Dear Editor,
Mucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with un controlled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during second wave of covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later pa...
Dear Editor,
Mucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with un controlled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during second wave of covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later part of treatment .
Mucormycosis is a fatal fungal infections that mainly occurred during covid 19 pandemic in India. There have been multiple reports in news media's and in news papers across the country as termed it black fungus. Mucormycosis is not however a black fungus at all. Black fungus are rather different categories of fungus with melanin pigments. Mucormycosis fungi remain in the air and does not spread by contact or by oxygenation, humidifier,and water. The fungi remain in air indoor of wards or outdoor OPD system of hospital and in environment. The spores enters the respiratory tract via inhalation of air
Across the country india for last one month of very many incidence of mucormycosis against patients with covid -19 , especially who received dexamethasone with co morbidity diabetes mellitus and associated with high mortality and morbidities. The common presentation of covid 19 (active/recovering/or in post covid state) with mucormycosis are nasal blockade, nasal congestion, nasal discharge nasal bleeding ( bloody brown or black), local pain , facial pain, numbness,or swelling, head ache, orbital pain,tooth ache, loosening of maxillary tooth,jaw involvement,blurred or double vision with eye redness parasthesia, fever, skin rashes with eschar .When there is pulmonary involvement fever,cough, chest pain, pleural effusion,heamptosis, worsen respiratory symptoms.When HRCT lung is done may be confused with covid 19 related shadows ,reverse halo sign, cavity , multiple nodules,pleural effusion
The diagnosis is to be done either by pulmonary Bronchi alveolar lavage (BAL) ,mini BAL, nonbrochogenic lavage, sputum, larger transbronchial biopsy , CT guided biopsy from lung pleura by H&E stain followed by PAS stain and GMS or Grocot stain and culture in sabourdaud dextrose agar media. In GMS stain asptate or sparsely septate broad black hyphae found and in SDS agar media cottony rapid growth with or without black head. No serological or biochemical tests like galactomanan or beta D glycan tests will be positive. The treatment is control of blood sugar , diabetic ketoacidosis, in covid 19 patients, reduction of steroid with aim to sharp discontinue of steroid and other immunomodulators , if patients is receiving and use of liposomal amphotericin B promptly by IV infusion. There is no antifungal prophylaxis for mucormycosis
Acknowledgments 1)To Professor Dr Banya chakraborty , Prof and Head, microbiology of Calcutta School of Tropical Medicine ,108 Chittaranjan Avenue Kolkata 73 West Bengal India
2) To Prof . Dr Arunalok Chakraborty ,Prof and head microbiology at Post Graduate institutev of Medical Research ,Chandigarh India for discussion and formation of guidelines of diagnosis and treatment protocol for mucormycosis in covid 19 patients
References
1) RECOVERY Collaborative Group.
Dexamethasone in Hospitalized Patients with
Covid-19. N Engl J Med. 2021 Feb 25;384(8)
2). WHO Rapid Evidence Appraisal for COVID-19
Therapies (REACT) Working Group, . Association
Between Administration of Systemic
Corticosteroids and Mortality Among Critically
Ill Patients With COVID-19: A Meta-analysis.
JAMA. 2020 Oct 6;324(13):1330-1341
3.)https://www.mohfw.gov.in/pdf/ClinicalGuidanceonDiabetesManagementatCOVID... Facility.pdf
4.) Global guideline for the diagnosis &
management of mucormycosis. Lancet infectious disease
5) covid 19 associated mucormycosis (CAM) fungal infection study forum (FISF) recommendation http://www.fisttrust.org
The association between heart failure and energy drink consumption is based on the entire clinical course rather than the presentation alone. The patient remains in renal failure with renal biochemistry similar to presentation and has not received renal replacement therapy for some time. Despite this, the patient is no longer in heart failure with a significant improvement in cardiac function occurring prior to the introduction of heart failure medications - carvedilol, hydralazine and isosorbide dinitrite. The clinical course of spontaneous recovery was similar to the cited case report from Belzile and colleagues and hence our reason for bringing this to attention and contributing to greater awareness. We welcome the comments and debate as there is no test to confirm the relationship to energy drink intake and therefore extensive clinical characterisation is required to exclude alternative causes of severe heart failure. Severe heart failure which improves spontaneously to this magnitude - LVEF 9% to 51% is particularly rare.
