Cross-Leg Free Flap: Crossing the Border Zone of Ischemic Limb-A Case Report of Limb Salvage Procedure following a Delayed Diagnosis of Popliteal Artery Injury.

Vascular injury following traumatic knee injury quoted in the literature ranges from 3.3 to 65%, depending on the magnitude and pattern of the injury. Timely recognition is crucial to ensure the revascularization is done within 6 to 8 hours from the time of injury to avoid significant morbidity, amputation, and medicolegal ramifications. We present a case of an ischemic limb following delayed diagnosis of popliteal artery injury after knee dislocation. Even though we have successfully repaired the popliteal artery, the evolving ischemia over the distal limb poses a reconstruction challenge. Multiple surgical debridement procedures were performed to control the local tissue infection. Free tissue transfer with chimeric latissimus dorsi flap was done to resurface the defect. However, the forefoot became gangrenous despite a free muscle flap transfer. His limb appeared destined for amputation in the vicinity of tissue and recipient vessels, but we chose to use a cross-leg free flap as an option for limb salvage.

A Case Series of Plexiform Neurofibroma: The Unusual Presentations and Surgical Challenges.

Neurofibromatosis type one (NF-1) is an autosomal dominant neurocutaneous disorder also known as Von Recklinghausen disease. Plexiform neurofibroma is a rare kind of NF-1 where the neurofibroma originates from nerve sheath cells or subcutaneous peripheral nerves. It is pathognomonic of NF-1, and isolated occurrence is relatively rare. We reported three cases of solitary plexiform neurofibromas with an unusual presentation. We have two cases of spontaneous bleeding isolated plexiform neurofibroma that have never been reported in the literature. Neither one of them showed signs and symptoms associated with the neurofibromatosis spectrum. This unusual presentation poses substantial challenges in diagnosis and management.

Multiple modes of inhibition of human cytochrome P450 2J2 by dronedarone, amiodarone and their active metabolites.

Dronedarone, a multiple ion channel blocker is prescribed for the treatment of paroxysmal and persistent atrial fibrillation. While dronedarone does not precipitate toxicities like its predecessor amiodarone, its clinical use has been associated with idiosyncratic hepatic and cardiac adverse effects and drug-drug interactions (DDIs). As dronedarone is a potent mechanism-based inactivator of CYP3A4 and CYP3A5, a question arose if it exerts a similar inhibitory effect on CYP2J2, a prominent cardiac CYP450 enzyme. In this study, we demonstrated that CYP2J2 is reversibly inhibited by dronedarone (Ki=0.034 µM), amiodarone (Ki=4.8µM) and their respective pharmacologically active metabolites namely N-desbutyldronedarone (NDBD) (Ki=0.55 µM) and N-desethylamiodarone (NDEA) (Ki=7.4 µM). Moreover, time-, concentration- and NADPH-dependent irreversible inactivation of CYP2J2 was investigated where inactivation kinetic parameters (KI, kinact) and partition ratio (r) of dronedarone (0.05 µM, 0.034 min(-1), 3.3), amiodarone (0.21 µM, 0.015 min(-1), 20.7) and NDBD (0.48 µM, 0.024 min(-1), 21.7) were observed except for NDEA. The absence of the characteristic Soret peak, lack of recovery of CYP2J2 activity upon dialysis, and biotransformation of dronedarone and NDBD to quinone-oxime reactive metabolites further confirmed the irreversible inactivation of CYP2J2 by dronedarone and NDBD is via the covalent adduction of CYP2J2. Our novel findings illuminate the possible mechanisms of DDIs and cardiac adverse effects due to both reversible inhibition and irreversible inactivation of CYP2J2 by dronedarone, amiodarone and their active metabolites.