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.

• MeSH
• algoritmy * MeSH
• biopsie MeSH
• lidé MeSH
• patologové MeSH
• transplantace srdce * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Recurrence of immunoglobulin A nephropathy (IgAN) limits graft survival in kidney transplantation. However, predictors of a worse outcome are poorly understood. METHODS: Among 442 kidney transplant recipients (KTRs) with IgAN, 83 (18.8%) KTRs exhibited biopsy-proven IgAN recurrence between 1994 and 2020 and were enrolled in the derivation cohort. A multivariable Cox model predicting allograft loss based on clinical data at the biopsy and a web-based nomogram were developed. The nomogram was externally validated using an independent cohort (n = 67). RESULTS: Patient age <43 years {hazard ratio [HR] 2.20 [95% confidence interval (CI) 1.41-3.43], P < .001}, female gender [HR 1.72 (95% CI 1.07-2.76), P = .026] and retransplantation status [HR 1.98 (95% CI 1.13-3.36), P = .016] were identified as independent risk factors for IgAN recurrence. Patient age <43 years [HR 2.77 (95% CI 1.17-6.56), P = .02], proteinuria >1 g/24 hours [HR 3.12 (95% CI 1.40-6.91), P = .005] and C4d positivity [HR 2.93 (95% CI 1.26-6.83), P = .013] were found to be associated with graft loss in patients with IgAN recurrence. A nomogram predicting graft loss was constructed based on clinical and histological variables, with a C statistic of 0.736 for the derivation cohort and 0.807 for the external validation cohort. CONCLUSIONS: The established nomogram identified patients with recurrent IgAN at risk for premature graft loss with good predictive performance.

• MeSH
• alografty patologie   MeSH
• dospělí MeSH
• IgA nefropatie * komplikace   chirurgie   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• nomogramy MeSH
• přežívání štěpu MeSH
• prognóza MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• antigen Ki-67 genetika   MeSH
• imunohistochemie MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• messenger RNA genetika   MeSH
• nádorové biomarkery genetika   MeSH
• proteiny asociované s mikrotubuly MeSH
• proteiny buněčného cyklu MeSH
• represorové proteiny MeSH
• retrospektivní studie MeSH
• solitární fibrózní tumory * genetika   MeSH
• telomerasa * genetika   MeSH
• transkripční faktor STAT6 genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dermatitis herpetiformis * MeSH
• imunoglobulin A MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

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.

• MeSH
• antituberkulotika terapeutické užití   MeSH
• antitumorózní látky * MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• příjemce transplantátu MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• tuberkulóza * diagnóza   farmakoterapie   epidemiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• ANCA-asociované vaskulitidy diagnóza   farmakoterapie   MeSH
• aortální chlopeň diagnostické zobrazování   chirurgie   MeSH
• aortální insuficience diagnostické zobrazování   chirurgie   MeSH
• aplikace orální MeSH
• dítě MeSH
• lidé MeSH
• methylprednisolon aplikace a dávkování   terapeutické užití   MeSH
• počítačová rentgenová tomografie metody   MeSH
• prednison aplikace a dávkování   terapeutické užití   MeSH
• rituximab aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Cholangiocarcinoma (CCA) is a liver malignancy associated with a poor prognosis. Its main subtypes are peripheral/intrahepatic and hilar/extrahepatic CCA. Several molecular, morphological and clinical similarities between hilar/extrahepatic CCA and pancreatic ductal adenocarcinoma (PDAC) have been described. FOXF1 is a transcription factor which has been described to have prognostic significance in various tumors and it is involved in the development of bile ducts. The aim of this study is to determine occurrence of nuclear expression of FOXF1 in both subtypes of CCA and metastatic PDAC and assess its potential usefulness as a diagnostic marker. Secondary aims were to investigate the use of C-reactive protein (CRP) immunohistochemistry for diagnosing intrahepatic peripheral CCA and the significance of histological features in CCA subtypes. 32 archive specimens of CCA, combined hepatocellular carcinoma-CCA (HCC-CCA) and liver metastasis of PDAC were stained by FOXF1 and CRP immunohistochemistry and evaluated to determine histological pattern. The CCAs were classified radiologically into peripheral/intrahepatic and hilar subtype. Using Fisher exact test, we identified nuclear FOXF1 as a fairly specific (87%) but insensitive (65%) marker of hilar and extrahepatic CCA and metastatic PDAC (p = 0.005). CRP immunohistochemistry was characterized by a high sensitivity and specificity, of 79% and 88%, respectively (p = 0.001). We did not identify any histomorphological features associated with either types of CCA or metastatic PDAC. As a conclusion of novel finding, FOXF1 immunohistochemistry may be regarded as a specific but insensitive marker of hilar/extrahepatic CCA and metastatic PDAC and it may help distinguish them from peripheral CCA.

