Limitations of antifungal prophylaxis in preventing invasive Candida surgical site infections after liver transplant surgery.

Invasive primary Candida surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of Candida IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten Candida IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive Candida IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of Candida IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.

Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition.

AIM: To test the cross-immunogenicity of anti-CT-P13 IBD patients' sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera. METHODS: Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes. RESULTS: All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P < 0.001). Anti-CT-P13 sera of patients with IBD (n = 32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naïve individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator. CONCLUSIONS: These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.

Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis.

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.

Ex-vivo liver perfusion for organ preservation: Recent advances in the field.

Liver transplantation is the optimal treatment for end-stage liver disease but is limited by the severe shortage of donor organs. This shortage has prompted increased utilization of marginal grafts from DCD and extended criteria donors, which poorly tolerate cold storage in comparison to standard criteria grafts. Ex-vivo liver perfusion (EVLP) technology has emerged as a potential alternative to cold storage for organ preservation, but there is no consensus regarding the optimal temperature or conditions for EVLP. Herein, we review recent advances in both pre-clinical and clinical studies, organized by perfusion temperature (hypothermic, subnormothermic, normothermic).

Liver transplantation in an adolescent with acute liver failure from acute lymphoblastic leukemia.

The most common identifiable causes of acute liver failure in pediatric patients are infection, drug toxicity, metabolic disease, and autoimmune processes. In many cases, the etiology of acute liver failure cannot be determined. Acute leukemia is an extremely rare cause of acute liver failure, and liver transplantation has traditionally been contraindicated in this setting. We report a case of acute liver failure in a previously healthy 15-yr-old male from pre-B-cell acute lymphoblastic leukemia. He underwent liver transplantation before the diagnosis was established, and has subsequently received chemotherapy for pre-B-cell acute lymphoblastic leukemia. He is currently alive 31 months post-transplantation. The published literature describing acute lymphoblastic leukemia as a cause of acute liver failure is reviewed.

Fatigue behavior of thin-walled grade 2 titanium samples processed by selective laser melting. Application to life prediction of porous titanium implants.

Because of its biocompatibility and high mechanical properties, the commercially pure grade 2 titanium (CPG2Ti) is largely used for fabrication of patient specific implants or hard tissue substitutes with complex shape. To avoid the stress-shielding and help their colonization by bone, prostheses with a controlled porosity are designed. The selective laser melting (SLM) is well adapted to manufacture such geometrically complicated structures constituted by struts with rough surfaces and relatively small diameters. Few studies were dedicated to characterize the fatigue properties of SLM processed samples and bulk parts. They followed conventional or standard protocols. The fatigue behavior of standard samples is very different from the one of porous raw structures. In this study, the SLM made "as built" (AB) and "heat treated" (HT) tubular samples were tested in fatigue. Wöhler curves were determined in both cases. The obtained endurance limits were equal to σD(AB)=74.5MPa and σD(HT)=65.7MPa, respectively. The heat treatment worsened the endurance limit by relaxation of negative residual stresses measured on the external surface of the samples. Modified Goodman diagram was established for raw specimens. Porous samples, based on the pattern developed by Barbas et al. (2012), were manufactured by SLM. Fatigue tests and finite element simulations performed on these samples enabled the determination of a simple rule of fatigue assessment. The method based on the stress gradient appeared as the best approach to take into account the notch influence on the fatigue life of CPG2Ti structures with a controlled porosity. The direction dependent apparent fatigue strength was found. A criterion based on the effective, or global, nominal stress was proposed taking into account the anisotropy of the porous structures. Thanks to this criterion, the usual calculation methods can be used to design bone substitutes, without a precise modelling of their internal fine porosity.

Posterior reversible encephalopathy syndrome independently associated with tacrolimus and sirolimus after multivisceral transplantation.

