Migraine

Abortive Medication Stratification by Headache Severity

Moderate	Severe	Extremely Severe
NSAIDs	Naratriptan	DHE (IV)
Isometheptene	Rizatriptan	Opioids
Ergotamine	Sumatriptan (SC,NS)	Dopamine antagonists
Naratriptan	Zolmitriptan
Rizatriptan	Almotriptan
Sumatriptan	Frovatriptan
Zolmitriptan	Eletriptan
Almotriptan	DHE (NS/IM)
Frovatriptan	Ergotamine
Eletriptan	Dopamine antagonists
Dopamine antagonists

Table 2. Preventive Drugs

First line	High efficacy	Beta-blockers Tricyclic antidepressants Divalproex Topiramate
	Low efficacy	Verapamil NSAIDs SSRIs
Second line	High efficacy	Methysergide Flunarizine MAOIs
	Unproven efficacy	Cyproheptadine Gabapentin Lamotrigine

Comorbid Condition	Medication
Hypertension	Beta-blockers
Angina	Beta-blockers
Stress	Beta-blockers
Depression	Tricyclic antidepressants, SSRIs
Underweight	Tricyclic antidepressants
Epilepsy	Valproic acid, Topiramate
Mania	Valproic acid

Carcinoma Breast

In hormone receptor-positive, HER2-negative disease, endocrine therapy should be a clinician’s first choice. Single-agent chemotherapy and combination chemotherapy are also possible options. Chemotherapy and hormone therapy should not be given concomitantly.

For postmenopausal women with ER-positive:

Table 1. Available Endocrine Therapies

Agent Class	Drugs Available
Anabolic steroids	nandrolone decanoate
AIs, third-generation, nonsteroidal	anastrozole; letrozole
AIs, third-generation, steroidal	exemestane
Estrogens	estrogens
ER downregulator	fulvestrant
Luteinizing hormone-releasing hormone analogues	goserelin; leuprorelin; triptorelin
Progestins	medroxyprogesterone acetate; megestrol acetate
Selective ER modulators	tamoxifen, toremifene

Letrozole- oral non steroidal aromatase inhibitor 
For postmenopausal women with ER-positive disease, several endocrine therapy options are considered standard. If AIs have not been used in the adjuvant setting, several studies have shown they are superior to other endocrine therapy, including tamoxifen. The third-generation AIs — letrozole, exemestane, and anastrozole — provided statistically significant survival benefits. Fulvestrant, an ER downregulator, is available in 2 doses: 250 mg or 500 mg. Recently published data from the phase 2 FIRST trial compared fulvestrant with anastrozole as first-line endocrine therapy for postmenopausal women with hormone receptor-positive advanced breast cancer. Specifically, they compared high-dose fulvestrant (500 mg intramuscularly on days 0, 14, and 28, and monthly thereafter) with anastrozole (1 mg per day). Median time to progression (TTP), the primary endpoint, was 23.4 months in the fulvestrant arm and 13.1 months in the anastrozole arm (HR, 0.66; 95% CI, 0.47-0.92; P = .01).


Bone-modifying agents beneficial in bone secondaries of breast CA (also caused by hormonal therapy):
1 of 3 bone-modifying agents:

Denosumab-targets RANKL(RANK ligand)-a protein that acts as the primary signal for bone removal. In many bone loss conditions, RANKL overwhelms the body's natural defenses against bone destruction.-120 mg subcutaneously every 4 weeks,
intravenous (IV) pamidronate (90 mg over no less than 2 hours),
 or zoledronic acid (4 mg over no less than 15 minutes every 3 to 4 weeks)

Other Agents:
Everolimus- inhibitor of Mammalian Target of Rapamycin (mTOR)- an immunosuppressant
Patients who become resistant to endocrine therapy have a poor prognosis. The targeted agent everolimus, which has just been approved, helps patients circumvent endocrine resistance. Resistance to endocrine therapy has been associated with the activation of the P13K-mTOR pathway, which, in turn, activates the ER. Everolimus inhibits the mTOR pathway.

Bevacizumab-monoclonal antibody-angiogenesis inhibitor-inhibits VEGF-A. The use of bevacizumab in breast cancer has been surrounded by controversy in recent years. In 2009, the EMA approved the combination of paclitaxel and bevacizumab in MBC, based on the E2100 clinical trial. This study showed a 5.5-month improvement in PFS for the combination over paclitaxel monotherapy. With longer follow-up of E2100, however, investigators found the PFS benefit did not translate into an OS benefit.

