Vosoritide Therapy in Children with Achondroplasia: Early Experience and Practical Considerations for Clinical Practice.

INTRODUCTION: Vosoritide is the first precision medical therapy approved to increase growth velocity in children with achondroplasia. Sharing early prescribing experiences across different regions could provide a framework for developing practical guidance for the real-world use of vosoritide. METHODS: Two meetings were held to gather insight and early experience from experts in Europe, the Middle East, and the USA. The group comprised geneticists, pediatric endocrinologists, pediatricians, and orthopedic surgeons. Current practices and considerations for vosoritide were discussed, including administration practicalities, assessments, and how to manage expectations. RESULTS: A crucial step in the management of achondroplasia is to determine if adequate multidisciplinary support is in place. Training for families is essential, including practical information on administration of vosoritide, and how to recognize and manage injection-site reactions. Advocated techniques include establishing a routine, empowering patients by allowing them to choose injection sites, and managing pain. Patients may discontinue vosoritide if they cannot tolerate daily injections or are invited to participate in a clinical trial. Clinicians in Europe and the Middle East emphasized the importance of assessing adherence to daily injections, as non-adherence may impact response and reimbursement. Protocols for monitoring patients receiving vosoritide may be influenced by regional differences in reimbursement and healthcare systems. Core assessments may include pubertal staging, anthropometry, radiography to confirm open physes, the review of adverse events, and discussion of concomitant or new medications-but timing of these assessments may also differ regionally and vary across institutions. Patients and families should be informed that response to vosoritide can vary in both magnitude and timing. Keeping families informed regarding vosoritide clinical trial data is encouraged. CONCLUSION: The early real-world experience with vosoritide is generally positive. Sharing these insights is important to increase understanding of the practicalities of treatment with vosoritide in the clinical setting.

Clostridium perfringens liver abscess after pancreatic resection.

BACKGROUND: Liver abscess is a rare complication after pancreatectomy. Clostridium perfingens is a rare cause of intrahepatic infections. CASE REPORT: A 65-year-old woman with pancreatic cancer underwent explorative laparotomy, during which encasement of the hepatic artery by the tumor was found. Neoadjuvant radiochemotherapy with capecitabine was started, which caused tumor regression, and duodenopancreatectomy was performed. The portal vein was occluded and infiltrated by cancer and therefore was resected and not reconstructed. After a slow recovery, the patient developed hemorrhage at the gastrojejunal anastomosis, which was controlled by fibrin injection. Within a few days, she presented with signs of sepsis, and blood cultures yielded Clostridium perfringens, Streptococcus oralis, Staphylococcus aureus, and Candida albicans. The source of the sepsis proved to be a 9-cm liver abscess, which was drained; cultures grew C. perfringens, Hafnia alvei, and Enterobacter cloacae. Despite antibiotic treatment, the patient died from sepsis and multiorgan failure 27 days after pancreatic surgery. CONCLUSION: Such rare infections can follow pancreatic resection with neoadjuvant radiochemotherapy. Clostridium perfringens-associated liver abscess maintains a high mortality rate.

A case of fulminant post-transplant lymphoproliferative disorder and septicemia.

The fulminant form of post-transplant lymphoproliferative disorder (PTLD) is very uncommon and occurs in approximately 1% of PTLD patients. Approximately 85% of these lesions are of B-cell origin, and most of them are associated with Epstein-Barr virus infection. Fulminant PTLD is frequently associated with a systemic inflammatory response syndrome, and may be difficult to differentiate from septicemia. We describe the case of a 59-yr-old man who suffered from prolonged septicemia in the immediate post-transplant period, and presented again four months after cardiac transplantation with fever, painful liver edge and gastrointestinal bleeding. The diagnosis of fulminant PTLD with advanced multiorgan infiltration by a diffuse large-cell lymphoma of B-cell phenotype was made. During treatment with rituximab, the patient died from Enterococcus faecium septicemia. The sequence of septicemia, PTLD and, finally again, septicemia is an unusual challenge and urges for an aggressive diagnostic approach, where markers like procalcitonin may aid in the discrimination of fulminant PTLD from septicemia.