Strongyloidiasis

Thanks to the Human Dx Project for providing us with this fascinating case of a middle aged woman with history of asthma who presented with acute onset of fever and epigastric abdominal pain as well as a chronic progressive cough, found to be febrile, tachycardic, and ill appearing, with E coli bacteremia of unknown source.  Further history taking revealed a similar hospitalization several months prior with idiopathic E coli bacteremia.  Strongyloides titers were sent and markedly elevated.  She was treated with ceftriaxone and ivermectin and made a full recovery.


Clinical Pearls: 

  • Absence of eosinophilia does not rule out strongyloides.  Keep in mind that those presenting with severe illness and hemodynamic instability are commonly in a high cortisol state which can lead to eosinophil apoptosis.  Also, in those with history of steroid use (even for short periods of time), eosinophil count can be negative.
  • Think of strongy in anyone with the right travel history, older age, malnutrition, HIV, or steroid use.
  • Signs and symptoms can be quite non-specific so a high index of suspicion is required to make the diagnosis.
  • Think of strongyloides in a patient with history of recurrent GNR bacteremia of unknown etiology!

Strongyloidiasis 

Epidemiology

  • Higher incidence noted going from yellow to orange to red on the map above
  • Epidemiology
    • Typically in travelers to endemic areas, immigrants from endemic regions, or anyone with barefoot contact with infested soil.
    • Risk factors include older age, malnutrition, HIV, and steroid use
  • Signs and symptoms
    • Infected people can be asymptomatic or minimally symptomatic for years:
      • Could also have mild waxing and waning GI, skin, or pulmonary symptoms for years
      • Eosinophilia without symptoms
    • Skin: urticarial, larvae currens (see picture below), angioedema, erythrodermalarvae currens
    • Pulmonary: chronic cough, hemoptysis, recurrent pneumonia, astham that gets worse with steroids
    • GI: upper abdominal pain, duodenitis, diarrhea, anorexia, recurrent enteric GNR bacteremia
    • Disseminated disease/hyperinfection syndrome:
      • Increased parasite burden due to autoinfection (see picture below)
      • Massive dissemination of larvae to lungs, liver, heart, CNS, and endocrine glands
      • Can present with septic shock or multiorgan failure

        Strongy life cycle
        Greaves, D. BMJ 2013; 347:f4610
  • Diagnosis:
    • Stool O&P: <50% sensitive and requires multiple samples due to intermittent shedding
    • Serologies: 89% sensitive
  • Treatment:
    • Ivermectin or albendazole
    • Hyperinfection/disseminated disease: above PLUS broad-spectrum antibiotics

Quick review of endemic dimorphic fungi:

  • Southwest US ⇒ Cocci
  • Ohio & Mississippi River Valley ⇒ Histo
  • Southeast/South-central US ⇒ Blasto
  • Southeast Asia ⇒ Penicillium
  • South America ⇒ Paracocci, histo, blasto, cocci

Hydralazine-induced ANCA associated vasculitis!

Thanks to Jen for presenting the case of a middle-aged lady with h/o HTN on hydralazine and PE noted to have progressively worsening glomerulonephritis and a discoid skin rash, with anti-MPO and anti-histone antibody positive serologies concerning for drug-induced ANCA associated vasculitis!


Clinical Pearls

  • Many cases of drug-induced lupus are actually drug-induced ANCA vasculitis!
  • Medications associated with drug induced ANCA-vasculitis include hydralazine (most common and most severe presentation), followed by methimazole/PTU, and minocycline.
  • Drug-induced vasculitis tends to present with anti-histone antibody positivity (sensitive but less specific).  Drug-induced ANCA vasculitis can be anti-MPO positive especially in the case of hydralazine.
  • Treatment involves witholding the offending agent.  In the case of hydralazine induced ANCA-vasculitis, steroids and additional immunosuppressive therapy (cytoxan or rituxan) are also indicated to reduce progression to ESRD.

