Submission: Tips for Step 2 CK

Hello All,

I am currently preparing for my step 2 CS exam. I gave my step 2 CK in June 2018 and scored >250.

Here are the resources I used-

1) Onlinemeded lectures+MTB

2) U world Q bank

3) NBME /UWSA

Here is what I. Used to do-

Listen to Online meded lectures and take notes on MTB but I did not read them again. I just listened to OME lectures  2nd time while exercising.

I printed the pdf file circulating with UWorld tables and Followed listening lectures of online meded  with doing questions of Usmle World and taking notes on Tables file.

Then I used to revise whole system I did in the week on weekends

Initially I started with one system a week and in the end I did 2 systems in a week.

Some important points to note-

1) U world and Online meded are the basic resources. 

2) Listen to all the online meded lectures  before solving U world Qs. It helps alot and makes the process of going through Usmle world Qs a lot easier.

3) Memorise Usmle World tables on your tips. 

4) Every option of Usmle world Qs is important. Go through not only the right one but also the wrong options properly.

5) I used to give a NBME every 3-4 weeks to track my progress and gave UWSA in the end. I started with 200’s and went upto 250’s.

-Parneet kaur

Mechanistic insights regarding Lesch-Nyhan syndrome

Hello friends! Let's refresh our biochemistry knowledge today.

Lesch-Nyhan syndrome is characterized by choreoathetosis, dystonia, hyperuricemia, gout, self mutilatory behavior especially self-biting of fingers, and intellectual disability due to HGPRTase mutations.

So how do HGPRTase mutations actually cause dystonia and other extrapyramidal signs and symptoms?

1.)  For the synthesis of dopamine tetrahydrobiopterin as a cofactor for tyrosine hydroxylase is required.
Tetrahydrobiopterin itself is derived by a series of reactions in which GTP cyclohydrolase is a rate-limiting enzyme.
Now HGPRTase deficiency causes depletion of GTP thereby ultimately depleting tetrahydrobiopterin.

In fact, GTP cyclohydrolase mutations are known to cause dopa-responsive dystonia and phenotype similar to Lesch-Nyhan syndrome.

2.)  Secondly, dopamine receptors are linked to G-protein coupled receptors which alternate between GTP-GDP bound states, yet another link between GTP depletion and perturbation of dopamine signaling.

3.) Adenosine deficiency due to the reduction in salvage may adversely affect the role of adenosine as a neuroprotective agent.

Lastly, in Lesch Nyhan syndrome no characteristic imaging abnormalities are seen but reduced dendritic arborizations in the caudate nucleus, putamen, and nucleus accumbens are thought to underlie clinical manifestations.

So to summarise, Lesch Nyhan syndrome can be considered as one of the basal ganglia disorders with Wilson's disease and Huntington's disease being the other notable ones.

Have a great day!

-Kirtan Patolia

Submission :Dexmedetomidine and Bradycardia

-By Parneeet Kaur

Submission: Thyroid Acropachy

Let's go through quick review regarding Thyroid Acropachy! 

1)It is an uncommon finding of Graves disease.

2)It is a triad of clubbing+swelling of soft tissue of digits + periosteal reaction of extremity bones. 

3)It is usually associated with Thyroid Ophthalmopathy and Dermopathy.

X ray findings-Hands and feet involvement,soft tissue swelling, fluffy, asymmetric periosteal reaction

Skin biopsy- Fibroblast activation and GAG deposition.

Differentials: 

1)Pulmonary Osteoarthropathy-.

2)Symmetric periosteal reaction  -can involve long bones of forearms and legs

Treatment-
No Specific treatment available, Treatment directed at associated Ophthalmopathy and Dermopathy using Local corticosteroids and systemic immunosuppressive therapy.

By Parneet kaur

Cyanide poisoning

Cyanide is a mitochondrial toxin that causes death within minutes to hours of exposure.

PATHOPHYSIOLOGY:

1)Cyanide avidly binds to the ferric ion (Fe3+) of complex IV thus inhibiting the Electron transport chain.

2)The cell must then switch to anaerobic metabolism of glucose to generate ATP.Anaerobic metabolism leads to the formation of lactic acid and the development of metabolic acidosis.

TREATMENT:

1)Sodium nitrite and Amyl nitrite induce formation of methemoglobin. Cyanide has high affinity to metHb. This provides an attractive alternative binding site for cyanide which makes the ETC free.

2)Sodium thiosulfate can be given which converts cyanomethemoglobin to thiocyanate and metHb. Thiocyanate is then renally excreted and metHb can be converted back to normal Hb by using methylene blue.

3) Hydroxocobalamin, a precursor of vitamin B12, avidly binds to intracellular cyanide (with greater affinity than cytochrome oxidase) forming cyanocobalamin. This molecule is stable and readily excreted in the urine.

-Srikar Sama

Early morning workout and weight loss.

To reduce weight, early morning exercise is recommended but question is why?
Let's get back to basics before answering this question.

Body has three sources of blood glucose to maintain level uniformly.
1) Food.
2) Liver Glycogen.
3) ‎Gluconeogenesis.

Now, Liver Glycogen can provide energy for around 12-18 hours. Gluconeogenesis uses lots of energy to maintain blood glucose level. Between dinner and breakfast we have gap of around 12 hours. This mean before taking breakfast  liver glycogen stock is null! And body is using now gluconeogenesis to maintain blood glucose level and as you know it's going to take hell lots of ATPs to maintain it. Also, exercise uses lots of energy. Hence both in turn helps in reducing body weight.

What is wrong with evening workout?

Suppose a person has taken lunch around 2 pm and he's working out around 5-6 pm. Which stores will be used by body to maintain glucose level - food obviously! Hardly any Liver glycogen is used up. Also extra food will be stored.

That's all!

-Demotional bloke

Authors diary: Goodbyes

It's heart breaking when you leave work in the evening and show up 10 hours later only to find that the patient you were taking care of passed away during the night.

