Tough

It's a tough test ahead of me;
i must look at the matter in a large perspective
and show my true character
as i believed it appears in difficulties

6 Fixtures

The schedule til February 19th:

1-Sunday 31 Jan : Gasteroenerology Ward

2-Thuesday 2 Feb : Emergency Ward

3-Thursday 11 Feb : General Medical Ward IV

4-Friday 12 Feb : Rheumatology-Endocrinology Ward

5-Sunday 14 Feb : Emergency Ward

6-Wednesday 17 Feb : General Medical Ward II

ALS:A Bunch Of Muscles,Thinking !

Rolled on to the stage in an electric wheelchair,a blanket wrapped around his body so that all could be seen was his neck and head,to which breathing tube was attached like a bit of facial Tupperwave.

Allegoricly he says:"The last time anyone had seen me in public i'd been bouncing around the stage full of fitness and energy,now they saw this quadriplegic with plastic on his face."

A few weeks ago the English historian Tony Judt delivered a speech at his home in NYU .More than 1000 people turned up,and few left disappointed.

What they heard was classic Tony Judt :the lecture ,a plea for positive virtues of social democracy,was an erudite as might be from the autjor of Postwar ,his epic portrait of Europe since 1945,and as politically pointed as his contraversial writings on Middle East.

He was concerned about how his audience would react to the new-look him,and tried hard to make them feel at ease.It worked and at the end of the speech he received a standing ovation.

18 months ago Judt was,by his own description "a 61 year-old ,very healthy,very fit,very independent,travelling sports-playing guy".He had a slight shortness of breath walking up hills and found himself hitting the wrong keys when he typed,nothing more.

Then in September 2008 he was diagnosed with motor neuron disease,ALS(Amyotrophic Lateral Sclerosis),known as Lou Gehrig's disease after the legendary New York Yankees hitter who died in 1941.

ALS ravage Judt with astonishing speed.By December he had lost the use of his hands.By March he was in wheelchair .By May he was wearing the"the silly-looking facial tubing" as he puts it,because his diaphragm muscles were no longer strong enough to effect the bellows motion that induces breathing.

ALS is the most common form of progressive motor neuron disease.It 's a prime example of neurodegenerative disease and is arguably the most devastaing of the neurodegenerative disorders.

Cused by death of lower motor neurons (consisting of anterior horn cells in the spinal cord and their brainstem homologues innervating bulbar muscles)and upper or corticospinal,motor neurons.

Clinical manifestations of ALS are somewhat variable depending on the site of damaged neurons.With lower motor neuron dysfunction and early denervation,typically the first evidence of the disease is insidiously developing asymmetric weakness ,usually first evident distally in one limb.Recent development of cramping with volitional movements typically in the early hours of morning.Weakness is associated with progressive wasting and atrophy of muscles .

When the initial denervation involves bulbar rather than limb muscles onset is difficulty with chewing,swallowing and movements of the face and tongue.

Early involvement of respiratory muscles may lead to death before the disease is far advanced elsewhere.

Degeneration of the corticobulbar projections innervating brainstem rsults in dysarthria and exaggeration of the motor expressions of emotion.

It's characteristic of ALS that,regardless of wether the initial disease involves upper or lower motor neurons,both will eventually be implicated.

Even in the late stages of ALS sensory,bladder,blowel and cognitive functions are preserved.

Dementia is not a component of sporadic ALS.In some families ,ALS is co-inherited with frontotemporal dementia in some families..

ALS is relentlessly progressive ,leading to death from respiratory paralysis;the median survival is from 3-5 yeards .Several endemic foci of higher prevalence exist in the western Pacific.

The suddenness of the catastrophe in Judt's case would leave many people paralysed not just physically but emotionally.Judt's response was somehow different . He's embarked on a fascinating ,albeit involuntary,intellectual journey ;a forced march of the mind.

The product of this existential delving is a series of essays that Judt has written – or rather dictated – for the New York Review of Books (NYRB) that will be published over the next three months. One tackles his illness head on. In Night, reproduced here, Judt subjects his own deterioration to the same unsparing scrutiny as he would the Israel-Palestine conflict, say. Its absence of any self-pity makes for harrowing reading.