Eosinophilia

  • Severity:
    • >500 eos ⇒ eosinophilia
    • > 1500 eos ⇒ severe eosinophilia
    • > 5000 eos ⇒ severe eosinophilia at risk of end organ damage
  • Etiology (NAACP-P)
    • Neoplasms
      • Monoclonal leukemias (eosinophil proliferation)
      • Polyclonal: T cell lymphomas, Hodgkin lymphoma, some solid organ tumors (cervical, ovarian, gastric, colon, urotherlial, and squamous cell carcinomas)
    • Allergies
    • Adrenal insufficiency (super rare)
    • CTD
      • EGPA, RA
    • Parasites/bugs
      • Parasites: remember that only multicellular parasites can cause eosiniphilia
      • Other bugs: ABPA, cocci, HIV
    • Primary eosinophilic syndromes

Drug-induced lupus:

  • M:F is 1:1 but hydralazine induced lupus is more common in women
  • Mechanism is poorly understood and genetic predisposition may play a role. More likely to happen in patients who are slow acetylators
  • Autoantibodies:
    • Anti-histone antibodies: 95% sensitive
    • Other antibodies are uncommon
  • Drugs: long list!
    • Procainamide, hydralazine, chlorpromazine, quinidine, minocycline, PTU, statins, anti-TNF agents, IFN, methyldopa
    • Weaker associations: AEDs, antimicrobials, beta blockers, lithium, HCTZ, amiodarone, cipro etc.
  • Treatment:
    • Stop offending agent
    • Joint symptoms: NSAIDs
    • Skin symptoms: topical steroids
    • Hydral-induced vasculitis: need cytotoxic or other immunosuppressive therapy. Treatment similar to ANCA positive vasculitis
  • Prognosis:
    • Resolution of symptoms weeks to months

Drug induced ANCA positive vasculitis:

  • Patients typically present with constitutional symptoms, arthralgias/arthritis, and cutaneous vasculitis
  • Strongest association with hyperthyroidism meds, hydralazine, and minocycline (hydral is the most common)
  • Rare, but should be aware of this association because it impacts management and because it is often not diagnosed until too late in the disease course.  In fact, many cases of drug induced lupus are actually drug induced ANCA-associated vasculitis
  • In a small case series of hydral-induced ANCA-associated vasculitis of 10 patients, 90% had renal involvement of whom 7 recovered at 6 month follow up (though one required HD).
    • Hydralazine-induced ANCA vasculitis is generally p-ANCA pattern with anti-MPO positivity (might also have anti-lactoferrin or anti-elastase)
    • Treatment involves immunosuppression with steroids and cytoxan or rituxan.
  • Non-hydralazine drug-induced ANCA vasculitis is typically treated with stopping the offending agent and has a better prognosis than its hydralazine-induced counterpart. In fact, ANCA positivity without clinical vasculitis is common especially in cases involving PTU.

Monthly M&M 5/10/2019

Thank you everyone for coming to our monthly M&M Conference!

This was case of a young man with undisclosed chronic HBV and cocaine use who presented with first onset hematemesis and melena. On presentation, he was tachycardic, anemic, but normotensive. His heart rate improved with more fluid resuscitation and at the time, he did not require ICU level of care.

While on the floor, his tachycardia gradually worsened, and his Hgb also downtrended from 9.6 from 7.8 in the span of 12 hours, which was initially attributed to dilutional error given he was given 3 L of fluids. He acutely decompensated in the evening, and despite our best efforts, we could not keep up with the amount of hemorrhage likely from variceal bleeding.


Cocaine

Mechanism in a nutshell: Inhibits catecholamines reuptake, leading to to increased levels or norepi, dopamine, and serotonin. This subsequently leads to elevated BP, tachycardia, fever, and inc risk of coronary artery vasospasm, arrhythmia, and QTc prolongation.

Onset of action: Peak cardiovascular effect seen 5-15 minutes after use.

Half life: 45-90 minutes

Metabolism: Metabolized in seurm and liver into ecgonine methyl ester and benzoylecgonine, which is what Utox picks up! Utox will be positive for cotaine 48-72 hours after use, and it can remain positive up to 10 days (even longer for chronic users).


Cocaine & Anesthesia

  • Compared to controls, pts who are cocaine positive on utox undergoing elective procedures requiring general anesthesia are no different in terms of:
    • Arrhythmia risk
    • Cardiovascular events (fluctuations in BP, HR)
    • Anesthesia duration
    • Medical dosage
    • PACU recovery time
  • This study in particular was insightful, but keep in mind that patients > 70, ESRD, or acutely intoxicated were excluded.

