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.
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
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
Jiang presents a very interesting and unique case of bilateral corneal decompensation in a patient with COVID pneumonitis. We would like to offer a similar case to support their hypothesis of viral endotheliitis. These cases demonstrate an ocular manifestation of COVID-19 infection which was previously unknown. This manifestation is important to be aware of as the subsequent visual impairment may be profound, though likely amenable to treatment.
Jiang pointed out the unclear onset for their case and possible delayed presentation from 34 days of ventilation. While we cannot assume the onset time of Jiang’s patient, our patient provides an interesting comparison. Our case describes a male patient who developed significant and painless overnight vision loss. He had gone to bed with only cough as a symptom of COVID infection and awoke to find himself only able to perceive light and gross motion. This patient presented to our local accident and emergency department with this sudden and profound bilateral loss of vision. He required admission due to his inability to self-care.
On examination the patient was found to have significant bilateral corneal oedema. Both eyes were white with no evidence of local infection, inflammation, or ocular surface trauma. There was no epithelial uptake with fluorescein in either eye. Intraocular pressure was within normal limits and symmetrical. No corneal dystrophy could be seen with biomicroscopy. The patient was started on topi...
Jiang presents a very interesting and unique case of bilateral corneal decompensation in a patient with COVID pneumonitis. We would like to offer a similar case to support their hypothesis of viral endotheliitis. These cases demonstrate an ocular manifestation of COVID-19 infection which was previously unknown. This manifestation is important to be aware of as the subsequent visual impairment may be profound, though likely amenable to treatment.
Jiang pointed out the unclear onset for their case and possible delayed presentation from 34 days of ventilation. While we cannot assume the onset time of Jiang’s patient, our patient provides an interesting comparison. Our case describes a male patient who developed significant and painless overnight vision loss. He had gone to bed with only cough as a symptom of COVID infection and awoke to find himself only able to perceive light and gross motion. This patient presented to our local accident and emergency department with this sudden and profound bilateral loss of vision. He required admission due to his inability to self-care.
On examination the patient was found to have significant bilateral corneal oedema. Both eyes were white with no evidence of local infection, inflammation, or ocular surface trauma. There was no epithelial uptake with fluorescein in either eye. Intraocular pressure was within normal limits and symmetrical. No corneal dystrophy could be seen with biomicroscopy. The patient was started on topical Predforte drops which were administered 2 hourly to both eye. He was also given topical lubrication in the form of celluvisc 0.5% four times a day to both eyes. Notably, viral eye swabs taken from the conjunctival sac were positive for COVID and negative for HSV and VZV. Viral eye swabs as a diagnostic tool for aetiology of ocular pathology is of unknown specificity, though has been widely suggested in the literature (1).
This gentleman was rather comorbid with, notably, diabetes, hypertension, obesity and stable sarcoidosis. He had no ophthalmic history or family history of note. Though he suffered from polypharmacy, he was not on any medication known to cause corneal decompensation and no significant medication changes had been made within 12 months of his admission. His chest x-ray on admission showed only air space shadowing consistent with COVID pneumonitis. Therefore, there were no other obvious causes of corneal decompensation (2).
Systemically our gentleman was also found at admission to have an acute kidney injury and hypoglycaemia. This was thought to be secondary to his inability to feed himself with his acutely deteriorated eyesight. Hypoglycaemia was treated by the paramedics, but his kidney injury worsened and ultimately, sadly, resulted in death at 72 hours after admission. The patient was reviewed daily and interestingly, as his kidney function continued to deteriorate his corneal oedema began to improve. His vision improved to counting fingers in each eye. As noted by Jiang, this systemic upset is unlikely to be the cause of corneal decompensation which is usually due to a more local insult. Hence the most likely cause and perhaps supported by the positive swab is viral endotheliitis secondary to COVID-19 infection.
Supporting Jiang’s case, we, similarly have a case of profound bilateral corneal decompensation for which all differentials for cause had been ruled out and leaving viral endotheliitis secondary to COVID infection the most likely cause. In comparison to Jiang’s case, our gentleman shows that acute deterioration is possible, and importantly, this manifestation of disease may occur throughout the range of the severity of COVID pneumonitis. Reassuringly, both patients have shown good initial responses to topical treatment with steroids. The literature continues to grow with profound manifestations of COVID pneumonitis, it remains of utmost importance to be aware of these presentations especially when they may present across the range of COVID severity.
