Intrinsically explainable deep learning architecture for semantic segmentation of histological structures in heart tissue.

BACKGROUND: Analysis of structures contained in tissue samples and the relevant contextual information is of utmost importance to histopathologists during diagnosis. Cardiac biopsies require in-depth analysis of the relationships between biological structures. Statistical measures are insufficient for determining a model's viability and applicability in the diagnostic process. A deeper understanding of predictions is necessary in order to support histopathologists. METHODS: We propose a method for providing supporting information in the form of segmentation of histological structures to histopathologists based on these principles. The proposed method utilizes nuclei type and density information in addition to standard image input provided at two different zoom levels for the semantic segmentation of blood vessels, inflammation, and endocardium in heart tissue. RESULTS: The proposed method was able to reach state-of-the-art segmentation results. The overall quality and viability of the predictions was qualitatively evaluated by two pathologists and a histotechnologist. CONCLUSIONS: The decision process of the proposed deep learning model utilizes the provided information sources correctly and simulates the decision process of histopathologists via the usage of a custom-designed attention gate that provides a combination of spatial and encoder attention mechanisms. The implementation is available at https://github.com/mathali/IEDL-segmentation-of-heart-tissue.

Thermal evaporation as sample preparation for silver-assisted laser desorption/ionization mass spectrometry imaging of cholesterol in amyloid tissues.

Cholesterol plays an important biological role in the body, and its disruption in homeostasis and synthesis has been implicated in several diseases. Mapping the locations of cholesterol is crucial for gaining a better understanding of these conditions. Silver deposition has proven to be an effective method for analyzing cholesterol using mass spectrometry imaging (MSI). We optimized and evaluated thermal evaporation as an alternative deposition technique to sputtering for silver deposition in MSI of cholesterol. A silver layer with a thickness of 6 nm provided an optimal combination of cholesterol signal intensity and mass resolution. The deposition of an ultrathin nanofilm of silver enabled high-resolution MSI with a pixel size of 10 µm. We used this optimized method to visualize the distribution of cholesterol in the senile plaques in the brains of APP/PS1 mice, a model that resembles Alzheimer's disease pathology. We found that cholesterol was evenly distributed across the frontal cortex tissue, with no evidence of plaque-like accumulation. Additionally, we investigated the presence and distribution of cholesterol in myocardial sections of a human heart affected by wild-type ATTR amyloidosis. We identified the presence of cholesterol in areas with amyloid deposition, but complete colocalization was not observed.

Clinical experience of reoperative right ventricular outflow tract reconstruction with valved conduits: risk factors for conduit failure in long-term follow-up.

Reconstruction of right ventricular outflow tract in patients with congenital heart disease in various age groups remains a controversial issue. Currently, a little is known about the fate of secondary and subsequent conduit. The aim of the study was to determine risk factors of conduit failure, evaluate long-term conduit survival, find out which type of conduit should be preferred in case of reoperations. We performed a retrospective analysis of a total of 249 records of valved conduit secondary and subsequent replacement in right ventricular outflow tract in 197 patients. Median follow-up was 5.7 years. The study endpoints were defined as conduit explants; balloon dilatation of the graft (excluding balloon dilatation of left/right pulmonary artery), transcatheter pulmonary valve implantation; heart transplantation or death of the patient. There were total of 21 deaths (11% mortality) among 197 patients during the follow-up, 2 patients underwent heart transplant, in 23 implanted conduits pulmonary angioplasty or/including transcatheter pulmonary valve implantation was afterwards performed due to graft failure, conduit had to be explanted in 46 cases. After 28 years follow-up, freedom from graft failure after 5 years was 77%, 48% after 10 years and 21% after 15 years. Reoperative right ventricular outflow tract reconstruction demonstrates good mid-term and acceptable long-term outcomes regardless of the type of conduit implanted. Worse long-term graft survival of secondary and further conduits is associated with younger age of the recipient at implantation, small size of the conduit, younger age of donor and male donor in case of allograft implantation.

Digital pathology in cardiac transplant diagnostics: from biopsies to algorithms.

