Sunday, May 3, 2020
Thursday, April 30, 2020
Metronidazole : spectrum of organisms covered mnemonic
Hello
Metronidazole has bactericidal activity against
Protozoa:
- Giardia
- Entamoeba
- Trichomonas
Bacteria: (anaerobic gram-negatives)
- Bacteroides
- Clostridium sp (doc in pseudomembranous colitis)
- GARDNerella
- H. pylori
mnemonic: GET BaC in the GARDEN, Hippo
- Jaskunwar Singh
Metronidazole has bactericidal activity against
Protozoa:
- Giardia
- Entamoeba
- Trichomonas
Bacteria: (anaerobic gram-negatives)
- Bacteroides
- Clostridium sp (doc in pseudomembranous colitis)
- GARDNerella
- H. pylori
mnemonic: GET BaC in the GARDEN, Hippo
- Jaskunwar Singh
Wednesday, April 29, 2020
Red man syndrome - ADR of vancomycin
Hello
Red man syndrome, RMS is an adverse reaction to rapid infusion of vancomycin that leads to flushing/redness of face, neck and upper torso. The mechanism of this reaction is histamine release (anaphylactoid reaction).
Prevention - slow IV infusion of vancomycin over 1 hr
PS - I remember this as lots of wine causes flushing, so does v(w)ancomycin ;D
That's all
- Jaskunwar Singh
Red man syndrome, RMS is an adverse reaction to rapid infusion of vancomycin that leads to flushing/redness of face, neck and upper torso. The mechanism of this reaction is histamine release (anaphylactoid reaction).
Prevention - slow IV infusion of vancomycin over 1 hr
PS - I remember this as lots of wine causes flushing, so does v(w)ancomycin ;D
That's all
- Jaskunwar Singh
Clinical vignette: Meningitis due to Listeria monocytogenes
Hello
Listeria monocytogenes is the 3rd most common organism that causes bacterial meningitis.
Cephalosporins do not cover this gram - positive bacteria under its spectrum. More aptly saying, the cephs do not kill this bacteria. So, especially in high-risk patients such as neonates, elderly, and the immunocompromised, cephalosporins are given in combination with ampicillin, and never alone.
Ceftriaxone is avoided for use in neonates due to its decreased biliary metabolism and sludging.
The choice of ceph in neonates and other high-risk groups in the case of meningitis is cefotaxime.
That's all
- Jaskunwar Singh
Listeria monocytogenes is the 3rd most common organism that causes bacterial meningitis.
Cephalosporins do not cover this gram - positive bacteria under its spectrum. More aptly saying, the cephs do not kill this bacteria. So, especially in high-risk patients such as neonates, elderly, and the immunocompromised, cephalosporins are given in combination with ampicillin, and never alone.
Ceftriaxone is avoided for use in neonates due to its decreased biliary metabolism and sludging.
The choice of ceph in neonates and other high-risk groups in the case of meningitis is cefotaxime.
That's all
- Jaskunwar Singh
Tuesday, April 28, 2020
Clinical correlate: Sildenafil contraindicated for pilots
Hello
PDE-6 is present in the eyes.
What is AI and Why You Should Be Excited About It
In 1950, Alan Turing asked, “Can machines think?”. Fast-forward to 2010 and artificial intelligence can diagnose diseases, fly drones, translate between languages, recognise emotions, trade stocks and even beat humans at Chess and Go.
Artificial Intelligence (AI), in essence, is machines mimicking human intelligence. Now, that can be of two types:
1. One that's already here, narrow AI, where a computer performs some very specific task. Take for example, Apple's Siri or Netflix's recommender system.
2. The other, general AI, that remains science fiction for now. If you're thinking of Jarvis in “Iron Man" or R2-D2 in “Star Wars”, you're quite right.
An application of AI is Machine Learning, where the computer automatically improves at performing a task, with more experience. Deep Learning is a subset of machine learning that is more intensive; uses more data and more complex algorithms.
Now, as a community of medicos, why should we bother about tech at all? Well, the future of healthcare looks increasingly facilitated by technology. The aim is to shift from "treating illness" to "sustaining wellness"; to have have a more proactive, rather than a reactive, model of care delivery. AI will help redesign our services and better utilise our resources. The goal isn't to replace what humans do, but instead augment it.
Here are a few ways AI can potentially help medicine:
1. Image recognition and diagnostic radiography, eg: Qure.ai, and Stanford's CheXpert system
2. Preliminary diagnoses, eg: Babylon Health, and DeepMind's Streams application
3. Virtual nursing assistants, eg: Care Angel's virtual nurse assistant
4. Clinical trials participant identifier, eg: deep6.ai
5. Computer-assisted robotic surgery, eg: Heartlander miniature robot
6. 3D mapping and printing, eg: 3D printed heart stents
7. Administrative workflow assistance, eg: IBM Watson
8. Fraud detection and Cybersecurity, eg: H2O.ai
[The list is by no means exhaustive. I implore you to know more about the examples mentioned by simply copy-pasting them into Google search.]
To conclude, the future of healthcare looks exciting and will be far more collaborative than it is today, working in alliance with AI, data science, statistics, engineering, and genomics. The ultimate objective is always to improve quality of treatment and patient outcomes.