You don't get to say goodbyes. But my wish for you is that you get to give your condolences 💔 

-IkaN 

USMLE Step 3 CCS sheet guide

Hey guys,

So I recently took my USMLE Step 3 and I gathered some of this from various resources. I think this may be of some help to the beginners.

Let's get started!

In relevant emergency cases (order the ones that are relevant):
ABC:
Airway
Breathing
Circulation

P.O. ICESS:
Pulse oximetry
Oxygen
Intravenous line and fluids (Please remember to type NSS/Normal Saline or Dextrose, etc. CCS software won't take orders that are less than 3 characters!)
Cardiac monitor
ECG
Sugar (fingerstick)
Suction

For chest pain add MONA:
Morphine
Oxygen
Nitrates
Aspirin
~~~
Then order relevant Physical Exam (In Office cases, you'd want to order most physical exams and in the Emergency Department cases, you'd want to order more symptom-based system specific exam)
~~~
Laboratory orders: CBC LFT ICU PAX
Complete Blood Count (CBC), ESR
Basic Metabolic Profile (BMP)
Cardiac enzymes (if not ordered earlier)

Liver Function Tests (LFT) or Lipid profile
FOBT
TFT

Imaging (CT/MRI/USG/etc) Iron profile Immunologic tests (HIV/HepB/HepC/Rubella/etc)
Cultures (Blood/urine/fluid/etc)
Urine (routine, microscopy, culture & sensitivity)

Pregnancy test (urine) & Pap test (if female) PT/INR PTT d-Dimer PFT
Amylase ABG
Xray
~~~
You can now forward the time to get some results or decide whether the location needs to be changed
~~~
CCC
Comfort: if the patient is in pain- give NSAIDs/Morphine based on the situation; vomiting- antiemetic; etc
Cure: if you suspect a particular infection-give antibiotic; if it's an MI- angiography v/s other management options; etc
Consult: you may want to order a Psych or Surgery or OBGYN or any other relevant consult based on the case
~~~
If the patient needs to get admitted on floors or ICU:  ADIC

Activity: Bed rest/ ambulation
Diet
Input/output charting
Compression stockings

