Aneurysmally dilated major aorto-pulmonary collateral in tetralogy of Fallot

Haemodynamically significant systemic-to-pulmonary artery collaterals may present as a cause of cardiorespiratory compromise in tetralogy of Fallot (TOF) with pulmonary atresia. We present here a case of TOF with pulmonary atresia with aneurysmally dilated aorto-pulmonary collateral causing compression over trachea, presenting as dry irritating cough who died suddenly with haemoptysis probably due to rupture of hypertrophied bronchial collaterals or direct erosion of large major aorto-pulmonary collateral arteries (MAPCA) into the respiratory tract.     

Probing chelation motifs in HIV integrase inhibitors

A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer inhibitors (INSTIs) were evaluated in vitro in cell-free enzyme activity assays, and the in vitro results were further validated in cell culture experiments. All of the active compounds showed selective inhibition of the strand-transfer reaction over 3'-processing, suggesting a common mode of action with raltegravir. The results of the in vitro activity suggest that the nature of the MBG donor atoms, the overall MBG structure, and the specific arrangement of the MBG donor atom triad are essential for obtaining maximal HIV-1 IN inhibition. At least two compounds (RCD-4, RCD-5) containing a hydroxypyrone MBG were found to display superior strand-transfer inhibition when compared to an abbreviated analogue of raltegravir (RCD-1). By isolating and examining the role of the MBG in a series of INSTIs, we have identified a scaffold (hydroxypyrones) that may provide access to a unique class of HIV-1 IN inhibitors, and may help overcome rising raltegravir resistance.     

Diagnostic yield of dual-phase computed tomography enterography in patients with obscure gastrointestinal bleeding and a non-diagnostic capsule endoscopy

Background and Aim: In patients with obscure gastrointestinal (GI) bleeding, capsule endoscopy is widely used to determine the source of bleeding. However, there is currently no consensus on how to further evaluate patients with obscure GI bleeding with a non‐diagnostic capsule endoscopy examination. This study aims to determine the diagnostic yield of dual‐phase computed tomographic enterography (CTE) in patients with obscure GI bleeding and a non‐diagnostic capsule endoscopy. Methods: Patients with obscure GI bleeding who were referred for capsule endoscopy were prospectively enrolled. Obscure GI bleeding was defined as overt if there was obvious GI bleeding; otherwise it was defined as occult. Patients with a non‐diagnostic capsule endoscopy and no contraindications underwent a CTE. Results: Capsule endoscopy was performed in 52 patients; 26 patients (50%) had occult GI bleeding and 26 patients (50%) had overt GI bleeding. CTE was then performed in 25 of the 48 patients without a definitive source of bleeding seen on capsule endoscopy. The diagnostic yield of CTE was 0% (0/11) in patients with occult bleeding versus 50% (7/14) in patients with overt bleeding (P < 0.01). Using clinical follow up as the gold standard, for the 25 patients with a non‐diagnostic capsule, CTE had a sensitivity of 33% (95% confidence interval 0.15, 0.56) and a specificity of 75% (95% confidence interval 0.22, 0.99). Conclusions: In patients with a non‐diagnostic capsule endoscopy examination, CTE is useful for detecting a source of GI bleeding in patients with overt, but not occult, obscure GI bleeding.