Early morbidity associated with fasciotomies for acute compartment syndrome in children.

PURPOSE: Acute compartment syndrome (ACS) requires urgent fasciotomy to decompress the relevant muscle compartment/s prior to onset of irreversible myonecrosis and nerve injury. A fasciotomy is not a benign procedure. This study aims to describe and quantify early morbidity directly associated with fasciotomies for ACS in children. METHODS: Clinical charts of 104 children who underwent 112 fasciotomies over a 13-year period at a tertiary children's hospital were reviewed. The following were analyzed: ACS aetiology, fasciotomy site, number of subsequent procedures, method of wound closure, short-term complications and length of hospital stay. RESULTS: Short-term complications included wound infections (6.7%) and the need for blood transfusion (7.7%). Median number of additional operations for wound closure was two (0 to 10) and median inpatient stay was 12 days (3 to 63; SD 11.7). After three unsuccessful attempts at primary closure, likelihood of needing skin grafting for coverage exceeded 80%. Analyses showed that fasciotomy-wound infections were associated with higher risk for four or more closure procedures. Number of procedures required for wound closure correlated with longer inpatient stay as did ACS associated with non-orthopaedic causes. CONCLUSION: Fasciotomy is associated with significant early morbidity, the need for multiple closure operations, and prolonged hospital stay. The decision for fasciotomy needs careful consideration to avoid unnecessary fasciotomies, without increasing the risk of permanent injury from missed or delayed diagnosis. Skin grafting should be considered after three unsuccessful closure attempts. Less invasive tests or continuous monitoring (for high-risk patients) for compartment syndrome may help reduce unnecessary fasciotomies. LEVEL OF EVIDENCE: Level IV, Case series.

MMSET regulates expression of IRF4 in t(4;14) myeloma and its silencing potentiates the effect of bortezomib.

Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. In t(4;14) MM, the MM SET domain (MMSET) protein is universally overexpressed and has been suggested to have an important tumorigenic role. However, the exact molecular targets underlying MMSET activity are not well understood. Here, we found in t(4;14) MM cells that MMSET knockdown decreases interferon regulatory factor 4 (IRF4) expression, and ectopic MMSET increases IRF4 expression, suggesting that MMSET is an upstream regulator of IRF4. Further analyses indicated an interaction between MMSET and nuclear factor-κB, which both bind to the IRF4 promoter region. A luciferase reporter assay showed that MMSET is an important functional element for the IRF4 promoter. MMSET knockdown induces apoptosis and potentiates the effects of bortezomib in vitro and in vivo. Importantly, we found that bortezomib could reduce expression of MMSET and IRF4. This might partly explain the additive effect of combining MMSET knockdown and bortezomib treatment. These results identify MMSET as a key regulator involved in the regulatory network of transcription factor IRF4, which is critical for MM cell survival, suggesting that the combination of MMSET inhibition and bortezomib is likely to improve patient outcome in MM.

Small bowel permeability--a variable effect of NSAIDS.

The baseline permeability of small bowel in 57 healthy volunteers was assessed by measuring the mannitol and chromium-EDTA recovery in a 5-hour urine collection after ingestion of a drink containing a mixture of 1 g of mannitol and 3.7 MBq of 51Cr-EDTA. Subjects were treated with medication for 1 week followed by permeability studies as described above. The regimens used were diclofenac sodium (Voltaren) 50 mg po tid (21 subjects), Voltaren SR 75 mg bid for 1 week (34 subjects), indomethacin 50 mg tid (10 subjects), and tenoxicam (Mobiflex) 20 mg daily (13 subjects). There was no significant difference between the mannitol recoveries at baseline or after any of the drugs. The permeability was clearly increased by indomethacin and by Voltaren SR. Conventional-release Voltaren increased permeability, but the results were not significantly above baseline. Mobiflex had no influence on the measured permeability. Our results suggest that the SR preparation of diclofenac has a more pronounced effect than regular diclofenac sodium; thus different NSAIDs and different preparations of the same NSAID may have different effects on small bowel permeability.