~~~

If the patient is scheduled to undergo a procedure: ABC PIN

Antibiotics

Blood grouping and crossmatching

Consent

PT/ PTT

INR

NPO

~~~

When you get your 2-minute screen: Counsel and order follow-up labs!

You may want to counsel them on their diagnosis, lifestyle habits, medication adherence/ compliance/ side effects and so on.

Hope this helps!

Stay awesome :)

-Rippie

Lifestyle modifications for managing hypertension

Hey guys,

Happy New Year!

Let's get started on lifestyle modifications for treating or managing hypertension.

We Decide to Eat less Salt & drink less Alcohol!

Weight loss: Reduce BMI to <25 
DASH: Diet high in fruits and vegetables and low in saturated fat and total fat
Exercise: 30minutes/day for 5-6 days/week
Dietary Sodium: <3 g/day
Alcohol: 2 drinks/day in men and 1 drink/day in women

The effect of these interventions is in descending order, with weight loss having an impact of about 5-20 mmHg lowering per 10 kg weight loss and reducing alcohol intake can lower BP by 2-4 mmHg!

Remember: If a patient's BMI is already lower than 25, you don't have to ask them to reduce weight any further for this therapeutic effect. Instead, you ask them to switch over to DASH diet!

Hope this is helpful!

Stay awesome!
-Rippie

In short: Vasopressin in the ICU

Hello!

Here are some quick points + mnemonics on Vasopressin!

1. Effects are preserved during hypoxia and severe acidosis and catecholamine-resistant states.

Mnemonic: Vasopressin presses when other pressors can't press the vasculature anymore.

2. Vasopressin decreases norepinephrine requirement.

3. Onset: fast, offset: fast.
Mnemonic: VasopressIN is IN and OUT fast.

4. It is often weaned off last in patients on multiple pressors for the same reason.

5. Used in:
- Refractory hypotension (potentiates the actions of over vasoconstrictors)
- Esophageal variceal bleed
- Cardiac arrest
Non ICU indications: vWD, DI, hemophilia

That's all!

-IkaN

In short: Dexmedetomidine and bradycardia

If a patient who is intubated and sedated develops bradycardia, go through the sedatives list - it might give you a hint on what is causing the bradycardia.

Dexmedetomidine (Precedex) is notorious for causing bradycardia. Another sedative associated with bradycardia is propofol.

That's all!

Will update this post at a later date. What you can do if you are free: Read up on it, write a small post on it and email it to us so we can post it and learn from you :)

-IkaN

Authors diary: In short

Hello!

I am planning to write short one line posts on things that I learn in the everyday.

Pediatrics residency series: 1. Intro

Hey Medicowesomites :) Happy new year everyone (writing this post on 1-1-19)

Residency is time-consuming as you know. It’s been a long time since I last posted but I came back to tell you that I will be starting a new series on “Pediatrics Residency”. Useful apps, cases and other things will be discussed.

Stay tuned :)

-Murad

Hair tansplant or follicular transplant

Hello Awesomites!

This is going to be fun. :D

Q. A male diagnosed with AGA (Androgenetic alopecia) came to me with grade 3 alopecia. Asking me that he is frustrated from taking medication and heard of hair transplant surgery. What advice would you give him?

A.I have seen lot of misconception regarding this concept. Hair transplant doesn't mean actual hair. We take follicle from occiput. Why? Because it is not responsive to androgen as there is no Androgen receptor.

Hair transplant is for already bald area. Androgen receptor blockade is given for remaining vellus hair. So that means hair transplantation surgery is not substitute for minoxidil/finasteride. For grade 3 AGA alopecia patient can undergo hair transplantation for bald area but have to take medication for remaining vellus hairs.
This is for AGA alopecia. Scarring alopecia won't show good response with hair transplantation surgery as much as AGA alopecia,

Q. AGA is genetic alopecia. So why don't it appear at birth itself?
A. At birth, androgen receptor is present but insensitive. When genetic component become active, the receptor become sensitive and balding occur.

Have a great day ahead.
Upasana Y. :)

Warfarin: a procoagulant or anticoagulant?

Hello Awesomites!

No doubt ! Warfarin is an oral anticoagulant.
Confused? Don't be. :D

Warfarin inhibits reduction of Vitamin K to its active form and leads to depletion of the vitamin K-dependent clotting factors II,VII,IX and X, and protein C,S and Z.

Because of the rapid depletion of the anti-coagulant Protein C and a slower depletion of factor II, patients might develop increased hypercoagulability during the first few days of warfarin therapy. So warfarin is combined with a parenteral initially. Treatment of DVT/PE with warfarin requires overlap therapy/bridging therapy with a parenteral anticoagulant (UFH,LMWH, or pentasaccharide) for atleast 4-5 days and until the INR reaches atleast 2.0.

The starting dose of warfarin depends on many factors. During warfarin therapy INR monitoring should occur frequently during the first month of warfarin therapy (e.g.twice weekly for 1-2 weeks, then weekly for 2 weeks, then less frequently).

Have a great day ahead.
Upasana Y. :)

ARNI

Hello Awesomites !

I have something with weird titles. :D

ARNI stands for Angiotensin receptor-neprilysin inhibitor.

This is combination of ARB Valsartan and neprilysin inhibitor Sacubitril recently approved for use in patients with HFrEF and NYHA Class II-IV symptoms.

NEPRILYSIN:- It is a neutral endopeptidase involved in the degradation of vasoactive peptides including natriuretic peptides, bradykinin, adrenomedullin. Inhibition of neprilysin increased the availability of these peptides, which exert favorable effects in HF.

Effects of Natriuretic peptides are-
1.Vasodilation
2.Lower blood pressure
3.Reduced sympathetic tone
4.Reduced aldosterone levels
5.Natriuresis/Diuresis

In a large trial, this agent was shown to be superior to enalapril in reducing death and rehospitalization among NYHA class II-IV patients with HFrEF.

Have a great day ahead.
Upasana Y. :)

Vestibulo ocular reflex

The vestibulo-ocular reflex is a reflex, where activation of the vestibular system causes eye movement. This reflex functions to stabilize images on the retinas during head movement by producing eye movements in the direction opposite to head movement, thus preserving the image on the center of the visual field. For example, when the head moves to the right, the eyes move to the left, and vice versa. Since slight head movement is present all the time, VOR is necessary for stabilizing vision.

Circuit:

1)It starts in the vestibular system, where semicircular canals get activated by head rotation and send their impulses via the vestibular nerve and end in the vestibular nuclei in the brainstem.In addition the hair cells of opposite ear are inhibited because endolymph in that ear flows away from hair cells.