In the field of heart transplantation, the ability to accurately and promptly diagnose cardiac allograft rejection is crucial. This comprehensive review explores the transformative role of digital pathology and computational pathology, especially through machine learning, in this critical domain. These methodologies harness large datasets to extract subtle patterns and valuable information that extend beyond human perceptual capabilities, potentially enhancing diagnostic outcomes. Current research indicates that these computer-based systems could offer accuracy and performance matching, or even exceeding, that of expert pathologists, thereby introducing more objectivity and reducing observer variability. Despite promising results, several challenges such as limited sample sizes, diverse data sources, and the absence of standardized protocols pose significant barriers to the widespread adoption of these techniques. The future of digital pathology in heart transplantation diagnostics depends on utilizing larger, more diverse patient cohorts, standardizing data collection, processing, and evaluation protocols, and fostering collaborative research efforts. The integration of various data types, including clinical, demographic, and imaging information, could further refine diagnostic precision. As researchers address these challenges and promote collaborative efforts, digital pathology has the potential to become an integral part of clinical practice, ultimately improving patient care in heart transplantation.

Exome sequencing reveals IFT172 variants in patients with non-syndromic cholestatic liver disease.

BACKGROUND AND AIM: Gene defects contribute to the aetiology of intrahepatic cholestasis. We aimed to explore the outcome of whole-exome sequencing (WES) in a cohort of 51 patients with this diagnosis. PATIENTS AND METHODS: Both paediatric (n = 33) and adult (n = 18) patients with cholestatic liver disease of unknown aetiology were eligible. WES was used for reassessment of 34 patients (23 children) without diagnostic genotypes in ABCB11, ATP8B1, ABCB4 or JAG1 demonstrable by previous Sanger sequencing, and for primary assessment of additional 17 patients (10 children). Nasopharyngeal swab mRNA was analysed to address variant pathogenicity in two families. RESULTS: WES revealed biallelic variation in 3 ciliopathy genes (PKHD1, TMEM67 and IFT172) in 4 clinically unrelated index subjects (3 children and 1 adult), heterozygosity for a known variant in PPOX in one adult index subject, and homozygosity for an unreported splice-site variation in F11R in one child. Whereas phenotypes of the index patients with mutated PKHD1, TMEM67, and PPOX corresponded with those elsewhere reported, how F11R variation underlies liver disease remains unclear. Two unrelated patients harboured different novel biallelic variants in IFT172, a gene implicated in short-rib thoracic dysplasia 10 and Bardet-Biedl syndrome 20. One patient, a homozygote for IFT172 rs780205001 c.167A>C p.(Lys56Thr) born to first cousins, had liver disease, interpreted on biopsy aged 4y as glycogen storage disease, followed by adult-onset nephronophthisis at 25y. The other, a compound heterozygote for novel frameshift variant IFT172 NM_015662.3 c.2070del p.(Met690Ilefs*11) and 2 syntenic missense variants IFT172 rs776310391 c.157T>A p.(Phe53Ile) and rs746462745 c.164C>G p.(Thr55Ser), had a severe 8mo cholestatic episode in early infancy, with persisting hyperbilirubinemia and fibrosis on imaging studies at 17y. No patient had skeletal malformations. CONCLUSION: Our findings suggest association of IFT172 variants with non-syndromic cholestatic liver disease.

A Current State of Proteomics in Adult and Pediatric Inflammatory Bowel Diseases: A Systematic Search and Review.

Inflammatory bowel diseases (IBD) are systemic immune-mediated conditions with predilection for the gastrointestinal tract and include Crohn's disease and ulcerative colitis. Despite the advances in the fields of basic and applied research, the etiopathogenesis remains largely unknown. As a result, only one third of the patients achieve endoscopic remission. A substantial portion of the patients also develop severe clinical complications or neoplasia. The need for novel biomarkers that can enhance diagnostic accuracy, more precisely reflect disease activity, and predict a complicated disease course, thus, remains high. Genomic and transcriptomic studies contributed substantially to our understanding of the immunopathological pathways involved in disease initiation and progression. However, eventual genomic alterations do not necessarily translate into the final clinical picture. Proteomics may represent a missing link between the genome, transcriptome, and phenotypical presentation of the disease. Based on the analysis of a large spectrum of proteins in tissues, it seems to be a promising method for the identification of new biomarkers. This systematic search and review summarize the current state of proteomics in human IBD. It comments on the utility of proteomics in research, describes the basic proteomic techniques, and provides an up-to-date overview of available studies in both adult and pediatric IBD.