Author's note: If, as a med student or a doctor, you're interested in kickstarting your own career towards AI and healthcare, please let me know in the comments. I will appropriately refer you to the relevant resources. To give you a brief background, I’ve worked with data scientists on seven medicine related portfolio projects, utilising machine and deep learning algorithms. I worked as a clinician and a programmer (have professional working proficiency in Python). Here’s my top 3:
1. Breast Cancer Detection Using Python & Machine Learning, with a model accuracy of 95% using artificial neural networks and support vector machine, on Wisconsin diagnostic data set
2. Identifying Skin Lesions Using Python & Deep Learning, with a model accuracy of 79% using convolution neural networks, on Cornell HAMNIST-10000 data set
3. Determining the Efficacy of Corrective Spinal Surgery in Childhood Kyphosis Using Python & Machine Learning, with a model accuracy of 88% using decision trees and random forest classifier on a Kaggle datset
Thank you for reading.
- Ashish Singh
Artificial Intelligence (AI), in essence, is machines mimicking human intelligence. Now, that can be of two types:
1. One that's already here, narrow AI, where a computer performs some very specific task. Take for example, Apple's Siri or Netflix's recommender system.
2. The other, general AI, that remains science fiction for now. If you're thinking of Jarvis in “Iron Man" or R2-D2 in “Star Wars”, you're quite right.
An application of AI is Machine Learning, where the computer automatically improves at performing a task, with more experience. Deep Learning is a subset of machine learning that is more intensive; uses more data and more complex algorithms.
Now, as a community of medicos, why should we bother about tech at all? Well, the future of healthcare looks increasingly facilitated by technology. The aim is to shift from "treating illness" to "sustaining wellness"; to have have a more proactive, rather than a reactive, model of care delivery. AI will help redesign our services and better utilise our resources. The goal isn't to replace what humans do, but instead augment it.
Here are a few ways AI can potentially help medicine:
1. Image recognition and diagnostic radiography, eg: Qure.ai, and Stanford's CheXpert system
2. Preliminary diagnoses, eg: Babylon Health, and DeepMind's Streams application
3. Virtual nursing assistants, eg: Care Angel's virtual nurse assistant
4. Clinical trials participant identifier, eg: deep6.ai
5. Computer-assisted robotic surgery, eg: Heartlander miniature robot
6. 3D mapping and printing, eg: 3D printed heart stents
7. Administrative workflow assistance, eg: IBM Watson
8. Fraud detection and Cybersecurity, eg: H2O.ai
[The list is by no means exhaustive. I implore you to know more about the examples mentioned by simply copy-pasting them into Google search.]
To conclude, the future of healthcare looks exciting and will be far more collaborative than it is today, working in alliance with AI, data science, statistics, engineering, and genomics. The ultimate objective is always to improve quality of treatment and patient outcomes.
Author's note: If, as a med student or a doctor, you're interested in kickstarting your own career towards AI and healthcare, please let me know in the comments. I will appropriately refer you to the relevant resources. To give you a brief background, I’ve worked with data scientists on seven medicine related portfolio projects, utilising machine and deep learning algorithms. I worked as a clinician and a programmer (have professional working proficiency in Python). Here’s my top 3:
1. Breast Cancer Detection Using Python & Machine Learning, with a model accuracy of 95% using artificial neural networks and support vector machine, on Wisconsin diagnostic data set
2. Identifying Skin Lesions Using Python & Deep Learning, with a model accuracy of 79% using convolution neural networks, on Cornell HAMNIST-10000 data set
3. Determining the Efficacy of Corrective Spinal Surgery in Childhood Kyphosis Using Python & Machine Learning, with a model accuracy of 88% using decision trees and random forest classifier on a Kaggle datset
Thank you for reading.
- Ashish Singh
Saturday, April 25, 2020
COVID-19: Whose Virus Is It Anyway? Possible origins of SARS-CoV-2
It's only reasonable you may want to know about the origins of the COVID-19 pandemic. After all, our lives have been affected, one way or the other. But was it the bat? Was it the pangolin? Or was it a lab experiment gone wrong? Let's look at the two most definitive evidence we have at hand: virus genomics and structure.
Evidence #1
The receptor binding domain (RBD) in the spike protein is the most variable part of the coronavirus family genome. SARS-CoV-2 seems to have an RBD that binds with high affinity to ACE2 from humans, and other species with high receptor homology. This RBD has six key amino acid residues.
Evidence #2
The second notable feature of SARS-CoV-2 is a polybasic cleavage site at the junction of S1 and S2, the two subunits of the spike. This allows effective cleavage by furin and other proteases and has a role in determining viral infectivity and host range. Insertion of proline to this site and subsequent addition of O-linked glycans are unique to SARS-CoV-2.
Keeping these in mind, we have:
Theory #1
Natural selection in animal before zoonotic transfer
As many early cases of COVID-19 were linked to the Huanan market in Wuhan, it is possible that an animal source was present at this location.
Given the similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses, it is likely that bats serve as reservoir hosts for its progenitor. This "bat virus" or more formally, RaTG13 is nearly 96% identical to SARS-CoV-2. Its spike diverges in the RBD, which suggests that it may not bind efficiently to human ACE2.
Malayan pangolins illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-2. Some "pangolin coronavirus" exhibit strong similarity to SARS-CoV-2 in the RBD, including all six key RBD residues. This clearly shows that the SARS-CoV-2 spike protein optimised for binding to human-like ACE2 is the result of natural selection.