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.
We reported this case as a possible early association during the first wave when it was impossible to discern whether there was a true connection between COVID and SSNHL, let alone determine the incidence. The paper was clear that direct causation wasn’t proven, but it served to highlight the importance of prompt treatment of SSNHL which is often associated with viral aetiologies.
The case report was written to create early awareness of a possible link. Since then, a BRC funded team in Manchester have published a systematic review linking the two and are also undertaking a year-long study into the association. An NIHR/BRC team in Nottingham are doing similarly.
We reported this case as a possible early association during the first wave when it was impossible to discern whether there was a true connection between COVID and SSNHL, let alone determine the incidence. The paper was clear that direct causation wasn’t proven, but it served to highlight the importance of prompt treatment of SSNHL which is often associated with viral aetiologies.
The case report was written to create early awareness of a possible link. Since then, a BRC funded team in Manchester have published a systematic review linking the two and are also undertaking a year-long study into the association. An NIHR/BRC team in Nottingham are doing similarly.
Hopefully these studies will provide further clarification and answer the questions posed in your letter which our case report was never designed to do.”
The authors implicate caffeine as the causative agent of the cardiomyopathy in this case, caffeine being the main active ingredient within energy drinks. They ask that we enquire about energy drinks within our social histories; consumption of caffeinated products indeed not part of a standard cardiovascular history (1).
It is therefore conspicuous that within the article there are no calls to enquire about other, more widely used caffeine containing products, specifically tea and coffee. Dare I say, we would be unlikely to baulk at the idea of a patient drinking three or four coffees in a day. In fact, on the wards we offer patients tea or coffee eight times a day, yet think little of the caffeine burden we are imposing upon them. This almost tacit caffeine consumption is unlikely to make it into the medical notes, yet these patients would potentially be consuming levels of caffeine far in excess of the quantity consumed in this case report.
We seem to apply different value judgements to different drinks, assuming those drinking excess caffeine from expensive coffee machines are doing so knowingly, and as part of a healthy lifestyle. Yet we don’t afford those choosing to consume energy drinks with the same level of ability to make an informed choice. We medicalise the consumption of such drinks, assuming those using them must be doing so for sinister reasons.
We should treat all caffeinated products equally, given there is no pharmacological differen...
The authors implicate caffeine as the causative agent of the cardiomyopathy in this case, caffeine being the main active ingredient within energy drinks. They ask that we enquire about energy drinks within our social histories; consumption of caffeinated products indeed not part of a standard cardiovascular history (1).
It is therefore conspicuous that within the article there are no calls to enquire about other, more widely used caffeine containing products, specifically tea and coffee. Dare I say, we would be unlikely to baulk at the idea of a patient drinking three or four coffees in a day. In fact, on the wards we offer patients tea or coffee eight times a day, yet think little of the caffeine burden we are imposing upon them. This almost tacit caffeine consumption is unlikely to make it into the medical notes, yet these patients would potentially be consuming levels of caffeine far in excess of the quantity consumed in this case report.
We seem to apply different value judgements to different drinks, assuming those drinking excess caffeine from expensive coffee machines are doing so knowingly, and as part of a healthy lifestyle. Yet we don’t afford those choosing to consume energy drinks with the same level of ability to make an informed choice. We medicalise the consumption of such drinks, assuming those using them must be doing so for sinister reasons.
We should treat all caffeinated products equally, given there is no pharmacological difference between them. Indeed, the caffeine found in energy drinks is extracted from coffee; a by-product of decaffeinated coffee production.
Further, I feel it unfair to suggest manufactures should provide warnings on cans, given that they already do – displaying both caffeine content, and warnings about its excessive consumption in certain groups. Indeed, these warnings and caffeine contents are absent from the sides of tea and coffee packaging, therein further preventing us from quantifying caffeine consumption.
That said, it is undeniable that the caffeine content of these drinks has increased over time, and it is not an unreasonable assumption that caffeine is to blame for the symptoms described in this case. Twenty years ago, the humble initial offerings of these drinks were a 250ml can with 75mg of caffeine. Today the bar has shifted to 200mg of caffeine in one can, and the market trend of increasing caffeine shows no signs of abating. This could be problematic, and lead to unwitting excess consumption as in this case report.