The other eight essays take us back in time to formative aspects of his childhood in England. He was born in 1948 to lower middle-class parents and spent six years living in Putney in south-west London – a location that forms the theme of one of the essays. In others he introduces us to Joe Craddock, his school German teacher, lamenting that Craddock's insistence on excellence ("Yer utterly useless!" he would shout at pupils) is unthinkable in today's pampering education system. He finds meaning in the melange of largely bad food he was served as a child and revels in his love affair with trains that is now deprived him by his immobile condition.

Taken together, the essays illuminate the many contradictions in Judt's make-up that give him such a distinctive voice. He is a Jew with no religion who has questioned the legitimacy of the state of Israel; a naturalised American citizen who is a consistent critic of overweening US power; a person of the left who subscribes to no leftist ideology.

He is, to use a phrase that Judt applied to Edward Said, a rootless cosmopolitan. "Today I'm regarded outside New York University as a looney tunes leftie self-hating Jewish communist; inside the university I'm regarded as a typical old-fashioned white male liberal elitist. I like that. I'm on the edge of both, it makes me feel comfortable."

His current intellectual preoccupation is with the role of the state in western societies – the subject matter of his NYU lecture. His thesis is that over the past 40 years, western democracies have forgotten the positive virtues of collective action. "What has gone catastrophically wrong in England and the States is that for 30 years we've lost the ability to talk about the state in positive terms," he says. "We've raised a generation or two of young people who don't think to ask, what can the state do that is good?"

At the end of the lecture he was struck by how many young people came up to him expressing amazement at ideas they had never heard before. "This is the second generation of people who can't imagine change except in their own lives, who have no sense of social collective public goods or services, who are just isolated individuals desperately striving to better themselves above everybody else."

Judt now intends, in the time he has left, to devote himself to writing a book to help young people think collectively again. "It could really have an impact if I get it right. Something that will get the next generation to see there is a way to think about politics that is not just the way we've been habituated to do it. I care about that and I think I can do it."

Judt is already working on the book, using the same memory technique that he deployed for his NYRB essays. During the night he builds in his mind a Chinese memory palace – or in his case a modest Swiss house – and into each of its rooms he imagines placing a paragraph or theme of the piece he is composing. The next day he recalls each room in sequence, unloading its contents by dictating it to his assistant.

Some people have tried to comfort him with the thought that such mental discipline renders Judt's condition bearable. How wrong they are. "There have been people who have said to me, 'Tony, you are so lucky. More than anyone you live the life of the mind. It could have been so much worse.'"

To which he replies: "Hello! Are you from Planet Zurg? This is one of the worst diseases on Earth. It is like being in a prison which is shrinking by six inches each day."

It is true that he has exceptional mental strength. Against that, there are torments that come with this disease. An intensely independent and proudly autonomous man, he can now never, not for a second, be left alone.

The overriding truth, he says, is that "this is just hell. Because there is no hope, no help, and you know what the ending is going to be, each day is going to be like the last day only maybe a little bit worse. Sisyphus-like, you are going to have to roll this bloody rock up the hill tomorrow in exactly the same way."

We've been talking now for more than an hour, and Judt asks his assistant to move his legs and arms into a new position. He lets out a faint groan of relief. Being motionless for so long, his body hurts; it also grows cold from lack of blood circulation, which explains the sweltering heat in the room.

His ALS has come upon him so swiftly that, under usual expectations, he would be dead within months. But the degeneration of his upper motor neurones, which control his head and voice, appears to be occurring very slowly, raising the hope – or is it fear? – that he may stay as he is for quite a while. Inevitably, though, he will lose all power of communication, bar the ability to wink.

So does he think of euthanasia, of putting an end to an existence that he calls "cumulatively intolerable"?

"There are times when I say to myself, this is so damn miserable I wish I was dead, in an objective sense of I wish I didn't have to get up this morning and do it all over again. I've thought about euthanasia a lot, not for tomorrow, but one has to plan for it because the likely trajectory is that you lose your capacity to express yourself long before you die.

"No one wants to live in a wheelchair unable to talk, only winking once for yes and twice for no. It's perfectly reasonable that there will come a point where the balance of judgment of life over death swings the other way." At that point, he says: "The biggest thing to take into account is not your own feelings but your family's."