Neither the bat nor the pangolin coronavirus, however, has polybasic cleavage sites. This means, no animal coronavirus has been identified that is sufficiently similar to be the direct progenitor of SARS-CoV-2. That said, the diversity of coronaviruses in bats and other species is massively undersampled. Mutations, insertions and deletions can occur near the S1–S2 junction of coronaviruses, which shows that the polybasic cleavage site can arise by a natural evolutionary process. This perfectly sets us up for our next theory.
Theory #2
Natural selection in human after zoonotic transfer
It is possible that a progenitor of SARS-CoV-2 jumped into humans to acquire the genomic features described above through adaptation, during undetected human-to-human transmission. Once acquired, these adaptations would enable the pandemic to take off.
All SARS-CoV-2 genomes sequenced so far have the genomic features described above and are thus derived from a common ancestor that had them too. The "pangolin coronavirus" has an RBD very similar to that of SARS-CoV-2, by the process of natural selection. From this, we can infer the same happened with the virus that jumped to humans. So we can say, with some degree of confidence, the insertion of polybasic cleavage site occured during human-to-human transmission.
From what we know the first case of COVID-19 has been traced back to November 2019. This presumes a period of unrecognised human-to-human transmission, between the initial zoonotic event and the acquisition of the polybasic cleavage site.
Theory #3
Lab experiment gone wrong
Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and animal models has been ongoing for many years in biosafety level 2 laboratories across the world, and there are documented instances of laboratory escapes of SARS-CoV. In theory, it is possible that SARS-CoV-2 acquired RBD mutations during adaptation to passage in cell culture.
Having said that, the "pangolin coronavirus" with nearly identical RBDs, provides a much stronger explanation of how SARS-CoV-2 acquired these via recombination or mutation. The high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2.
The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polygenic cleavage sites have only been observed after prolonged in-vivo passage whereas generating O-linked glycans likely involves an immune system.
Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for coronaviruses would probably have been used. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone.
These are strong arguments that SARS-CoV-2 is not the product of purposeful manipulation.
Conclusion
Theory #2 seems most likely, given the information currently available, but more scientific data could swing the balance of evidence to favour one hypothesis over another. What's important is to further study the possible origins, not just for understanding the current zoonotic pandemic but also to prevent the potential future ones.
References
1. 'The proximal origin of SARS-CoV-2' by Andersen et al: www.nature.com/articles/s41591-020-0820-9
2. 'A pneumonia outbreak associated with a new coronavirus of probable bat origin' by Zhou et al: www.nature.com/articles/s41586-020-2012-7
3. 'A new coronavirus associated with human respiratory disease in China' by Wu et al: www.nature.com/articles/s41586-020-2008-3
- Ashish Singh
Evidence #1
The receptor binding domain (RBD) in the spike protein is the most variable part of the coronavirus family genome. SARS-CoV-2 seems to have an RBD that binds with high affinity to ACE2 from humans, and other species with high receptor homology. This RBD has six key amino acid residues.
Evidence #2
The second notable feature of SARS-CoV-2 is a polybasic cleavage site at the junction of S1 and S2, the two subunits of the spike. This allows effective cleavage by furin and other proteases and has a role in determining viral infectivity and host range. Insertion of proline to this site and subsequent addition of O-linked glycans are unique to SARS-CoV-2.
Keeping these in mind, we have:
Theory #1
Natural selection in animal before zoonotic transfer
As many early cases of COVID-19 were linked to the Huanan market in Wuhan, it is possible that an animal source was present at this location.
Given the similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses, it is likely that bats serve as reservoir hosts for its progenitor. This "bat virus" or more formally, RaTG13 is nearly 96% identical to SARS-CoV-2. Its spike diverges in the RBD, which suggests that it may not bind efficiently to human ACE2.
Malayan pangolins illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-2. Some "pangolin coronavirus" exhibit strong similarity to SARS-CoV-2 in the RBD, including all six key RBD residues. This clearly shows that the SARS-CoV-2 spike protein optimised for binding to human-like ACE2 is the result of natural selection.
Neither the bat nor the pangolin coronavirus, however, has polybasic cleavage sites. This means, no animal coronavirus has been identified that is sufficiently similar to be the direct progenitor of SARS-CoV-2. That said, the diversity of coronaviruses in bats and other species is massively undersampled. Mutations, insertions and deletions can occur near the S1–S2 junction of coronaviruses, which shows that the polybasic cleavage site can arise by a natural evolutionary process. This perfectly sets us up for our next theory.
Theory #2
Natural selection in human after zoonotic transfer
It is possible that a progenitor of SARS-CoV-2 jumped into humans to acquire the genomic features described above through adaptation, during undetected human-to-human transmission. Once acquired, these adaptations would enable the pandemic to take off.
All SARS-CoV-2 genomes sequenced so far have the genomic features described above and are thus derived from a common ancestor that had them too. The "pangolin coronavirus" has an RBD very similar to that of SARS-CoV-2, by the process of natural selection. From this, we can infer the same happened with the virus that jumped to humans. So we can say, with some degree of confidence, the insertion of polybasic cleavage site occured during human-to-human transmission.
From what we know the first case of COVID-19 has been traced back to November 2019. This presumes a period of unrecognised human-to-human transmission, between the initial zoonotic event and the acquisition of the polybasic cleavage site.
