeutics, or radiation during pregnancy [5], the fact that the patient could be safely monitored without the need for adjuvant therapies is commendable [4].
The surgical strategy for eloquent malignant glioma in a pregnant patient offers two options. One is the two-staged strategy, as Filippi and colleagues presented, and the other is a single-stage operation with awake craniotomy in order to achieve maximum tumor resection with minimum postoperative neurological deficits. While awake craniotomy in pregnant patients is still challenging, several reports show that extensive resection with neurological monitoring is the best way to preserve the patient's motor and speech function [6-7]. Compared with the tumor removal under general anesthesia, awake craniotomy has some advantages on fetal-maternal wellbeing. The higher reliability of functional reservation is considered the most significant benefit of awake craniotomy. Especially among pregnant patients, electrophysiological monitoring and functional mapping should be minimized to reduce the risk of seizure occurrence and subsequent fetal hypoxia. As our previous case shows, the patient's subjective movement is a substitute for motor-evoked potential monitoring [7]. Maternal use of 5-ALA can be avoided in cases of awake craniotomy. In the last two decades, 5-ALA-induced fluorescence was introduced as a valuable technique for intraoperative visualization and improved resection of malignant gliomas [8]. However, its use during pregnancy is still prohibited in the European Public Assessment Report released by European Medicines Agency [9]. Fluorescence-guided surgery using 5-ALA is helpful for the identification of residual malignant glioma intraoperatively, but in the case presented by the authors, cortical or subcortical stimulation is truly informative to determine the resectable edge from the eloquent area. Considering the possible adverse reaction of 5-ALA to both the patient and fetus, fluorescence-guided surgery cannot be considered the best approach. The last concern is the detrimental effects of general anesthetics. Propofol, the most common sedative in neuroanesthesia, caused maternal mild metabolic acidosis after prolonged infusion [10]. On the other hand, volatile anesthetics have a significant tocolytic effect. Thus, awake craniotomy can reduce these unfavorable effects of general anesthesia on the patient and the fetus.
Due to the limited evidence on the use of adjuvant therapy during pregnancy, tumors causing neurological symptoms and seizures must be treated to stabilize the maternal condition and enable a safe birth. As far as the extent of tumor resection in malignant glioma is a decisive prognosis factor, the single-stage strategy with awake craniotomy should be considered an alternative. The multidisciplinary discussion should take place within the decision-making process, and careful perioperative preparation is mandatory.
References
1. Filippi V, Leu SM, Marengo L, et al. Anaplastic astrocytoma during pregnancy: the importance of an effective multidisciplinary approach. BMJ Case Rep 2021;14:e242135.
2. Weller M, van den Bent M, Hopkins K, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 2014;15:e395-403.
3. Lynch JC, Gouvêa F, Emmerich JC, et al. Management strategy for brain tumour diagnosed during pregnancy. Br J Neurosurg 2011;25:225-30.
4. Nitta M, Muragaki Y, Maruyama T, et al. Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection. Neurosurg Focus 2015;38:E7.
5. Zwinkels H, Dörr J, Kloet F, et al. Pregnancy in women with gliomas: a case-series and review of the literature. J Neurooncol 2013;115:293-301.
6. Al-Mashani AM, Ali A, Chatterjee N, et al. Awake craniotomy during pregnancy. J Neurosurg Anesthesiol 2018;30:372-3..
7. Kamata K, Fukushima R, Nomura M, et al. A case of left frontal high-grade glioma diagnosed during pregnancy. JA Clin Rep 2017;3:18.
8. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomized controlled multicentre phase Ⅲ trial. Lancet Oncol 2006;7:392-401.
9. European Public Assessment Report (EPAR) GLIOLAN. Available at: https://www.ema.europa.eu/en/documents/overview/gliolan-epar-summary-pub.... Accessed 20 April 2021.