All that lies ahead. For now though there is the daily rock to be rolled up the hill, the Swedish house to be filled with night-time compositions, the book to be completed. Tony Judt is in hell. But he's by no means yet defeated.

Reference : Guardian(Ed Pilkington),Harrison

Cold Caress

It's more than music;more than simple hobby,when the sound targets deeper layers of cognition,it's a rare classy experience nowadays;finding the pure revelation of what goes inside.

I lived with the growls,i felt the agony the bleak atmosphere ...it's all familiar to what i've felt,all these years ,every 5:30 morning rise-up,every moment of mine being secluded...

Solitude;a key element of my life...now i really adore this kingdom of mine;to share this with people who ruin all the senses,denying all the beauty with their color blind eyes?

This was the honest sound;ringing in my ear...and i am to listen to them...to feel them

It's a privilege to understand the difficult distorted screams;the inoccent who don't find another way to express their pale existence .

It's a honor belonging to a minority ...

By Choosing Death

i am wondering

wether it's a sophisticated angle

to condemn life

for failure we've made

for chances we've missed

all i can feel is that

there's nothing holier than life

i don't believe in words of prophecy

i believe in my will and thirst

enough with images of death

i visit the old man in the lobby almost every day

looking at me; i can see the the hatred in his eyes

whispering words like this:"punks,idiots,..."

the old man serves me fueling streak of life in my veins

His sulk is easy to forget ; thrashed by images of ethereal impunity

Ready to face the fraud

"....arbitrary

...Absurd"

whatever you call

i won't swap a second of this succulent endeavor

I let this flimsy rope save me

and you let the sullen troll swallow

we'll see who's under illusion

who's on the up

we'll wait and see

Pedram

Jan 16th 2010

As You Pray For Me

And you pray

for me

to fall

to fail

big fish: hooked

Nemesis flourished inside

lonely child

gazing at the sky

as pure as snow

visions of innocence

turned black

as you prayed for me

Pedram 12 jan 2010

Photo : Maciej Tyszeck

The Invention of Solitude

I'm busy reading Paul Auster's debut book "The Invention Of Solitude",it's the 4th Auster's book in my shelf after:"New York Trilogy","Leviathan" and "In The Country Of Last Things" .I have to say it's been really touching so far.

key phrases i faced"Invisible to others and most likely invisible to himslf as well"

Underneath...

Underneath the growing grass,

Underneath the living flowers,

Deeper than the sound of showers:

There we shall not count the hours

By the shadows as they pass

Youth and health will be but in vain,

Beauty reckoned of no worth:

There a very little girth

Can hold round what once the earth

seemed too narrow to contain

Christina Rossetti

3days this week fixed

Schedule set up:

I'll be on call on Sunday (General Medical Ward)

Emergency Ward on Wednesday,

Rheumatology/Endocrine Ward on Thursday,

Friday i'll be off

There's no on call program mentioned for me in next week time table.Which is against my interest;I'll try to discuss the matter tomorrow.

The Mystery Of Painful Purple Toes

A 57-year-old man presented to the emergency department with painful purple toes. On the day of presentation, he had first been seen in another hospital but left against medical advice before the evaluation was complete. He had first noted a painful discoloration of his left great toe 2 weeks earlier. The pain and discoloration progressed to involve the left second and third toes (Figure 1A). During the 3 weeks preceding presentation, the patient also had intermittent blurry vision, intermittent chest pain, fatigue, anorexia, drenching night sweats, and a weight loss of 6.8 kg (15 lb). His roommate commented that thepatient had also been slightly confused.

Fig1A,B

This patient's painful purple toes are suggestive of peripheral arterial ischemia. The differential diagnosis includes arterial thromboembolism resulting from a hypercoagulable state or from disseminated intravascular coagulation, perhaps related to cancer; embolus of infectious or thrombotic material from endocarditis; paradoxical embolus through an intracardiac shunt; precipitation of cryoglobulins; small-vessel vasculitis; and secondary vasculitis from an underlying connective-tissue disease, such as systemic lupus erythematosus. The possibility of cholesterol emboli should also be considered, particularly in patients who have aortic aneurysms or who have recently undergone vascular procedures. Thromboangiitis obliterans, or Buerger's disease, would be a consideration if the patient smokes. His history suggests at least two and perhaps three separate vascular events in the left foot, serially affecting the digital arteries of the great, second, and third toes. Combined with the report of blurry vision and confusion, the patient's history raises the possibility that a central vascular process is affecting the peripheral and cerebral circulatory beds. The intermittent nature of the chest pain and visual symptoms suggests the possibility of sporadic emboli. Finally, the night sweats, fevers, and weight loss point to a systemic illness, such as infection, cancer, or connective-tissue disease. Specific points to review include risk factors for subacute bacterial endocarditis, such as injection-drug use, and risk factors for hypercoaguable states, such as a family history. Further history taking and physical examination should be performed to seek evidence of hypercoagulability or a systemic illness, such as endocarditis, cancer, or vasculitis.