Posterior reversible encephalopathy syndrome (PRES) is a small vessel microangiopathy of the cerebral vasculature that occurs in 0.5-5% of solid organ transplant recipients, most commonly associated with tacrolimus (Tac). Clinical manifestations include hypertension and neurologic symptoms. We report an adult multivisceral transplant recipient who experienced recurrent PRES initially associated with Tac and subsequently with sirolimus. A 49-year-old woman with short bowel syndrome underwent multivisceral transplantation due to total parenteral nutrition-related liver disease. She was initially maintained on Tac, mycophenalate mofetil (MMF) and prednisone. Three months after transplantation, she developed renal dysfunction, leading to a reduction in Tac and the addition of sirolimus. Eight months after transplantation, she developed PRES. Tac was discontinued and PRES resolved. Sirolimus was increased to maintain trough levels of 12-15 ng/mL. Fourteen months after transplant, she experienced recurrent PRES which resolved after discontinuing sirolimus. Currently 3 years posttransplant, she is maintained on cyclosporine, MMF and prednisone with no PRES recurrence. In addition to calcineurin inhibitors, sirolimus may also be associated with PRES after solid organ transplantation. Ours is the first report of sirolimus-associated PRES in the setting of multivisceral transplantation. Identifying a safe alternative immunosuppression regimen was challenging but ultimately successful.

Development and mechanical characterization of porous titanium bone substitutes.

Commercially Pure Porous Titanium (CPPTi) can be used for surgical implants to avoid the stress shielding effect due to the mismatch between the mechanical properties of titanium and bone. Most researchers in this area deal with randomly distributed pores or simple architectures in titanium alloys. The control of porosity, pore size and distribution is necessary to obtain implants with mechanical properties close to those of bone and to ensure their osseointegration. The aim of the present work was therefore to develop and characterize such a specific porous structure. First of all, the properties of titanium made by Selective Laser Melting (SLM) were characterized through experimental testing on bulk specimens. An elementary pattern of the porous structure was then designed to mimic the orthotropic properties of the human bone following several mechanical and geometrical criteria. Finite Element Analysis (FEA) was used to optimize the pattern. A porosity of 53% and pore sizes in the range of 860 to 1500 µm were finally adopted. Tensile tests on porous samples were then carried out to validate the properties obtained numerically and identify the failure modes of the samples. Finally, FE elastoplastic analyses were performed on the porous samples in order to propose a failure criterion for the design of porous substitutes.

Chronic aspiration shifts the immune response from Th1 to Th2 in a murine model of asthma.

BACKGROUND: Chronic aspiration associated with gastro oesophageal reflux disease (GERD) is thought to play a substantial role in the development of asthma, the incidence of which is dramatically increasing in industrially developed countries. The majority of data examining the association between aspiration and asthma has been obtained from epidemiological studies, which show that between 50 and 90% of individuals with asthma experience some element of GERD. This study describes the effect of chronic aspiration on a model of experimentally induced airway hypersensitivity in Balb/c mice. MATERIALS AND METHODS: Four experimental groups were utilized: Aspiration/Asthma, Sham/Asthma, Aspiration/Sham and Sham/Sham. Mice were sensitized with aerosolized 1% ovalbumin on days 1 to 10 (sensitization phase), followed by repeated exposure on days 31 to 40 (challenge phase). Aspiration events occurred on days 1, 8,15, 22, 29, 36, 43 and 50. Animals were sacrificed on days 56 and 57. RESULTS: Chronic aspiration of 10 microL of murine gastric fluid per week for eight weeks produced an injury pattern distinct from that of acute aspiration, with lung injury characterized by hyperplasia, neutrophil infiltration of the bronchioles and relative parenchymal sparing. Aspiration during induction of ovalbumin-induced airway hypersensitivity was associated with a trend toward decreased production of antiovalbumin IgG, antiovalbumin IgE, and total IgE. Further, aspiration induced a substantial and significant increase in antiovalbumin IgG1/IgG2a ratios, consistent with a shift toward a predominantly Th2 response. CONCLUSION: These findings indicate that chronic aspiration has a profound effect on the nature of the immune response to aerosolized allergens in a model of experimentally induced airway hypersensitivity.