Morphological aspects of small-duct cholangiopathies: A minireview.

The biliary system consists of intrahepatic and extrahepatic bile ducts lined by biliary epithelial cells (cholangiocytes). Bile ducts and cholangiocytes are affected by a variety of disorders called cholangiopathies, which differ in aetiology, pathogenesis, and morphology. Classification of cholangiopathies is complex and reflects pathogenic mechanisms (immune-mediated, genetic, drug- and toxin-induced, ischaemic, infectious, neoplastic), predominant morphological patterns of biliary injury (suppurative and non-suppurative cholangitis, cholangiopathy), and specific segments of the biliary tree affected by the disease process. While the involvement of large extrahepatic and intrahepatic bile ducts is typically visualised using radiology imaging, histopathological examination of liver tissue obtained by percutaneous liver biopsy still plays an important role in the diagnosis of cholangiopathies affecting the small intrahepatic bile ducts. To increase the diagnostic yield of a liver biopsy and determine the optimal therapeutic approach, the referring clinician is tasked with interpreting the results of histopathological examination. This requires knowledge and understanding of basic morphological patterns of hepatobiliary injury and an ability to correlate microscopic findings with results obtained by imaging and laboratory methods. This minireview describes the morphological aspects of small-duct cholangiopathies pertaining to the diagnostic process.

Serum and Mucosal CD30 in Pediatric Inflammatory Bowel Diseases: Useful Biomarker for Diagnosis and Disease Activity Monitoring?

BACKGROUND: Inflammatory bowel diseases (IBD) frequently manifest in pediatric age, but may have atypical clinical, histological and laboratory features. Their underlying immune pathophysiology is incompletely understood, rendering quick diagnosis followed by tailored therapy difficult. The tumor necrosis factor superfamily receptor CD30 has been proposed as a potential marker of ulcerative colitis (UC) and has also been associated with elevated Th2 helper T cells. METHODS: A cohort of pediatric patients with UC and Crohn's disease (CD) was evaluated for serum soluble CD30 (sCD30) using ELISA and expression of CD30 and subpopulations of Th1/Th2/Th17 lymphocytes in the gastrointestinal mucosa using flow cytometry (FCM). The dataset is supported by endoscopic and microscopic activity of the disease and basic laboratory markers of inflammation. RESULTS: The cohort consisted of 102 observations from 94 patients. sCD30 levels did not differ between patients with CD or UC. However, sCD30 levels correlated with levels of CRP, ESR, fecal calprotectin and albumin and also with clinical activity of the disease in patients with both UC and CD. FCM was not helpful in evaluation of mucosal CD30, which was lowly expressed and not associated with the diagnosis or disease activity. We show augmented Th2 and Th1/17 response in terminal ileum and right-sided colon and decreased Th1/17 response in left-sided colon of UC patients. T lymphocyte subsets were also affected by anti-TNF treatment and patients' age. CONCLUSIONS: Neither sCD30 nor mucosal CD30 expression was helpful in differentiating between UC and CD. sCD30 seems to reflect a degree of systemic inflammation and clinical activity in IBD.

Histopathological assessment of the microscopic activity in inflammatory bowel diseases: What are we looking for?