2)From these nuclei, fibers cross to the contralateral cranial nerve VI nucleus.

3a)There they synapse with 2 additional pathways. One pathway projects directly to the lateral rectus of the eye via the abducens nerve.
  b) Another nerve tract projects from the abducens nucleus by the medial longitudinal fasciculus to the contralateral oculomotor nucleus, which contains motorneurons specifically activating the medial rectus muscle of the eye through the oculomotor nerve. 

4)For instance, if the head is turned clockwise, then excitatory impulses are sent from the semicircular canal on the right side via the vestibular nerve to the right vestibular nuclei in the brainstem. From this nuclei excitatory fibres cross to the left abducens nucleus.There they project and stimulate the lateral rectus of the left eye via the abducens nerve. In addition, by the right medial longitudinal fasciculus, fibers cross and go to right oculomotor nuclei, they activate the medial rectus muscles on the right eye. As a result, both eyes will turn counter-clockwise.

-Srikar Sama

Basics of Fat necrosis.

Hello, let's dissect fat necrosis in this post.

Fat necrosis is seen where fat concentration is more or lipase concentration is more.
Example- Injury to Breast or Omentum tissue or in Acute pancreatitis with gall stones or alcohol intake.

Alcohol intake leads to activation of lipase enzyme. This lipase enzyme converts lipids to fatty acids. Always remember fatty acids loves calcium! This love affair leads to formation of "Fatty acids - Calcium complex formation". This is called as "Saponification".
This gives yellow - white chalk like color. This helps surgeon to identify fat necrosis.

For prognosis we use serum calcium level. Why?

Suppose there is severe pancreatitis. This leads to more activation of the lipase enzyme. This leads to formation of the fatty acids. More fatty acids, more saponification. Hence less calcium level in serum!

Low calcium level suggest bad prognosis!

Chediak Higashi syndrome.

Hello! This is Ultra short post regarding Chediak higashi syndrome! Hope you like it.

In normal person, when bacteria is engulfed by WBCs, they are carried to lysosome enzyme by LYST protein.
LYST protein stand for Lysosomal transfer protein.

Defect in LYST protein causes Chediak Higashi syndrome. It is autosomal recessive disorder.
No LYST protein so no phagocytosis of macrophages. Hence recurrent infections.

Clinical features:

1) Recurrent infections.

2) Absence of Melanin - Albinism.
LYST also helps in transfer of melanin to superficial layer of skin

3) Decrease in Myelin formation - Delayed conduction.

4) Hemorrhage.
LYST helps in maturation of megakaryocytes to platelets.

Confirmation: Incomplete digestion of bacteria leads to formation of  "Giant granules inside cell"

Mnemonic:
CHEDIAK

C- CNS involvement
HE- Hemorrhage
DI- Decrease immunity
A-Albinism

That's it!

-Demotional bloke.

Horner Syndrome

Horner syndrome is a classic neurologic syndrome whose signs include miosis, ptosis, and anhidrosis.

NEUROANATOMY - Horner syndrome can result from a lesion anywhere along a three-neuron sympathetic pathway that originates in the hypothalamus:
●The first-order neuron descends caudally from the hypothalamus to the first synapse, which is located in the cervical spinal cord (levels C8-T2, also called ciliospinal center of Budge).

●The second-order neuron travels from the sympathetic trunk over the lung apex. It then ascends to the superior cervical ganglion, located near the bifurcation of the common carotid artery.

●The third-order neuron from superior cervical ganglia then ascends within the adventitia of the internal carotid artery, through the cavernous sinus. In the orbit and the eye, the oculosympathetic fibers innervate the iris dilator muscle as well as Müller's muscle, a small smooth muscle in the eyelids responsible for a minor portion of the upper lid elevation and lower lid retraction.

First-order syndrome - Lesions of the sympathetic tracts in the brainstem or cervicothoracic spinal cord can produce a first-order Horner syndrome.
The most common causes are:
(a)occlusion of PICA, which produces Horner syndrome as part of the Wallenberg syndrome.
(b)Brown-Séquard syndrome above T1, patient may present with ipsilateral Horner syndrome due to damage of oculosympathetic pathway.

Second-order syndrome — Second-order or preganglionic Horner syndromes can occur with trauma or surgery involving the spinal cord, thoracic outlet, or lung apex.Other causes include pancoast tumor involving the lung apex.

Third-order syndrome — Third-order Horner syndromes often indicate lesions of the internal carotid artery such as an arterial dissection, thrombosis, or cavernous sinus aneurysm

CLINICAL FEATURES -The classic signs of a Horner syndrome are ptosis, miosis, and anhidrosis.
1)The ptosis occurs as a result of paralysis of the Müller's muscle.
2)The degree of anisocoria is more marked in the dark than in light.
3)Anhidrosis is present in central or preganglionic (first- or second-order) lesions because the sympathetic fibers responsible for facial sweating branch off at the superior cervical ganglion along the external carotid artery and its branches.
4)Horner syndrome is also a common feature of cluster headache.

SOURCE-UpToDate, Kaplan.

-Srikar Sama.

True or False #10

Hallux valgus is also known as bunion. T or F

T

●Hallux valgus (HV) deformity (ie, bunion) is a common, potentially debilitating deformity consisting of lateral deviation of the hallux on the first metatarsal . The etiology is unknown. The deformity is more common among women and shod populations.

●Although HV is easily recognized by clinical examination, radiographs may be necessary to determine the presence of articular damage . Neither radiographic nor clinical appearance provides the basis for surgical referral, which is determined by patient pain and disability.

●There is little evidence that conservative treatments are useful in the treatment of HV. Nevertheless, we suggest patients without debilitating symptoms avail themselves of conservative therapies before being referred for surgery.

Possible treatments include:

•Shoe modification: wide, low-heeled shoes, or specially altered shoes with increased medial pocket for first metatarsophalangeal (MTP) joint to minimize deforming forces

•Orthoses to improve support and alignment

•Night splinting to improve toe alignment

•Stretching and/ormobilization/manipulation to maintain joint mobility

•Medial bunion pads to prevent irritation

•Ice applied after activity to reduce inflammation
•Analgesics: acetaminophen or NSAIDs

●We suggest that patients with severe pain or dysfunction and those whose symptoms do not improve under a conservative treatment regimen be referred for surgical repair.