The patient had a history of hypertension, anxiety, chronic back pain, and gastroesophageal reflux disease. While in the Marine Corps in Vietnam, he had malaria and injuries to the hip and skull. Since serving in Vietnam he had also had post-traumatic stress disorder. Two years before presentation, a screening colonoscopy detected benign polyps. His medications included alprazolam, oxycodone with acetaminophen, and esomeprazole. The patient worked for the U.S. Postal Service and was living with a friend. He reported smoking half a pack of cigarettes daily for 30 years, weekly alcohol use, and rare but ongoing intranasal cocaine use, but no intravenous drug use. He was divorced and had not recently been sexually active. There was no family history of cancer, autoimmune diseases, diabetes, or clotting disorders.
Smoking increases the risks of several cancers, including lung and pancreatic cancers, which may in turn induce a hypercoaguable state. Intranasal cocaine use can cause vasospasm, which may exacerbate digital ischemia, and is also associated with otherbehaviors that are predisposing factors for hepatitis C, a common cause of cryoglobulinemia, and acquisition of the human immunodeficiency virus (HIV). Suspicion of limb ischemia, in addition to prompting an evaluation for physical findings indicative of such systemic disease processes, calls for a thorough examination of the peripheral pulses and may warrant consultation with a vascular surgeon.
On physical examination, the patient's temperature was 36.4°C; pulse, 104 beats per minute; blood pressure, 167/86 mm Hg; respiratory rate, 14 breaths per minute; and oxygen saturation, 96% while he was breathing ambient air. No Roth's spots were seen on funduscopy. The carotid pulses were normal, without bruits, and the chest was clear on auscultation. Cardiac examination revealed a normal S1 sound and a physiologically split S2 sound, without a murmur or rub, and the presence of an S4 gallop. The abdomen was not tender, and neither the liver nor the spleen was enlarged. There was no lymphadenopathy or thrush. The dorsalis pedis and posterior tibialis pulses in the left foot were diminished but palpable, and the foot was warm. On each of the first three toes of the left foot there was a well-demarcated, cool, tender area of nonblanching, dark-purple discoloration. Capillary refill in the unaffected toes was normal. There was no rash, edema, or livedo reticularis of the legs. Distal splinter hemorrhages were noted in several fingernails (Figure 1B). There were no Janeway's lesions or Osler's nodes. Neurologic examination revealed a deficit in the left visual field. The patient received a score of 29 points out of 30 on the Mini–Mental State Examination, having difficulty only when attempting to repeat the phrase, "no ifs, ands, or buts."
The white-cell count was 15,510 per cubic millimeter, with 80% granulocytes, 14% lymphocytes, 5% monocytes, and 1% eosinophils. The hemoglobin and platelet counts were normal, and the erythrocyte sedimentation rate was 19 mm per hour. Levels of electrolytes, blood urea nitrogen, creatinine, albumin, and globulin were normal. The level of C-reactive protein was 32.1 mg per liter (reference range, 1.0 to 3.0). The serum level of creatine kinase was 40 U per liter (reference range, 41 to 266); creatine kinase MB, 2.7 ng per milliliter (reference value, <5.0);> I, 2.22 ng per milliliter (reference value, <0.04).> normalized ratio for the prothrombin time was 1.1, the partialthromboplastin time 25.7 seconds (reference range, 23.8 to 36.6), and the fibrinogen level 264 mg per deciliter (reference range, 200 to 450). A blood smear showed hypochromia; no schistocytes were identified. An electrocardiogram showed a normal sinus rhythm with ST-segment elevations in the inferior and anteroseptal leads.