Advances in diagnostics of inflammatory bowel diseases (IBD) and improved treatment strategies allowed the establishment of new therapeutic endpoints. Currently, it is desirable not only to cease clinical symptoms, but mainly to achieve endoscopic remission, a macroscopic normalization of the bowel mucosa. However, up to one-third of IBD patients in remission exhibit persisting microscopic activity of the disease. The evidence suggests a better predictive value of histology for the development of clinical complications such as clinical relapse, surgical intervention, need for therapy escalation, or development of colorectal cancer. The proper assessment of microscopic inflammatory activity thus became an important part of the overall histopathological evaluation of colonic biopsies and many histopathological scoring indices have been established. Nonetheless, a majority of them have not been validated and no scoring index became a part of the routine bioptic practice. This review summarizes a predictive value of microscopic disease activity assessment for the subsequent clinical course of IBD, describes the most commonly used scoring indices for Crohn's disease and ulcerative colitis, and comments on current limitations and unresolved issues.

Structural Integrity and Cellular Viability of Cryopreserved Allograft Heart Valves in Right Ventricular Outflow Tract Reconstruction: Correlation of Histopathological Changes with Donor Characteristics and Preservation Times

Abstract Introduction: Cryopreserved allograft heart valves (CAHV) show longer event-free survival compared to other types of protheses. However, all patients develop early and/or late allograft failure. Negative predictors are clinical, and there is a lack of evidence whether they correspond with the microscopic structure of CAHV. We assessed histopathological signs of structural degeneration, degree of cellular preservation, and presence of antigen-presenting cells (APC) in CAHV and correlated the changes with donor clinical characteristics, cryopreservation times, and CAHV types and diameters. Methods: Fifty-seven CAHV (48 pulmonary, nine aortic) used for transplantation between November/2017 and May/2019 were included. Donor variables were age, gender, blood group, height, weight, and body surface area (BSA). Types and diameters of CAHV, cold ischemia time, period from decontamination to cryopreservation, and cryopreservation time were recorded. During surgery, arterial wall (n=56) and valvar cusp (n=20) samples were obtained from the CAHV and subjected to microscopy. Microscopic structure was assessed using basic staining methods and immunohistochemistry (IHC). Results: Most of the samples showed signs of degeneration, usually of mild degree, and markedly reduced cellular preservation, more pronounced in aortic CAHV, correlating with arterial APC counts in both basic staining and IHC. There was also a correlation between the degree of degeneration of arterial samples and age, height, weight, and BSA of the donors. These findings were independent of preservation times. Conclusion: CAHV show markedly reduced cellular preservation negatively correlating with the numbers of APC. More preserved CAHV may be therefore prone to stronger immune rejection.

Tuberculosis dissemination in kidney transplant recipient treated with anti-CD40 monoclonal antibody: a case report.

BACKGROUND: Tuberculosis (TBC) in solid organ transplant recipients represents a severe complication. The incidence among transplant recipients is higher than in the general population, and the diagnosis and treatment remain challenging. We present a case of active disseminated tuberculosis in a kidney transplant recipient treated with an anti-CD40 monoclonal antibody, who had been previously exposed to an active form of the disease, but latent tuberculosis (LTBI) was repeatedly ruled out prior to transplantation. To the best of our knowledge, no other case has been reported in a patient treated with the anti-CD40 monoclonal antibody. CASE PRESENTATION: A 49-year-old patient, 1.5 years after primary kidney transplantation, presented with vocal cord problems, a dry irritating cough, and a sore throat. A detailed investigation, including a high-resolution chest CT scan, revealed the diagnosis of disseminated tuberculosis. The antituberculosis treatment consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol was started immediately. The patient's condition became complicated by relapsing diarrhoea. The colonoscopy revealed a circular stenosis above Bauhin's valve. Microscopical findings showed active colitis and vaguely formed collections of epithelioid macrophages without fully developed caseous granulomas and were consistent with the clinical diagnosis of tuberculosis. The antituberculosis treatment was subsequently enhanced by moxifloxacin and led to a great improvement in the patient's condition. CONCLUSION: In this case, false negativity of interferon-γ release assays and possibly higher risk for intracellular infections in patients on costimulatory signal blockers are discussed.

The role of endoscopy in non-oncologic gastrointestinal disorders in pediatric patients.