HER2-Positive Metastatic Breast Cancer

Trustuzumab- Monoclonal antibody that interfers with HER2/nu receptor

More recently, level 1 evidence has shown that clinicians should continue blockade of the HER2 pathway even after a patient progresses on an anti-HER2 agent. The German Breast Group enrolled 78 patients with HER2-positive breast cancer that had progressed during treatment with trastuzumab and randomized them to received capecitabine alone or in combination with trastuzumab.

Lapatinib-Dual tyrosine kinase inhibitor- Inhibitor of  HER2/nu receptor + EGFR pathways

ESMO guidelines state that available evidence suggests continuing anti-HER2 therapy for as long as possible.

Capecitabine:

5-FU prodrug, converted enzymatically to 5-FU in tumour

Pertuzumab:

The first of its class in a line of agents called "HER dimerization inhibitors"

Table 2. Available Chemotherapy Agents

Anthracycline-containing regimens	Doxorubicin or epirubicin monotherapy Doxorubicin/cyclophosphamide or epirubicin/cyclophosphamide Liposomal doxorubicin with or without cyclophosphamide Fluorouracil/doxorubicin/cyclophosphamide or fluorouracil/epirubicin/cyclophosphamide
Taxane-containing regimens	Paclitaxel monotherapy Docetaxel monotherapy Nab-paclitaxel Anthracycline (doxorubicin or epirubicin)/taxane (paclitaxel or docetaxel) Docetaxel/capecitabine Paclitaxel/gemcitabine Paclitaxel/vinorelbine Paclitaxel/carboplatin
Newer cytotoxic regimens	Eribulin Ixabepilone (not approved by EMA) Cyclophosphamide/methotrexate/fluorouracil (CMF) Platinum-based combinations (eg, cisplatin + 5-fluouracil; carboplatin + gemcitabine) Capecitabine Vinorelbine Capecitabine + vinorelbine Vinorelbine with or without gemcitabine Oral cyclophosphamide with or without methotrexate Eribulin The recently approved chemotherapeutic eribulin mesylate is only approved for heavily pretreated women with locally recurrent or MBC. The label states it is approved for patients who have progressed after at least 2 chemotherapeutic regimens for advanced disease. Brain Metastasis: Brain metastases occur in 30% to 50% of patients with HER2-positive MBC. Patients with a small number of potentially resectable brain metastases should be treated with surgery or radiosurgery. Patients who respond to anti-HER2-based therapy and have controlled extracranial disease can live for several years after the diagnosis and treatment of brain metastases. Recently the phase 2 LANDSCAPE trial, investigating the combination of lapatinib and capecitabine for the treatment of previously untreated brain metastases from HER2-positive MBC, showed that 65.9% had an objective central nervous system (CNS) response. Results from a phase 2 trial have shown that brain metastases can respond to a combination of lapatinib plus capecitabine Rebiopsy: National Comprehensive Cancer Network (NCCN), and others state that hormone receptor status and HER2 status should be re-evaluated at least once in a metastatic lesion. NOTE- These are personal notes.They don't qualify be quoted.

Pericardium

The heart and its pericardium make up the contents of the middle mediastinum. The left and right phrenic nerves and their adjacent arteries (pericardiacophrenic) lie to the left and right of the pericardium and anterior to the roots of the lungs.

Parietal and visceral pericardium are continuous. This continuity takes place at the points where the major blood vessels enter and leave the heart. The parietal pericardium has two inseparable parts, an outer fibrous part and an inner smooth part, the serous part.The potential space between the visceral and serous parietal pericardium is the pericardial cavity.

Second View:

The fibrous pericardium is the outermost layer, and it is firmly bound to the central tendon of the diaphragm. Extrapericardial fat, which may be visible radiographically, is often found in the angles between the pericardium and diaphragm on each side. The pericardium is attached to the sternum (by the sternopericardial ligaments) and is adherent to the mediastinal pleura except where the two are separated by the phrenic nerves.

The serous pericardium  is a closed sac, the parietal layer of which lines the inner surface of the fibrous pericardium and is reflected onto the heart as the visceral layer, or epicardium. The potential space between the parietal and visceral layers contains a thin film of fluid and is known as the pericardial cavity.

Pericardial Sinuses

Within the pericardial cavity, at the points where the visceral and parietal pericardia are continuous with one another, small chambers or sinuses are located. In this diagram, the heart has been removed and you are looking toward the posterior wall of the pericardial cavity.

