A bleeding Blalock–Taussig shunt

 

Since birth, an 8-month-old child has had truncus arteriosus, a left pulmonary artery sling (Panel A), and tracheal stenosis. She received an operation for main pulmonary artery division from truncus, right modified Blalock-Taussig (mBT) shunt, and sliding tracheoplasty at the age of 13 days due to complex pulmonary artery anatomy and bilateral pulmonary artery hypoplasia. Cardiogenic shock due to blockage of the mBT shunt occurred two weeks after surgery. Right mBT shunt revision and fresh left mBT shunt implantation were conducted after extracorporeal cardiopulmonary resuscitation. She was discharged home with a tracheostomy at the age of 7 months after an extended stay in the hospital for post-resuscitation complications. After a month, the patient was readmitted due to respiratory discomfort and a high temperature. At the time of admission, the patient was moderately anaemic (haemoglobin was 11.3 g/dL), and his blood pressure was 94/40 mmHg. Bacteremia caused by Burkholderia cepacia was later proven. Surprisingly, a continuous colour flow jet was discovered at the confluence of the left subclavian artery and the left mBT shunt on follow-up echocardiography. Around the left mBT shunt, the swirling jet flowed into an aneurysm-like area (Panel B, Supplementary material online, Videos S1 and S2; star indicates pseudoaneurysm; arrow indicates flow jet of the bleeding site; arrowhead indicates the mBT shunt). 

The patient had a ruptured left mBT shunt with ongoing bleeding and pseudoaneurysm development. The filling contrast in a partially thrombosed huge pseudoaneurysm around the left mBT shunt was seen on computed tomography (Panel C, Supplementary material online, Video S3; star indicates pseudoaneurysm; arrow indicates flow jet of the bleeding site; arrowhead indicates the mBT shunt) and 3D reconstruction (Panel D, Supplementary material online, Video S4). Surprisingly, despite the fact that active bleeding remained for more than a month in subsequent follow-up, it appeared to be effectively contained inside the pseudoaneurysm with no major haemodynamic damage. We decided on palliative care after consulting with her family.

CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis

 

 

Transthyretin amyloidosis, also known as ATTR amyloidosis, is a life-threatening condition marked by the accumulation of misfolded transthyretin (TTR) protein in tissues, primarily the nerves and heart. NTLA-2001 is a gene-editing therapeutic drug that works in vivo to cure ATTR amyloidosis by lowering TTR levels in the blood. It is based on a clustered model. CRISPR-Cas9 is an acronym for regularly interspaced short palindromic repeats and associated Cas9 endonuclease, and it consists of a lipid nanoparticle encasing Cas9 protein messenger RNA and a single guide RNA targeting TTR.

TTR knockdown was shown to be persistent after a single dosage in preclinical investigations. During the first 28 days following infusion, serial safety assessments in patients revealed few adverse events, and those that did occur were minor in severity. Pharmaco dynamic effects were shown to be dose-dependent. The mean reduction in serum TTR protein concentration from baseline was 52 percent (range, 47 to 56) in the group that got a 0.1 mg per kilogramme dosage and 87 percent (range, 80 to 96) in the group that received a 0.3 mg per kilogramme dose at day 28.

Administration of NTLA-2001 to a small sample of patients with hereditary ATTR amyloidosis and polyneuropathy was accompanied with fairly minor side effects and resulted in lower serum TTR protein concentrations due to targeted TTR deletion.