Theory #3
Lab experiment gone wrong
Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and animal models has been ongoing for many years in biosafety level 2 laboratories across the world, and there are documented instances of laboratory escapes of SARS-CoV. In theory, it is possible that SARS-CoV-2 acquired RBD mutations during adaptation to passage in cell culture.
Having said that, the "pangolin coronavirus" with nearly identical RBDs, provides a much stronger explanation of how SARS-CoV-2 acquired these via recombination or mutation. The high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2.
The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polygenic cleavage sites have only been observed after prolonged in-vivo passage whereas generating O-linked glycans likely involves an immune system.
Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for coronaviruses would probably have been used. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone.
These are strong arguments that SARS-CoV-2 is not the product of purposeful manipulation.
Conclusion
Theory #2 seems most likely, given the information currently available, but more scientific data could swing the balance of evidence to favour one hypothesis over another. What's important is to further study the possible origins, not just for understanding the current zoonotic pandemic but also to prevent the potential future ones.
References
1. 'The proximal origin of SARS-CoV-2' by Andersen et al: www.nature.com/articles/s41591-020-0820-9
2. 'A pneumonia outbreak associated with a new coronavirus of probable bat origin' by Zhou et al: www.nature.com/articles/s41586-020-2012-7
3. 'A new coronavirus associated with human respiratory disease in China' by Wu et al: www.nature.com/articles/s41586-020-2008-3
- Ashish Singh
Friday, April 24, 2020
Coronary artery anatomy mnemonic and video for visualization
Let's learn about the coronary artery anatomy today (and never forget it!)
Watch the video. Text and images below.
Watch the video. Text and images below.
Coronary artery dominance and EKG changes
Hello, hello!
Coronary arterial dominance is defined by the vessel which gives rise to the posterior descending artery (PDA).
Coronary arterial dominance is defined by the vessel which gives rise to the posterior descending artery (PDA).
Funnel Plot
-also called as Begg’s plot
-type of scatter plot
-used to examine biases in meta-analyses
An ideal funnel plot is symmetric.
If no biases, 95% of studies lie within the triangle.
-type of scatter plot
-used to examine biases in meta-analyses
An ideal funnel plot is symmetric.
If no biases, 95% of studies lie within the triangle.
Wednesday, April 22, 2020
Thursday, April 16, 2020
Thioamides in pregnancy
Hello
Propylthiouracil is a pro. It always comes first (used in first trimester of pregnancy).
Methimazole causes Malformations in the embryo (teratogenic).
There are two M's in MethiMazole. This drug is used in second (and third trimester of pregnancy).
Propylthiouracil piles up, causing liver toxicity, thus limiting its use.
Hope it helps
- Jaskunwar Singh
Propylthiouracil is a pro. It always comes first (used in first trimester of pregnancy).
Methimazole causes Malformations in the embryo (teratogenic).
There are two M's in MethiMazole. This drug is used in second (and third trimester of pregnancy).
Propylthiouracil piles up, causing liver toxicity, thus limiting its use.
Hope it helps
- Jaskunwar Singh
Wednesday, April 15, 2020
Importance of Ischial spine
Following are the important points of the ishial spine :-
Mnemonic SID BPL
1) Station of fetal head is calculated with respect to Ischial spine.
2) Internal rotation of fetal head occurs at this level.
3) Deep transverse arrest occurs at this level.
4) It is site for giving pudendal block.
5) Place at which ring pessory inserted.
6) Levator ani muscle is attached here.
PS : Question which was asked in central institute examination (I felt it should be mentioed here)
Which ligament is felt while giving pudendal block?
Sacrospinal ligament.
Clinical pearl : TNF-alpha therapy
Hello
In case of granulomatous diseases, macrophages activated by Th1 cells lead to increased levels of TNF-alpha. Now, TNF-alpha induces and maintains granuloma formation. Basic, right?
So we give anti-TNF drugs (adalimumab, infliximab, etc.). However, they cause the granuloma to break down, thus leading to disseminated disease.
Bottom line - Always remember to check for the presence of latent TB before starting anti-TNF therapy.
That's all
- Jaskunwar Singh
In case of granulomatous diseases, macrophages activated by Th1 cells lead to increased levels of TNF-alpha. Now, TNF-alpha induces and maintains granuloma formation. Basic, right?
So we give anti-TNF drugs (adalimumab, infliximab, etc.). However, they cause the granuloma to break down, thus leading to disseminated disease.
Bottom line - Always remember to check for the presence of latent TB before starting anti-TNF therapy.
That's all
- Jaskunwar Singh
Tuesday, April 14, 2020
COVID-19: effects on reproduction
Hello
In this post, I will be talking about effects of SARS-CoV-2 on the male reproductive system, as evidenced from a recent study.
In this post, I will be talking about effects of SARS-CoV-2 on the male reproductive system, as evidenced from a recent study.