The finding of a well-demarcated, discolored area on each of the three toes of the left foot supports the possibility of a separate embolus to each of the three small digital arteries feeding the affected toes, rather than a single, more proximal thrombotic or embolic event. The lesions are consistent with localized ischemia, infarction, or thromboangiitis obliterans, but the fact that the foot is warm, with palpable pulses, rules out critical limb ischemia. Although the findings on physical examination do not rule out the possibility of a small-vessel vasculitis, the absence of livedo reticularis makes the presence of cholesterol emboli unlikely. The splinter hemorrhages are consistent with systemic emboli, but these hemorrhages are a nonspecific finding that can also be associated with nail trauma, autoimmune disease, connective-tissue disease, cancer, or endocarditis. Splinter hemorrhages are more specific for subacute bacterial endocarditis when they are present in the proximal, rather than distal, nail plate.
The elevated white-cell count suggests infection, but it is a nonspecific finding. The normal coagulation studies and absence of schistocytes on the blood smear are not consistent with a diagnosis of disseminated intravascular coagulation. The combination of the elevated level of troponin I and the ST-segment abnormalities raises the possibility of an acute coronary syndrome, although the apparent involvement of two vascular territories (right and left anterior descending coronary arteries) on electrocardiography and evidence of ischemia elsewhere make emboli to the coronary circulation seem more likely. Echocardiography might identify a cardiac source of emboli and would help to gauge the extent of myocardial injury. Brain imaging is warranted to evaluate the cause of the patient's visual field deficit and slightly altered mental status.


Magnetic resonance imaging (MRI) of the brain ), including diffusion-weighted imaging, revealed multiple small lesions in the right temporal and occipital lobes, right thalamus, both parietal lobes, left frontal lobe, and both cerebellar hemispheres; there was also a large area of enhancement in the right occipital and parietal lobes. Magnetic resonance angiography of the head and neck showed decreased blood flow in the posterior communicating artery (Fig2A,B). A transthoracic echocardiogram showed a mildly thickened mitral valve, with mild regurgitation, and structurally normal aortic, tricuspid, and pulmonary valves. The left ventricular ejection fraction was normal, and therewere no abnormalities in wall motion. The results of venous ultrasonography and computed tomographic (CT) pulmonary angiography performed at the other hospital were obtained; they showed thrombi in the great saphenous veins of both legs and a small pulmonary embolus in the lower lobe of the right lung.
Fig-2A,B

The MRI findings are consistent with embolic disease of the brain, with the emboli mostly likely traveling through both the carotid and vertebrobasilar arteries from the left heart or proximal aorta. The disease process is not limited to the arterial circulation, as evidenced by the pulmonary embolus and venous thrombi of the legs. Further evaluation should focus on identifying a disease process that would explain both the venous and the arterial thrombosis, including evaluation for an underlying hypercoaguable state. Paradoxical embolism from a venous source, passing through an intracardiac shunt, could also explain the presence of both arterial and venous lesions. Although the transthoracic echocardiogram showed no evidence of a shunt, studies performed without the injection of agitated saline, such as this one, have a low sensitivity for atrial septal defects. Because of the high clinical suspicion for subacute bacterial endocarditis, further evaluation with transesophageal echocardiography is appropriate. Empiric antibiotic treatment should be initiated after blood cultures are obtained.
Emergency cardiac catheterization warrants consideration in any patient with ST-segment elevations, but in this case the normal ventricular wall motion on the echocardiogram, the presence of ST-segment abnormalities in two distinct vascular distributions, and the absence of ongoing chest pain all favor coronary emboli as the cause of the patient's symptoms and elevated troponin levels. Cerebral emboli are associated with a risk of hemorrhage, particularly if they are infectious, which in turn increases the risk of systemic anticoagulation, in addition to the anticoagulation that would be required with a percutaneous intervention performed at cardiac catheterization.
Anticoagulant therapy was deferred pending further evaluation. A transesophageal echocardiogram showed a 7-mm mobile echodensity on the atrial aspect of the posterior mitral-valve leaflet, with no evidence of perivalvular abscess or leaflet perforation, and mild-to-moderate mitral regurgitation (Figure 3). Treatment with ceftriaxone, vancomycin, and gentamicin was initiated for presumed infective endocarditis. However, multiple blood cultures — including cultures grown from samples obtained before antibiotic therapy was begun, cultures held for 2 weeks, and fungal blood cultures — were all negative. Serologic tests for HIV, coxiella, bartonella, treponema, and hepatitis B virus were negative. Serum hepatitis C virus RNA was undetectable.