Hemorrhage Shock

Capture.JPG

To put this into perspective, a patient (let’s say “Average” 70 kg adult) presenting with GIB can lose up to 1.5L of blood prior to seeing any chances in blood pressure. The first signs of clinical instability is HR, with mild tachycardia up to the lower 100s!

Also the Glawgow Blatchford Score is useful for risk stratification. If pt scores 0, there is a very low risk of complications. The higher the score is, the higher in terms of potential for complications and need for more urgent intervention.


When to Transfuse

See this study for more details. In general for UGIB, a restrictive transfusion strategy (transfuse when Hgb < 7 g/dL) has better outcomes (survival, rebleeding, mortality) vs a liberal approach (transfuse when Hgb < 9 g/dL).


In cirrhotic patients, is there such thing as over-resuscitation? YES.

In animal studies, severity of bleeding was directly related to portal venous pressure. Restrictive transfusion protocol also showed less portal pressure gradient vs the liberal arm, and less rebleeding and improved survival. Per the Baveno V Consensus, for variceal bleed, the target Hgb is between 7-8 g/dL.


What about when stuff hits the fan?

ABC comes first, don’t even worry about the numbers any more.

Remember when you order blood, it needs to be typed, screened, and cross-matched. It can take hours!

Know when to call the massive transfusion protocol (MTP). You can find the protocol on HHS-Connect on any desktop.

In a nutshell, activate MTP if you have a patient you anticipate requiring > 4 units PRBC within the first hour, or with high probability of requiring > 10 units within 12 hours. The blood bank will then start bringing in uncrossed blood, platelet, and FFP very quickly. Make sure to deactivate the protocol once your patient has been stabilized.

Also plan ahead for access! AT LEAST 2x large bore IV (18g or bigger) but know that in an acute situation, two PIVs can be easily overwhelmed. If you anticipate risk for decompensation, establish plan for access early on so you won’t get overwhelmed when the patient decompensates (i.e. IO kit or find an opportunity for a Cordis catheter).

Pneumocystis jiroveci pneumonia with a cavitary lesion 5/8/2019

Credit goes to Dr. Scott Burns from Roper Hospital in Charleston for his case on the Human Diagnosis Project.

Today we discussed a case of a young man with otherwise no medical history presenting with subacute dry cough, malaise, and weight loss. On exam he was septic on presentation with notable oral thrush. CXR revealed bilateral interstitial infiltrates and a RUL cavity with air fluid level which was confirmed on CT. LDH was elevated. He was confirmed HIV positive with a low CD4 count in the single digits, and BAL confirmed the diagnosis of PCP/PJP pneumonia!


Oral Thrush: NEVER assume normal, extremely rare in immunocompetent patients, so if you see this, consider whether the patient could be immunocompromised.


Cavitary Lung Lesion DDX

  • Mycobacteria
    • TB
    • M kansasii
  • Bacterial
    • Pseudomonas
    • Enterobacteriaceae
    • Klebsiella
    • Streptococci
    • Nocardia
    • Anaerobes
    • Staph aureus
  • Fungi
    • Crypto
    • Aspergillus
    • Histoplasma
  • Rare
    • Bacterial: Legionella, rhodococcus
    • Mycobacteria: MAC
    • Fungi: PCP/PJP, mucormycosis, blasto
    • Others: Vasculitis

PCP

Epidemiology

  • Immunocompromised patients
    • HIV with CD4 < 200
    • BMT, organ transplant patients
    • Leukemia/lymphomas
    • Rheumatology conditions
    • Primary immunodeficiencies
  • Rarely occurs in immunocompetent patients

Presentation

  • Typically subacute onset of pulmonary symptoms, non-productive cough, fever chills, malaise, SOB
  • Might have other clues of immunocompromised status

Diagnosis

  • CXR: Classic description is bilateral interstitial infiltrates
    • Rare instances: Lobar infiltration, nodules, cavitary lesions, pneumothorax
  • CT: Higher sensitivity but might not be necessary for the dx
  • LDH: Sensitive but not specific if elevated. An elevated LDH in an HIV patient without other medical co-morbidities that might inc LDH should raise suspicions for PCP
  • Beta D glucan: For HIV patients, good sensitivity, not that specific. If elevated, raises suspicions for PCP.
  • Gold standard: either visualize the organism via induced sputum (yield is variable, variable sensitivity but 100% specific), or via BAL.
  • Can also use 18S PCR