Friday, April 10, 2020
COVID-19: Whatsapp group
I created a COVID-19 Whatsapp group to strictly discuss the medical aspect of the disease, the latest research/community practices. Email me if interested: medicowesome@gmail.com
-IkaN
-IkaN
Thursday, April 9, 2020
COVID-19: Neurological manifestations
Since the Chinese health authorities confirmed the first case of novel coronavirus infection, almost all of the clinical focus has been on the viral's prodromal symptoms and severe life-threatening adverse effects such as ARDS. However, neurologists all over the world have been reporting the neurological manifestations of COVID-19 such as, ataxia, encephalopathy, myelitis among others. One neurological symptom in particular received inordinate attention, anosmia, even though it barely has any diagnostic relevance. It is safe to say that the neurological deficits are ongoing in this pandemic without getting noticed appropriately. However, since we are in the early phases of understanding the clinical conundrum of the COVID-19, such relative blindness is expected.
How does SARS-CoV-2 enter the CNS?
Two pathways have been postulated:
1. Through the cribriform plate
2. Systemic circulatory dissemination after infecting the lungs.
Reported neurological manifestations:
1. Anosmia - Can be explained by the proximity of the olfactory bulb to the cribriform plate
2. Hypoguesia, dysguesia
3. Headache, malaise
4. Unstable walking or ataxia, dizziness
These four can occur in the early phase of the disease.
5. Cerebral hemorrhage - This has been hypothesized to be due to decrease in expression and function of ACE2 proteins, especially in hypertensive patients in whom the expression of ACE2 is already low. Given that ACE2 signaling lowers BP, lack of ACE2 function would lead to higher BP which might precipitate cerebral hemorrhage.
6. Cerebral infarction (acute cerebrovascular disease causing stroke)
7. Ondine's curse - The central respiratory centres lose their function, which consequently impairs involuntary respiration severely.
8. Acute encephalopathy - headache, altered mental status, convulsions.
9. Myopathy
Interestingly, the CSF in the patients were normal, which implies that COVID-19 does not cross the blood brain barrier and hence cannot cause meningitis or encephalitis. We should keep in mind that the neurological manifestations could be secondary to hypoxia, respiratory or metabolic acidosis and other complications of the COVID-19 infection.
Thank you!
-Vinayak
References:
1. Necrotizing Encephalopathy: CT and MRI Features
https://pubs.rsna.org/doi/10.1148/radiol.2020201187
2. Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy
https://www.cureus.com/articles/29414-neurological-complications-of-coronavirus-disease-covid-19-encephalopathy
3. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study
https://www.medrxiv.org/content/10.1101/2020.02.22.20026500v1
COVID-19: Lymphopenia and pneumonia
Hello everyone!
In the context of COVID-19, we will talk about two specific terms: Lymphopenia and Pneumonia.
COVID-19 Pneumonia
We mention "pneumonia" when there is an acute inflammation of the lungs following an infection. Pneumonia is one of the common features in infected patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pneumonia has various clinical and radiological characteristics depending on the stage of the disease. It evolves rapidly, even in asymptomatic patients from local unilateral to diffuse bilateral ground-grass opacities which progress within 1-3 weeks to consolidation or co-exists with. A retrospective study at Wuhan describes radiological findings from 81 patients with COVID-19 pneumonia. The predominant pattern of abnormality observed was bilateral (79%), peripheral (54%), ill-defined (81%) and ground-glass opacification (65%), mainly involving the right lower lobes. [1]
In the context of COVID-19, we will talk about two specific terms: Lymphopenia and Pneumonia.
COVID-19 Pneumonia
We mention "pneumonia" when there is an acute inflammation of the lungs following an infection. Pneumonia is one of the common features in infected patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pneumonia has various clinical and radiological characteristics depending on the stage of the disease. It evolves rapidly, even in asymptomatic patients from local unilateral to diffuse bilateral ground-grass opacities which progress within 1-3 weeks to consolidation or co-exists with. A retrospective study at Wuhan describes radiological findings from 81 patients with COVID-19 pneumonia. The predominant pattern of abnormality observed was bilateral (79%), peripheral (54%), ill-defined (81%) and ground-glass opacification (65%), mainly involving the right lower lobes. [1]
Instructions for new authors: Images, plagiarism, and grammar
Hello awesome authors,
I thought of writing a small guide on things to be mindful when posting images or writing new blogs.
I thought of writing a small guide on things to be mindful when posting images or writing new blogs.
COVID-19: Use of masks
Hi everyone!
We used the WHO guidelines to write the pdf and uploaded it over here
We used the WHO guidelines to write the pdf and uploaded it over here
COVID 19: How to limit the spread?
COVID19 spreads primarily through droplets of saliva or discharge from the nose when an infected patient coughs or sneezes (we should so cough or sneeze into a tissue or flexed elbow). The SARS-CoV-2 can also be carried, that's why the handwashing is so important.
We use other means of prevention to limit the spreading, for example, masks and negative pressure rooms. Let us see how it is done.
We use other means of prevention to limit the spreading, for example, masks and negative pressure rooms. Let us see how it is done.
Wednesday, April 8, 2020
COVID-19: Containment strategy by South Korea
Hello everyone!
In this post, we will discuss the manner with which South Korea managed to contain the virus rather successfully.
So let me help you catch up:-
In this post, we will discuss the manner with which South Korea managed to contain the virus rather successfully.
