Sunday, May 24, 2020

Tuesday, May 19, 2020

High-yield : Risk of stroke with cardioversion

Hello

Electrical/chemical cardioversion performed in a case of atrial fibrillation may carry a high-risk of stroke, especially if >48 hours of time has passed (thrombus formation takes about 48 hours).

Monday, May 18, 2020

Causes of holosystolic murmur mnemonic

Hello

Causes of holosystolic murmur: MTV reality shows
- Mitral regurgitation
- Tricuspid regurgitation
- Ventricular septal defect

- Jaskunwar Singh

Sunday, May 17, 2020

High-yield : Absence of tachycardia in cardiac tamponade (mnemonic)

Hello

Tachycardia is a characteristic feature of decreased systolic blood pressure in the patients of cardiac tamponade. However, there are exceptions to be taken care of during diagnosis and workup on the patients with following conditions (absence of tachycardia):

A Factor A Day Keeps Colon Cancer Away

Protective Factors For Colon Carcinoma

A - Aspirin,vitamin A 

B - Bisphosphonates
C - Calcium, Coffee, vitamin C
D - Dietary Fiber
E - vitamin E
F - Fruits
G - Green Vegetables

Clinical vignette: Chest pain in acute pericarditis

Hello

Acute myocardial infarction is one of the miscellaneous causes of acute pericarditis. Differentiating features of chest pain in these two cases are many, but the high-yield points to be noted are:-

Saturday, May 16, 2020

Friday, May 15, 2020

Pericardial knock v/s Pericardial rub

Hello

Pericardial knock:
- most common cause is constrictive pericarditis
- occurs during the healing phase of the disease (fibrocalcifications)
- during the early diastolic phase of cardiac cycle (after opening snap)
- On auscultation: high frequency sound

Pericardial rub:
- commonly seen in acute fibrinous or sero-fibrinous pericarditis
- sero-fibrinous exudate in between two layers of pericardium (disease process going on)
- may occur during ventricular systole, or ventricular early diastole (due to expansion) or late diastole (due to atrial contraction).
- on auscultation: rough scraping sound described as "leather rubbing against leather"


That's all
- Jaskunwar Singh

Thursday, May 14, 2020

Apraxia vs autotopagnosia

Hello Awesomites !

Here we will discuss two from many parietal lobe lesion.

1.APRAXIA
Inability to carry out well organized voluntary movement correctly.
Despite motor, sensory & coordinated functions are not significantly impaired.

Ideomotor : It is a type of apraxia.
Patient performs the task but makes errors; there is a common tendency to substitute a body part for an object.
2.AGNOSIA
Abnormalities of perception of sensation despite normal sensory pathways.
Visual & body perception are impaired in parietal lobe lesions 

Agnosia of body scheme or autotopagnosia
Inability to locate, identify & orient one’s body parts.

Suppose while on rounds in neurology ward:- You see a patient brushing his knee early morning.(according to above discussion)

Apraxia -Patient has forgotten how to use toothbrush.Brushing knee as a toothbrush rather than pretending to hold one.
Autotopagnosia- the patient has forgotten the body part itself.

In either case localisation of lesion is PARIETAL LOBE.

Isn't the interpretation of one neurological sign seems interesting?
"Eyes see what mind knows"

Below is the link which is very descriptive and I came across it while reading more on this topic.
Happy studying !
-Upasana Y.

Beta 2 agonist and effect on muscles

Hello Awesomites !

I used to have a doubt why does Salbutamol cause uterine relaxation but causes contraction of skeletal muscle and cardiac muscle(tremors and tachycardia)?

Despite they have same receptors (Beta 2) how can be the action on muscle is so different.
Grossly it seems like one receptor Beta 2. This beta2 adrenergic receptor is a type of GPCR.
GPCR  are Gs, Gq ,Gi type.

Beta 2 receptor anywhere (Uterus -smooth muscle, heart- cardiac muscle, hands- skeletal muscle) is also same type of GPCR i.e Gs.

Still no difference.

Gs activates adenyl cyclase to form cAMP from ATP.
cAMP increases in all type of muscle on stimulation of Beta 2 receptor.
But it cause relaxation in smooth muscle (inhibit myosin light chain kinase)
And causes contraction of heart and skeletal muscle (activate cAMP dependent protein kinase A lead to activation of L-type calcium channel).