The pericardial sinuses: transverse pericardial sinus oblique pericardial sinus The transverse pericardial sinus can easily be reached by sticking your finger between the superior vena cava and the ascending aorta and pulmonary trunk. This sinus is a leftover from heart development in the embryo. Again, slide two or three fingers under and behind the heart until they reach a dead end. Your fingers are now in the oblique pericardial sinus. 1. The pericardium starts to form during the _______ week of developme Correct . 5th 2. Which statement is true about the pleuropericardial folds? Correct answer: a. they partition the thorax into a pericardial cavity and two pleural cavities 3. What anatomic structure is located within, and migrates with, each pleuropericardial fold? Correct answer: b. phrenic nerve 4. The pleuropericardial folds initially form and grow along a _________ plane. Correct answer: d. coronal (frontal)

Cranial Nerves

CN which is the smallest -- olfactory n. CN which enters cerebrum directly - olfactory nerve CN with longest intracranial (subarachnoid) course -- trochlear n CN which emerges posterior to brain stem- trochlear nerve CN with dorsal exit -- trochlear n. CN which is the largest and thickest -- trigeminal n. CN which is largest -- trigeminal nerve CN with longest extracranial course --vagus n. CN having longest intraosseous course -- facial nerve CN with longest  intradural course - abducent nerve CN passing through cavernous sinus -- abducent nerve CN involved in raised intracranial tension -- abducent nerve  Abducent nerve has the longest intra-cranial INTRADURAL course!! Thickest nerve is SCIATIC nerve Thickest cutaneous nerve is GREATER OCCIPITAL nerve Labourer’s nerve-median nerve Dentist’s nerve-inferior alveolar nerve Alderman’s nerve-auricular branch of vagus nerve Nerve of laterjet-largest gastric branch of vagus nerve CN with longest intracranial course -- trochlear n. CN with longest extracranial course --vagus- Longest nerve:CN X (Vagus) which reaches from the medulla to the digestive and urinary organs    CN which is the largest and thickest -- trigeminal n. CN with dorsal exit -- trochlear n. CN which is the smallest -- olfactory n.

Longest course within the skull is the trochlear, while Largest is trigeminal, longest outside skull is vagus-from medulla to digestive and urinary organs

Thyroid Replacement Therapy

Complications of overreplacement with levothyroxine sodium Include the following:

• Accelerated bone loss
• Reduction in bone mineral density
• Osteoporosis
• Increased heart rate
• Increased cardiac wall thickness
• Increased contractility

The last three problems above increase the risk of cardiac arrhythmias (especially atrial fibrillation), particularly in the elderly population.

Medications that suppress TSH production include steroids, dopamine, dobutamine, and octreotide.


Up to 30-40% of patients with hypothyroidism have anemia, usually from decreased erythropoiesis. In 15% of patients, the anemia is of the iron deficiency type, with microcytosis and hypochromia. Although this can be a normocytic normochromic anemia, the most common morphologic abnormality is a macrocytic anemia that may be partially due to insufficient vitamin B-12 and folate intake.


Glomerular filtration rate, renal plasma flow, and renal free water clearance are all decreased in hypothyroidism and may result in hyponatremia.


Prolactin may be elevated in primary hypothyroidism. This is thought to be caused by overlap secretion due to stimulation of the lactotroph by the elevated TRH level. The decreased clearance of prolactin in hypothyroidism may also play a contributory role. The elevated prolactin level leads to decreased gonadotropin secretion and decreased responsiveness to GnRH. The result of this is anovulatory cycles with menstrual abnormalities, galactorrhea, and infertility in some patients.

Other studies may be performed in the evaluation of complications of primary hypothyroidism (when indicated). These tests are usually not performed and are not necessary in routine diagnosis or evaluation of hypothyroid patients.

• Chest radiograph - May show small pleural effusions
• Electrocardiogram (ECG) - May show low-voltage QRS tracing, nonspecific ST-wave changes, and premature ventricular contractions; prolongation of the QT interval with torsade de pointes and ventricular tachycardia may be noted
• Echocardiogram - May show some pericardial effusion in severe cases of hypothyroidism
  
  
  
  

  Long-Term Monitoring

  Upon the initiation of the levothyroxine replacement therapy, check thyroid function tests, specifically TSH, initially every 6-8 weeks as dose adjustments are made. After the attainment of the clinical euthyroid state and a normal TSH level, patients and the TSH levels may be checked every 6-12 months.

  More frequent follow-up and TSH checks may need to be performed when patients start taking medications, such as ferrous sulphate, calcium supplementation, and multivitamins, that have the potential to impair the absorption of levothyroxine and therefore to affect the TSH level. Patients need to be advised to separate these medications from levothyroxine by at least 4 hours.

  Follow-up care should include clinical evaluation for symptoms of hypothyroidism or iatrogenic hyperthyroidism.

  Physical examination should routinely include weight measurement, pulse and blood pressure determinations, and thyroid examination for the presence of nodules.