Direct regulation of these markets is often a wise solution. Rather than posting unheeded warnings of sugar content on the side of cans, the tax on sugar forced the hand of the market to adapt and reduce the sugar content within energy drinks, often to nil, and therein obviating the detrimental effects of sugar outright (2).
The same could be done for caffeine content; a cap of 20mg/100ml, or an overall cap of 100mg in any one drink would seem appropriate, though admittedly little can be done to stop people drinking multiple cans as in this case.
Like them or loathe them, these products do at least appeal to an ideal of activity, which should be celebrated in our overly sedentary society.
(1) Innes, J.A. et al., 2018. Macleod's Clinical Examination, Elsevier, pp.39-74
(2) Pell, D., Mytton, O., Penney, T.L., Briggs, A., Cummins, S., Penn-Jones, C., Rayner, M., Rutter, H., Scarborough, P., Sharp, S.J., Smith, R.D., White, M., Adams, J., 2021. Changes in soft drinks purchased by British households associated with the UK soft drinks industry levy: Controlled interrupted time series analysis. The BMJ 372. https://doi.org/10.1136/bmj.n254
Thanks for the comments on our manuscript entitled "Plexiform neurofibromatosis of penis: a rare presentation of type 1 neurofibromatosis."
We think that this is a very good suggestion for treating such cases. Selumetinib has been found to be effective to treat neurofibromatosis type 1 in children 2 years of age and older. It is an inhibitor of mitogen-activated protein kinase and has been recommended as a first-line therapy approved for paediatric neurofibromatosis patients who have inoperable and bulky lesions.
Selumetinib therapy was a good option for this particular child but there were several reasons to choose surgery for this patient. Firstly the deformity was unsightly and grotesque considering the almost double length of the penis was leading to social discrimination, peer pressure and solitary life for this child. The patient has been rehabilitated with just one surgical operation in which after debulking the penile size is within socially acceptable limits. S...
Thanks for the comments on our manuscript entitled "Plexiform neurofibromatosis of penis: a rare presentation of type 1 neurofibromatosis."
We think that this is a very good suggestion for treating such cases. Selumetinib has been found to be effective to treat neurofibromatosis type 1 in children 2 years of age and older. It is an inhibitor of mitogen-activated protein kinase and has been recommended as a first-line therapy approved for paediatric neurofibromatosis patients who have inoperable and bulky lesions.
Selumetinib therapy was a good option for this particular child but there were several reasons to choose surgery for this patient. Firstly the deformity was unsightly and grotesque considering the almost double length of the penis was leading to social discrimination, peer pressure and solitary life for this child. The patient has been rehabilitated with just one surgical operation in which after debulking the penile size is within socially acceptable limits. Secondly, there were financial issues in procuring the drug as the treatment is expensive considering the high monthly costs that are involved in therapy with this particular drug. Thirdly medical treatment with this drug if available would have taken some time for the lesion to regress and the patient's parents were looking for a treatment that could immediately restore normalcy to the deformity.
We will definitely consider drug therapy with Selumetinib for this patient in the follow-up period as it has been shown to be quite effective in treating extensive neurofibromatosis as was seen in this paediatric patient.
A close comparison of baseline and exercise ECGs show mild ST elevation in V1 and mild inferolateral ST depression. Though the ST depression is mostly slow upsloping type, in lead I and V6 it is almost horizontal. The magnified view of the ECG makes ST elevation in V1 quite clear.
The author proposes two possible mechanisms for Aza induced hyperglycemia 1. Impaired beta cell function in pancreas via epigenetic mechanism 2. Increased secretion of cortisol. I suggest another possibility. A recent paper by Strand et al reports that Aza, a DNMT1 inhibitor, is a potent inducer of PTEN (this work done in vascular smooth muscle cells). It is well known that PTEN is an inhibitor of downstream elements of the insulin pathway, specifically PI3K-AKT-mTOR pathway and this results in insulin resistance. I suggest that the hyperglycemic activity of Aza is by PTEN induction of insulin resistance.
Strand KA, Lu S, Mutryn MF, et al. High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN. Arterioscler Thromb Vasc Biol. 2020;40:1854–1869.