(A note to the editor: we have submitted this letter with the purpose outlined above. If consent from this patient’s relatives is required, please let us know. Many thanks for reading this letter.)
References:
1. Kaur P, Sehgal G, Shailpreet, Singh K, Singh B. Evaluation and comparison of conjunctival swab polymerase chain reaction results in SARS-CoV-2 patients with and without ocular manifestations. 2021.
2. Moshirfar M, Murri M, Shah T, Skanchy D, Tuckfield J, Ronquillo Y et al. A Review of Corneal Endotheliitis and Endotheliopathy: Differential Diagnosis, Evaluation, and Treatment. 2021.
Summary:
A supporting case from Dr Evelyn Qian, Lothian describes similar ocular manifestation and positive conjunctival swab PCR relating to severe COVID pneumonitis, in support of our hypothesis of SARS-CoV-2 viral endotheliitis which was previously unknown.
Qian describes a case of acute bilateral corneal oedema in the presence of severe COVID-19. Conjunctival swabs were positive for SARS-CoV-2 by rRT-PCR assay, and negative for HSV and VZV. His ocular condition was treated with topical steroid drops which demonstrated clinical improvement before he passed away from acute kidney injury at 72 hours after admission.
We read with interest the case report by Yap et al regarding “A near-fatal consequence of chiropractor massage: massive stroke from carotid arterial dissection and vertebral arterial oedema,”(1) which describes a 35-year-old man with a massive stroke purportedly caused by massage. Cerebrovascular disease is an invested topic for manual therapists, considering such providers are responsible for recognizing emergent signs/symptoms of a cervical artery dissection (CeAD) and referring accordingly,(2) however, we are concerned about appropriate and accurate reporting of details of the case including several inconsistencies and evident biases.
We believe this case report likely misclassifies the treating provider as a chiropractor. The report does not specify the credentials of the person providing massage during the business trip. As pointed out by the authors, there is limited regulation and licensing of chiropractic in China.(3) Furthermore, spinal manipulation is by far the most common treatment intervention provided by chiropractors(4) but the authors did not mention its use in the case presentation.
We request the authors clarify the credentials of the massage provider, and elaborate on treatment interventions, specifically if cervical spinal manipulation was performed. Previous case reports have misrepresented the treating provider as a chiropractor when describing potential adverse events.(5) This practice is spurious and adds to over-reporting of adverse...
We read with interest the case report by Yap et al regarding “A near-fatal consequence of chiropractor massage: massive stroke from carotid arterial dissection and vertebral arterial oedema,”(1) which describes a 35-year-old man with a massive stroke purportedly caused by massage. Cerebrovascular disease is an invested topic for manual therapists, considering such providers are responsible for recognizing emergent signs/symptoms of a cervical artery dissection (CeAD) and referring accordingly,(2) however, we are concerned about appropriate and accurate reporting of details of the case including several inconsistencies and evident biases.
We believe this case report likely misclassifies the treating provider as a chiropractor. The report does not specify the credentials of the person providing massage during the business trip. As pointed out by the authors, there is limited regulation and licensing of chiropractic in China.(3) Furthermore, spinal manipulation is by far the most common treatment intervention provided by chiropractors(4) but the authors did not mention its use in the case presentation.
We request the authors clarify the credentials of the massage provider, and elaborate on treatment interventions, specifically if cervical spinal manipulation was performed. Previous case reports have misrepresented the treating provider as a chiropractor when describing potential adverse events.(5) This practice is spurious and adds to over-reporting of adverse events incorrectly linked to the chiropractic profession.(5)
The authors also conflate “massage” with “chiropractic manipulation” which are two distinct forms of treatment. Spinal manipulation performed by a chiropractor typically involves a thrust or impulse directed to the spine, while massage does not.(6) While the case presentation states massage was the treatment rendered, the title, the discussion, and learning points all highlight chiropractic cervical spine manipulation—which by definition, is not massage. The authors’ literature review included the search term “chiropractic manipulation” which is inappropriate to introduce, as their case pertains to massage.