Approximately 150 surgical procedures for the correction of HV deformity have been described. Few prospective, randomized trials evaluating these procedures have been performed. Patients should be referred to a foot surgery specialist with experience repairing HV deformity.

●Managing patient expectations about surgery is important. Patients should understand that 10 to 25 degrees of valgus angulation is normal at the MTP joint, and that resolution of postoperative pain and swelling may require several months. Most patients will remain unable to fit into narrower shoes.

Do not forget to look up pictures of how a bunion looks.

Over and out.

Atropine poisoning

Atropine poisoning is also called as Anti-muscarinic poisoning.

It is caused due to ingestion of :-
1) Datura plant
2) ‎Atropa belladona
3) Hyoscyamus
4) ‎Anti-histamine drugs
5) Anti-psychotic drugs
6) ‎Anti-depressants like TCA
7) ‎Anti-Parkinsonism

Clinical features:

Let's go from head to toe!

1) Brain:
Atropine causes following symptoms
-Hallucinations
-‎Confusion
-‎Delirium

Also called as Mad as hatters!

Remember: Atropine drives you crazy!

2) Eyes:
AcH causes constriction of pupils. No or less AcH causes Mydriasis

Fun fact 1: In ancient times, women used to apply Atropa belladona in eye for attracting men by dilating pupil.

Fun fact 2: Most of the dinner dates are candle night dinner, why? To dilate pupils and look attractive.
Also described as "Blind as a bat"

Remember: Atropine makes you look seductive!

3) Eyes and Mouth:-
AcH is responsible for secretion of saliva and tears.
Lack of AcH action causes - Dry mouth and Dry eyes.

Also described as "Dry as a bone"
Most common feature in Adults.

Remember: Atropine Dries you!

4) Face:
AcH causes constriction of blood vessels. Atropine blocks this action and hence causes dilation of the blood vessel. Hence this causes flushing of face.

Also described as - Red as a beet.

Remember: Atropine makes you blush!

5) Body temperature:
AcH is responsible for secretion of the glands. Lack of secretion causes decrease or no cooling effect. Hence it causes-Hyperthermia.

Also described as - Hot as a hare
Most common feature in children.

Remember: Atropine makes you hot!

Most common cause of death is Respiratory paralysis.
Next common is Shock.

I remember all this feature with the help of story:

I went on a candle night dinner with hot girl. Ofcourse, she was blushing because I'm crazy to have dry resins after dinner! (Okay that's lame and I know!)

Key points:-

Candle night dinner - Mydriasis
Hot-Hyperthermia
Blushing-Flushing of face
Crazy-Deliruim, Hallucination and confusion
Dry resins-Dry secretion

Treatment:
1) Supportive treatment:

Gastric lavage using Tannic acid : To remove unabsorbed poison. Avoid potassium permagnate.

Forced acidic diuresis: Because Atropine is an alkaline drug

Seizures are treated by Diazepam

Patient is kept in dark quiet room-To avoid hallucination.

Ice bags given to treat maintain temperature.

2) Antidote: Physostigmine since it crosses BBB.

That's it
-Demotional bloke.

Wiskott-Aldrich syndrome

1)Wiskott-Aldrich syndrome is an X-linked recessive disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp).

2)All hematopoietic cells produce WASp protein, and there is WIPF1 that encodes WASp-interacting protein (WIP), a protein that stabilizes WASp. Both of these proteins are required to reorganize cell's cytoskeleton.

3)Its absence impairs the:
 (a)Formation of the immunologic synapse, the site of interaction between T cells and antigen-presenting cells leading to immunodeficiency.
 (b)NK cell function is impaired as a result of defective immune synapse formation on the cell surface which leads to increase risk of malignancy.
 (c)Regulatory T cells are incapable of controlling autoimmunity, so there is increased risk of Autoimmune disease.
 (d)Myeloid lineage cells exhibit impaired phagocytosis and chemotaxis - susceptible to recurrent pyogenic infections.
 (e)Impaired cytoskeleton in megakaryocytes → Decrease in size and number of platelets →microthrombocytopenia.

4)Clinical manifestations :
(a)Bleeding-microthrombocytopenia.
(b)Recurrent pyogenic infections.
(c)Eczema
(d)Increase in risk of autoimmune diseases and malignancy.

5)Laboratory findings :
(a)low to normal IgG and IgM and high IgA and IgE.
(b)Peripheral smear-Thrombocytopenia with small platelets.


Mnemonic: Remember the movie Antman and thewasp :p. So WASP helps you remember,
(1)WASp mutation  (2)wasp is a small bee like insect🐝→small platelets and if wasp bites, you get eczema(↑IgE).


SOURCE-UpToDate.

-Srikar Sama.

Peculiar pattern of pulmonary edema

Usually, left-sided cardiac pathology causes bilateral pulmonary edema but still, the unilateral pattern is seen in a fair number of cases, usually involving right lung parenchyma.

Likely mechanisms include:

1) Lymphatic drainage on the right side is via low caliber right bronchomediastinal trunk as opposed to the more robust thoracic duct on the left side.

2) Numerous conditions ranging from hypertension to valvular pathology can cause enlargement of the left side of the heart.

This will preferentially impinge on the left pulmonary artery causing reduced capillary perfusion and ultimately congestion of left lung parenchyma.

3) In cases of mitral regurgitation jet of regurgitating can preferentially impact either of the right or left pulmonary veins, hence explaining more profound edema on either side.

So, if according to the patient's history and clinical examination suspicion of cardiac failure remains high, then immediate intervention with diuretics and nitrates is warranted in spite of a unilateral pattern of pulmonary edema.

Kirtan Patolia

Obesity in Prader-Willi syndrome and WAGR syndrome

The delicate balance between food consumption and energy expenditure involves the modulation of orexigenic and anorexigenic signals at the hypothalamus.

OREXIGENIC PATHWAY- It involves peripheral mediators like ghrelin and neuropeptide-Y. 

They act on NPY-AgRP(neuropeptide-Y and agouti-related peptide) neurons which subsequently mediates orexigenic signals via second-order neurons that release peptides like orexin at the hypothalamus.

ANOREXIGENIC PATHWAY- It involves peripheral mediators like leptin, amylin, and PYY(Peptide YY).

They act on POMC/CART(Pro-opio melanocortin/Cocaine and amphetamine-regulated transcript) neurons.

These neurons release an alpha-melanocyte-stimulating hormone which in turn stimulates second-order neurons that release TRH, CRH and hence mediate catabolism.

They also simultaneously inhibit the anabolic pathway.

Now back to the pathogenesis of obesity in these syndromes.

In Prader-Willi syndrome levels of PYY are low due to loss of imprinted genes on chromosome 15q11-q13.

This results in reduced catabolism and enhanced uninhibited anabolism.