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]
Dear Editor,
Show MoreMucormycosis is a fatal fungal infections that mainly affects people who are on medications for other health problems that reduces their ability to fight for environmental pathogens.India is a known to have high burden of mucormycosis cases especially in those with un controlled type 2DM and prevalence of mucormycosis has gone this time up to 2.1times to 3 times during second wave of covid 19 pandemic in India. This may be termed as Covid Associated Mucormycosis or CAM.Prvalance of CAM amongst the covid-19 patients is 0.27/%,and in ICU or in CCU is 1.6% when they are treated with steroid and to those in patients who had high level of blood sugar due to covid- 19 or have high level of ferritin.Occasionally in patients with unconrolled DM ( whose neutrophils functions is impaired in diabetic and those who have neutropenia or altered NL ratio as in covid 19 , as primary defence of mucormycosis is done with neutrophils attached with hyphae ) or in hematlogical malignancies, or in hemopoietic stem cells transplant or in solid organ transplant or in patient's with vercanzole therapy or with immunomodulatory drugs or other immunosuppressive drugs develop fatal mucormycosis.
In covid 19 wards or in SARI wards mucormycosis may develop due to 1) That NL ratio is altered 2) from treatment of steroid dexamethasone injection 3) use of tocilizumab therapy 4) uses of Immunomodulatory drugs like Baricitinib ,tofacitinib and usually found in later pa...
The association between heart failure and energy drink consumption is based on the entire clinical course rather than the presentation alone. The patient remains in renal failure with renal biochemistry similar to presentation and has not received renal replacement therapy for some time. Despite this, the patient is no longer in heart failure with a significant improvement in cardiac function occurring prior to the introduction of heart failure medications - carvedilol, hydralazine and isosorbide dinitrite. The clinical course of spontaneous recovery was similar to the cited case report from Belzile and colleagues and hence our reason for bringing this to attention and contributing to greater awareness. We welcome the comments and debate as there is no test to confirm the relationship to energy drink intake and therefore extensive clinical characterisation is required to exclude alternative causes of severe heart failure. Severe heart failure which improves spontaneously to this magnitude - LVEF 9% to 51% is particularly rare.
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...
The authors implicate caffeine as the causative agent of the cardiomyopathy in this case, caffeine being the main active ingredient within energy drinks. They ask that we enquire about energy drinks within our social histories; consumption of caffeinated products indeed not part of a standard cardiovascular history (1).
It is therefore conspicuous that within the article there are no calls to enquire about other, more widely used caffeine containing products, specifically tea and coffee. Dare I say, we would be unlikely to baulk at the idea of a patient drinking three or four coffees in a day. In fact, on the wards we offer patients tea or coffee eight times a day, yet think little of the caffeine burden we are imposing upon them. This almost tacit caffeine consumption is unlikely to make it into the medical notes, yet these patients would potentially be consuming levels of caffeine far in excess of the quantity consumed in this case report.
We seem to apply different value judgements to different drinks, assuming those drinking excess caffeine from expensive coffee machines are doing so knowingly, and as part of a healthy lifestyle. Yet we don’t afford those choosing to consume energy drinks with the same level of ability to make an informed choice. We medicalise the consumption of such drinks, assuming those using them must be doing so for sinister reasons.
We should treat all caffeinated products equally, given there is no pharmacological differen...
Show MoreA close comparison of baseline and exercise ECGs show mild ST elevation in V1 and mild inferolateral ST depression. Though the ST depression is mostly slow upsloping type, in lead I and V6 it is almost horizontal. The magnified view of the ECG makes ST elevation in V1 quite clear.
The author proposes two possible mechanisms for Aza induced hyperglycemia 1. Impaired beta cell function in pancreas via epigenetic mechanism 2. Increased secretion of cortisol. I suggest another possibility. A recent paper by Strand et al reports that Aza, a DNMT1 inhibitor, is a potent inducer of PTEN (this work done in vascular smooth muscle cells). It is well known that PTEN is an inhibitor of downstream elements of the insulin pathway, specifically PI3K-AKT-mTOR pathway and this results in insulin resistance. I suggest that the hyperglycemic activity of Aza is by PTEN induction of insulin resistance.
Strand KA, Lu S, Mutryn MF, et al. High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN. Arterioscler Thromb Vasc Biol. 2020;40:1854–1869.
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...
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