Givosiran for the Treatment of Pediatric Acute Intermittent Porphyria.

Acute intermittent porphyria (AIP) causes neurovisceral symptoms and organ toxicity resulting in acute and chronic health conditions. Treatment has traditionally involved avoiding triggers and utilizing carbohydrates and hemin infusions for acute attacks. Givosiran, an FDA-approved small interfering RNA, has shown benefit in adults in reducing attacks. However, its usage in pediatrics is extremely limited. We present a pediatric patient with AIP, requiring frequent hemin infusions for severe attacks, which have a resolution of her disease state and symptoms with the initiation of givosiran therapy.

Successful Treatment of Relapsed Pediatric Acute Myeloid Leukemia Presenting as Central Nervous System Myeloid Sarcoma: A Single-Institution Case Series.

Relapsed acute myeloid leukemia presenting as an isolated central nervous system myeloid sarcoma (CNS MS) is very rare and generally entails poor outcomes. CNS MS treatment is not well defined and can include systemic chemotherapy, intrathecal chemotherapy, radiation therapy, or hematopoietic stem cell transplant. Thiotepa, vinorelbine, topotecan, and clofarabine (TVTC) has been successful for reinduction therapy in relapsed/refractory leukemia to induce remission before hematopoietic stem cell transplant. There is no published evidence of TVTC being utilized for CNS MS. In this series, we report 2 symptomatic patients with isolated CNS MS at relapse who demonstrated near complete resolution after reinduction with TVTC and additional intrathecal chemotherapy.

A Case of Small Cell Lung Carcinoma in a 15-Year-Old Boy and Literature Review.

Small cell lung carcinoma (SCLC), also known as high-grade neuroendocrine tumor of the lung, is exceedingly rare in the pediatric population. SCLC is usually fast growing and often has metastasized at diagnosis. It frequently responds well to therapy initially, however, has a high relapse and mortality rate. There are limited published data on SCLC in children and no existing pediatric treatment protocols. In this report, we present a case of extensive stage SCLC in a 15-year-old boy who responded to single-agent gemcitabine therapy and review similar cases reported in the medical literature.

Photochemical sealing improves outcome following peripheral neurorrhaphy.

INTRODUCTION: Peripheral nerve transection initiates a complex molecular response in the severed nerve endings, resulting in the release of neurotrophic and neurotropic factors that are central to axonal survival and regeneration. In this study we tested the hypothesis that sealing the neurorrhaphy site from the surrounding environment using a photochemically bonded nerve wrap would optimize the endoneural environment and enhance regeneration and nerve function recovery. MATERIALS AND METHODS: Adult rats underwent unilateral sciatic nerve transection and standard epineural nerve repair. The repair site was wrapped with amniotic membrane or autologous vein and then was either sealed using photochemical tissue bonding (PTB) or secured with sutures. Photochemical sealing without a wrap was also carried out. Functional recovery was assessed at 2-wk intervals using walking track analysis and nerve histomorphometry was assessed at 12 wk. RESULTS: Treating nerves with PTB-sealed amnion significantly improved functional recovery and increased distal axon and fiber diameters and myelin thickness compared to nerves treated with standard neurorrhaphy alone. Direct PTB sealing of the repair site also improved function. Neither amnion secured with sutures nor vein wraps exhibited improved functional or histological recovery compared to standard neurorrhaphy. CONCLUSIONS: These results suggest that sealing the peripheral nerve repair site with amnion using a photochemical technique may lead to earlier restoration of neural homeostasis and consequent enhanced repair of nerve injury.

Preparation and integration of human amnion nerve conduits using a light-activated technique.