So let me help you catch up:-
Club foot: Age-wise Management Flowchart
Club foot is one that resembles a golf club. It is also called Congenital Talipes Equino Varus or CTEV.
 |
| Figure 1. Dennis-Brown Splint |
Saturday, April 4, 2020
How to cite articles
Hi everyone,
I wanted to write a quick post on how to cite references for Medicowesome Student Guest Authors (MSGAites!). Medicowesome is not a peer-reviewed journal, we are just a website where we post mnemonics, study material, and cool facts. Recently, we've been writing about COVID-19. Because there has been so much fake news and miscommunication about the characteristics of this disease, we decided that all posts related to COVID-19 would have journal articles in literature as references.
There are many styles in which you can format references. You can read more about it in this paper by Kambhampati & Maini, 2019. [1] It is preferred that you use a particular formatting style for all the references in your article. Simply adding links is not preferred because websites change their links all the time. The best way to ensure that your reader finds the article you're referencing is by using a proper reference format. A DOI is guaranteed never to change, so you can use it as a permanent link to any electronic article.
I wanted to write a quick post on how to cite references for Medicowesome Student Guest Authors (MSGAites!). Medicowesome is not a peer-reviewed journal, we are just a website where we post mnemonics, study material, and cool facts. Recently, we've been writing about COVID-19. Because there has been so much fake news and miscommunication about the characteristics of this disease, we decided that all posts related to COVID-19 would have journal articles in literature as references.
There are many styles in which you can format references. You can read more about it in this paper by Kambhampati & Maini, 2019. [1] It is preferred that you use a particular formatting style for all the references in your article. Simply adding links is not preferred because websites change their links all the time. The best way to ensure that your reader finds the article you're referencing is by using a proper reference format. A DOI is guaranteed never to change, so you can use it as a permanent link to any electronic article.
COVID-19: SARI treatment facility design
Hi everyone,
One of our guest authors, Tanay Saxena, recently completed a course on Severe Acute Respiratory Infections Treatment Centre. He compiled a very thorough set of notes during the course based on the WHO Severe Acute Respiratory Infections Treatment Centre practical manual that has been developed for the COVID-19 pandemic.
One of our guest authors, Tanay Saxena, recently completed a course on Severe Acute Respiratory Infections Treatment Centre. He compiled a very thorough set of notes during the course based on the WHO Severe Acute Respiratory Infections Treatment Centre practical manual that has been developed for the COVID-19 pandemic.
Friday, April 3, 2020
COVID-19: Trained immunity from BCG vaccine
Would BCG vaccination really help in immunizing up against SARS-CoV-2?
Let's dig in.
BCG is a live-attenuated strain derived from an isolate of Mycobacterium bovis used widely across the world as a vaccine for tuberculosis (TB). But that's not all, BCG vaccination is a potential goldmine against so many diseases.
COVID-19: Hydroxychloroquine mechanism and role in management of SARS-CoV-2 infection
Hello everyone, this post aims to highlight all the important aspects of the recently famous drug hydroxychloroquine in the management of COVID-19.
Mechanism of action: In a study by Aartjan et al, zinc ions (Zn2+) in high intracellular concentrations have been shown to inhibit viral RNA polymerase. However, zinc being an ion cannot enter the cell through the plasma membrane, so it needs ionophores such as pyrithione (PT) to enter the cell, where, in high concentrations, it can efficiently impair the replication of a variety of RNA viruses. Chloroquine can also act as an ionophore that can increase zinc ions transport into the cell.
According to Harrison’s principles of internal medicine, “Infection of tissue culture cells by viruses such as Semliki Forest virus, vesicular stomatitis virus, and certain strains of influenza virus can be prevented by chloroquine, an agent that blocks the function of lysosomes. Chloroquine is a weak base that diffuses into lysosomes and becomes protonated, raiding the pH and ionic strength of the lysosome. When the pH rises, the lysosomal enzymes fail to function. Viruses that require acid pH to fuse with cell membranes can no longer do so in the presence of chloroquine, and the cells are protected from infection.”
Studies revealed that it also has potential broad-spectrum antiviral activities by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV. The anti-viral and anti-inflammatory activities of chloroquine may account for its potent efficacy in treating patients with COVID-19 pneumonia.
Chloroquine can also prevent orf1ab, ORF3a, and ORF10 from attacking the heme to form the porphyrin and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieving the symptoms of respiratory distress. The infectivity of the nCoV pneumonia was not completely prevented by the drugs, because the binding of E2 glycoprotein and porphyrin was not inhibited. You can read more about this on our previous post on: Coronavirus and hemoglobin https://www.medicowesome.com/2020/04/covid-19-coronavirus-and-hemoglobin.html
1. In India, ICMR has recommended this drug for prophylaxis to healthcare workers dealing with infected patients and asymptomatic contacts of infected people at a dose of 400 mg per week. Besides AIIMS(New Delhi) has recommended this drug for the treatment of moderate to severe cases who are admitted in the hospital at a dose of 400 mg BD for 1 day which is followed by 200 mg BD for 5 days.
Mechanism of action: In a study by Aartjan et al, zinc ions (Zn2+) in high intracellular concentrations have been shown to inhibit viral RNA polymerase. However, zinc being an ion cannot enter the cell through the plasma membrane, so it needs ionophores such as pyrithione (PT) to enter the cell, where, in high concentrations, it can efficiently impair the replication of a variety of RNA viruses. Chloroquine can also act as an ionophore that can increase zinc ions transport into the cell.
