Recurrent Infective Endocarditis of the Mitral Valve after Orthotopic Heart Transplantation.

Introduction: Orthotopic heart transplantation is the gold standard for the treatment of advanced heart failure in the absence of contraindications. Infective endocarditis is a rare complication in patients after heart transplantation. The treatment of endocarditis after heart transplantation is challenging since there is a need for ongoing immunosuppression. Case description: We present the case of a 51-year-old orthotopic heart transplant recipient enrolled in a chronic dialysis program, in whom we diagnosed and successfully treated recurrent infective endocarditis of the mitral valve caused by Enterococcus and Enterobacter species. Despite the complicated course of the disease, the treatment was successful. Conclusions: Recurrent infective endocarditis after heart transplantation can be treated successfully with a multidisciplinary approach and robust antimicrobial therapy. LEARNING POINTS: There is a high risk of bacteraemia and subsequent endocarditis in patients with recurrent catheter-related sepsis.The spectrum of bacteria causing endocarditis in patients after heart transplantation differs from that in the general population.Scrupulous targeted antibiotic treatment is warranted for the treatment of immunosuppressed patients with endocarditis.

CT quantification of COVID-19 pneumonia extent to predict individualized outcome.

OBJECTIVES:  This study aimed to predict individual COVID-19 patient prognosis at hospital admission using artificial intelligence (AI)-based quantification of computed tomography (CT) pulmonary involvement. BACKGROUND: Assessing patient prognosis in COVID-19 pneumonia is crucial for patient management and hospital and ICU organization. METHODS: We retrospectively analyzed 559 patients with PCR-verified COVID-19 pneumonia referred to the hospital for a severe disease course. We correlated the CT extent of pulmonary involvement with patient outcome. We also attempted to define cut-off values of pulmonary involvement for predicting different outcomes. RESULTS:  CT-based disease extent quantification is an independent predictor of patient morbidity and mortality, with the prognosis being impacted also by age and cardiovascular comorbidities. With the use of explored cut-off values, we divided patients into three groups based on their extent of disease: (1) less than 28 % (sensitivity 65.4 %; specificity 89.1 %), (2) ranging from 28 % (31 %) to 47 % (sensitivity 87.1 %; specificity 62.7 %), and (3) above 47 % (sensitivity 87.1 %; specificity, 62.7 %), representing low risk, risk for oxygen therapy and invasive pulmonary ventilation, and risk of death, respectively. CONCLUSION: CT quantification of pulmonary involvement using AI-based software helps predict COVID-19 patient outcomes (Tab. 4, Fig. 4, Ref. 38).

Photon-counting CT using multi-material decomposition algorithm enables fat quantification in the presence of iron deposits.

PURPOSE: A new generation of CT detectors were recently developed with the ability to measure individual photon's energy and thus provide spectral information. The aim of this work was to assess the performance of simultaneous fat and iron quantification using a clinical photon-counting CT (PCCT) and its comparison to dual-energy CT (DECT), MRS and MRI at 3 T. METHODS: Two 3D printed cylindrical phantoms with 32 samples (n = 12 fat fractions between 0 % and 100 %, n = 20 with mixtures of fat and iron) were scanned with PCCT and DECT scanners for comparison. A three-material decomposition approach was used to estimate the volume fractions of fat (FF), iron and soft tissue. The same phantoms were examined by MRI (6-echo DIXON, a.k.a. Q-DIXON) and MRS (multi-echo STEAM, a.k.a. HISTO) at 3 T for comparison. RESULTS: PCCT, DECT, MRI and MRS computed FFs showed correlation with reference fat fraction values in samples with no iron (r > 0.98). PCCT decomposition showed slightly weaker correlation with FFref in samples with added iron (r = 0.586) compared to MRI (r = 0.673) and MRS (r = 0.716) methods. On the other hand, it showed no systematic over- or underestimation. Surprisingly, DECT decomposition-derived FF showed strongest correlation (r = 0.758) in these samples, however systematic overestimation was observed. FF values computed by three-material PCCT decomposition, DECT decomposition, MRI and MRS were unaffected by iron concentration. CONCLUSIONS: This in-vitro study shows for the first time that photon-counting computed tomography may be used for quantification of fat content in the presence of iron deposits.

