COVID-19: Pathophysiology and microbiology

COVID-19: Pathophysiology and microbiology

COVID-19: ACE-inhibitors and SARS-Co-V2

Nowadays, many are aware of the pandemic spreading all around the world and causing victims on a daily basis. This infection which appears for the first time at Wuhan in China represents a great concern. Today, let us explore some questions relating to the disease.

1) ACE-inhibitors and SARS-Co-V2, what is the link existing between them?
The angiotensin-converting-enzyme is secreted by pneumocytes 2 of the lungs and allows the conversion of angiotensin 1 to angiotensin 2, a powerful vasoconstrictor. The receptors for this enzyme are found in various places, including the heart and lungs. Normally, the inhibitor of this enzyme is used in case of high blood pressure, coronary heart disease and also diabetes thanks to its protective effect for the kidneys. However, in the context of COVID19 infection, the virus (SARS-Cov2) uses the converting enzyme receptors to enter the lungs. Given the increase in the number of these receptors in the event of therapy based on ACE inhibitors, the maintenance of this drug in patients infected with SARS-Cov2 is controversial.

COVID-19: Cardiovascular complications

Hi everyone... 

Virus infections are the most common cause of myocarditis. The previous severe acute respiratory syndrome (SARS) beta-coronavirus SARS-CoV-1 was associated with tachyarrhythmias, signs, and symptoms of heart failure.

Let's learn about SARS-CoV-2:

• COVID-19 patients who died had higher levels of troponin, myoglobin, C-reactive protein, serum ferritin, and IL-6.
• This is because of the high inflammatory burden in COVID-19.

Let’s find out and understand about CVS complications by COVID-19:

• Mainly, vascular inflammation, myocarditis, and cardiac arrhythmias
• The possible late phenomenon of the viral respiratory infection
• Commonly observed in severe cases
• Strongly associated with mortality

Cardiovascular complications of COVID-19 

COVID19 and research: What can I do?

With the COVID19 pandemic hitting us, it is imperative to know where to get our trusted info from. Multiple research papers are emerging these days with one main big goal: Understanding this disease and how to stop it!

In addition to reading and following these research papers, you, yes you, can be a researcher yourself. You can help in fighting this disease and aid humanity.

The studies mentioned below are international studies aiming at understanding COVID19 and its implications:

1- Covidsurg:

Covidsurg is an international cohort study, aiming to assess the outcomes of surgery in patients diagnosed in COVID-19.

It is for patients who undergo surgery with either suspected or confirmed COVID-19 infection (either before or after surgery). Cases can be entered either prospectively or retrospectively.

There is no evidence to inform the management of surgical patients with COVID-19 infection. Capturing real-world data and sharing international experience will support the management of this complex group of patients, improving their clinical care.

To start, register at: http://tiny.cc/covidsurg

==================

2- CovidSurg-Cancer: 

CovidSurg-Cancer is an international cohort study assessing the safety of surgery for all types of cancer during the COVID-19 pandemic and the impact of the pandemic in cancer delay and treatment pathways.

For more info : https://globalsurg.org/cancercovidsurg/

=================

-You can start these studies at your hospital anywhere now! Get the required IRB approval and collect data.

-All publications will be Pub-Med indexed. A corporate authorship model will be used under CovidSurg Collaborative group.


Stay safe

Murad

COVID-19: The journey of a viral pandemic

Modes of transmission of SARS-CoV-2

A novel human coronavirus that emerged in Wuhan, China in the later months of 2019 has now dissipated all around the world, causing a pandemic. Let's analyze how this virus manages to spread so virulently breaching our usual barriers.

Modes of transmission of SARS-CoV-2

COVID-19: Coping with GRIEF in midst of coronavirus pandemic

The known death toll from the coronavirus has surpassed 25,000 globally. The pandemic has ended communal prayer and congregational funeral gatherings at many major churches, synagogues, mosques, and temples. With these restrictions and isolation measures, dying people can’t see their families at the endpoint of their life. The internet, however, offered some solace to others ( Facebook live streaming, Video calling, etc.) 

Tragic losses of life…Let’s understand grief in the midst of coronavirus.

Normal grief reaction :

Precipitated by the loss of a loved one (bereavement).

Sadness revolves around feelings of loss and typically occurs in "waves" intermixed with positive memories of the deceased.  

Simple hallucinations ( Visual / Auditory ) of the deceased one. 

Thoughts of dying involve wish to join the deceased but active suicidality uncommon 
For most, the natural mourning process lasts 6-12 months 

f/b the integration of grief, in which the individual continues to feel transient but less pronounced sadness, and life plans/routines have adapted to living without the deceased.

There are 5 stages of grief according to the Kübler-Ross model are denial, anger, bargaining, depression, and acceptance (may occur in any order).

“Mnemonic” = ABCD 

COVID-19: Remdesivir (GS-5734)

Here is a short post about Remdesivir (GS-5734).

Compound:
A '-cyano-substituted adenosine nucleotide analog prodrug.

Mnemonic for TNF-alpha inhibitors

https://youtu.be/S9Z2ObWhPlA

Video by Drashtant

COVID-19: From authors' diary for health care workers

I want to write this post and acknowledge that the pandemic is a very stressful time for healthcare workers. 

We are looking at the epidemiology that shows the increase in mortality related to the COVID-19 disease. Even though we see death everyday, addition of deaths due to SARS-CoV-2 is heartbreaking. Thoughts about not having enough ventilators, not having proven medical therapies, or a vaccine in the near future are distressing. It is in our inherent nature as healthcare professionals to try and help, it's saddening when we can't. 

Hearing the news is also very depressing. Some don't believe it. Some aren't serious enough... Yet. But when you hear the stories instead of looking at the numbers, it becomes real. How strange must it be, to be in quarantine and see your old grandparent go to the hospital alone? How sad must it be to think that it may be the last time that you see them? 

There are concerns about our safety as healthcare workers. We are being exposed on a daily basis and there are concerns about having not enough personal protective equipment such as masks in the future. Even worse, there are concerns about our families safety. We expose them every time we come home. 

I just want to tell you that all your anxieties and concerns are valid. You're not the only one thinking about these things. As we fight this pandemic together, our mental health is important. I'm proud of you for being concerned. I'm proud of you for continuing to fight everyday. 

If you are a health care provider and are distressed by this like I was and want to talk about it, email me at medicowesome@gmail.com. We also have a well being group on Whatsapp to help each other stay strong! 

I was recently talking to a colleague about how we have chosen this profession because this is what we always wanted to do - treat patients. We spoke about the retired physician in Italy who came back to work for his patients. It's noble. It's humbling. If we don't take care of the sick, who will?

-IkaN

COVID-19: Water transmission and the effects of heat on the SARS-CoV-2 virus

Hi!

I am going to be writing a series of COVID-19 posts and answering frequently asked questions by patients. Today's post is about water transmission and the effects of heat on the SARS-CoV-2 virus.

Mnemonic for Foley’s Catheter: French scale & Color code

Video by Drashtant

Recent updates about treatment of COVID19

All things you need to know about COVID19 

https://www.youtube.com/watch?v=A6WpCkjqJSM

Recent Updates: 

At present Best Option = HydroxyCQ +/- Azithromycin 

HydroxyCQ for 10 day ( 200 mg TDS ) 

As ACE 2 enzyme is receptor for SARS-Cov-2 & these RAS inhibitors ⬆️ ACE2 enzyme. So hypothetically, there's an ⬆️ Risk of Covid19. But the guidelines recommend that ACEI / ARBs should not be discontinued. 

Drugs under Clinical Trials:

Remdesivir (USA) 

Ritonavir-Lopinavir 

Tocilizumab (IL6) 

Sarilumab (IL6) 

Favipiravir+ Tocilizumab 

Meplazumab (CD147) 

Fingolimod 

Darunavir + Cobicistat 

Which Rx is used in your country now?  Please comment below ⬇️

Thank you.. 

- Drashtant 

Isatuximab (Novel monoclonal antibody)

Isatuximab (a novel monoclonal antibody that binds
selectively to CD38), which is widely expressed on the plasma
cells, and kills myeloma cells via multimodal mechanisms
including antibody-dependent cellular cytotoxicity,
antibody-dependent cellular phagocytosis, complement-
dependent cellular cytotoxicity, and immune cell
depletion or inhibition of immunosuppressive cells, as has been described with daratumumab.

 Additionally, isatuximab, similar to other CD38 antibodies, modulates
the NADase enzymatic activity of CD38.
However, isatuximab differentiates itself from daratumumab in its
ability to induce direct apoptosis without cross-linking, and in its binding epitope.

Isatuximab is approved in combination with pomalidomide and dexamethasone for adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

A pretty amazing mechanism, right?


Kirtan

How to approach Ankle sprain

Hi!

I sprained my ankle and thought of making a video on it 

-Drashtant

Layers Of The Abdomen

SUB - Skin

CUTANEOUS- Camper's Fascia

SYSTEM - Scarpa's Fascia

EXITS - External Oblique

INTESTINAL- Internal Oblique

TRANSPORTw/ - Trs Abdominis 

FREE- Fascia Transversalis 

EXIT- Extra Peritoneal C/T 

PASS- Parietal peritoneum 

Everything you need to know about coronavirus COVID-19

Resources: CDC, UpToDate, WHO website.
Video by Drashtant Prajapati, MBBS.

Pulsus paradoxus concept

-IkaN

Everything you need to know about coronavirus COVID-19

Resources: CDC, UpToDate, WHO website.
Video by Drashtant Prajapati, MBBS.

Tricuspid Annular Plane Systolic Excursion (TAPSE) concept

Acquired coagulopathy

Apart from congenital disorders, various clinical scenarios can give rise to altered hemostatic patterns leading to the state of so-called "acquired coagulopathy".

1.) Due to Factor inhibitors:
Classically it is seen in pregnant patients and those with lymphoproliferative disorders like CLL. However, it could be idiopathic.
Usually, it leads to the acquired factor Vlll and V deficiency.

Mixing studies are employed to differentiate between acquired and congenital factor deficiency. Failure of correction of clotting assays after mixing studies suggests the presence of inhibitors.

2.) Amyloidosis
Sequestration of Factor X by amyloid fibrils leads to an acquired deficiency-like state. Amyloid vasculopathy along with factor X deficiency often leads to purpura and ecchymosis in these patients.

3.) Myeloproliferative neoplasms
Apart from acquired vWD due to loss of HMW vWF multimers, acquired factor V deficiency can also be seen. This has been attributed to adherence of Factor V to megakaryoblasts similar to the relation between factor X and amyloid fibrils. However, severe clinical manifestations might not necessarily reflect upon clotting assays or factor levels with the latter suggesting functional factor V deficiency.

3.) Thrombotic microangiopathies and DIC
Usually leads to both thrombotic and bleeding manifestations. The spectrum of TMA includes HUS, aHUS, TTP, HELLP syndrome, DIC, cAPLA, scleroderma renal crisis, malignant hypertension, and radiation or HSCT-induced vasculopathy.

4.) Coagulopathy of liver failure
Classically seen in the setting of fulminant liver injury which may be due to the infections, drugs, autoimmune hepatitis, ischemic hepatitis/shock liver, or rarely in Wilson's disease due to massive hepatocyte destruction.
One of the hallmark lab findings includes normal factor VIII levels. This is due to the fact that factor VIII, unlike other factors, is chiefly produced by endothelial cells rather than by hepatocytes. In fact, due to its reduced metabolism by hepatocytes in the state of liver failure, factor VIIl levels are often elevated.

Other miscellaneous causes include Acute fatty liver of pregnancy, fat embolism syndrome, amniotic fluid embolism, and other pregnancy-associated complications.

- Kirtan Patolia

Acquired Von willebrand disease

Von Willebrand disease is one of the most commonly encountered congenital bleeding disorders in clinical practice. Broadly speaking they are classified as type 1, 2A, 2B, 2M, 2N, and 3. Each one of them is distinct from the other in subtle ways.

However, it could be acquired in a number of ways.

 a.) In patients with thrombocytosis > 1 million cells/ microliter, especially in essential thrombocythemia, loss of HMW  vWD multimers leads to reduced vWF Ristocetin activity: vWF antigen ratio (<0.6)  suggesting type 2 like pattern.

 b.) In patients with aortic stenosis, due to extreme shear stress, vWF unfolds prematurely at the site of the valve revealing ADAMTS13 binding sites, ultimately resulting in its cleavage and loss of HMW multimers. So basically, it could be visualized as the pattern that is just opposite to TTP wherein defective ADAMTS13 activity results in excess of HMW vWF multimers.

It is often associated with either angiodysplasia or AVMs of the GI tract that further predisposes to bleeding. Although the exact pathogenesis of these lesions is not understood, one postulated mechanism suggests chronic colonic ischemia leading to sympathetic nervous system-induced vasodilation as a potential culprit.
 In this context, it is also known as Heyde's syndrome.

c.) Sometimes in severe hypothyroidism, often the production of vWF by endothelial cells itself is markedly reduced.

d.) Rarely in the setting of multiple myeloma and various other neoplasms, tumor cells express the excess of Gpllb/llla leading to enhanced clearance of vWF from circulation.

One of the common lab findings in acquired vWD is reduced vWF Ristocetin activity: vWF antigen ratio pointing to the disproportionate decrease in activity compared to antigen levels.
It is due to the loss of HMW  multimers.

- Kirtan Patolia

Mnemonic for Ranson criteria, BISAP & HAPS score for Acute Pancreatitis

Acute diarrhea

Congestive hepatopathy

Short post!

In congestive heart failure, the elevated pressure is transmitted from the right heart chambers (right ventricle and atrium) to the hepatic veins and sinusoids leading to intrahepatic edema, decreased perfusion and oxygen diffusion as well as hemorrhagic injury and modification on the hepatocyte architecture and atrophy with associated collagen deposition, and fibrosis to the hepatic veins and sinusoids.

Mnemonic for Clinical Signs of Aortic Regurgitation video

Schroeder's Vs Bandl's ring

Schroeder's  Vs Bandl's ring

Bandl's ring:- 

1) It is seen in obstructed labour

2) It is a pathological ring

3) It is a retraction ring

4) It moves up with uterine contractions

5) It can be palpable per-abdominally but not pervaginally

(Remember- Bandl has A after B which stands for per-abdominally)

6) Management: Like obstructed labour, C-section and antibiotics.

Schroeder's ring:-

1) Seen when oxytocin is used injudiciously.

2) It is a physiological ring.

3) It is a constriction ring.

4) It is fixed ring, does not move with uterine contractions

5) It can be palpable pervaginally but not per-abdominally.

6) Management: It dissolves on it's own.

If not, then management in first stage of labour includes C-section.

Management in second stage includes forceps or c section.

That's it!

Demotional bloke

Post Partum Hemorrhage - Updates

Following bleeding scenarios amount to PPH under the latest WHO document

1. Blood loss >500 mL in c/o Vaginal delivery
2. Blood loss > 1 L in c/o C Section + in c/o twins
3. Blood loss > 1.5 L in c/o Hysterectomy
4. Blood loss on any case more than what is expected over a period of 24 hours

Following bleeding scenarios amount to PPH as per the latest ACOG recommendations

1. Blood loss equal to or more than 1 L irrespective of mode of delivery
2. Bleeding with signs and symptoms of hypovolemia

Updates in Management of PPH

1. Uterine massage is added along with uterotonics
2. PGE1 if given Per Rectally (not recommended), 1000 micrograms is advised
3. Inj Tranexamic Acid is recommended in all bleeding diasthesis - 1 gram slow IV (over 20 minutes) 
4. Mechanical Devices allowed
1. Sengstaken Blakemore Catheter
2. Bakri Balloon Catheter

Actions of Intrinsic laryngeal muscles of Vocal cord mnemonic video

Hello!

This is video is on Actions of Intrinsic laryngeal muscles.

HMG CoA synthase,reductase and lyase

Hello Awesomites!

LONG TIME. 
As I promised, the future blogs will be on confusers.
Here I go.

Study hard!

-Upasana Y :)

Mnemonic for Catalytically perfect enzymes !!

Hii...

Certain rare enzymes , 

They are so efficient that almost every time enzyme meets its substrate, the reaction occurs. 

E + S ➡️ ES Complex ➡️ Instantaneously Product formed 

For such enzymes this becomes the rate limiting step & is only determined by 

Rate of Diffusion of molecules in solution.

Means , Catalytically perfect reactions are only limited by substrate diffusion rate.( Substrate diffusion into active site ) 

This enzymes are called Diffusion limited/ Catalytically perfect enzymes.

Catalytic efficiency reaches the diffusion limit.

Examples =

Furiously trying to CAtCh ( think Ball) diffusion limit in Superover.

Fumarase 

Triose phosphate isomerase 

Catalase 

Cytochrome C peroxidase

CAH ( Carbonic anhydrase )

AchE ( Ach esterase ) 

Ball = Beta lactamase 

Superover = SOD = Superoxide Dismutase 

Thank you...

By Drashtant