Management

  • First line: TMP-SMZ, 15-20 mg/kg. PO just as good as IV, duration 21 days
  • Sulfa allergy:
    • Mild to moderate: Desensitization
    • Severe: alternative agents
      • Clinda + primaquine
      • Trimethoprim + dapsone
      • Atorvaquone
      • Pentamidine
      • For severe disease, Clinda + primaquine or IV pentamidine is preferred.
    • Adjunctive steroids
      • ABG: If PaO2 < 70, or Aa gradient > 35, or hypoxemia on pulse ox, adjunctive steroid is indicated and has been shown to improve mortality
      • Pred 40mg BID x 5 days, then 40mg daily x 5 days, then 20mg daily x 11 days, total 21 days

Remember your Aa gradient equation!

Aa-gradient = PAO2 (calculated from the alveolar gas equation) – PaO2 (measured PaO2 on ABG)

PAO2 = FiO2 (baromeric pressure – water pressure) – PaCO2/(respiratory quotient)

Assuming sea level and a standard respiratory quotient of 0.8, this equation can be simplified to:

PAO2 = 150 – PaCO2/0.8

Culture Negative Endocarditis 5/7/2019

We recently had a case of a middle age man with SLE on chronic prednisone, ESRD on PD, presenting with acute on chronic shoulder pain x 10 days. Presentation was initially concerning for septic arthritis, and joint washout revealed gross purulence from the shoulder joint. Cultures were sent but no additional fluid studies were obtained.

A subsequent TTE, and later a TEE, confirmed a mitral valve vegetation concerning for concurrent infective endocarditis. However, multiple sets of blood cultures, fungal cultures, synovial fluid culture from the initial I&D/wash out, and even 16S PCR of the synovial fluid were all negative. This is a rare case of culture negative endocarditis which is later thought to be more likely Libman Sacs!


Septic Arthritis

  • Epidemiology
    • Risk factors: Advanced age, pre-existing joint dz, recent surgery or injection, SSTI, IVD, indwelling catheter, immunosuppression.
    • Most cases arise from hematogenous seeding, hence bacteremia is common.
    • Direct inoculation: usually due to trauma, surgery/injections, or wounds.
  • Microbiology
    • Usually mono-microbial, and Staph aureus is the most common cause of septic arthritis in adults.
    • GNR can be seen in older adults or in immunocompromised patients
  • Presentation
    • Monoarthritis is most common
      • Edematous, painful, warmth, limited ROM
      • Older patients may not be febrile
    • 20% of cases can present as oligoarticular or polyarticular infection. Polyarticular septic arthritis is more likely to occur in pts with RA
    • Most common affected joint is the knee
    • Could be a manifestation of infective endocarditis, esp amongst IVDU
  • Diagnosis
    • Synovial fluid analysis and culture, should be obtained prior to abx
    • Positive gram stain or culture is gold standard and diagnostic
      • PCR only required in rare cases since most non-gonococcal cultures obtained prior to antibiotics return positive. Negative cultures can result due to recent abx or atypical organism.
    • In pts with purulent synovial fluid (WBC 50k-150k) but culture negative, a presumptive dx can be made.
      • Likelihood of septic arthritis inc with inc leukocyte count
    • Blood cultures should be obtained
    • Should also evaluate for endocarditis given most common organism is staph aureus
    • Imaging:
      • Always get a radiograph to evaluate for concurrent bone/joint involvement
      • CT/MRI can be useful if looking for an effusion
  • DDx
    • Infectious
      • Gonococcal arthritis
      • Lyme disease
      • TB arthritis
      • Viral (usually polyarticular), i.e. Zika, Dengue, chikungunya, parvo, rubella, adenovirus
    • Non-infectious
      • Crystal dz
      • Reactive arthritis
  • Management
    • Joint drainage, severe infectious may require repeated aspiration or even wash out.
    • Abx
      • Most cases are staph, MRSA cases on the rise
      • Suspect pseudomonas if pt is immunocompromised or has h/o IVDU
      • Intra-articular abx: typically not used
      • Duration:
        • Staph aureus with bacteremia: At least 4 weeks
        • Staph aureus without bacteremia: at least 14 days IV, followed by 1-2 weeks PO
        • Bone involvement: 4-6 weeks
        • Any organisms, any bone involvement: 4-6 weeks
        • Other organisms: Typically at least 4 weeks