At one level we all may appear to be doing same thing yet at other level we are different and have our role.:)

 Happy studying !
-Upasana Y.

Wednesday, May 13, 2020

COVID-19 and Vasculopathy

Over the past few months, overwhelming evidence has accumulated suggesting the dysregulation of the coagulation pathways in COVID patients stemming from the altered immune and inflammatory response towards SARS-CoV2.

Observed coagulation abnormalities have multi-faceted pathogenesis. Most likely suspect is microvascular dysfunction secondary to cytokine storm like state, tipping the balance towards thrombosis. Direct vascular injury is also likely with evidence of endothelial viral inclusions in some cases.

-Pulmonary Intravascular Thrombosis

Evidence suggests that starking discrepancy exists between hypoxemia onset and respiratory failure in COVID patients, with former occurring fairly early in the disease course, pointing to the fact that it's not classic ARDS like pathology that is responsible for the marked deterioration in the pulmonary gas exchange process. It is appropriately explained by the diffuse thrombosis affecting the pulmonary vasculature. In fact, it's so prominent that a whole new entity called "Pulmonary Intravascular Thrombosis" has been proposed as the framework for explaining this phenomenon.

Pulmonary Intravascular Thrombosis could be considered as lying along the spectrum of classic DIC with few important dissimilarities. It is usually localized to the pulmonary vascular bed at least initially and doesn't feature hypofibrinogenemia, consistent with the acute phase response driving continued fibrinogen production. D-dimers levels, however, are significantly elevated suggesting the thrombus formation and ongoing hyperfibrinolysis.

-Pathogenesis

ACE2 is expressed in huge numbers on the alveolar epithelial cells, especially type 2 cells and also pulmonary endothelial cells. Hence, in contrast to patchy involvement classically seen in bronchopneumonia, in COVID, extensive involvement of the alveolo-capillary network is seen. This, in turn, results in florid interstitial inflammation resulting in efflux and activation of macrophages in the alveoli. It is so rampant that it has been likened to Macrophage Activation Syndrome (MAS) or sHLH like state. Activated epithelial cells and macrophages then orchestrate the cytokine storm leading to microvascular dysfunction and widespread thrombosis in the juxtaposed capillary network. Enhanced tissue factor and thrombin expression, coupled simultaneously with the reduced levels of PAI-1 drives thrombosis. Hypoxemia due to V/Q mismatch further exacerbates this process.

Levels of ACE2 in alveoli initially decreases as the virus particles are internalized. ACE2, by virtue of it's ability to convert AngII to anti-inflammatory Ang1-7 peptide, keeps excessive inflammation in check. Hence, reduced ACE2 expression compounds the thrombotic propensity in the vascular bed. Direct involvement of endothelial cells by virus leading to endothelitis/vasculitis has also been suggested, although endothelial activation due to inflammatory cytokines seems more likely.

Reduced type 1 interferon signalling pathways is another intriguing possibility contributing to hyperinflammation. The role of positive pressure ventilation in forcing the viral particles and cytokines in vasculature also merits consideration.

- Skin manifestations

A variety of skin manifestations ranging from pseudo-chilblains to livedoid lesions have been described in COVID patients. While some of the lesions, like acral vesicles and pustules, confer to the pattern of viral exanthem, livedoid lesions suggest the possibility of vascular injury. These vasculopathic eruptions are known as "toevids", appearing as violaceous plaque-like eruptions over toes. Upon molecular testing, such patients often are negative, suggesting that they have probably cleared the infection and vascular injury is perhaps immune-mediated.
Interestingly, papular gloves and socks syndrome, occasionally seen in association with viral infections, especially Parvovirus, bears substantial similarity to certain COVID lesions, both clinically and histologically, with some reports even documenting evidence of leukocytoclastic vasculitis in former.



-Clinical Relevance

Significant elevations in pulmonary pressures due to diffuse thrombosis strains the right ventricle causing hemodynamic dysfunction. Elevated D-dimer, pro- BNP, and troponin levels have been proven to be poor prognostic markers consistently across various studies. Development of overt DIC like state certainly portends dismal prognosis.