Sex differences in long-term effects of collagen-induced arthritis in middle-aged mice.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disorder with high prevalence among middle-aged women. Collagen-induced arthritis (CIA) is the most widely used animal model of RA, however, sex differences and long-term effects of CIA in mice are poorly described in the literature. Aim: Therefore, the present study aimed to analyze the long-term effects of CIA on the joints of middle-aged mice of both sexes and to describe potential sex differences. Materials and methods: CIA was induced in middle-aged DBA/1J mice by immunization with bovine type II collagen and complete Freund's adjuvant. Saline was administered to control mice. Arthritis score assessment, plethysmometry, and thermal imaging of the joints were performed weekly for 15 weeks. Locomotor activity, micro-computed tomography, joint histology and biochemical analyses were performed at the end of the experiment. Results: Our results indicate a similar prevalence of arthritis in both sexes of mice-67% (8/12) of females and 89% (8/9) males with an earlier onset in males (day 14 vs. day 35). After the arthritis scores peaked on day 56 for males and day 63 for females, they steadily declined until the end of the experiment on day 105. A similar dynamics was observed in paw volume and temperature analyzing different aspects of joint inflammation. Long-term consequences including higher proteinuria (by 116%), loss of bone density (by 33.5%) and joint damage in terms of synovial hyperplasia as well as bone and cartilage erosions were more severe in CIA males compared to CIA females. There were no significant differences in locomotor activity between CIA mice and CTRL mice of any sex. Conclusion: This is the first study to describe the long-term effects of the CIA model in terms of sex differences in DBA/1J mice. Our results indicate sex differences in the dynamics, but not in the extent of arthritis. An earlier onset of arthritis and more severe consequences on joints, bones and kidneys were found in males. The underlying immune pathomechanisms responsible for the limited duration of the arthritis symptoms and the opposite sex difference in comparison to RA patients require further investigation.

Lung Cancer Screening Initiative in Slovakia: Guidelines of screening implementation.

Lung cancer (LC) represents a major healthcare issue worldwide. It is the leading cause of cancer-related mortality in Slovakia and European Union. Data from multiple randomized controlled trials have shown significant evidence of a mortality benefit in LC using screening with low-dose computed tomography of the chest (LDCT). Therefore, European healthcare authorities, relevant expert societies, and professional organizations recommend implementing national LC screening (LCS) programs in their member countries. This article outlines the basic methodology, guidelines, and practical aspects of LCS implementation strategies in Slovakia. We describe fundamental principles to identify asymptomatic high-risk patients reduce false positive and false negative results, decrease benign resection rates, and avoid unnecessary invasive procedures. The efficacious utilization of public resources to secure the highest possible quality standards of LDCT plays a crucial role in successfully implementing a nationwide LCS program (Tab. 1, Fig. 4, Ref. 31). Text in PDF www.elis.sk Keywords: lung cancer, screening, early detection, smoking cessation.

An EGFR-mutant lung adenocarcinoma that transformed into small-cell lung cancer. A case report.