The authors’ discussion references case reports only, missing seminal studies relevant to manipulation and CeAD, and their conclusions regarding “chiropractic massage” being a “fatal practice” is not supported by the literature. A systematic review of several large observational studies including more than 100 million person-years of data did not identify evidence of a causal association between chiropractic spinal manipulation and CeAD.(7) This is supported by a systematic review of 47 prospective trials that did not identify any incidents of CeAD in recipients of spinal manipulation.(8) Further, to our knowledge there is no epidemiologic evidence linking massage and stroke, and only one case report describing a potential relationship.(9)
Protopathic bias, or confounding by indication, have been proposed as explanations for rare instances in which a stroke is preceded by chiropractic spinal manipulation. In both models, neck pain or headache, common prodromal symptoms of CeAD, prompt a patient to seek care from a chiropractor when the dissection is already in progress.(7, 10-14) This hypothesis is supported by case reports describing such patients presenting to chiropractors with evolving CeAD and referring appropriately.(15-18)
The current case is potentially another example of a dissection-in-progress considering the patient sought massage for neck, shoulder girdle, and upper back pain. The details of initial presentation and physical examination (if performed) for this “chiropractor massage” are not reported, which may have led to a different outcome if the case was managed by a qualified/licensed chiropractor.
The authors’ report of symptom onset coinciding solely with this “chiropractor massage” is not supported in the literature. We propose alternative explanations to the authors regarding the mechanism and resulting conclusions for the case report. Cervical artery dissections are often spontaneous without a known cause.(19) However, there are hypothesized triggers of CeAD which the authors did not mention and could have played a role in the current case such as airplane travel20 and/or viral infection such as mild case of COVID-19 given the timing of this report.(21,22)
In summary, the authors’ conclusions regarding a correlation between chiropractic spinal manipulation and carotid artery dissection and are superseded by higher levels of epidemiologic evidence that has not identified such a causal link. Additionally, the postulated causal relationship between carotid artery dissection and massage exceeds the available data. The patient’s stroke could have been precipitated by a spontaneous CeAD and was treated with massage therapy rather than emergency care. This case should not deter health care providers from referring to, or patients from seeking care from, qualified chiropractors.
References
1. Yap T, Feng L, Xu D, Zhang J. A near-fatal consequence of chiropractor massage: massive stroke from carotid arterial dissection and bilateral vertebral arterial oedema. BMJ Case Rep. 2021 Aug 6;14(8):e243976. doi: 10.1136/bcr-2021-243976. PMID: 34362754; PMCID: PMC8351484.
2. Chaibi A, Russell MB. A risk-benefit assessment strategy to exclude cervical artery dissection in spinal manual-therapy: a comprehensive review. Ann Med. 2019 Mar;51(2):118-127. doi: 10.1080/07853890.2019.1590627. Epub 2019 Apr 6. PMID: 30889367; PMCID: PMC7857472.
3. World Federation of Chiropractic: Legal Status of Chiropractic by Country. (Accessed August 23, 2021) https://www.wfc.org/website/index.php?option=com_content&view=article&id...
4. Beliveau PJH, Wong JJ, Sutton DA, Simon NB, Bussières AE, Mior SA, French SD. The chiropractic profession: a scoping review of utilization rates, reasons for seeking care, patient profiles, and care provided. Chiropr Man Therap. 2017 Nov 22;25:35. doi: 10.1186/s12998-017-0165-8. PMID: 29201346; PMCID: PMC5698931.
5. Wenban AB. Inappropriate use of the title 'chiropractor' and term 'chiropractic manipulation' in the peer-reviewed biomedical literature. Chiropr Osteopat. 2006 Aug 22;14:16. doi: 10.1186/1746-1340-14-16. PMID: 16925822; PMCID: PMC1570468.
6. Hurwitz EL. Epidemiology: Spinal manipulation utilization. J Electromyogr Kinesiol. 2012;22(5):648-654. doi:10.1016/j.jelekin.2012.01.006
7. Church EW, Sieg EP, Zalatimo O, Hussain NS, Glantz M, Harbaugh RE. (2016). Systematic Review and Meta-analysis of Chiropractic Care and Cervical Artery Dissection: No Evidence for Causation. Cureus. 2016;8(2):e498.
8. Coulter ID, Crawford C, Vernon H, Hurtwitz L, Khorsan R, et al. Manipulation and mobilization for treating chronic nonspecific neck pain: a systematic review and meta-analysis for an appropriateness panel. Pain Physician 2019;22(2):E55-E70.