Gastrointestinal (GIT) diseases represent an important part of pediatric health disorders. The recent years have brought not only significant improvement of digestive endoscopy technologies and a new equipment suitable for pediatric age but also progress in management of diagnostic approach and treatment of the pediatric GIT diseases. In contrast to adult patients, endoscopic examination in pediatrics is in most cases performed for diagnostic, not therapeutical purposes. The histological assessment of biopsy specimens taken during endoscopy therefore forms an integral part of the endoscopic examination and in most cases the diagnosis cannot be concluded without their evaluation. In particular, the clinical gastroenterologist expects from the pathologist a description that will help confirm or contradict the diagnosis considered after the macroscopic examination. In this review, we would like to highlight the most common endoscopic findings of the gastrointestinal tract in pediatric population and the role of histology in determining the correct diagnosis.

Histopathological diagnosis of colitis: differential diagnosis and interpretation.

Non-neoplastic inflammatory conditions of a large bowel mucosa are commonly encountered in bioptic practice. Their interpretation yields many challenges especially due to their limited and often non-specific and overlapping morphological spectrum. However, an accurate assessment of colonic biopsy still represents an important part of multidisciplinary diagnostic process and identification and subsequent interpretation of proper morphological pattern should be in a competence of any routine pathologist. This article provides systematic approach to histopathological assessment of inflammatory diseases of colonic mucosa, focusing mainly on diagnoses other than inflammatory bowel disease (IBD).

Morphology of inflammatory bowel diseases (IBD).

Inflammatory bowel diseases (IBD) represent a group of chronic systemic inflammatory conditions with predilection to gastrointestinal tract and include Crohns disease and ulcerative colitis. If the IBD cannot be further specified, a term unclassified IBD is used. Histopathological diagnosis of IBD relies on identifying a chronic inflammatory pattern in proper topographic distribution, showing structural abnormalities of the intestinal mucosa and characteristic cellular composition of the inflammatory infiltrate. The intestinal involvement in Crohns disease is typically segmental, with predilection for terminal ileum and presence of epithelioid granulomas in histology. Ulcerative colitis shows a diffuse pattern of the inflammation and usually affects a rectum, with variable extension towards a terminal ileum. However, there is an expanding knowledge about etiopathogenesis, morphology and clinical presentation of IBD, which led to detailed phenotypic subclassification and defined many atypical variants. As a result, diagnosis of IBD became complex multidisciplinary process. The aim of this work is to present an overview of IBD morphology and to provide a base for histopathological diagnosis of IBD on both bioptic samples and surgical resections.

Vascular Remodeling of Clinically Used Patches and Decellularized Pericardial Matrices Recellularized with Autologous or Allogeneic Cells in a Porcine Carotid Artery Model.

Background: Cardiovascular surgery is confronted by a lack of suitable materials for patch repair. Acellular animal tissues serve as an abundant source of promising biomaterials. The aim of our study was to explore the bio-integration of decellularized or recellularized pericardial matrices in vivo. Methods: Porcine (allograft) and ovine (heterograft, xenograft) pericardia were decellularized using 1% sodium dodecyl sulfate ((1) Allo-decel and (2) Xeno-decel). We used two cell types for pressure-stimulated recellularization in a bioreactor: autologous adipose tissue-derived stromal cells (ASCs) isolated from subcutaneous fat of pigs ((3) Allo-ASC and (4) Xeno-ASC) and allogeneic Wharton's jelly mesenchymal stem cells (WJCs) ((5) Allo-WJC and (6) Xeno-WJC). These six experimental patches were implanted in porcine carotid arteries for one month. For comparison, we also implanted six types of control patches, namely, arterial or venous autografts, expanded polytetrafluoroethylene (ePTFE Propaten® Gore®), polyethylene terephthalate (PET Vascutek®), chemically stabilized bovine pericardium (XenoSure®), and detoxified porcine pericardium (BioIntegral® NoReact®). The grafts were evaluated through the use of flowmetry, angiography, and histological examination. Results: All grafts were well-integrated and patent with no signs of thrombosis, stenosis, or aneurysm. A histological analysis revealed that the arterial autograft resembled a native artery. All other control and experimental patches developed neo-adventitial inflammation (NAI) and neo-intimal hyperplasia (NIH), and the endothelial lining was present. NAI and NIH were most prominent on XenoSure® and Xeno-decel and least prominent on NoReact®. In xenografts, the degree of NIH developed in the following order: Xeno-decel > Xeno-ASC > Xeno-WJC. NAI and patch resorption increased in Allo-ASC and Xeno-ASC and decreased in Allo-WJC and Xeno-WJC. Conclusions: In our setting, pre-implant seeding with ASC or WJC had a modest impact on vascular patch remodeling. However, ASC increased the neo-adventitial inflammatory reaction and patch resorption, suggesting accelerated remodeling. WJC mitigated this response, as well as neo-intimal hyperplasia on xenografts, suggesting immunomodulatory properties.