Troponinemia in COVID can be attributed to severe right ventricular strain in the setting of pulmonary embolism and/or Pulmonary Intravascular Thrombosis. Some evidence also exists regarding the possibility of myocarditis, however, without classic lymphocytic infiltration characteristic of viral myocarditis.



To summarize, intricate interplay of diffuse pulmonary intravascular thrombosis and MAS like state drives the severe and often fatal pulmonary microvascular dysfunction in COVID.

SARS-CoV2 infection--> diffuse alveolar damage--> interstitial inflammation--> MAS like state--> massive activation of macrophages--> local inflammatory cytokine milieu--> Microvascular dysfunction--> Pulmonary  Intravascular Thrombosis

-Kirtan Patolia


Reference:

1.) https://doi.org/10.1016/S2665-9913(20)30121-1
https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30121-1/fulltext

2.) https://doi.org/10.1111/bjd.19163
https://onlinelibrary.wiley.com/doi/abs/10.1111/bjd.19163

Monday, May 4, 2020

Bugs causing bloody diarrhoea - mnemonic

Hello

Bugs that cause bloody diarrhoea : HE Is ClASSY

enteroHEmorragic E coli
enteroInvasive E coli

Campylobacter
EntAmoeba histolytica
Salmonella (non-typh)
Shigella
Y enterocolitica


Hope that helps
- Jaskunwar Singh

Thursday, April 30, 2020

Friedreich's Ataxia Mnemonic

Check out this mnemonic if you have difficulty memorizing it :)



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

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

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

Authors' diary: No visitors policy during the COVID-19 pandemic

Clinical correlate: Sildenafil contraindicated for pilots

Hello

Not just type-5, but Sildenafil is also a phosphodiesterase type-6 inhibitor.
PDE-6 is present in the eyes.

Tuesday, April 28, 2020

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

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

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.


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).

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.


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

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

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.

Saturday, April 11, 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

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]

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.

COVID-19: Use of masks

Hi everyone!

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.

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:-

Wednesday, April 8, 2020

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.

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.

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.

Friday, April 3, 2020

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


Current place in the management of COVID-19


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.

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.

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.


Structure of SARS-CoV-2



Image by Upasana Yadav

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

COVID-19 and Pregnancy: Should Mothers Be Concerned?

Pregnancy is a special phase in a woman’s life, more so because of the various changes which her body undergoes during these 9 months. Perhaps that is why, the concern about the threat of the novel coronavirus is valid- after all pregnancy is a state of slight immunocompromise, and also because there are two lives at stake. WHO declared the COVID-19 outbreak a pandemic on March 11, 2020. Most countries have taken stringent measures to control the spread of this disease, but do pregnant women need to take more measures? So, avid obstetricians out there, let’s find out deeply about the connection between these two:

WHO’s official stand is that there is no higher risk in pregnancy of severe illness BUT because there are trials underway and due to the bodily changes in pregnancy, one can not know the extent of COVID-19 in these patients. [1] Due to the evolving crisis, we are seeing newer studies every day with new results. A study conducted in early February on 38 pregnant women showed that it did not lead to maternal deaths, and neither were there any confirmed cases of intrauterine transmissions, with rt-PCR being negative in all the neonatal specimens tested, hence leading to the belief that there is no intrauterine or transplacental transmission. [2] Even the CT scans done on pregnant women with COVID-19 positive samples, did not show major changes and recovered from pneumonia adequately. [3]

Thursday, April 2, 2020

Lysosomal storage diseases mnemonic


COVID-19: Case fatality rate in Italy

Hello everyone, this post explains the factors behind the higher case fatality rate in Italy compared to the other COVID-19 infected countries.

As of today, there are 937,941 coronavirus cases in the world with 47,273 deaths; that comes down to a mortality rate of around 5%. On the other hand, China, the former epicenter of the disease has a COVID-19 case fatality rate of approximately 4%; while Italy has a much higher rate of 11.897%.

COVID-19: Vaccines under development

COVID-19 pandemic has led researchers around the world to work on developing a safe and effective vaccine. At present, there are 5 agents which are being extensively tested as potential vaccines. Here is some information about them.
1. mRNA- 1273 

Trial: Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis SARS CoV-2 Infection
   
- novel lipid nanoparticle encapsulated mRNA based vaccine that encodes for spike protein of SARS-CoV-2
- an open-label phase I dose-ranging clinical trial in the United States
- Study Population: 45 healthy people, males and non-pregnant women aged 18-55
    - enrolled in one of three cohorts - 25mcg, 100mcg, 250mcg
    - IM injection of the vaccine on Day 1 and 29 in deltoid
    - Follow up: 1,2,4 weeks post each vaccination, 3,6,12 months post second vaccine

- Objective
    - To evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults 
    - To evaluate the immunogenicity as measured by Immunoglobulin G (IgG) enzyme-linked immunosorbent assay ELISA to the SARS-CoV-2 S (spike) protein following a 2-dose vaccination schedule of mRNA-1273 at Day 57

2. BCG Vaccine

BCG vaccine — developed for Tuberculosis. It has favorable in vitro or in vivo effect against RSV, Yellow fever, HSV, HPV. The hypothesis is that it may induce partial protection against the susceptibility to and/or severity of SARS-CoV-2 infection

Trial 1: BCG-CORONA reducing health care workers absenteeism in SARS-CoV-2 pandemic through Bacillus Calmette-Guérin vaccination, a randomized controlled trial (BCG-CORONA)

- RCT in the Netherlands 

- Study population: 1000 Health care workers with direct COVID-infected patient      
  contact
- Study duration: 6 months
- Objective: 
    - To reduce absenteeism among HCW with direct patient contacts during the epidemic phase of COVID19
    - To reduce hospital admission, ICU admission or death in HCW with direct patient contacts during the epidemic phase of COVID19

Trial 2: BRACE - BCG Vaccination to Reduce the Impact of COVID-19 in Australian Healthcare Workers Following Coronavirus Exposure (BRACE) Trial

- Open-label two group phase III RCT in Australia

- Study population: 4170 Healthcare workers
- Study duration: 12 months
- Objective:
    - COVID 19 disease incidence over 6 months, by 12 months
    - severe COVID 19 disease incidence over 6 months, by 12 months


3. Synthetic Minigene Vaccine

Artificial antigen-presenting cell Vaccine - a synthetic minigene that has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease. The vaccine will be produced using a vector system to express viral proteins and immune modulators genes to modify artificial antigen-presenting cells (APC) and to activate T cells


Trial 1: Safety and Immunity of COVID-19 aAPC Vaccine

- Open-label phase I study in China

- Study population: 100 participants aged 6months to 80 years
- Objective: 
    - Injection of COVID-19/aAPC vaccine to volunteers to evaluate the safety
- To evaluate the anti- COVID-19 reactivity of the COVID-19/aAPC vaccine

Trial 2: Phase I/II Multicenter Trial of Lentiviral Minigene Vaccine (LV-SMENP) of COVID-19 Coronavirus

- Open-label Phase I/II study in China

-Study population: 100 participants aged 6months to 80 years
- Objective:
    - Injection and infusion of LV-SMENP DC and antigen-specific cytotoxic T cell vaccines to  
healthy volunteers and COVID-19 infected patients to evaluate the safety
- To evaluate the anti- COVID-19 efficacy of the LV-SMENP DC and antigen-specific  
cytotoxic T cell vaccines

4. ChAdOx1 nCoV-19 Vaccine

Trial: A Phase I/II Study to Determine Efficacy, Safety, and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19 in UK Healthy Adult Volunteers

- Single-blinded, Randomized Phase I/II study in UK
-Study population: 510 participants aged 18 to 55 years
- Objective: 
    - To assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19
    - To assess safety of the candidate ChAdOx1 nCoV


5. Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)

Trial: A Single-center,Open-label,Dose-escalating Phase I Clinical Trial to Evaluate Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in Healthy Adults Aged 18-60 Years Old

- Open label, dose-escalating Phase I study in China
-Study population: 108 participants aged 18 to 60 years
- Objective:
    - To evaluate the safety, reactogenicity and immunogenicity of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)

Written by Devi Bavishi
Reference: clincialtrials.gov

COVID-19: App based clinical trials

Let’s see how scientists are using app technology to generate data for research on COVID-19.

Wednesday, April 1, 2020

COVID-19: Lessons from coronavirus outbreak in China and formulating a strategy

Hello awesomites!

The following information is regarding the situation of COVID19 in China and how did China manage to reduce the incidence of new cases.


Image by  Nakeya. Medicowesome 2020