According to Harrison’s principles of internal medicine, “Infection of tissue culture cells by viruses such as Semliki Forest virus, vesicular stomatitis virus, and certain strains of influenza virus can be prevented by chloroquine, an agent that blocks the function of lysosomes. Chloroquine is a weak base that diffuses into lysosomes and becomes protonated, raiding the pH and ionic strength of the lysosome. When the pH rises, the lysosomal enzymes fail to function. Viruses that require acid pH to fuse with cell membranes can no longer do so in the presence of chloroquine, and the cells are protected from infection.”
Studies revealed that it also has potential broad-spectrum antiviral activities by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV. The anti-viral and anti-inflammatory activities of chloroquine may account for its potent efficacy in treating patients with COVID-19 pneumonia.
Chloroquine can also prevent orf1ab, ORF3a, and ORF10 from attacking the heme to form the porphyrin and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieving the symptoms of respiratory distress. The infectivity of the nCoV pneumonia was not completely prevented by the drugs, because the binding of E2 glycoprotein and porphyrin was not inhibited. You can read more about this on our previous post on: Coronavirus and hemoglobin https://www.medicowesome.com/2020/04/covid-19-coronavirus-and-hemoglobin.html
Current place in the management of COVID-19
2. Chen et al in an unpublished RCT of 30 patients did not find HCQ provided benefit. The study suggests that if it has an impact, it is likely small.
3. Gautret et al in a non-RCT of 36 patients suggested that HCQ reduced the duration of viral shedding in infected patients. 6 patients in a post-hoc analysis who received HCQ in combination with azithromycin showed further reduction in the viral carriage. However, this was not statistically significant and groups were not well balanced at baseline.
4. Chen et al in a double-blind RCT of 62 patients showed that HCQ can significantly shorten the time to clinical recovery and promote the absorption of pneumonia among patients with COVID-19. However, this study has not yet been certified by peer review.
5. The Marseille study, an unblinded, non-randomized study of 26 infected patients showed a significant reduction in viral load with HCQ. And the number of positive cases was spectacularly reduced by the combination of HCQ with azithromycin. However, this study was full of flaws, there wasn’t adequate matching between the two groups, there were 6 dropouts who weren’t accounted in the study, patients in the control group didn’t have uniform testing, and the patients in the HCQ group had more severe symptoms and were further along in their clinical course. Apparently, this was the study, based on which President Trump promoted the use of HCQ!
6. The patients taking HCQ should be closely monitored for toxicity, in particular, QT prolongation; especially if it is used with azithromycin. Combining lopinavir/ritonavir with HCQ or chloroquine can cause serious arrhythmias and drug interactions due to the increased QT interval.
Effect of the pandemic on drug supplies for Rheumatology patients
Hydroxychloroquine has been in use since the 1940s for the treatment of rheumatological conditions such as RA, SLE, and Sjögren’s syndrome. The sudden interest in this drug has led to shortages for patients who rely on it for the treatment of their autoimmune conditions. The Lupus Foundation of America has called on drug manufacturers to increase the production of HCQ, in order to ensure that patients with SLE are still able to access it without much difficulty.
Overall, no agent has proven efficacy for COVID-19. A number of approaches are being investigated based on in vitro or extrapolated evidence, including remdesivir, hydroxychloroquine, chloroquine, interleukin-6 pathway inhibitors, and convalescent plasma. When treatment of COVID-19 is being considered, patients should be referred to a clinical trial whenever possible. A registry of international clinical trials can be found at clinicaltrials.gov.
Thank you! :)
-Vinayak
References:
1. CHEN J. ,LIU D. et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang Univ (Med Sci), 2020, 49(1): 0-0.
2. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020. [PMID:32205204]
3. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020. [PMID:32020029]
4. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. Zhaowei Chen, Jijia Hu, et al. medRxiv 2020.03.22.20040758; doi: https://doi.org/10.1101/2020.03.22.20040758
5.te Velthuis AJ, et al. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS
Pathog. 2010 Nov 4;6(11):e1001176. doi: 10.1371/journal.ppat.1001176. PubMed
PMID: 21079686; PubMed Central PMCID: PMC2973827.
2. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020. [PMID:32205204]
3. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020. [PMID:32020029]
4. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. Zhaowei Chen, Jijia Hu, et al. medRxiv 2020.03.22.20040758; doi: https://doi.org/10.1101/2020.03.22.20040758
5.te Velthuis AJ, et al. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS
Pathog. 2010 Nov 4;6(11):e1001176. doi: 10.1371/journal.ppat.1001176. PubMed
PMID: 21079686; PubMed Central PMCID: PMC2973827.
COVID-19: Coronavirus and hemoglobin
Hello Awesomites!
Please refer to the diagrams for better understanding.
Why do we have abnormal hemoglobin-related biochemical indices in COVID-19 patients?
Reports demonstrate that the hemoglobin and neutrophil counts decrease in most patients with SARS-CoV-2 infection, and values of serum ferritin, erythrocyte sedimentation rate, C-reactive protein, albumin, and lactate dehydrogenase increase significantly.
What makes hemoglobin an attractive molecule for the coronavirus?
Porphyrins!
Porphyrins in the human body are mostly iron porphyrins i.e heme. And a lot of heme is not free, but bound to hemoglobin. Viruses require porphyrins to survive. Therefore, the novel coronavirus targets hemoglobin, attacks heme, and hunts porphyrins.