9. Birkett W, Pouryahya P, Meyer ADM. Bilateral vertebral artery dissection and cerebellar stroke: a rare complication of massage. N Z Med J. 2020 Apr 3;133(1512):88-92. PMID: 32242183.
10. Cassidy JD, Bronfort G, Hartvigsen J. Should we abandon cervical spine manipulation for mechanical neck pain? No. BMJ. 2012;344:e3680. doi:10.1136/bmj.e3680
11. Hutting N, Kerry R, Coppieters MW, Scholten-Peeters GG. Considerations to improve the safety of cervical spine manual therapy. Musculoskelet Sci Pract. 2018;33:41-45.
12. Perle SM, Jung H, Ham J, Choi H. Letter to the Editor: A Case of Posterior Inferior Cerebellar Artery Infarction after Cervical Chiropractic Manipulation (Korean J Neurotrauma 2018; 14: 159–163). Korean J Neurotrauma. 2019;15(1):72-73.
13. Murphy DR, Schneider MJ, Perle SM, Bise CG, Timko M, Haas M. Does case misclassification threaten the validity of studies investigating the relationship between neck manipulation and vertebral artery dissection stroke? No. Chiropr Man Ther. 2016;24(1):43. doi:10.1186/s12998-016-0124-9
14. Bronson MA, Perle SM, Tuchin P. Issues with vertebral artery dissections. Interv Neuroradiol. 2017;23(2):154-155. doi:10.1177/1591019916680111
15. Michaud TC. Uneventful upper cervical manipulation in the presence of a damaged vertebral artery. Journal of Manipulative and Physiological Therapeutics. 2002;25(7):472-483.
16. Tarola G, Phillips RB. Chiropractic response to a spontaneous vertebral artery dissection. Journal of Chiropractic Medicine 2015;14(3):183-190.
17. Futch D, et al. Vertebral artery dissection in evolution found during chiropractic examination. BMJ Case Reports. 2015: bcr2015212568.
18. Mosby JS, Duray SM. Vertebral artery dissection in a patient practicing self-manipulation of the neck. Journal of Chiropractic Medicine. 2011;10(4):283-287.
19. Schievink WI. Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med. 2001 Mar 22;344(12):898-906. doi: 10.1056/NEJM200103223441206. PMID: 11259724.
20. Humaidan H, et al. Airplane stroke syndrome. Journal of Clinical Neuroscience. 2016;29:77-80.
21. Morassi M, et al. Bilateral carotid artery dissection in a SARS-CoV-2 infected patient: causality or coincidence? Journal of Neurology. 2020.;267(10):2812-2814.
22. Gencler OS, Meltem RE, Aydın A. Unilateral common carotid artery dissection in a patient with recent COVID-19: An association or a coincidence? Journal of Clinical Neuroscience. 2021;87: 26-28.
Thanks for your interest in our case report and the literature review on CeAD and spinal manipulation, which is the most important element of patient care.
All clinicians would like to have a positive outcome for their patients using evidence-based practice.
Unfortunately, the patient in this case had a near fatal outcome by a chiropractor practising in a major metropolitan region of China. The chiropractor is a graduate of a traditional Chinese medical university. The patient could only recall heavy massage and possibly using an equipment (activator? we did not put in the paper because of the uncertainty).
The side effect with this mode of chiropractor treatment is extremely rare as what we have reviewed. This mode of treatment can certainly be the risk factors for the outcome (we ruled out most of the other risk factors presented in our case). We are sharing this case purely for education purpose without the intention of criticising any individual and the chiropractor profession. We did not want to see any more similar cases with an almost fatal outcome. We do appreciate that the whole profession of chiropractors constantly reviews their practice to ensure the delivery of evidence-based practice for treatment effectiveness of various aches and pain (shoulder girdle and neck pain in our case), which all health professionals should practice routinely.
Thanks for your interest in our case report and the literature review on CeAD and spinal manipulation, which is the most important element of patient care.
All clinicians would like to have a positive outcome for their patients using evidence-based practice.
Unfortunately, the patient in this case had a near fatal outcome by a chiropractor practising in a major metropolitan region of China. The chiropractor is a graduate of a traditional Chinese medical university. The patient could only recall heavy massage and possibly using an equipment (activator? we did not put in the paper because of the uncertainty).