Culture Negative Endocarditis

  • Definition: Endocarditis without an identified organism in at least 3 independent blood cultures with negative growth after 5 days
  • Epidemiology
    • 2-7% of IE cases
    • 3 most common causes:
      • Previous abx
      • Inadequate samples
      • Atypical organisms (fastidious bacteria i.e. zoonotic microbes, fungal)
  • Microbiology
    • Farm animal exposure: Brucella, Coxiella (Q-fever)
    • Homeless: Bartonella Quintana
    • Cat: Bartonella hensale
    • Ingestion of unpasteurized milk: Brucella, Coxiella
    • Immunocompromised: Fungi, Coxiella
    • HACEK: Most common agents of culture negative endocarditis
      • Haemophilis aphrophulus
      • Actinobacillus
      • Cardiobacterum hominis
      • Eikenella corrdens
      • Kingella
  • Diagnosis
    • PCR, histology, special cultures are helpful.
    • PCR
      • 16S Ribosomal DNA: Bacteria
      • 18S Ribosomal DNA: Fungi
  • Non-infectious DDx
    • APLS, associated with Q fever
    • Acute rheumatic fever
    • Atrial myxoma
    • Libman Sachs endocarditis (non-bacterial thrombotic endocarditis or NBTE)
      • Seen in:
        • SLE
        • Advanced cancer
        • Hypercoagulable state
    • Vasculitis
    • Mural thrombus

NBTE (Non-bacterial thrombotic endocarditis)

  • Epidemiology
    • Rare affected all age group with no sex preference, most commonly 40s – 80s
    • Most commonly associated with pts with concurrent SLE or advanced malignancy (lung cancer, pancreatic cancer, gastric cancer)
    • Other associated conditions: APLS, rheumatic heart disease, RA.
  • Pathophysiology
    • A form of non-infectious endocarditis characterized by deposition of thrombi on halve valves, most commonly mitral or aortic
  • Presentation
    • Usually asx but high risk of thromboembolic events
    • May present with acute stroke or coronary ischemia
  • Diagnosis
    • Exclusion: Demonstration of vegetations on echo in absence of systemic infection in patients with risk factors.
  • Management
    • Systemic anticoagulation
      • Clinical experience and retrospective studies had shown this is beneficial due to high rate of emboli in pts with NBTE
    • Treat underlying condition
    • Surgery
      • Surgical excision for NBTE vegetation, can be considered in only selective cases and generally avoided.

Hepatocellular Carcinoma 5/6/2019

Katie presented an elderly man presenting with few weeks of unintentional 40lbs weight loss and abdominal pain, found to be jaundiced on exam with notable hepatomegaly. Labs notable for mild hepatitis and mix conjugated and unconjugated hyperbilirubinemia with mild coagulopathy. He was ultimately diagnosed with cirrhosis and extremely likely HCC with “numerous” masses of varying size (largest one was 10 cm) with portal vein invasion.


Please refer to this previous post on etiology of hyperbilirubinemia.

Please refer to this other post on hepatitis serologies made ridiculously simple.


Hepatomegaly and jaundice: Think infiltrative/malignant process!

For patients with cirrhosis and abdominal distension, palpating and percussing the liver can be challenging.

A strategy we went over during the last physical exam round was the scratch test, which relies on the principle of the different of sound transmission through materials of various densities.

To perform the scratch test, place your stethoscope over the RUQ just above the costal margin or just below the xiphoid, and from the RLQ, lightly scratch the patient horizontally and then slowly move superiorly toward the costal margins until the sound intensities. The location of sound intensification marks the inferior edge of the liver.

Small study re: accuracy of using the scratch test.


