De novo head and neck cancer after liver transplant with antibody-based immunosuppression induction

Background Powerful antibody-based immunosuppression induction is now used routinely during organ transplantation, and may place patients at even higher risk of post-transplant cancer. Materials and Methods Incidence of de-novo head and neck cancer was extracted from the records of 1685 consecutive adult, deceased donor liver transplant recipients with a minimum 1-year follow-up from 2001 to 2015. There were 121 patients positively identified as having developed de-novo head and neck cancer post-liver transplant. Records of these patients were analyzed to determine demographics, history of cancer pre-liver transplant, de-novo cancer type and location, treatment modalities, and alcohol and tobacco exposure. Results Of the 121 patients who developed cancer of the head and neck (7%), there were 103 cutaneous (6%) and 25 non-cutaneous (1%). For non-cutaneous cancers, factors associated with increased risk of cancer included alcohol abuse (p<0.001), any smoking history (p=0.05), and increasing exposure to tobacco (p<0.01). Ten-year Cox regression patient survival demonstrates a survival disadvantage for patients who develop non-cutaneous cancer (p=0.06), but a survival advantage for patients who develop cutaneous cancer (p<0.01). Conclusions The incidence and pattern of head and neck cancer in this population of liver transplant patients was similar to those published previously, suggesting that induction immunosuppression does not increase risk of these types of cancers. Long term survival was worse for patients with non-cutaneous cancers, but better for those with cutaneous cancers, though the reason is unclear

De novo head and neck cancer after liver transplant with antibody-based immunosuppression induction

Background Powerful antibody-based immunosuppression induction is now used routinely during organ transplantation, and may place patients at even higher risk of post-transplant cancer. Materials and Methods Incidence of de-novo head and neck cancer was extracted from the records of 1685 consecutive adult, deceased donor liver transplant recipients with a minimum 1-year follow-up from 2001 to 2015. There were 121 patients positively identified as having developed de-novo head and neck cancer post-liver transplant. Records of these patients were analyzed to determine demographics, history of cancer pre-liver transplant, de-novo cancer type and location, treatment modalities, and alcohol and tobacco exposure. Results Of the 121 patients who developed cancer of the head and neck (7%), there were 103 cutaneous (6%) and 25 non-cutaneous (1%). For non-cutaneous cancers, factors associated with increased risk of cancer included alcohol abuse (p<0.001), any smoking history (p=0.05), and increasing exposure to tobacco (p<0.01). Ten-year Cox regression patient survival demonstrates a survival disadvantage for patients who develop non-cutaneous cancer (p=0.06), but a survival advantage for patients who develop cutaneous cancer (p<0.01). Conclusions The incidence and pattern of head and neck cancer in this population of liver transplant patients was similar to those published previously, suggesting that induction immunosuppression does not increase risk of these types of cancers. Long term survival was worse for patients with non-cutaneous cancers, but better for those with cutaneous cancers, though the reason is unclear

Tracheostomy Post Liver Transplant: Predictors, Complications, and Outcomes

BACKGROUND Liver transplant (LT) patients have an increased risk of postoperative respiratory failure requiring tracheostomy. This study sought to characterize objective clinical predictors of tracheostomy. MATERIAL AND METHODS The records for 2017 LT patients at a single institution were reviewed. Patients requiring tracheostomy were first compared with all other patients. A case-control subgroup analysis was conducted in which 98 tracheostomy patients were matched with 98 non-tracheostomy LT patients. For the case-control study, muscle mass was assessed using preoperative computed tomography scans. RESULTS Among 2017 LT patients, 98 required tracheostomy (5%), with a 19% complication rate. Tracheostomy patients were older and had a higher model for end-stage liver disease score, a lower body mass index (BMI), and a greater smoking history. Tracheostomy patients had a longer hospital stay (45 vs. 10 days, P<0.001) and worse 1-year survival (65% vs. 91%, P<0.001). Ten-year Cox regression patient survival for tracheostomy patients was significantly worse (32% vs. 68%, P<0.001). In the case-control analysis, respiratory failure patients were older (P<0.01) and had a lower BMI (P=0.05). They also had a muscle mass deficit of -39% compared with matched LT controls (P<0.001). No significant differences were seen with pre-LT total protein or albumin or with forced expiratory volume in 1 s divided by forced vital capacity (FEV1/FVC) values. CONCLUSIONS Predictors for respiratory failure requiring post-LT tracheostomy include higher model for end-stage liver disease score, older age, lower BMI, greater smoking history, and worse sarcopenia. Patients requiring tracheostomy have dramatically longer hospital stays and worse survival

Macroeconomic Conditions, Firm Characteristics, and Credit Spreads

Default risk, Macroeconomic conditions, Credit spreads, G12, G13, E43, E44,

A <em>trans</em>-acting protein effect causes severe eye malformation in the <em>mp </em>mouse

Mp is an irradiation-induced mouse mutation associated with microphthalmia, micropinna and hind limb syndactyly. We show that Mp is caused by a 660 kb balanced inversion on chromosome 18 producing reciprocal 3-prime gene fusion events involving Fbn2 and Isoc1. The Isoc1-Fbn2 fusion gene (Isoc1(Mp)) mRNA has a frameshift and early stop codon resulting in nonsense mediated decay. Homozygous deletions of Isoc1 do not support a significant developmental role for this gene. The Fbn2-Isoc1 fusion gene (Fbn2 (Mp)) predicted protein consists of the N-terminal Fibrillin-2 (amino acids 1-2646, exons 1-62) lacking the C-terminal furin-cleavage site with a short out-of-frame extension encoded by the final exon of Isoc1. The Mp limb phenotype is consistent with that reported in Fbn2 null embryos. However, severe eye malformations, a defining feature of Mp, are not seen in Fbn2 null animals. Fibrillin-2(Mp) forms large fibrillar structures within the rough endoplasmic reticulum (rER) associated with an unfolded protein response and quantitative mass spectrometry shows a generalised defect in protein secretion in conditioned media from mutant cells. In the embryonic eye Fbn2 is expressed within the peripheral ciliary margin (CM). Mp embryos show reduced canonical Wnt-signalling in the CM - known to be essential for ciliary body development - and show subsequent aplasia of CM-derived structures. We propose that the Mp "worse-than-null" eye phenotype plausibly results from a failure in normal trafficking of proteins that are co-expressed with Fbn2 within the CM. The prediction of similar trans-acting protein effects will be an important challenge in the medical interpretation of human mutations from whole exome sequencing