Sudden death in lambda light chain AL cardiac amyloidosis: a review of literature and update for clinicians and pathologists

Light chain (AL) amyloidosis is the most common type of systemic amyloidosis, affecting around 10 people per million per year. In Europe, approximately 5000 new diagnosis per year are reported. Deposition of amyloid fibrils derived from antibody light chains are key pathogenic agents in AL amyloidosis. They can be deposited in multiple organs but cardiac involvement carries a major risk of mortality. The prognosis is poor in cases associated with multiple myeloma. The average survival is around 1 year. Up to half of all patients with cardiac amyloidosis die suddenly; 75% ofthose deaths are due to heart failure. Ventricular arrhythmia is also associated with cardiac amyloidosis and unexpected death. It is crucial to make a diagnosis and start treatment at an early stage. Recent data suggest that cardiac amyloidosis has become a treatable and curable condition with a combination of agents targeting multiple steps of the amyloid cascade. ICD implantation may not be as effective for the therapy of light chain (AL) cardiac amyloidosis as supposed earlier. In cases of unexpected and sudden death, autopsy may show unknown conditions and is valuable to assess existing risks for family members. Even after careful autopsy, a proportion of sudden deaths, ranging from 2 to 54%, remain unexplained and this broad range of values is likely due to the heterogeneity of autopsy protocols. Post mortem diagnosis of cardiac amyloidosis still represents a challenge for forensic pathologists. Detailed morphologic study of the heart and a complete histopathologic study are mandatory. Immunohistochemistry is essential for amyloid subclassification. A review of existing literature is performed by the authors and a methodological approach in post mortem diagnosis of light chain AL cardiac amyloidosis is proposed. Both macroscopic and microscopic findings are discussed

Development of a patient-centered aggregate score to predict survival after lung resection for non–small cell lung cancer

ObjectiveThe objective of this analysis was to develop a survival aggregate score (SAS), including objective and subjective patient-based parameters, and assess its prognostic role after major anatomic resection for non–small cell lung cancer.MethodsA total of 245 patients underwent major lung resections for non–small cell lung cancer with preoperative evaluation of quality of life (Short-Form 36v2 survey) and complete follow-up. The Cox multivariable regression and bootstrap analyses were used to identify prognostic factors of overall servival, which were weighted to construct the scoring system and summed to generate the SAS.ResultsCox regression analysis showed that the factors negatively associated with overall survival and used to construct the score were 36-item short-form health survey physical component summary score less than 50 (hazard ratio [HR], 1.7; P = .008), aged older than 70 years (HR, 1.9; P = .002), and carbon monoxide lung diffusion capacity less than 70% (HR, 1.7; P = .01). Patients were grouped into 4 risk classes according to their SAS. The 5-year overall survival was 78% in class SAS0, 59% in class SAS1, 42% in class SAS2, and 14% in class SAS3 (log-rank test, P < .0001). SAS maintained its association with overall survival in patients with stages pT1 (log-rank test, P = .01), pT2 (log-rank test, P = .02), or pT3-4 (log-rank test, P = .001), and in those with stages pN0 (log-rank test, P = .0005) or pN1-2 (log-rank test, P = .02). The 5-year cancer-specific survival was 83% in class SAS0, 71% in class SAS1, 63% in class SAS2, and 17% in class SAS3 (log-rank test, P < .0001).ConclusionsThis system may be used to refine stratification of prognosis for clinical and research purposes

Ichthyosis Linearis Circumflexa as the Only Clinical Manifestation of Netherton Syndrome.

Ichthyosis linearis circumflexa (ILC) presents as serpiginous and migratory erythematous patches with double-edged scales. ILC is rarely an isolated skin manifestation, but most commonly a part of Netherton syndrome (NS). NS is caused by SPINK5 mutations, which lead to absent or sometimes reduced expression of the serine protease inhibitor LEKTI. NS is characterised by congenital ichthyosiform erytroderma, trichorrhexis invaginata (TI) and atopy. We report 2 children who presented since the first months of life cheek erythema followed by the appearance of sparse ILC lesions on the face, trunk and proximal extremities. Erythroderma at birth, TI and atopy were absent. LEKTI immunoreactivity was reduced in patient epidermis, and serine protease activity was modestly increased, while desmoglein-1 expression remained unaffected. SPINK5 mutation and expression analysis in patient keratinocytes revealed compound heterozygous splicing variants, which allowed residual LEKTI secretion. Our results show that ILC can be the only clinical manifestation of NS

Co-Transplantation of endothelial progenitor cells and pancreatic islets to induce long-lasting normoglycemia in streptozotocin-treated diabetic rats

Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3–5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards

Hygromechanical behaviour of wooden panel paintings: classification of their deformation tendencies based on numerical modelling and experimental results

AbstractWooden panel paintings are among the most important historical and artistic artworks from the Middle Ages and the Renaissance period. Currently, they represent a challenge for conservators and scientists who face complex issues related to their conservation. Panel paintings can be considered multilayer objects, that for brevity can be considered to consist of a wooden support and various paint layers. The wooden support is known to be hygroscopic and is continuously seeking hygroscopic equilibrium with the humidity of the environment, thus it tends to deform. Based on various hygroscopic tests carried out on 6 real panel paintings chosen by expert restorers to represent different periods and construction techniques, this paper describes the deformation tendencies of the selected panel paintings. Among possible variables, three most important variables were identified: (a) tree ring orientation of the wooden support, (b) stiffness and (c) emissivity of the paint layers. The internal equilibrium of the forces, governed by the moisture gradients across the thickness of the wood, changes drastically according to the varying characterisation of these factors. To observe their individual contributions, the 6 panel paintings underwent various humidity cycles, were completely free to deform and were always in complete safety. To characterise the stiffness and emissivity of the paint layers, the 6 panel paintings underwent a few humidity cycles with the front face totally waterproofed; thus, the moisture exchange was forced from the back only, and one of the three variables was eliminated. A complex system emerges where the tree ring orientation of the wooden support, the stiffness and emissivity of the paint layers are strongly coupled and determine the deformation modes of the panel paintings. A numerical analysis was conducted to classify the various general deformation modes of panel paintings and the specific classification of the 6 real panel paintings analysed experimentally. The complexity of the interaction of the variables studied suggests that experimental procedures must be conducted in preparation for numerical analyses of real panel paintings