Structural Integrity and Cellular Viability of Cryopreserved Allograft Heart Valves in Right Ventricular Outflow Tract Reconstruction: Correlation of Histopathological Changes with Donor Characteristics and Preservation Times.

INTRODUCTION: Cryopreserved allograft heart valves (CAHV) show longer event-free survival compared to other types of protheses. However, all patients develop early and/or late allograft failure. Negative predictors are clinical, and there is a lack of evidence whether they correspond with the microscopic structure of CAHV. We assessed histopathological signs of structural degeneration, degree of cellular preservation, and presence of antigen-presenting cells (APC) in CAHV and correlated the changes with donor clinical characteristics, cryopreservation times, and CAHV types and diameters. METHODS: Fifty-seven CAHV (48 pulmonary, nine aortic) used for transplantation between November/2017 and May/2019 were included. Donor variables were age, gender, blood group, height, weight, and body surface area (BSA). Types and diameters of CAHV, cold ischemia time, period from decontamination to cryopreservation, and cryopreservation time were recorded. During surgery, arterial wall (n=56) and valvar cusp (n=20) samples were obtained from the CAHV and subjected to microscopy. Microscopic structure was assessed using basic staining methods and immunohistochemistry (IHC). RESULTS: Most of the samples showed signs of degeneration, usually of mild degree, and markedly reduced cellular preservation, more pronounced in aortic CAHV, correlating with arterial APC counts in both basic staining and IHC. There was also a correlation between the degree of degeneration of arterial samples and age, height, weight, and BSA of the donors. These findings were independent of preservation times. CONCLUSION: CAHV show markedly reduced cellular preservation negatively correlating with the numbers of APC. More preserved CAHV may be therefore prone to stronger immune rejection.

Predictive value of tissue calprotectin for disease recurrence after ileocecal resection in pediatric Crohn's disease.

AIM: Detection of possible predictive factors of endoscopic recurrence after ileocecal resection in Crohn's disease could be very beneficial for the individual adjustment of postoperative therapy. The aim of this study was to verify, whether immunohistochemical detection of calprotectin in resection margins is useful in diagnostics of endoscopic recurrence. METHODS: In this study we included pediatric patients with Crohn's disease who underwent ileocecal resection, regardless of pre-operative or post-operative therapy (n=48). We collected laboratory, clinical, surgical, endoscopic and histopathological data at the time of surgery and at 6 months after surgery. The immunohistochemical staining of calprotectin antigen was performed on all paraffin blocks from the resection margins. RESULTS: Out of 48 patients 52% had endoscopic recurrence in the anastomosis (defined by Rutgeerts score) within 6 months after surgery. The number of cells positive for calprotectin in the proximal resection margin was negatively associated with recurrence (P=0.008), as was the elevated level of total calprotectin (from both resection margins). There was no correlation of calprotectin in distal resection margin and endoscopic recurrence. Fecal calprotectin over 100 ug/g (P=0.0005) and high CRP (P<0.001) at 6 months after ileocecal resection and peritonitis (P=0.048) were associated with endoscopic recurrence. CONCLUSION: Approximately half of the patients developed endoscopic recurrence within 6 months after ileocecal resection. The predictive value of tissue calprotectin is questionable, as it is negatively associated with endoscopic recurrence. There are other potentially useful predictors, such as CRP and fecal calprotectin at 6 months after resection and the presence of peritonitis.