Fig3- Transesophageal Echocardiogram

A midesophageal commissural view of the mitral valve shows the lesion (arrow). LA denotes left atrium, LV left ventricle, and MV mitral valve.

The negative results of tests for infection increase my suspicion that the causes of the cardiac valvular vegetations and thromboembolic disease are noninfectious. Nonbacterial thrombotic endocarditis (commonly known as marantic endocarditis) is a potential complication of connective-tissue diseases and cancer, either of which could explain the patient's weight loss and night sweats, and may also be associated with concurrent venous and arterial thromboembolism. Further studies should include assays for the lupus anticoagulant and anticardiolipin antibodies, since the antiphospholipid-antibody syndrome could explain the valvular lesion and the venous and arterial thromboses. In the absence of localizing symptoms, imaging of the abdomen and pelvis should be considered to look for evidence of cancer.
Anticardiolipin antibodies were not detected, and a test for lupus anticoagulant was negative. CT of the abdomen revealed multiple low-attenuation lesions in the liver, a finding suggestive of metastatic disease, as well as a small low-attenuation lesion in the head of the pancreas, an enlarged gastrohepatic lymph node, and bilateral wedge-shaped renal infarcts (Figure 4). CT-guided fine-needle aspiration of a liver lesion was performed, and cytologic examination of the aspirate revealed a poorly differentiated adenocarcinoma of undetermined primary origin (Figure 5). Serum levels of alpha-fetoprotein and prostate-specific antigen were normal. The level for the beta subunit of human chorionic gonadotropin was 20 mIU per milliliter (reference range, 1.5), and that for carcinoembryonic antigen was 4.7 ng per milliliter (reference range, 2.5). The serum level of the carbohydrate antigen 19-9 (CA 19-9) was 16,611 U per liter (reference value, <35).



Fig4-Contrast Enhanced CT of the Abdomen
Multiple low-attenuation lesions can be seen in the liver (Panel A), and a small low-attenuation lesion is visible in the head of the pancreas (Panel B, arrow)

Figure 5.-Specimen from Fine-Needle Aspiration of a Liver Lesion.
Staining of the aspirate with hematoxylin and eosin shows sheets of poorly differentiated malignant cells (Panel A) and the mitotic figures and abundant clear cytoplasm that are consistent with adenocarcinoma (Panel B).


Although measurement of the CA 19-9 level should not be used as a screening test for pancreatic cancer in the general population because of its very low positive predictive value, in a patient with a pancreatic mass and suggestive clinical findings, such as this patient, a positive test result strongly supports a diagnosis of pancreatic carcinoma. Slight elevations in the levels of human chorionic gonadotropin and carcinoembryonic antigen are nonspecific and can be seen in pancreatic cancer, especially when it has metastasized to the liver. The identification of metastatic adenocarcinoma confirms the diagnosis of nonbacterial thrombotic endocarditis associated with cancer. Although concurrent arterial and venous thromboemboli are a rare complication of cancer, they are more common in cases of nonbacterial thrombotic endocarditis, as was true with this patient. Anticoagulant therapy with unfractionated heparin should be initiated to decrease the risk of recurrent thromboembolism.
Treatment with unfractionated heparin was initiated on hospital day 8; the regimen was subsequently changed to low-molecular-weight heparin. Over the course of the next week, progressive renal insufficiency, visual impairment, and episodes of psychosis with flashbacks to the Vietnam War developed. Plans for chemotherapy were deferred because of progressive multiorgan dysfunction and the poor prognosis, even with treatment. The patient requested transition to palliative care, and he died within weeks after his initial presentation. A postmortem examination was not performed.
Commentary
This patient's evaluation reveals how a careful history taking and a broad consideration of the possible causes of seemingly disparate events — including limb ischemia, blurred vision, chest pain, and weight loss — can lead to the unifying diagnosis of a systemic condition. The patient's history, the findings on physical examination, and the radiologic studies prompted consideration of a source of systemic emboli and the initiation of empirical therapy for infective endocarditis while an evaluation for noninfectious causes was performed. A key feature of this case was the presence of concurrent arterial and venous thromboemboli, which can be attributed to only a small number of unifying diagnoses.