The side effect with this mode of chiropractor treatment is extremely rare as what we have reviewed. This mode of treatment can certainly be the risk factors for the outcome (we ruled out most of the other risk factors presented in our case). We are sharing this case purely for education purpose without the intention of criticising any individual and the chiropractor profession. We did not want to see any more similar cases with an almost fatal outcome. We do appreciate that the whole profession of chiropractors constantly reviews their practice to ensure the delivery of evidence-based practice for treatment effectiveness of various aches and pain (shoulder girdle and neck pain in our case), which all health professionals should practice routinely.
Hope the response helps to clarify the queries.
kind regards
Daniel
Dr Daniel Xu
MBBS, PhD, FRACGP
Academic Coordinators, General Practice Research & International Health
Curtin Medical School
Visiting Professor
The First Affiliated Hospital, Sun Yat-Sen University
Guangzhou, China
Senior Research Fellow
CCRE, School of Public Health
Faculty of Health Sciences
Curtin University
Location Building 408, Level 3, Room 3516
Postal Address |GPO Box U1987, Perth, Western Australia, 6845 | AUSTRALIA
Tel | +61 (0)8 9266 1740
Mobile | +61 (0)415288896
Email |daniel.xu@curtin.edu.au
We read, with interest, “Obstetric rectal laceration in the absence of an anal sphincter injury” by Awomolo et al in your journal [1]. We commend the authors on reviewing this rare injury.
We appreciate your detailed case report and were pleased to read that your patient recovered well from her injury. We agree that these rare injuries require careful repair with experience, good surgical technique and detailed knowledge of perineal anatomy. Your extensive literature review found other similar cases, many of which we included in our most comprehensive case series [2], but we were surprised to see that our case series was not included in your paper. Although rectal buttonhole tears are rare they are now defined in many National guidelines in the world [3]. What our paper also adds is a standardised approach for repair of isolated rectal tears and follow up, with a video demonstration on a porcine specimen. In addition, we have highlighted that rectal button hole tears can occur concomitantly with a third or 4th degree tear when there is intact bridge of anorectal mucosa between the two injuries.
We appreciated the insufficiencies in training regarding classification, diagnosis and repair of obstetric anal sphincter injuries (OASIS) over 20 years ago and began the first hands-on course in 2000 (www.perineum.net). We have also introduced the Prevention and Repair Of perineal Trauma Episiotomy through Co...
We read, with interest, “Obstetric rectal laceration in the absence of an anal sphincter injury” by Awomolo et al in your journal [1]. We commend the authors on reviewing this rare injury.
We appreciate your detailed case report and were pleased to read that your patient recovered well from her injury. We agree that these rare injuries require careful repair with experience, good surgical technique and detailed knowledge of perineal anatomy. Your extensive literature review found other similar cases, many of which we included in our most comprehensive case series [2], but we were surprised to see that our case series was not included in your paper. Although rectal buttonhole tears are rare they are now defined in many National guidelines in the world [3]. What our paper also adds is a standardised approach for repair of isolated rectal tears and follow up, with a video demonstration on a porcine specimen. In addition, we have highlighted that rectal button hole tears can occur concomitantly with a third or 4th degree tear when there is intact bridge of anorectal mucosa between the two injuries.
We appreciated the insufficiencies in training regarding classification, diagnosis and repair of obstetric anal sphincter injuries (OASIS) over 20 years ago and began the first hands-on course in 2000 (www.perineum.net). We have also introduced the Prevention and Repair Of perineal Trauma Episiotomy through Coordinated Training (PROTECT) course certified by the International Urogynecological Association (www.IUGA.org). We are currently appraising OASIS diagnosis and repair training for doctors and midwives in the UK, through online surveys and evaluation of training courses. We hope to publish our data in the coming year, making recommendations about content and frequency of training.
Yours sincerely,
Joanna C. Roper MRCOG
Ranee Thakar MD FRCOG
Abdul H. Sultan MD FRCOG
References:
1. Awomolo A, Hardman D, Louis-Jacques A (2021) Obstetric rectal laceration in the absence of an anal sphincter injury. BMJ Case Rep 14:e243296. https://doi.org/10.1136/bcr-2021-243296
2. Roper JC, Thakar R, Sultan AH (2020) Isolated rectal buttonhole tears in obstetrics: case series and review of the literature. Int Urogynecol J. https://doi.org/10.1007/s00192-020-04502-2
3. Roper JC, Amber N, Wan OYK, et al (2020) Review of available national guidelines for obstetric anal sphincter injury. Int Urogynecol J 31:2247–2259. https://doi.org/10.1007/s00192-020-04464-5
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.