10. Sethuraman M, Neema PK, Rathod RC. Prolonged propofol infusion in pregnant neurosurgical patients. J Neurosurg Anesthesiol 2007;19:67-8.
Sindgikar et al. report a severe paradoxical reaction in a 15-year-old HIV-uninfected patient with stage III tuberculous meningitis, during her fifth month of treatment. After improving with re-initiation of corticosteroids, the paradoxical reaction worsened after the prednisolone was weaned over 8 weeks. The patient continued 4 months of corticosteroids in addition to 13 months anti-TB treatment (ATT) with significant morbidity at one year follow up, including permanent disability.
Whilst corticosteroids are the mainstay of treatment for paradoxical reactions, their effectiveness for this difficult-to-treat complication has not been assessed in randomised controlled trials (RCT)(1). TNF-alpha is a key cytokine implicated in the exaggerated inflammatory response underlying paradoxical reactions (2,3). We have used infliximab, a monoclonal antibody targeting TNF-alpha, in the management of severe paradoxical reactions in paediatric central nervous system TB with positive outcomes (4,5). Anti-TNFα monoclonal antibodies, including infliximab, have also been used with encouraging results in adults for this indication (6,7). Thalidomide, another anti-TNF-alpha therapy was evaluated in an RCT of children with stage II and III tuberculous meningitis (8), however, this trial was ceased early due to increased deaths and adverse outcomes with a thalidomide dose of 24 mg/kg/day. A subsequent case series of 38 children treated with low-dose thalidomide (3-5 mg/kg) with life-th...
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.
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 Sir/Madam,
Thank you for your comments
Please see below for clarification to your queries:
1) What was Central Venous Pressure:
The CVP pressure was not measured as the patient was relatively well. Are you perhaps referring to JVP which was unremarkable.
2) If patient was, presumably Conscious, Oriented, able to take Food and Fluids by Mouth, could the Intravenous Administration of Fluids be avoided?
It is possible that IV fluids could have been avoided but in view of his AKI it was felt prudent to rehydrate with IV fluids. We appreciate that management in this scenario will differ.
3) How did the Elevated Blood Pressure evolved during Hospitalization, either with or without Medications.
He had only one dose of amlodipine as inpatient and didn’t require any further doses for BP control. On discharge his Blood pressure was within normal limits and his GP was advised to continue monitoring his blood pressure as he had previously been doing.
4) What was Patient's Diet and Fluid Intake Both Quantitative and Qualitative during the Hospitalization?
AKI resolved within 24 hours of admission so exact fluid intake, urinary output and diet were not documented.
5) Whether the Patient took any Formal or Alternative Medicines or Home Remedies for Coryza he had Two Weeks before Episode of Shortness of Breath, that could have caused Autoimmune Hemolysis?
The patient had not...
Show MoreDear Dr. Biswas,
Show MoreIn their recent article ‘Anaplastic astrocytoma during pregnancy: the importance of an effective multidisciplinary approach’, Filippi and colleagues described the therapeutic strategy for a pregnant patient whose left parietal glioma was discovered after a new-onset generalized seizure [1]. Following the multidisciplinary conference, they planned to attain a full-term pregnancy with staged tumor resection. First, the mass reduction was performed with neuronavigation and fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) under general anesthesia. Then awake craniotomy was planned for the residual tumor removal after delivery. Although the authors have provided excellent perioperative care for this complicated case, we have some reservations about the therapeutic strategy for malignant glioma in a pregnant patient.
The guidelines for the diagnosis and treatment of gliomas, released by the European Association for Neuro-Oncology, present the following management options for newly diagnosed malignant glioma: resection or biopsy, followed by radiotherapy or chemotherapy (or combined modality treatment) [2]. In pregnant patients, the neurosurgical intervention for a malignant tumor is recommended regardless of gestational age, although the 32 week gestation point is generally used as the cutoff [3]. The extent of glioma resection is a decisive prognosis factor irrespective of tumor subtype [4]. In view of the absence of information on th...
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