Hepatocellular Carcinoma

Epidemiology

  • Most of the time a complication from liver cirrhosis
  • Risk Factors
    • Cirrhosis, any etiology
    • Chronic HBV even without cirrhosis (oncogenic virus)
    • HCV with cirrhosis
    • Fungal aflatoxins
  • Higher prevalence in East and SE Asia + Sub-Saharan African nations
  • HBV inc risk by 100x

Presentation

  • Variable initial presentation
    • Asx
    • Decompensated cirrhosis
    • Jaundice, abd pain, B-sx, +/- palpable pass
    • Variceal hemorrhage
    • Tumor rupture leading to acute hemorrhagic shock
    • Obstructive jaundice due to biliary tree invasion
    • 10-15% with metastatic dz at time of dx.
      • Most common sites: Lung, lymph nodes, adrenal glands.
    • Paraneoplasic: Hypoglycemia (adv HCC), erythrocytosis, hypercalcemia, diarrhea

Diagnosis

  • Imaging: Sensitivity generally dec with small lesions, but imaging alone to establish dx of HCC without a biopsy in certain patient populations.
    • Contrast enhanced CT (triphasic)
      • Arterial phase hyperenhancement: Characteristic of HCC lesions but not specific, can be small hemangiomas, focal nodular hyperplasia, atypical focal fibrosis, non-HCC malignancy
      • Venous phase Washout: Again characteristic of HCC but not specific, cirrhosis nodules can be similar.
      • Capsular appearance: Pretty specific for HCC
      • All 3 of the above = diagnostic of HCC, very specific not but as sensitive.
      • Highest PPV for pts with cirrhosis with lesions > 2cm
    • MRI
      • Contraindicated in GFR < 30, Nephrogenic systemic fibrosis
      • More sensitive than CT, ~ specificity,
    • US: Can be use as diagnosis but cannot evaluate disease burden, transplant candidacy, operator dependent. 90% sensitive and 97% specifc
    • LIRADS
      • Should only be applied to pts with cirrhosis, chronic HBV, lesions identified on surveillance US for HCC, current or prior dx of HCC.
      • Should NOT be applied to: no risk factors for HCC, < 18, cirrhosis secondary to congenital hepatic fibrosis or vascular etiology.
    • LIRADS definitions for hepatocellular carcinoma based on ACR v2017:
      • LR-1: Definitely benign
      • LR-2: Probably benign
      • LR-3: Intermediate probability for HCC
      • LR-4: Probably HCC
      • LR-5 – Definitely HCC
      • LR-5V: Definitely HCC with tumor in vein
      • LR-M: Probably malignancy, not specific for HCC
      • LR-TR Viable: Treated, probably or definitely viable HCC
      • LT-TR Nonviable: Treated, probably or definitely not viable
      • LR-TR Equivocal: Treated, equivocally viable
      • LR-TR Nonevaluable: TReated, response not evaluable
  • Labs
    • Alpha-fetoprotein: Elevated in 40-65% of patients with HCC
      • Normally produced during gestation, not during adulthood.
      • Levels do not correlate well with degree of disease
      • Sensitivity: 60%, spec: 80%, not good as a screening tool.
      • Higher levels > 400 are very specific for HCC.
      • May be seen in chronic liver disease so not very sensitive.
      • Elevated levels are associated with advanced fibrosis, pregnancy
  • Biopsy: Reserved for indeterminate nodules that do not meet radiologic criteria for HCC.
    • Not recommended for LR1, LR2, LR3, or LR5 lesions
    • Risk: spread of tumor along needle track, sampling error (false negative), usual surgical risk (bleeding, infection, etc)
  • Staging:
    • TNM
    • Barcelona Clinic Liver Cancer staging system