The possible mechanism is that orf1ab bound to the alpha chain and attacks the beta chain, causing conformational changes in the alpha and beta chains; ORF3 attacks the beta chain and exposes heme. ORF10 then quickly attaches to the beta chain and directly impacts the iron atoms on the heme of the beta chain. The heme is dissociated into porphyrin, and
orf1ab finally captures porphyrin. Orf1ab plays a vital role throughout the attack. Attack of oxidized hemoglobin by viral proteins leads to less and less hemoglobin that can carry oxygen. The invasion of viral proteins on deoxidized hemoglobin will cause less and less hemoglobin that can carry carbon dioxide.
This study found that ORF8 and surface glycoprotein had a function to combine with porphyrin to form a complex, while orf1ab, ORF10, ORF3a coordinately attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. This mechanism of the virus inhibited the normal metabolic pathway of heme, and made people show symptoms of the disease.
What causes the high infectivity of the novel coronavirus?
Medical workers have detected the novel coronavirus from urine, saliva, feces, and blood. The virus can also live in body fluids. In such media, porphyrin is a prevalent substance. At the beginning of life, virus molecules with porphyrins directly move into the original membrane structure by porphyrin permeability. This study showed that the E2 glycoprotein and Envelope protein of the novel coronavirus could bind well to porphyrins. Therefore, the coronavirus may also directly penetrate the human cell membrane through porphyrin. (Means If the virus can bind with porphyrins, it can enter these secretory cells without ACE2 receptors by using the membrane permeability)
What is the importance of knowing the above information?
The drugs based on this mechanism: Chloroquine and Favipiravir.
The primary function of the Envelope protein is to help the virus enter host cells. The primary role of Favipiravir is to prevent the virus from entering host cells and catching free porphyrins. Favipiravir's ability to improve respiratory distress is lower. Favipiravir can only prevent the binding of Envelope protein and porphyrin.
Chloroquine could prevent orf1ab, ORF3a, and ORF10 from attacking the heme to form the porphyrin and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress.
The infectivity of the nCoV pneumonia was not completely prevented by the drugs, because the binding of E2 glycoprotein and porphyrin was not inhibited.
Note for Diabetic patients
Diabetic patients and older people have higher glycated hemoglobin. Glycated hemoglobin was reduced by the attack, which made patients' blood sugar unstable. Since the porphyrin complexes of the virus produced in the human body inhibited the heme anabolic pathway.
Written by Upasana Yadav
(Courtesy:-Thank you Ikan for all the help)
References:
1. Wenzhong, liu; hualan, Li (2020): COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.11938173.v5
Link to the article: https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
Please refer to the diagrams for better understanding.
Why do we have abnormal hemoglobin-related biochemical indices in COVID-19 patients?
Reports demonstrate that the hemoglobin and neutrophil counts decrease in most patients with SARS-CoV-2 infection, and values of serum ferritin, erythrocyte sedimentation rate, C-reactive protein, albumin, and lactate dehydrogenase increase significantly.
What makes hemoglobin an attractive molecule for the coronavirus?
Porphyrins!
Porphyrins in the human body are mostly iron porphyrins i.e heme. And a lot of heme is not free, but bound to hemoglobin. Viruses require porphyrins to survive. Therefore, the novel coronavirus targets hemoglobin, attacks heme, and hunts porphyrins.
 |
| Structure of SARS-CoV-2 |
Image by Upasana Yadav
This study found that ORF8 and surface glycoprotein had a function to combine with porphyrin to form a complex, while orf1ab, ORF10, ORF3a coordinately attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. This mechanism of the virus inhibited the normal metabolic pathway of heme, and made people show symptoms of the disease.
What causes the high infectivity of the novel coronavirus?
Medical workers have detected the novel coronavirus from urine, saliva, feces, and blood. The virus can also live in body fluids. In such media, porphyrin is a prevalent substance. At the beginning of life, virus molecules with porphyrins directly move into the original membrane structure by porphyrin permeability. This study showed that the E2 glycoprotein and Envelope protein of the novel coronavirus could bind well to porphyrins. Therefore, the coronavirus may also directly penetrate the human cell membrane through porphyrin. (Means If the virus can bind with porphyrins, it can enter these secretory cells without ACE2 receptors by using the membrane permeability)
What is the importance of knowing the above information?
The drugs based on this mechanism: Chloroquine and Favipiravir.
The primary function of the Envelope protein is to help the virus enter host cells. The primary role of Favipiravir is to prevent the virus from entering host cells and catching free porphyrins. Favipiravir's ability to improve respiratory distress is lower. Favipiravir can only prevent the binding of Envelope protein and porphyrin.
Chloroquine could prevent orf1ab, ORF3a, and ORF10 from attacking the heme to form the porphyrin and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress.
The infectivity of the nCoV pneumonia was not completely prevented by the drugs, because the binding of E2 glycoprotein and porphyrin was not inhibited.
Note for Diabetic patients
Diabetic patients and older people have higher glycated hemoglobin. Glycated hemoglobin was reduced by the attack, which made patients' blood sugar unstable. Since the porphyrin complexes of the virus produced in the human body inhibited the heme anabolic pathway.
Written by Upasana Yadav
(Courtesy:-Thank you Ikan for all the help)
1. Wenzhong, liu; hualan, Li (2020): COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.11938173.v5
Link to the article: https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
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