Stevens-Johnson syndrome/toxic epidermal necrolysis in an orthotopic liver transplant recipient: a case report.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare spectrum of acute, mucocutaneous drug reactions characterized by epidermal necrosis of the skin and mucous membranes with progressive multiorgan failure. Cutaneous presentation of SJS/TEN is similar to that of acute graft-versus-host disease, creating a diagnostic dilemma in solid-organ transplant recipients presenting with diffuse, erythematous eruptions, skin sloughing, and systemic sequelae, reflective of both diseases. This case report details a 48-year-old woman post-orthotopic liver transplantation (OLT) who developed a diffuse, painful, morbilliform rash with progressive desquamation, along with corresponding pathological analysis indicative of SJS/TEN. There are few documented reports of SJS/TEN in solid-organ transplant recipients, and this case illustrates successful intervention and resolution of SJS/TEN in an OLT recipient while managing intraabdominal sepsis and an episode of acute rejection. Despite its rarity, prompt diagnosis of SJS/TEN and the implementation of tailored therapeutic strategies are crucial in the care of solid-organ transplant recipients.

Our evolution in the treatment of hepatic artery and portal vein thrombosis in pediatric liver transplantation: Success with catheter-directed therapies.

BACKGROUND: In pediatric liver transplant recipients, hepatic artery thrombosis and portal vein thrombosis are major causes of acute graft failure and mortality within 30 days of transplantation. There is, however, a strong possibility of graft salvage if flow can be re-established to reduce ischemic injury. The current standard treatment is surgical revascularization, and if unsuccessful, retransplantation. Due to our success in treating these complications with catheter-directed therapies, we sought to summarize and publish the outcomes of all patients who experienced hepatic artery thrombosis or portal vein thrombosis within 30 days of liver transplantation. METHODS: We conducted a retrospective cohort analysis of 27 pediatric liver transplant recipients who experienced hepatic artery thrombosis (n = 13), portal vein thrombosis (n = 9), or both (n = 5) between September 2012 and March 2021. We collected and tabulated data on the patients and therapies performed to treat them, including success rates, primary and secondary patency, and clinical outcomes. RESULTS: Among these patients, 6 were managed with anticoagulation and relisting for transplant and 21 had a primary revascularization attempt. Surgical recanalization was attempted in 7 patients of which 3 had successful recanalization (43%) and catheter-directed recanalization was attempted in 14 patients with 100% success in re-establishing blood flow to the graft. Additionally, patency was increased, and mortality was decreased in patients treated with catheter-directed recanalization compared to surgical revascularization or anticoagulation alone. CONCLUSION: This data illustrates the need to further investigate catheter-directed thrombolysis as a potential first-line treatment for postoperative HAT and PVT in pediatric liver transplant recipients.

A call for standardization: Practice patterns and management of critical illness-related corticosteroid insufficiency in surgical intensive care units.

INTRODUCTION: Critical illness-rlated corticosteroid insufficiency (CIRCI) is a known sequela of severe injury and illness, yet its diagnosis and management are challenging. We hypothesized that CIRCI has significant variability in its diagnosis and management within surgical intensive care units (SICUs). Our study aimed to assess the state of practice of CIRCI in the American College of Surgery Committee on Trauma (ACS COT) certified level 1 trauma centers. METHODS: An 11-item questionnaire was developed based on a CIRCI literature search with expert input from medical endocrinology, acute care surgeons, and surgical intensivists to assess practice patterns of CIRCI.  Prior to distribution, it was validated across 2 separate institutions by board-certified critical care surgeons.  The questionnaire was distributed to trauma intensivists within level 1 trauma centers in Southeast United States and was open from April 2019 to January 2020. RESULTS: A total of 56 responses were collected with a response rate of 70%. 72% of respondents indicated they evaluate or manage CIRCI on a weekly basis.  In regards to the diagnosis of CIRCI, only 5% of respondents use a formal protocol and 32% do not use laboratory testing. While a majority of respondents (94%) use corticosteroids in septic shock, 67% of those surveyed have not implemented mineralocorticoids as part of the management.  83% of respondents indicated a knowledge gap exists in the therapeutic value of corticosteroids for hemorrhagic shock. CONCLUSIONS: This study demonstrates extreme variability in the diagnosis and management of CIRCI. In particular most providers acknowledge a knowledge gap in the diagnosis of CIRCI and the role of corticosteroids in hemorrhagic shock. Few providers are using adjunctive mineralocorticoids in septic shock, although recent level 1 evidence have shown a survival benefit. These responses reflect an opportunity for national improvement in the management of CIRCI.

A data-entrained computational model for testing the regulatory logic of the vertebrate unfolded protein response.

The vertebrate unfolded protein response (UPR) is characterized by multiple interacting nodes among its three pathways, yet the logic underlying this regulatory complexity is unclear. To begin to address this issue, we created a computational model of the vertebrate UPR that was entrained upon and then validated against experimental data. As part of this validation, the model successfully predicted the phenotypes of cells with lesions in UPR signaling, including a surprising and previously unreported differential role for the eIF2α phosphatase GADD34 in exacerbating severe stress but ameliorating mild stress. We then used the model to test the functional importance of a feedforward circuit within the PERK/CHOP axis and of cross-regulatory control of BiP and CHOP expression. We found that the wiring structure of the UPR appears to balance the ability of the response to remain sensitive to endoplasmic reticulum stress and to be deactivated rapidly by improved protein-folding conditions. This model should serve as a valuable resource for further exploring the regulatory logic of the UPR.