BACKGROUND: Photochemical tissue bonding is a developing light-activated technique that facilitates watertight sealing between tissue surfaces. Previous work has shown that sealing with photochemical tissue bonding can improve regeneration following primary nerve repair. The authors evaluated sealing of nerve stumps with photochemical tissue bonding within customized human amnion conduits. The authors hypothesized that light-activated integration could enhance regeneration across the nerve gap. METHODS: Photochemical crosslinked amnion conduits were placed across 1-cm sciatic nerve gaps in Sprague-Dawley rats and either secured with sutures or sealed using photochemical tissue bonding. Reversed autologous nerve grafts were used in the control group. Functional recovery was measured by walking track analysis; histology and histomorphometry of nerves and gastrocnemius muscles were evaluated. RESULTS: Regeneration within the photochemical tissue bonding-sealed amnion conduit was significantly better than that observed in the amnion conduit secured with sutures and did not differ significantly from that in the autologous nerve graft. CONCLUSIONS: Photochemical crosslinked amnion appears suitable as a nerve conduit. Sealing of compatible conduits with photochemical tissue bonding may have the potential to maximize regeneration.

Improving electrophysiologic and histologic outcomes by photochemically sealing amnion to the peripheral nerve repair site.

BACKGROUND: The surgical approach used today in the repair of peripheral nerve injuries rarely achieves full functional recovery. This study determines whether isolation of the nerve repair site using photochemical tissue bonding (PTB) in combination with human amniotic membrane can improve both functional and histologic recovery. METHODS: New Zealand white rabbits (n = 24) underwent transection of the right common peroneal nerve. Epineural nerve repair was performed using 10-0 nylon sutures. The repair site was then wrapped in a cuff of human amniotic membrane, which either was secured with sutures or sealed using PTB. Standard neurorrhaphy alone was assessed as a control group. Functional recovery was recorded at 30-day intervals postoperatively by electrophysiologic assessment. At 120 days, animals were killed humanely and nerves harvested for histomorphometry. RESULTS: Nerves treated with amnion wraps and sealed with PTB demonstrated a statistically significant improvement across both functional and histologic parameters. Functional recovery, as measured by repeated electrophysiologic studies over time, revealed a 26.2% improvement over standard neurorrhaphy alone (P < .05). Nerves treated with PTB-sealed amnion wraps had significantly greater (P < .001) axon (5.08 +/- 1.06 microm) and fiber diameters (7.46 +/- 1.37 microm), as well as myelin thickness (2.39 +/- 0.7 microm) and the g ratio (axon diameter/fiber diameter ratio; 0.68 +/- 0.07) distal to the repair site compared to standard neurorrhaphy alone (4.98 +/- 1.81 microm, 6.77 +/- 1.94 microm, 1.79 +/- 0.42 microm, and 0.71 +/- 0.09, respectively). CONCLUSION: Isolation of the repair site using a photochemically sealed amnion wrap improves electrophysiologic and histologic recovery compared to standard suture neurorrhaphy.

Microvascular anastomosis using a photochemical tissue bonding technique.

BACKGROUND AND OBJECTIVES: Photochemical tissue bonding (PTB) combines photoactive dyes with visible light to create fluid-tight seals between tissue surfaces without causing collateral thermal damage. The potential of PTB to improve outcomes over standard of care microsurgical reanastomoses of blood vessels in ex vivo and in vivo models was evaluated. STUDY DESIGN: The mechanical strength and integrity of PTB and standard microsurgical suture repairs in ex vivo porcine brachial arteries (n = 10) were compared using hydrostatic testing of leak point pressure (LPP). Femoral artery repair in vivo was measured in Sprague-Dawley rats using either standard microvascular sutures (n = 20) or PTB (n = 20). Patency was evaluated at 6 hours (n = 10) and 8 weeks post-repair (n = 10) for each group. RESULTS: PTB produced significantly higher LPPs (1,100+/- 150 mmHg) than suture repair (350+/-40 mmHg, P<0.001) in an ex vivo study. In an in vivo study all femoral arteries in both suture and PTB repair groups were patent at 6 hours post-repair. At 8 weeks post-repair the patency rate was 80% for both groups. No evidence of aneurysm formation was seen in either group and bleeding was absent from the repair site in the PTB-treated vessels, in contrast to the suture repair group. CONCLUSION: PTB is a feasible microvascular repair technique that results in an immediate, mechanically robust bond with short- and long-term patency rates equal to those for standard suture repair.