  Yearly thyroid ultrasonographic evaluation is important in patients with Hashimoto thyroiditis because of the increased risk of thyroid nodules in these patients and for follow-up of patients with existing benign thyroid nodules.

Facies

Hippocratic face (also known as "Hippocratic facies"; eyes are sunken, temples collapsed, nose is pinched with crusts on the lips and the forehead is clammy)
moon face (also known as "Cushingoid facies")
elfin facies - Williams syndrome
Potter facies - oligohydramnios
mask like facies - parkinsonism
Leonine facies - lepromatous leprosy
Mitral facies - mitral stenosis
Amiodarone facies (deep blue discoloration around malar area and nose)
Acromegalic facies - acromegaly
flat facies - down's syndrome
Marfanoid facies - marfan's syndrome
snarling facies - myasthenia gravis
Myotonic facies - myotonic dystrophy
torpid facies - myxoedema
mouse facies - chronic renal failure
plethoric facies - cushing's syndrome and polycythemia vera
'bird-like' facies- pierre robin sequence
ashen grey facies - myocardial infarction
gargoyle facies - hurler's syndrome
monkey facies - marasmus
hatchet facies - myotonia atrophica
gorilla-like face - acromegaly
bovine facies or cow face - craniofacial dysostosis or crouzons syndrome
marshall halls facies - hydrocephalus
frog face - intra nasal disease

Fractures

break in continuity of bone

• Traumatic-sustained due to excessive force-a qualified fracture usually means traumatic fracture
• Pathological-usually trivial-bone already weak by underlying disease
• Displaced fracture may occur due to fracturing force/muscle pull on fracture filaments/gravity-displacement may be shift/angulation/rotation
• Simple/closed
• Compound/open-

1. internal compounding-piercing of sharp fracture end
2. external compounding-lacreation+fracture from outside

• Transverse # fracture line perpendicular to long axis of bone, caused by tapping/bending force
• Oblique #line of # oblique, caused by a bending force which in addition has component along the long axis of the bone
• Comminuted #with miltiple fragments,caused by crushing/compression force along the long axis of the bone
• Segmental # two fractures in same bone@different levels

Fractures with Eponyms

• Monteggia #dislocation #proximal 1/3rd of ulna + dislocation of head of radius
• Galeazzi #dislocation # distal 1/3rd of radius with dislocation of distal radio-ulnar joint
• Night stick # isolated # shaft of ulna
• Colles' # occuring in adults@cortico-cancellous junction of distal end of radius + dorsal tilt & other displacements
• Smith's # occur in adults@cortico-cancellous junction of distal end of radius with ventral tilt & other displacements (reverse Colles')
• Barton's (marginal) # intra-articular# through distal articular surface of radius, taking a margin, anterior/posterior of the distal radius with the carpals displaced anteriorly/posteriorly
• Chauffeur's # intra-articular oblique # of styloid process of radius
• Bennet's # dislocation-oblique,intra-articular # of base of 1st metacarpal with sublaxation of trapezio-metacarpal joint
• Rolando # extra articular # of base of 1st metacarpal
• Boxer's # a ventrally displaced # through the neck of the 5th metacarpal-common in boxers
• Side swipe # an elbow injury, combination of #distal end of humerus with # proximal end of radius &/or ulna (baby car #)
• Bumper # comminuted depressed type-lateral condyle of tibia
• Pott's # bimalleolar ankle
• Cotton's # trimalleolar ankle
• Massonaise's # ankle with # neck of fibula
• Pilon # comminuted, depressed intra-articular # distal end of tibia
• Aviator's # neck of talus
• Chopart # dislocation # dislocation through inter tarsal joints
• Jone's # Avulsion # base of 5th metatarsal
• Jeffersen's # 1st cervical vertebra
• Whiplash Injury- cervical spine injury involving sudden flexion followed by hyperextension
• Chance # also called seat belt #, line of # runs horizontally through the body of vertebra through & through to the posterior elements
• March # fatigue # of shaft of 2nd & 3rd metatarsal
• Burst # comminuted # of vertebral body where fragments burst out in different directions
• Clay-Shoveller's # an avulsion # of spinous process of one or more of the lower cervical or upper thoracic vertebra
• Hangman's # pedicle & lalamina of C2 vertebra, with sublaxation of C2 over C3-sustained in hanging
• Dashboard # posterior lip # of acetabulum, often associated with posterior dislocation of hip
• Straddle # bilateral superior & inferior pubic rami #
• Malgaigne's # a type of pelvis # in which there is a combination of #s- pubic rami anteriorly & SI joint/ilium posteriorly, on the same side
• Mallet Finger- a finger flexed at the DIP joint d/t avulsion or rupture of extensor tendon@base of distal phallanx