Once a cardiac valvular mass was discovered, the clinicians chose to delay the use of systemic anticoagulation because of the risk of intracerebral hemorrhage. There is considerable controversy regarding the risk of hemorrhage when a patient has intracranial infective emboli. Some retrospective studies have shown a high risk of intracranial hemorrhage among patients with infective endocarditis and cerebral infarction who undergo anticoagulant treatment for cardiopulmonary bypass, whereas others have not. In this case, since the patient's blood cultures remained negative and radiologic imaging suggested disease that had metastasized to the liver, it became clear that nonbacterial thrombotic endocarditis was the likely diagnosis. Although the use of anticoagulation with heparin in the treatment of nonbacterial thrombotic endocarditis has not been studied in a randomized trial, it is thought to be beneficial, especially in cases that arise as a consequence of a malignant disease, and it does not seem to increase the risk of hemorrhage in association with cerebral emboli.
The prevalence of nonbacterial thrombotic endocarditis on autopsy ranges from 0.3% to 9.3%, depending on sample preparation and the prevalence of malignant disease in the source population. Although nonbacterial thrombotic endocarditis has been reported in neonates and children, frequently in association with congenital heart disease, it is most common in patients 40 years of age or older.In adults, it is often associated with cancer, but it has also been reported in association with systemic lupuserythematosus, burns, HIV infection, tuberculosis, uremia, radiation exposure, snakebites, and trauma from pulmonary catheters.When malignant disease is present, adenocarcinoma of the pancreas is cited as the most common primary cancer, as was most likely in this case; other cancers frequently found in patients with nonbacterial thrombotic endocarditis include lung, colon, and prostate cancers. The thrombophilia associated with malignant disease is thought to play an important role in the formation of valvular lesions; in a series of autopsy-proven cases of nonbacterial thrombotic endocarditis, disseminated intravascular coagulation was present in 71% of the cases. Although the laboratory findings in this patient were not typical of those associated with a consumptive coagulopathy, such as the presence of schistocytes, elevated clotting times, low fibrinogen levels, and low platelet levels, the pulmonary embolus and the venous thrombi in the legs were consistent with a hypercoaguable state induced by malignant disease.
The pathophysiology of nonbacterial thrombotic endocarditis is not well understood. Damage to the valvular endothelium is considered to be a critical first step in its pathogenesis, and patients with rheumatic or congenital heart disease are at elevated risk. Endothelial damage may be the result of high blood flow, direct trauma, immune-complex deposition, or complement activation, or it may be an elaboration of interleukin-1, interleukin-6, and tumor necrosis factor by tumor cells. The underlying thrombogenicsurface then acts as a nidus for platelet aggregation and fibrin deposition and leads to the formation of small verrucae, most of which are less than 3 mm in diameter.The valvular lesions of nonbacterial thrombotic endocarditis are usually present on the atrial surface of the mitral valve or on the ventricular surface of the aortic valve, at the point of valve coaptation. These lesions embolize frequently; the spleen, kidney, brain, and heart are the most frequently affected organs.
Current guidelines suggest that patients with nonbacterial thrombotic endocarditis and thromboembolism should be treated with full-dose heparin.As in the management of venous thromboembolism in patients with cancer, warfarin is less effective than heparin(unfractionated or low-molecular-weight) in the treatment of nonbacterial thrombotic endocarditis.Treatment of the underlying cause of the endocarditis is most likely to lead to a cure. Unfortunately, as in the present case, nonbacterial thrombotic endocarditis is often a sign of widely disseminated cancer and carries a poor prognosis.
There are no pathognomonic features in nonbacterial thrombotic endocarditis. Fever, cardiac murmur, leukocytosis, and elevated levels of C-reactive protein are present less frequently in patients with nonbacterial thrombotic endocarditis than in those with infective endocarditis. In this case, the final diagnosis of nonbacterial thrombotic endocarditis with underlying adenocarcinoma was established only after a thorough search for a cause of both the arterial and the venous thromboses.



@NEJM