We thank Dr Yap and colleagues for describing clearly the successful management of an unexpectedly challenging airway.1 We agree that the index case highlights the need for vigilance in all patients requiring airway management, particularly where an atypical presentation of a respiratory condition may indicate occult airway pathology.2 However, the case raises a number of important issues for airway assessment, intubation-related laryngeal pathology and the management of ‘can’t intubate, can’t ventilate’ scenarios which warrant further discussion, considered below.
Airway assessment can be encapsulated by the quote, “Hindsight is a wonderful thing but foresight is better, especially when it comes to saving life,” attributed the 19th Century English poet William Blake. Whilst subtle, there were a number of clues in the described case report that could, and perhaps should, have prompted a more thorough evaluation of the airway. It is surprising that the patient did not report their extreme prematurity at birth, or the fact that they spent the first year of their life in hospital. This would have almost certainly have involved prolonged ventilation and sequelae into childhood. Respiratory and airway complications are well recognised in premature neonates and may coexist.3 The authors highlight the Difficult Airway Society’s airway algorithms and the fact that any clinician managing an airway should prepare for failure.4-6 This should involve an examination of the front...
We thank Dr Yap and colleagues for describing clearly the successful management of an unexpectedly challenging airway.1 We agree that the index case highlights the need for vigilance in all patients requiring airway management, particularly where an atypical presentation of a respiratory condition may indicate occult airway pathology.2 However, the case raises a number of important issues for airway assessment, intubation-related laryngeal pathology and the management of ‘can’t intubate, can’t ventilate’ scenarios which warrant further discussion, considered below.
Airway assessment can be encapsulated by the quote, “Hindsight is a wonderful thing but foresight is better, especially when it comes to saving life,” attributed the 19th Century English poet William Blake. Whilst subtle, there were a number of clues in the described case report that could, and perhaps should, have prompted a more thorough evaluation of the airway. It is surprising that the patient did not report their extreme prematurity at birth, or the fact that they spent the first year of their life in hospital. This would have almost certainly have involved prolonged ventilation and sequelae into childhood. Respiratory and airway complications are well recognised in premature neonates and may coexist.3 The authors highlight the Difficult Airway Society’s airway algorithms and the fact that any clinician managing an airway should prepare for failure.4-6 This should involve an examination of the front of the neck, in case an emergency surgical airway is required. This may have revealed the tracheostomy scar, noted during the evolving airway crisis. Although we recognise that these scars often heal very well after childhood tracheostomy and may not always be visible.
Any previous intubation of the trachea is associated with a risk of laryngeal injury and dysfunction occurring even after a short general anaesthetic.7 Clinical symptoms of hoarseness, breathiness (audible breathing), stridor, vocal fatigue or even ‘shortness of breath’ may indicate significant occult laryngeal pathology, including arytenoid fibrosis or dislocation, vocal cord paralysis or (sub)glottic stenosis.8 Even without the full disclosure of the preterm birth and likely prolonged intubation/ventilation, the history of intensive care unit admission in childhood is potentially significant, particularly when combined with the ongoing symptoms.
Lastly, the international language around what constitutes a “can’t intubate, can’t ventilate” scenario and, more importantly, what to do about it is well established. Dr Yap and colleagues describe appropriate initial actions following a failure to intubate the trachea: the patient could be ventilated and therefore oxygenated throughout via the use of a supraglottic airway device. Whilst we commend the authors for highlighting a stepwise approach to managing an evolving airway crisis, two important points need clarification. Repeated laryngoscopy and attempted intubation of the trachea (five in this case) are: increasingly likely to fail; will lead to trauma, bleeding and oedema; and risk provoking catastrophic airway obstruction and subsequent failure of ventilation and oxygenation.9 Furthermore, should a ‘can’t intubate, can’t ventilate’ scenario become apparent, the most appropriate course of action is an immediate cricothyroidotomy, not a tracheostomy which takes significantly longer and requires considerable surgical expertise which may not be immediately available.10 Therefore, we are concerned that the take home message from this report is potentially confusing. The authors rightly point out that different approaches to emergency cricothyroidotomy are debated, but we strongly recommend that the final learning point from their report is that a ‘can’t intubate, can’t ventilate’ scenario should be dealt with immediately, by whoever is managing the airway, by performing emergency scalpel-bougie cricothyroidotomy.10 Waiting for an ENT surgeon, who may not be immediately available, to attend may cause life threatening delay. Reinforcing this message consistently and supporting airway practitioners with appropriate training should reduce the potentially catastrophic outcomes associated with difficult and failed airway management.
References
1. Yap T, Quick M, Moore P. Emergency tracheostomy for failed intubation due to glottic stenosis. BMJ Case Rep 2021;14(2) doi: 10.1136/bcr-2020-239806 [published Online First: 2021/02/28]
2. Garini G, Fecci L, Giacosa R, et al. Adult idiopathic subglottic stenosis: a diagnostic and therapeutic challenge. Ann Ital Med Int 2004;19(1):54-7. [published Online First: 2004/06/05]
3. Jones M. Effect of preterm birth on airway function and lung growth. Paediatr Respir Rev 2009;10 Suppl 1:9-11. doi: 10.1016/S1526-0542(09)70005-3 [published Online First: 2009/08/11]
4. Higgs A, Cook TM, McGrath BA. Airway management in the critically ill: the same, but different. British journal of anaesthesia 2016;117 Suppl 1:i5-i9. doi: 10.1093/bja/aew055
5. Higgs A, McGrath BA, Goddard C, et al. Guidelines for the management of tracheal intubation in critically ill adults. British journal of anaesthesia 2018;120(2):323-52. doi: 10.1016/j.bja.2017.10.021
6. Frerk C, Mitchell VS, McNarry AF, et al. Difficult Airway Society 2015 guidelines for management of unanticipated difficult intubation in adults. British journal of anaesthesia 2015;115(6):827-48. doi: 10.1093/bja/aev371
7. Mota L, de Cavalho G, Brito V. Laryngeal Complications by Orotracheal Intubation: Literature Review. International archives of otorhinolaryngology 2012;16(2):236-45. doi: 10.7162/S1809-97772012000200014
8. Ponfick M, Linden R, Nowak D. Dysphagia--a Common, Transient Symptom in Critical Illness Polyneuropathy: A Fiberoptic Endoscopic Evaluation of Swallowing Study. Critical care medicine 2015;43(2):365-72. doi: 10.1097/CCM.0000000000000705
9. Mort TC. Emergency Tracheal Intubation: Complications Associated with Repeated Laryngoscopic Attempts. 2004
10. Pracy JP, Brennan L, Cook TM, et al. Surgical intervention during a Can't intubate Can't Oxygenate (CICO) Event: Emergency Front-of-neck Airway (FONA)? British journal of anaesthesia 2016;117(4):426-28. doi: 10.1093/bja/aew221 [published Online First: 2016/09/21]
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
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,
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...
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 ....
Jiang presents a very interesting and unique case of bilateral corneal decompensation in a patient with COVID pneumonitis. We would like to offer a similar case to support their hypothesis of viral endotheliitis. These cases demonstrate an ocular manifestation of COVID-19 infection which was previously unknown. This manifestation is important to be aware of as the subsequent visual impairment may be profound, though likely amenable to treatment.
Jiang pointed out the unclear onset for their case and possible delayed presentation from 34 days of ventilation. While we cannot assume the onset time of Jiang’s patient, our patient provides an interesting comparison. Our case describes a male patient who developed significant and painless overnight vision loss. He had gone to bed with only cough as a symptom of COVID infection and awoke to find himself only able to perceive light and gross motion. This patient presented to our local accident and emergency department with this sudden and profound bilateral loss of vision. He required admission due to his inability to self-care.
On examination the patient was found to have significant bilateral corneal oedema. Both eyes were white with no evidence of local infection, inflammation, or ocular surface trauma. There was no epithelial uptake with fluorescein in either eye. Intraocular pressure was within normal limits and symmetrical. No corneal dystrophy could be seen with biomicroscopy. The patient was started on topi...
Show MoreWe read with interest the case report by Yap et al regarding “A near-fatal consequence of chiropractor massage: massive stroke from carotid arterial dissection and vertebral arterial oedema,”(1) which describes a 35-year-old man with a massive stroke purportedly caused by massage. Cerebrovascular disease is an invested topic for manual therapists, considering such providers are responsible for recognizing emergent signs/symptoms of a cervical artery dissection (CeAD) and referring accordingly,(2) however, we are concerned about appropriate and accurate reporting of details of the case including several inconsistencies and evident biases.