• MeSH
• dospělí MeSH
• duktální karcinom pankreatu metabolismus   sekundární   MeSH
• forkhead transkripční faktory metabolismus   MeSH
• hepatocelulární karcinom metabolismus   patologie   MeSH
• imunohistochemie MeSH
• Klatskinův nádor metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory jater metabolismus   sekundární   MeSH
• nádory slinivky břišní metabolismus   patologie   MeSH
• nádory žlučových cest metabolismus   patologie   MeSH
• následné studie MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

ALK-fused spitzoid neoplasms represent a distinctive group of melanocytic lesions. To date, few studies addressed genetic and chromosomal alterations in these lesions beyond the ALK rearrangements. Our objective was to study genetic alterations, including ALK gene fusions, telomerase reverse transcriptase promoter (TERT-p) mutations, chromosomal copy number changes, and mutations in other genes. We investigated 29 cases of Spitz lesions (11 Spitz nevi and 18 atypical Spitz tumors), all of which were ALK immunopositive. There were 16 female and 13 male patients, with age ranging from 1 to 43 years (mean, 18.4 years). The most common location was the lower extremity. Microscopically, all neoplasms were polypoid or dome shaped with a plexiform, predominantly dermally located proliferation of fusiform to spindled melanocytes with mild to moderate pleomorphism. The break-apart test for ALK was positive in 17 of 19 studied cases. ALK fusions were detected in 23 of 26 analyzable cases by Archer FusionPlex Solid Tumor Kit. In addition to the previously described rearrangements, 3 novel fusions, namely, KANK1-ALK, MYO5A-ALK, and EEF2-ALK, were found. Fluorescence in situ hybridization for copy number changes yielded one case with the loss of RREB1 among 21 studied cases. TERT-p hotspot mutation was found in 1 of 23 lesions. The mutation analysis of 271 cancer-related genes using Human Comprehensive Cancer Panel was performed in 4 cases and identified in each case mutations in several genes with unknown significance, except for a pathogenic variant in the BLM gene. Our study confirms that most ALK fusion spitzoid neoplasms can be classified as atypical Spitz tumors, which occurs in young patients with acral predilection and extends the spectrum of ALK fusions in spitzoid lesions, including 3 hitherto unreported fusions. TERT-p mutations and chromosomal copy number changes involving 6p25 (RRB1), 11q13 (CCND1), 6p23 (MYB), 9p21 (CDKN2A), and 8q24 (MYC) are rare in these lesions. The significance of mutation in other genes remains unknown.