It is not uncommon for such patients to have BMI above 40.

In WAGR syndrome there is haploinsufficiency of BDNF(Brain-derived neurotrophic factor).

Alpha melanocyte-stimulating hormone in the catabolic pathway acts through melanocortin receptors(MC4R) on second-order neurons.

Downstream signaling pathways of MC4R involve BDNF hence explaining obesity in these patients.

In fact, efforts are already underway to reduce PPY levels and modulate BDNF to control obesity in these disorders.

Kirtan Patolia

Paroxysmal nocturnal hemoglobinuria

1)PNH originates from an acquired mutation ( frame-shift that creates a premature stop codon) in a myeloid stem cell, the acquired mutation in PNH occurs in the PIGA gene which is responsible for the first step in the synthesis of the GPI anchor that attaches CD55 and CD59 to the cell surface.

2)Complement detects self vs nonself cells by these complement inhibitors. Function of these complement inhibitors is to:

3)In the absence of these inhibitors, complement proteins bind cell membranes of our own cells and through the alternative complement pathway can lyse self-cells.

4)CD55/DAF decrease → More C3 convertase→Increase C3b→Increase opsonization→Extra Vascular Hemolysis.

   CD59/MIRL decrease→More MAC→Intra Vascular Hemolysis.


5)Why nocturnal hemoglobinuria- hemolysis occurs throughout day but its more at night because:   (a)Increased hemolysis in night due to respiratory acidosis(Shallow breathing).
 (b)Overnight concentration of urine is more and hemoglobinuria is clearly evident.

6)Diagnosis:(a)Flow cytometry- decrease CD55 and CD59 levels.
                     (b)HAM test-confirmatory.
                     (c)Direct coombs test-Negative (Helps to differentiate PNH and AIHA- its positive in AIHA)                                                                           

7)Treatment: 

(a)Ravulizumab- long acting C5 complement inhibitor

(b)Eculizumab- It is an Antibody to C5 and prevents its clevage to C5a and C5b, so no MAC. Ravulizumab has a half life that is three to four times longer than eculizumab.

-Srikar Sama

SOURCE: UpToDate, Uworld.

Psammoma Body

Psammoma body :

1)Psammoma bodies are round microscopic calcific collections.

2)A single necrotic cell act as a nidus and calcium deposits around it in laminated and concentric fashion.Psammoma body is an example for dystrophic calcification (Ca2+ deposition in abnormal tissues secondary to injury/necrosis in context of Normal calcium levels).

3)It is used in histopathology for diagnosis of certain tumours like:

Mnemonic : Remember it as SPAMmoma

          S- Serous cystadenocarcinoma of ovary

              Somatostatinoma


        PA-Papillary thyroid carcinoma

              Papillary renal cell carcinoma

       M- Mesothelioma

             Meningioma.

-Srikar Sama

Atrial myxomas

Myxomas are the most common primary cardiac neoplasm. 90% occur in the atria (mostly left atrium). The cells originate from a multipotent mesenchyme that is capable of neural and endothelial differentiation. Myxomas produce vascular endothelial growth factor (VEGF), which probably contributes to the induction of angiogenesis and the early stages of tumor growth.

GROSS FEATURES :Typical myxomas are pedunculated, the surface may be smooth, villous or friable.

HISTOLOGY : Gelatinous material, myxoma cells immersed in glycosaminoglycan. 

CLINICAL MANIFESTATIONS : 

1)Obstruction : Myxomas are usually described as "ball valve" obstruction of AV valves which may cause syncopal episodes, Dyspnea.

2)Influenced by position : Upright position may exacerbate the condition whereas lying down may decrease it.

3)Embolization : If the myxomas are friable or villous, fragments of mass can detach and present with systemic emboli.

4)Constitutional symptoms (eg: fever, weight loss) : Some myxomas release cytokines like IL6 which may produce constitutional symptoms.

5)Auscultation may reveal early diastolic "tumor plop".

TREATMENT : Prompt resection is required because of the risk of embolization or cardiovascular complications, including sudden death.

-Srikar Sama

Dietary Risk Factors For Calcium Stones

1) Fluids:
A lower fluid intake will lead to lower urine output, thereby promoting stone formation by increasing the concentration of calcium and oxalate.

Warfarin Induced Skin Necrosis

Warfarin-induced skin necrosis is a complication of warfarin therapy in which the patient develops demarcated areas of purpura and necrosis of skin including the extremities, breasts, trunk, or penis.

Mechanism:
1)Mechanism of action of Warfarin is it inhibits VitK epoxide reductase,so there is decrease in synthesis of VitK dependent factors - (factors II, VII, IX, and X) and natural anticoagulants (protein S and protein C).


2)Now no new clotting factors are produced but the old circulating clotting factors are still present (warfarin has no effect on already circulating clotting factors).


3)Among the factors II, VII, IX, X, ProteinC that are already present,ProteinC has the shortest half life,So ProteinC is depleted more rapidly than the others.


4)Now there is no anticoagulant in the body to oppose the action of already present clotting factors,so there will be initial coagulation till factors II, VII, IX, X gets depleted i.e till their half lives are completed.


5)This initial coagulation occurs in dermal vasculature which causes Skin Necrosis.

Prevention:
Overlapping of warfarin with heparin during the first several days of warfarin administration(if Heparin is given along with warfarin, this prevents functioning of circulating factors since heparin inhibits the activity of circulating thrombin and factorXa) and then warfarin is continued for long term therapy.


Source: UpToDate, First Aid.

-Srikar Sama

New application process for ECFMG registration

Hello,

This post is regarding new application process for ecfmg registration.


STEP1 : The process for obtaining USMLE ID is still the same which has been described very clearly here http://www.medicowesome.com/2016/12/how-to-apply-for-usmle-exams.html#more


STEP2 - ECFMG CERTIFICATION USING IWA:

1)when you go to IWA and login to your account you will only have one option : apply for certification (no application for examination any more ) so you will just click on that.

2)simply follow the steps and confirm you information and you will end up getting a payment page of 125$.


STEP3 - FORM 186 :

1)After payment they will send you form 186 (unlike before you dont need to go to your medical school and have it signed by your deen)

2)You will simply go to the website :- https://www.notarycam.com/ecfmg/


STEP4 - INTERVIEW WITH ONLINE NOTARY :

1)Fill an application and upload form (186) and high quality image of your passport or photo ID preferably but not necessarily in english.

2)You will receive an email from one of the online notaries and schedule an appointment of an online meeting with him/her.

3)If you are ready at the moment you can schedule an appointment immediately(which is what i did) or you can schedule for an appointment later.

4)During your meeting with the notary please prepare your passport as you will be asked to show it, to confirm your identity.

5)Afterwards the notary will ask you to position your self to the mid of screen and ask your permission for taking a screenshot.(If your webcam is of low quality they will ask you to mail them a passport picture of yours,so be ready with that too)

6)Then you will have to electronically sign your form-no need to actually sign it,they will display your name in few fonts and you have select one.

7)Now you have done your part.The notary will seal the document and send it to the ecfmg.

8)You will get an 2 emails after this process-one from notary that they have sent your form186 to ECFMG and second email is from ECFMG which you will be getting after few days that they have accepted your form 186.

-Srikar Sama

A rare type of fistula-Arterioenteric fistula

As the name suggests, this type of fistula is characterized by an anomalous connection between the bowel and arterial lumen.

CAUSES- Diverticulitis, Inflammatory bowel disease, bowel wall perforation, penetrating ulcers, aneurysms, prosthetic vascular grafts, radiation, trauma, or foreign body ingestion.

CLINICAL PRESENTATION- Depending on the cause it could include abdominal pain, hematochezia, hematuria (say if diverticulitis perforates bladder wall), sepsis, syncope (due to volume depletion from major bleed), gangrenous involvement of limbs due to vascular insufficiency, etc...

MANAGEMENT- Prompt diagnosis with laparoscopic intervention to eliminate fistula and any revascularization procedures if needed is the key to reduce mortality in such patients.

Kirtan Patolia

A few USPSTF guidelines

Hello,

USPSTF guidelines are important to remember for step 2 CK, step 3 and residency!

Here are a few high yield ones!

Ingenious Immune System

Hello friends, today let's take a moment to appreciate how amazing is our immune system.

In our immune system, just like any regular car, there are brakes in place to regulate its working. Removing brakes can certainly enhance its function which underlies the concept of immune checkpoint blockade.

Two such molecules on the surface of T-cells are CTLA-4(Cytotoxic T-lymphocyte associated protein 4) and PD-1(Programmed cell death protein 1).

When CTLA-4 binds to its ligands B7-1 and B7-2 which are often expressed in increased numbers on tumor cells it results in inhibition of T-cells and hence allowing tumor cells to evade apoptosis and survive.

Similarly when PD-1 binds to PD-L1on tumor cells inhibitory signals are relayed to T-cells.

In macrophages signal, regulatory protein alpha mediates inhibitory signals on interacting with CD47 on tumor cells.

In NK-cells KIR2DL1(killer cell immunoglobulin-like receptor 2DL1) mediates inhibitory signals.

So blocking these inhibitory signals by monoclonal antibodies can remove "brakes" on the immune system ultimately enhancing their ability to kill tumor cells.

Approved antibodies include:

Anti CTLA-4-Ipilimumab

Anti PD-1-Nivolumab, Pembrolizumab

Anti PD-L1-Avelumab,Durvalumab

Kirtan Patolia

Authors' diary: 53 facts about me

Another vlog before my long weekend ends =)

Pemphigus vulgaris vs Paraneoplastic Pemphigus vulgaris (PNP)

Hello friends, today let's talk about subtle differences between pemphigus Vulgaris and Paraneoplastic Pemphigus Vulgaris

1. SITE OF INVOLVEMENT

Pemphigus Vulgaris usually involves buccal and labial mucosa.

PNP causes severe stomatitis as well as targetoid lesions on palms and soles much like erythema multiforme.

2. ANTIBODIES INVOLVED

In Pemphigus Vulgaris antibodies are directed against intercellular adhesion molecules desmoglein-1 and desmoglein-3.

However, in PNP apart from desmoglein-1 and desmoglein-3 antibodies are also directed against envoplakin, plectin, desmoplakin, periplakin, and BPAG-1. 

3. IMMUNOFLUORESCENT PATTERN

In Pemphigus Vulgaris typical chicken-wire pattern is seen due to the intercellular deposition of IgG and C3

In PNP, that is not the case as although there is IgG deposition in all layers but not intercellularly and furthermore C3 is deposited along basement membrane as in Bullous pemphigoid.

4. VISCERAL INVOLVEMENT

In Pemphigus Vulgaris it is rare while in PNP often mucosa of the esophagus, stomach, duodenum, intestines, and the pulmonary epithelium is seen.

Prognosis is quite poor in PNP with bronchiolitis obliterans and sepsis being chief complications.

Mostly seen in Non- Hodgkin's lymphoma and CLL.

- Kirtan Patolia

Talazoparib: Zenith of novelty

Recently, talazoparib was approved by FDA for BRCA mutated breast cancer. Several other drugs related to it such as niraparib, olaparib are already approved for ovarian and breast cancer.

So how they work:

In eukaryotic cells, there is highly intricated network of sensors, transducers and mediators for DNA damage recognition and subsequent successful repair.

One of the such molecule is PARP (polyADP ribose polymerase) which serves to identify single strand breaks (SSBs) and seal them.

If PARP is inhibited (say, by talazoparib) then SSBs would progress to double strand breaks (DSBs). DSBs can also be effectively repaired by BRCA 1 and BRCA 2 complex by homologous recombination method.

However, in cancer cells with mutated BRCA, DSBs would not be repaired, ultimately causing apoptosis via molecules such as PUMA (p53 upregulated modulator of apoptosis), NOXA and p21.

Furthermore, talazoparib is known to induce formation of cytotoxic PARP-DNA complex, further contributing to it's mechanism.

That is definitely zenith of novel mechanism.

Stones in Crohn's disease

Hello everyone, 

In this post, I'll be talking about the different types of stones seen in Crohn's disease. Let's learn why they form! 

CHOLESTEROL GALLSTONES: Either due to ileal involvement or ileostomy, in Crohn's, enterohepatic circulation of bile acids is perturbed resulting in supersaturation of bile with the cholesterol, altering the delicate composition of bile acids, phospholipids, and cholesterol of 10:3:1 in bile fluid.

CALCIUM BILIRUBINATE GALLSTONES: Due to alteration in colonic flora conjugated bilirubin is converted to unconjugated bilirubin, which along with seepage of excessive unabsorbed bile acids from the ileum, results in enhanced absorption of bilirubin from the colon causing increased concentration in bile.

CALCIUM OXALATE RENAL STONES:

Usually, calcium in the GI tract forms a complex with oxalate ions resulting in its excretion in stool but in Crohn's due to steatorrhea excessive unabsorbed negatively charged fatty acids bind with calcium, leaving unbound oxalate to be absorbed and subsequently excreted by urine causing nephrolithiasis.

