Flea Bytes: Oral Edoxaban in VTE Prophylaxis in Cancer Patients

Open label non-inferiority trial of 1046 cancer patients (1050 randomized). Non-inferiority margin of 1.5 (HR 1.5), appears to have been randomly decided upon. Expected event rate of 20%, but had an event rate of 13%. Primary endpoint combined VTE and bleeding events which had a HR of 0.97. However, edoxaban improved VTE risk (not reaching statistical significance) by reducing DVTs, but not pulmonary embolism. Further, it had more bleeding, but the increased bleeding event severity was mostly category 2, while category 3 bleeding was similar. This was mostly upper GI bleeding and the authors note in the discussion section that it was mostly in patients with GI cancers and whined that the dalteparin bleeding rate was lower than previously reported.

My takeaway – edoxaban seems like a reasonable option for VTE prophylaxis in cancer patients, although it might increase bleeding risks.

Source: N Engl J Med 2018; 378:615-624

Advertisements

Flea Bytes: HHV-6 Encephalopathy

HHV-6 reactivation is one of the most common causes (in 30-70% of patients) of encephalitis in allo-SCT. It is a ubiquitous viral infection that remains latent and can reactivate after transplant.

Risk factors: HLA mismatch, T-cell depletion therapy, treatment with glucocorticoids, and the use of cord blood as a source of stem cells; 90% of cases of HHV-6 reactivation occur in patients who with cord-blood transplants.

Encephalitis presents as subacute confusion, but some may have a more progressive course. Anterograde amnesia, personality changes, irritability and seizures. SIADH is common.

CSF analysis shows mild lymphocytic pleocytosis and protein elevation.

Treatment is based on in-vitro susceptibility testing and foscarnet is therapy of choice. Can add ganciclovir if not clinically improving. But need to monitor closely for side effects including bone marrow suppression and electrolyte derangement which can predispose to seizures. Alternative therapy is cidofovir, but watch out for nephrotoxicity.  Duration is 3-6 weeks and you shouldn’t monitor PCR levels to shorten treatment duration.

Notes from: N Engl J Med 2018; 378:659-669

Maester’s Collection: Cushing Syndrome

  • Central obesity, arterial hypertension, proximal muscle weakness, diabetes, oligomenorrhea, hirsutism, thin skin, and ecchymosis
  • Today, obesity is common. Anti-androgenic effects of Cushing syndrome can help differentiate it from obesity
    • +LR thin skin 112
    • +LR osteopenia 18
    • +LR ecchymoses 4
    • All 3 have a specificity of 95%
  • Prevalence of Cushing in obese/metabolic type patients 0.2%
    • 24,000 cases of Cushing/12 million patients with metabolic syndrome = 0.2%
  • 24 hour urinary free cortisol
    • 2-forms: 1) unbound to protein or 2) cortisol unconjugated to sulfuric or hyaluronic acid
    • Unbound cortisol is filtered and reabsorbed. 3% remains in urine.
    • Should measure 24-hour urine creatinine with cortisol to ensure adequate collection
      • Repeat if creatinine is less than 1.5g/day for men and 1g/day in women
    • 24-hour urine cortisol > 62mg/day has +LR 11
  • Dexamethasone Suppression test is used to differentiate ACTH dependent from ACTH independent Cushing syndrome.
    • This is now done by directly measuring ACTH levels
    • Should not be used to diagnose or screen for Cushing syndrome
      • Obese patients with depression will fail to suppress cortisol in response to dexamethasone challenge
  • For Cushingoid exam, but low or zero urinary free cortisol and suppressed ACTH levels suggests exogenous steroid and should prompt a review of medications.
  • ACTH-dependent Cushing syndrome can be due to pituitary secretion from an adenoma or ectopic secretion from a malignant source – typically in the chest.
  • Some experts recommend always doing petrosal sinus sampling due to the high prevalence of non-functioning pituitary adenomas and mortality associated with surgery. Some series report the prevalence of asymptomatic pituitary adenomas as high as 15-40%. Mortality associated with transsphenoidal micro-adenectomy is 1%.
  • ACTH-independent Cushing syndrome is usually caused by an adrenal neoplasm.
    • Characteristics of benign tumors: small (<5cm), <10 Hounsfield units, and have > 60% contrast washout at 15 minutes.
      • Benign tumors can be treated laparoscopically, while malignant tumors typically are resected with an open technique.

Flea Bytes: Duration of NG Tubes

  • You should consider a PEG in patients who are likely to require > 4-6 weeks of feeding and there is some evidence that you should consider it at 14 days
  • Polyurethane NG tubes (Dobhoff) should be replaced every 2 weeks due to the effects of gastric acid.
  • Long term NG/NJ tubes can be kept in place for 4-6 weeks

Flea Bytes: Treating Aspiration Pneumonia

For most patients: Ampicillin/Sulbactam is sufficient for oral aerobe/anaerobic coverage

For penicillin allergic patients: Clindamycin monotherapy covers oral aerobes/anaerobes

For hospital-acquired aspiration PNA: Coverage of aerobic bacteria, especially GPC and GNR are more important than anaerobes: Pip/Tazo or meropenem monotherapy

In patients with high risk factors for MRSA, can add an agent with MRSA activity but if MRSA is not detected, this agent should be discontinued

Flea Bytes: Heavy Metal Poisoning

How do patients with heavy metal toxicity present?

Here is a quick table:

Lead: Abdominal pain, irritability, fatigue, anemia, (confusion, seizure, encephalopathy at very high levels)

Cadmium: Interstitial Nephritis

Arsenic:
Acute: Nausea, vomiting, severe watery diarrhea.

Chronic: Distal polyneuropathy

Mercury:

Acute: Chest pain, cough, dyspnea

Chronic: Mild neuropsychiatric symptoms with predominant tremor

Flea Bytes: Polymixin/Meropenem Synergy

Meta-analysis found in vitro synergy.  Especially in A baumanii. Mechanism unclear

Synergy testing can be done on isolate if available

Can not necessarily infer in vivo synergy (Beta-lactam/aminoglycoside synergy is demonstrated in vitro but NOT in vivo for example).

Systematic Review and Meta-Analysis of In Vitro Synergy of Polymyxins and Carbapenems. Antimicrobial Agents and Chemotherapy. October 2013 Volume 57 Number 10. p.5104 – 5111.