Management

  • Surveillance for at risk patients:
    • Cirrhosis or HBV: Q6mo liver US
  • Resection
    • Preferred therapy for localized disease
    • Sufficient liver reserve, can’t be worse than Child Pugh A cirrhosis
    • 5 year survival rate as high as 90%
    • Stage IIIB, IVA, and IVB are incurable by resection (any invasion of a major portal or hepatic vein, other organs, visceral peritoneum, nodal mets)
  • Antiviral
    • Recommended for those with active viral infection and HBV related HCC.
  • Liver transplantation
    • Milan criteria widely accepted, to be considered a candidate for transplant, pt must meet all criteria
      • Solitary tumor < 5cm or up to 3 tumors all < 3cm
      • No evidence of regional nodal or distant mets
      • No evidence of vascular invasion
  • Ablation
    • Radiofrequency or microwave or localized ethanol/acetic acid/cryo localized ablation
    • Best outcomes for tumor size < 4 cm
    • Cirrhosis: Restricted to Child Class A or B
    • Can be used to bridge to liver transplant
  • TACE
    • Disruption of HCC supply, usually derived from the hepatic artery
    • Leads to tumor necrosis from ischemia.
    • Usually used for tx of large unresectable HCC not amenable to other tx i.e. resection or RFA.
    • Best candidates: No vascular invasion or extrahepatic spread, Child Puph A or B
    • Relative contraindication:
      • bili > 2
      • LDH > 425
      • AST > 100
      • Tumor > 50% of liver
      • Untreated EV
      • Significant medical comorbidities
  • Radiation
    • Localized external radiation vs radioembolization, HCC is radiation sensitive.
  • Systemic chemo
    • Sorafenib
      • SHARP trial, prolongs survival over supportive care in pts with adv HCC)
      • Might be more beneficial for HCC related to viral etiology
    • Other agents: Regorafenib, Lenvatinib
    • Complication during tx
      • Reactivation of viral hepatitis

Prognosis

  • 10-20% of cases are curable (resectable disease)
  • 5-yr survival rates of about 5% or less if beyond stage III (portal vein invasion)
  • Some evidence that sorafenib improves survival by around 3 months but it is a costly medication (60 tablets can cost up to $9000 after discount!)

Caffeine Overdose! 5/1/2019

The world’s #1 addictive substance of choice… Caffeine! And yes you can OD on it!

A 37yo F with history of anxiety presented with nausea and palpitations after ingesting 160 pills of Diurex in an attempt to fix her constipation for the past 2 weeks. Prior to arrival to the hospital, the paramedics administered activated charcoal. She was tachycardic, mildly hypotensive, hypokalemic, and acidotic (AG 20). Methamphetamine was found in her system as well. Fortunately she improved with fluids and supportive measures, but lethal cases of caffeine overdose, while rare, have been described in the medical literature!

Of note: An expresso doubt shot contains roughly 60-100mg of caffeine.

This patient took 16000mg (16g) of caffeine, equivalent to 160-260 shots of double expresso!


Caffeine Intoxication

  • Epidemiology
    • Caffeine = world’s #1 psychoactive compound consumed
    • Pure caffeine can be easily obtained, caffeine pills introduced in 2004.
    • Death from caffeine overdose is rare, only 92 cases have been described in literature.
    • Caffeine pills heavily advertised as weight loss supplements
  • Risk factors
    • Psychiatric conditions
    • Athletes (weight loss/work out supplements, these things are NOT regulated!)
    • Infants/young kids (accidental ingestion)
  • Pathophysiology
    • Dose-dependent MOA
    • CNS and cardiac stimulation, usually occurs at plasma concentration of 15mg/L or higher
    • Usually not food/beverages related. Most cases are related to caffeine-containing medications.
    • Lethal cases reported over 10g ingestion, highest reported ingestion is 100g (1000 double shots of Expresso)
    • Absorbed in the GI tract within 30 minutes
    • Half life 5-6 hours, metabolized in the liver
  • Presentation
    • Agitation, diaphoresis, anxiety, restlessness, insomnia, GI disturbances, tremors, psychomotor agitation
    • Complications
      • Serious cases: arrhythmias (SVT, VT), even V-fib (most common cause of death in caffeine intoxication)
      • Hypotension
      • Hypokalemia
      • Seizures
      • Lactic acidosis
      • Rhabdomyolysis
      • Renal failure
  • Diagnosis
    • Life threatening caffeine overdose more commonly associated with blood concentration > 80mg/L
    • Clinical history, serum measurement, ingestion history
  • Management
    • Activated charcoal for ingestions:
      • Effective only within a short time of ingestion, typically within 1-2 hour and patients have to be mentating
      • Interacts with caffeine and prevents it from being absorbed.
    • Hydration
    • Electrolyte repletion
    • Anti-arrhythmic agents (amiodarone, even lidocaine) in setting of arrhythmias, ACLS if unstable arrhythmias
    • Dialysis: Dialyzable

Source: GrepmedToxidrome Flow

A summary of toxidromes:

Toxidrome.jpg