URIC ACID RENAL STONES: Diarrhea in Crohn's causes metabolic acidosis due to decreased bicarbonate absorption or increased excretion from the colon which increases the acidity of tubular fluid. The increased acidity, simultaneous dehydration, hypocitraturia, and hypomagnesemia in such patients precipitate uric acid stones.

-Kirtan Patolia

Authors' diary: Residency and life so far (after moving to the US)

Hey!

I am video blogging now :)

True or False #9

1.Atopic dermatitis presents on flexor surfaces in infants. T or F

ANSWER

F

Extensor surfaces

Flexor in older children and adults

How to remember this?

Infants slEEEEEEEp a lot right.

Hence EEEEEEEExtensor surface involved in infants in atopic dermatitis

That will help you remember the opposite ( flexor surfaces) involved in older children and adults

That's all.

Calcium monitoring in ethylene glycol poisoning

Seizures often occurs in ethylene glycol poisoning.  It has multifaceted pathophysiology but one of the major cause is hypocalcemia.

Hypocalcemia occurs in ethylene glycol poisoning because ethylene glycol is metabolized to oxalate, which forms calcium oxalate depleting calcium from ECF.

Also, correcting associated metabolic acidosis by bicarbonate supplementation can further cause hypocalcemia due to increased binding of calcium to albumin.

This is why, calcium levels should always be monitored meticulously in such patients.

- Kirtan Patolia ( BJ medical college)

Cryptic conundrum in ET: Thrombosis or bleeding?

In essential thrombocytosis, contrary to what might be surmised, bleeding is more of threat than thrombosis.

This is because high platelet count especially above 1 million/mm3 cause acquired von willebrand disease, much like type 2b von willebrand disease, where excessive affinity of vWF for platelet Gpib result in excessive removal of platelet-vWF complex by spleen results in  thrombocytopenia and loss of high molecular weight vWF multimers.

However, incidence of erythromelalgia , transient ischemic attack and other microvascular events are also high in patients with essential thrombocytosis.

Pretty complex and contradictory, right?

- Kirtan Patolia ( BJ medical college).

Diabetic amyotrophy

Hello everyone!

Today, I will be talking about diabetic amyotrophy.

Diabetic amyotrophy has a lot of names!

It is also known as Bruns-Garland syndrome, diabetic myelopathy, proximal diabetic neuropathy, diabetic polyradiculopathy, diabetic motor neuropathy, diabetic radiculoplexopathy, diabetic lumbosacral plexopathy, and diabetic LRPN.

Diabetic amyotrophy typically occurs in patients with type 2 diabetes mellitus. The traditional features include the acute, asymmetric, focal onset of pain followed by weakness involving the proximal leg, with associated autonomic failure and weight loss. Progression occurs over months and is followed by partial recovery in most patients.

The diagnosis of diabetic amyotrophy is mainly based upon the presence of suggestive clinical features in a patient with known or newly diagnosed diabetes mellitus. Appropriate laboratory investigations, particularly electrodiagnostic studies, and neuroimaging in select patients, are useful to exclude other peripheral and central nervous system etiologies as a cause of the neurologic symptoms and signs.

No treatments are proven to be effective for diabetic amyotrophy or for idiopathic LRPN.

PS: Distal symmetric sensorimotor polyneuropathy is the most common type of diabetic neuropathy - it is characterized by a progressive loss of distal sensation correlating with loss of sensory axons, followed, in severe cases, by motor weakness and motor axonal loss. Classic "stocking-glove" sensory loss is typical in this disorder.

Source: UpToDate

That's all!

-IkaN

Zebra series: Lemierre's syndrome

Hello everyone!

Let's talk about Lemierre's syndrome today.

Lemierre's syndrome is characterized by disseminated abscesses and thrombophlebitis of the internal jugular vein after infection of the oropharynx. The predominant pathogen is a gram-negative anaerobic bacillus, Fusobacterium necrophorum.

That's the Zebra for the day!

IkaN

True or False #8 Lower GI Bleed

1. Angiodysplasia is a high volume arterial bleed. T or F

2. Diverticulosis is a low volume arterial bleed. T or F

ANSWERS

1. FALSE

Angiodysplasia  more often than not involves low volume venous bleeding.

Angiodysplasias are composed of ectatic, dilated, thin-walled vessels that are lined by endothelium alone or endothelium along with small amounts of smooth muscle. Studies in which casts of angiodysplasias were made by injecting a silicone material demonstrated that the most prominent feature in angiodysplasias is the presence of dilated, tortuous submucosal veins.
Small arteriovenous communications are also present and are due to incompetence of the precapillary sphincter. Enlarged arteries may be seen in larger angiodysplasias and may be associated with arteriovenous fistulas, which explains why bleeding can be brisk in some patients.
Histologic confirmation is often difficult. When obtained, it shows dilated vessels in the mucosa and submucosa, sometimes covered by only a single layer of surface epithelium.

2. FALSE

Diverticular bleeding involves high volume arterial bleed

Diverticular bleeding — As a diverticulum herniates, the penetrating vessel responsible for the wall weakness at that point becomes draped over the dome of the diverticulum, separated from the bowel lumen only by mucosa. Over time, the vasa recta is exposed to injury along its luminal aspect, leading to eccentric intimal thickening and thinning of the media. These changes may result in segmental weakness of the artery, predisposing to rupture into the lumen. Diverticular bleeding typically occurs in the absence of diverticulitis

Authors' diary: Internist's disease

Hello,

We had an interesting morning report today and I learnt this from Dr. L (L for Legend!)

Zebra series: Stauffer syndrome

Hello,

I'll be talking about Stauffer syndrome today!

Authors' diary: Zebra series

Hello!

I am starting a Zebra Series on Medicowesome.

True or False #7

1.Depression increases the risk of morbidity and mortality in Cardiovascular disease. T or F

2. Patients with Cardiovascular disease are more likely to develop Depression. T or F

True or False #6

1. Nightmare is a REM sleep behavior disorder. T or F

2. Night Terror is a REM sleep behavior disorder. T or F

ANSWERS

1. True

Things you should REMember for Nightmare disorder are :

REM

Second half of the night

Responsive to comfort

REMembers the dream

2. False

Night terrors:  Abrupt arousals from sleep (panicked scream, terror, autonomic arousal, unresponsive to comfort)

- Little or no dream recall

- Amnesia for episodes

Sleep is a gift, always be grateful for it.