We believe this case report likely misclassifies the treating provider as a chiropractor. The report does not specify the credentials of the person providing massage during the business trip. As pointed out by the authors, there is limited regulation and licensing of chiropractic in China.(3) Furthermore, spinal manipulation is by far the most common treatment intervention provided by chiropractors(4) but the authors did not mention its use in the case presentation.
We request the authors clarify the credentials of the massage provider, and elaborate on treatment interventions, specifically if cervical spinal manipulation was performed. Previous case reports have misrepresented the treating provider as a chiropractor when describing potential adverse events.(5) This practice is spurious and adds to over-reporting of adverse...
Show MoreDear Sir/Madam.
Thanks for your interest in our case report and the literature review on CeAD and spinal manipulation, which is the most important element of patient care.
All clinicians would like to have a positive outcome for their patients using evidence-based practice.
Unfortunately, the patient in this case had a near fatal outcome by a chiropractor practising in a major metropolitan region of China. The chiropractor is a graduate of a traditional Chinese medical university. The patient could only recall heavy massage and possibly using an equipment (activator? we did not put in the paper because of the uncertainty).
The side effect with this mode of chiropractor treatment is extremely rare as what we have reviewed. This mode of treatment can certainly be the risk factors for the outcome (we ruled out most of the other risk factors presented in our case). We are sharing this case purely for education purpose without the intention of criticising any individual and the chiropractor profession. We did not want to see any more similar cases with an almost fatal outcome. We do appreciate that the whole profession of chiropractors constantly reviews their practice to ensure the delivery of evidence-based practice for treatment effectiveness of various aches and pain (shoulder girdle and neck pain in our case), which all health professionals should practice routinely.
Hope the response helps to clarify the queries.
kind regards
...
Show MoreDear Editor,
We read, with interest, “Obstetric rectal laceration in the absence of an anal sphincter injury” by Awomolo et al in your journal [1]. We commend the authors on reviewing this rare injury.
We appreciate your detailed case report and were pleased to read that your patient recovered well from her injury. We agree that these rare injuries require careful repair with experience, good surgical technique and detailed knowledge of perineal anatomy. Your extensive literature review found other similar cases, many of which we included in our most comprehensive case series [2], but we were surprised to see that our case series was not included in your paper. Although rectal buttonhole tears are rare they are now defined in many National guidelines in the world [3]. What our paper also adds is a standardised approach for repair of isolated rectal tears and follow up, with a video demonstration on a porcine specimen. In addition, we have highlighted that rectal button hole tears can occur concomitantly with a third or 4th degree tear when there is intact bridge of anorectal mucosa between the two injuries.
We appreciated the insufficiencies in training regarding classification, diagnosis and repair of obstetric anal sphincter injuries (OASIS) over 20 years ago and began the first hands-on course in 2000 (www.perineum.net). We have also introduced the Prevention and Repair Of perineal Trauma Episiotomy through Co...
Show MoreSindgikar 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 MoreWe thank Dr Yap and colleagues for describing clearly the successful management of an unexpectedly challenging airway.1 We agree that the index case highlights the need for vigilance in all patients requiring airway management, particularly where an atypical presentation of a respiratory condition may indicate occult airway pathology.2 However, the case raises a number of important issues for airway assessment, intubation-related laryngeal pathology and the management of ‘can’t intubate, can’t ventilate’ scenarios which warrant further discussion, considered below.
Airway assessment can be encapsulated by the quote, “Hindsight is a wonderful thing but foresight is better, especially when it comes to saving life,” attributed the 19th Century English poet William Blake. Whilst subtle, there were a number of clues in the described case report that could, and perhaps should, have prompted a more thorough evaluation of the airway. It is surprising that the patient did not report their extreme prematurity at birth, or the fact that they spent the first year of their life in hospital. This would have almost certainly have involved prolonged ventilation and sequelae into childhood. Respiratory and airway complications are well recognised in premature neonates and may coexist.3 The authors highlight the Difficult Airway Society’s airway algorithms and the fact that any clinician managing an airway should prepare for failure.4-6 This should involve an examination of the front...
Show MoreDo 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...
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