• MeSH
• anaplastická lymfomová kináza genetika   MeSH
• dítě MeSH
• dospělí MeSH
• epiteloidní a vřetenobuněčný névus genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• mutační analýza DNA metody   MeSH
• nádory kůže genetika   patologie   MeSH
• onkogenní fúze genetika   MeSH
• předškolní dítě MeSH
• promotorové oblasti (genetika) genetika   MeSH
• sekvenční analýza DNA MeSH
• telomerasa genetika   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Spitz tumors represent a heterogeneous group of melanocytic neoplasms with a spectrum of biological behavior ranging from benign (Spitz nevus) to malignant (spitzoid melanoma). Prediction of the behavior of these lesions based on their histological presentation is not always possible. Recently, mutually exclusive activating kinase fusions, involving ALK, NTRK1, NTRK3, RET, MET, ROS1, and BRAF, have been found in a subset of spitzoid lesions. Some of these genetic alterations were associated with specific morphological features. Here, we report the histological presentation of 6 Spitz tumors with ROS1 fusion. The age of the patients ranged from 6 to 34 years, with strong female prevalence (5:1). All neoplasms were compound melanocytic proliferations with a predominant dermal growth but a conspicuous junctional component displaying atypical microscopic features qualifying them as atypical Spitz tumor. FIP1L1 and CAPRIN1 were identified as 2 novel 5'-fusion partners of ROS1 along with the known PWWP2A-ROS1 fusion. FISH for copy number changes of 9p21, 6p25, and 11q13 was negative in all but 1 neoplasm harboring isolated gain of 8q24. TERT-promoter hotspot mutation analysis was negative in all tumors. All patients are disease-free after a mean follow-up period of 30 months. It is concluded that ROS1-fused spitzoid neoplasms seem to have no distinctive histopathological features although consistent findings were spindled melanocytes arranged in confluent whorling nests, prominent transepidermal elimination of melanocytic nests, and myxoid/mucinous changes.

• MeSH
• chromozomální proteiny, nehistonové genetika   MeSH
• dítě MeSH
• dospělí MeSH
• epiteloidní a vřetenobuněčný névus genetika   patologie   MeSH
• faktory štěpení a polyadenylace mRNA genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• melanom genetika   patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutační analýza DNA MeSH
• nádory kůže genetika   patologie   MeSH
• onkogenní fúze MeSH
• proteiny buněčného cyklu genetika   MeSH
• protoonkogenní proteiny genetika   MeSH
• telomerasa genetika   MeSH
• tyrosinkinasy genetika   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND & AIMS: MiR-33a has emerged as a critical regulator of lipid homeostasis in the liver. Genetic deficiency of miR-33a aggravates liver steatosis in a preclinical model of non-alcoholic fatty liver disease (NAFLD), and relative expression of miR-33a is increased in the livers of patients with non-alcoholic steatohepatitis (NASH). It was unknown whether miR-33a is detectable in the serum of patients with NAFLD. We sought to determine whether circulating miR-33a is associated with histological hepatic steatosis, inflammation, ballooning or fibrosis, and whether it could be used as a serum marker in patients with NAFLD/NASH. METHODS: We analysed circulating miR-33a using quantitative PCR in 116 liver transplant recipients who underwent post-transplant protocol liver biopsy. Regression analysis was used to determine association of serum miR-33a with hepatic steatosis, inflammation, ballooning and fibrosis in liver biopsy. RESULTS: Liver graft steatosis and inflammation, but not ballooning or fibrosis, were significantly associated with serum miR-33a, dyslipidemia and insulin resistance markers on univariate analysis. Multivariate analysis showed that steatosis was independently associated with serum miR-33a, ALT, glycaemia and waist circumference, whereas inflammation was independently associated with miR-33a, HbA1 and serum triglyceride levels. Receiver operating characteristic analysis showed that exclusion of serum miR-33a from multivariate analysis resulted in non-significant reduction of prediction model accuracy of liver steatosis or inflammation. CONCLUSIONS: Our data indicate that circulating miR-33a is an independent predictor of liver steatosis and inflammation in patients after liver transplantation. Although statistically significant, its contribution to the accuracy of prediction model employing readily available clinical and biochemical variables was limited in our cohort.

• MeSH
• biologické markery MeSH
• biopsie MeSH
• cirkulující mikroRNA MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   genetika   MeSH
• nealkoholová steatóza jater krev   etiologie   metabolismus   patologie   MeSH
• ROC křivka MeSH
• senioři MeSH
• transplantace jater * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH