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
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
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
Acute: Nausea, vomiting, severe watery diarrhea.
Chronic: Distal polyneuropathy
Acute: Chest pain, cough, dyspnea
Chronic: Mild neuropsychiatric symptoms with predominant tremor
Randomized double blind placebo-control trial that faced slow recruitment thus faces the problem of being underpowered to detect a difference.
Outpatients without cancer or prior VTE with symptomatic calf DVT. Assigned 1:1 to receive nadroparin or placebo daily for 6 weeks. All were given compression stockings and followed for 90 days.
Primary outcome was extension to proximal vein, contralateral proximal DVT, or systemic embolism by day 42.
Safety outcome – non-major bleeding by day 42.
122 patients in nadroparin and 130 placebo.
Primary outcome 3% in the nadroparin and 5% in placebo. 5 patients had bleeding in nadroparin arm with 1 major bleeding event.
Need more information before change in practice.
Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial – M Righini et al; Lancet Haematology, The, 2016-12-01, Volume 3, Issue 12, Pages e556-e562.
More common in women, 1.5:1 female to male ratio. 5% of people have cysts on autopsy and 5% of these are neoplastic. The majority of liver cysts (90%) are asymptomatic. Found incidentally on US or CT. Neoplastic cysts are mostly solitary. US imaging is most helpful and CT scan are used in specific cases. US helps determine content of the cysts. Certain cysts are responsive to estrogen.
Location in the liver does not help differentiate neoplastic from non-neoplastic.
Non-neoplastic cysts: wall is smooth, no septa, and no debris. Presence of these suggests the possibility of biliary cystadenoma or cystadenocarcinoma.
Liver tests are normal. In cases of congenital polycystic liver disease alkaline phosphatase maybe elevated.
Surgical removal and histologic sectioning is the only way to determine if neoplastic or not.
First must rule out Echinococcus – endemic worldwide and associated with rural areas with sheep. Test with ELIZA which is 90% sensitive. If surgery is not an option can consider aspiration. Mucin in cystic fluid is concerning for malignancy, but absence does not rule out malignancy. Also can check CEA and CA 19-9 in the aspirate, but inadequate NPV.
Monitor cysts that are 1-2cm, but if they grow to 2-5 consider, and definitely > 5 cm must consider surgery.
If all of the cyst tissue is removed, recurrence is unlikely, however if any part of the cyst wall is left behind recurrence can be up to 50%.
Advances in Hepatology: Current Developments in the Treatment of Hepatitis and Hepatobiliary Disease: Managment of Heaptic Cysts – Jorge L Herrera
Baseline rates of treatment failure have varied in studies and rates have ranged from 8.5 to 17% in the best case scenarios to 43-75% in other studies. So even at baseline, we know that a significant number of patients will fail antibiotics and require surgery. Risk factors include diabetes mellitus, leukocytosis greater than 12.5, positive blood cultures, and C-reactive protein greater than 115. One risk factor increases failure rates for to 35.4%, two risk factors increases failure to 40.2%, and three or more risk factors increases failure rates to 76.9%.
So basically, most patients should ideally managed with surgery and barring that we should advocate for surgery in patients who have risk factors.