Determination of biological behavior of solitary fibrous tumors: correlation of expression of Ki-67, TPX2 and TERT mRNA subunit level and NAB2-STAT6 fusion compared to morphological aspects of SFTs.

We present a retrospective study of 65 cases of solitary fibrous tumors (SFTs) of several localizations including the most common site of origin in the pleura and lungs. SFTs are mesenchymal fibroblastic tumors with an unpredictable biological potential ranging from benign to malignant. We investigated morphologic characteristics, proliferation activity evaluated by immunohistochemical expression of Ki-67 antigen, and the existence of NAB2-STAT6 fusion gene together with Ki-67, TPX2, and TERT mRNA expression levels. The aim was to define relationships between proliferation activity and biological potential and progression of the disease. We measured Ki-67, TPX2, and TERT mRNA levels using quantitative real-time reverse transcription PCR (RQ-RT-PCR). We observed a significant association between increased Ki-67 and TERT mRNA levels and the SFTs with malignant potential. Also, we investigated the effect of TERT promoter mutation on telomerase activation and patient outcome in our SFT cohort. We verified that TERT promoter mutation was frequent (36.6%) and present in a majority of malignant SFTs and SFTs with uncertain biological behavior. TERT promoter mutation alone predicted the disease recurrence.

Alpha-1 Antitrypsin and Hepatocellular Carcinoma in Liver Cirrhosis: SERPINA1 MZ or MS Genotype Carriage Decreases the Risk.

Heterozygotes for Z or S alleles of alpha-1-antrypsin (AAT) have low serum AAT levels. Our aim was to compare the risk of hepatocellular carcinoma (HCC) in patients with liver cirrhosis carrying the SERPINA1 MM, MZ and MS genotypes. The study groups consisted of 1119 patients with liver cirrhosis of various aetiologies, and 3240 healthy individuals served as population controls. The MZ genotype was significantly more frequent in the study group (55/1119 vs. 87/3240, p < 0.0001). The MS genotype frequency was comparable in controls (32/119 vs. 101/3240, p = 0.84). MZ and MS heterozygotes had lower serum AAT level than MM homozygotes (medians: 0.90 g/L; 1.40 g/L and 1.67 g/L; p < 0.001 for both). There were significantly fewer patients with HCC in the cirrhosis group among MZ and MS heterozygotes than in MM homozygotes (5/55 and 1/32 respectively, vs. 243/1022, p < 0.01 for both). The risk of HCC was lower in MZ and MS heterozygotes than in MM homozygotes (OR 0.3202; 95% CI 0.1361-0.7719 and OR 0.1522; 95% CI 0.02941-0.7882, respectively). Multivariate analysis of HCC risk factors identified MZ or MS genotype carriage as a protective factor, whereas age, male sex, BMI and viral aetiology of cirrhosis increased HCC risk.

Giant cell myocarditis in young woman diagnosed at the autopsy: a case report.

Giant cell myocarditis (GCM) is a rare inflammatory disease of the heart that often affects younger patients. The clinical course is typically rapid with fulminant congestive heart failure. Prognosis is poor; the proper diagnosis is often rendered at the autopsy. Herein, we present a prototypical case of this rare type of myocarditis, affecting a 44-year-old previously healthy woman who was referred to the intensive care department due to an acute onset cardiac arrest followed by resuscitation. The heart ultrasound and imaging examinations revealed a severe dysfunction and dilatation of both ventricles, without any significant finding in the coronary arteries. Twelve days after the initial presentation, the patient died due to congestive heart failure refractory to intensive therapy. The post-mortem histology of the heart revealed multiple small necrotic foci in the myocardium in both ventricles, with dense inflammatory infiltration with abundant multinucleated giant histiocytes, in line with a diagnosis of GCM. The natural history, pathophysiology, and histological differential diagnosis is discussed, together with review of the relevant literature including uncommon and emerging units.