BACKGROUND: Transformation of EGFR (epidermal growth factor receptor) - mutant non-small cell lung cancer (NSCLC) into small-cell lung cancer (SCLC) is one mechanism of resistance to tyrosine kinase inhibitor (TKI) treatment, seen in approximately 3-10% cases. Such transformed SCLC often retains the original EGFR mutation (EGFRM), which is not otherwise observed in SCLC. CASE REPORT: We present a 67 y/o woman with pulmonary adenocarcinoma (AC) and EGFRM deletion on exon 19. After initial treatment with whole brain radiotherapy and 7 months of TKI afatinib, progression was observed. Liquid biopsy detected deletion on exon 19 and T790M mutation. Chemotherapy carboplatin plus pemetrexed was administered, with no response. Genetics from a rebiopsy of lung revealed deletion on exon 19. After 12 months treatment with TKI osimertinib, a progression in lung and pancreas lesions was detected, docetaxel was used, with followig progression. The lung biopsy revealed SCLC. Significant elevation of serum markers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) was observed at the time of the SCLC diagnosis. Treatment with carboplatin and etoposide was not effective. The next biopsy found two populations of cells: SCLC and AC. The biopsy from the pancreatic lesion revealed metastasis of SCLC. PCR confirmed EGFRM deletion on exon 19 in the lung SCLC tissue sample. The following treatment lines of topotecan, erlotinib were not effective. The patient survived 36 months from diagnosis, 7 months from detection of SCLC. CONCLUSION: Screening for transformation of EGFR-mutant NSCLC to SCLC should be considered in resistance to TKI. In the presented case, this rare transformation was confirmed by histopathologic examination and by PCR. EGFRM in the lung SCLC, identical to that found in the original lung AC, was detected. Further, the observed elevation of serum tumor markers NSE and CEA can indicate this infrequent transformation and help to decide on rebiopsy.

Diagnostic performance of edited 2HG MR spectroscopy of central glioma in the clinical environment.

OBJECTIVE: Oncometabolite D-2-hydroxyglutarate (2HG) is pooled in isocitrate dehydrogenase (IDH)-mutant glioma cells. Detecting 2HG by MR spectroscopy (MRS) has been proven viable in the last decade but has not entirely found its way into the clinical routine. This study aimed to explore the adoption of 2HG MRS while acknowledging factors that influence its performance in the clinical environment. METHODS: Thirty-nine MR spectra were acquired and reported prospectively in patients with suspected glioma using a 3 T system with Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence utilizing averaged free induction decay (FID) signals. Postprocessing and evaluation of spectra were performed with jMRUI and LCModel. 2HG concentration estimates, 2HG/Cr ratio, together with quality measures, including Cramér-Rao lower bounds (CRLBs), full-width at half-maximum (FWHM) values, and signal-to-noise ratio (SNR) were calculated using LCModel. Immunohistochemistry and genomic analysis results used as a ground truth were available for 15 patients. RESULTS: The threshold for test positivity was set according to the ROC curve at 1 mM. Calculated sensitivity was 57.14% (95% CI 0.20-0.88), specificity 87.5% (95% CI 0.46-0.99), positive predictive value 80%, and negative predictive value 70%. Overall diagnostic accuracy was 73.33% (95% CI 0.45-0.92). The 2HG/Cr ratio with the cutoff value 0.085 significantly improved sensitivity and overall diagnostic accuracy [85.71%, 95% CI 0.42-1.00 and 86.67%, (95% CI 0.60-0.98), respectively]. CONCLUSION: Multiple factors compromising spectral quality in the clinical adoption of edited 2HG MRS resulted in diminished sensitivity but clinically acceptable specificity. Furthermore, the 2HG/Cr ratio performs better than the sole 2HG concentration estimate in the pre-operative setting.

Dual-energy Computed Tomography Delayed Myocardial Enhancement in the Diagnostic Dilemma of True versus False Left Ventricular Aneurysm - A Case Report.

The aim of this case report is to show the capability of cardiac computed tomography (CT) in combination with dual-energy CT (DECT) delayed myocardial enhancement to support diagnostic decision making in the complicated differential diagnosis of true versus false left ventricle (LV) aneurysm, as well as provide additional information that can influence overall patient outcome. We present a 71-year-old obese patient with metabolic syndrome, stable chronic coronary syndrome with three-vessel disease, and recent chest discomfort. His coronary angiogram showed no significant coronary artery stenosis, but suspicion of LV apical pseudoaneurysm was expressed. Neither transthoracic nor transesophageal echocardiography was able to dismiss this suspicion. Consequently, coronary CT angiography (CCTA) followed by DECT delayed myocardial enhancement was performed. Findings on CCTA and DECT confirmed the diagnosis of a true aneurysm. Moreover, fibrotic changes within the hypertrophic myocardium were visualized. This finding will influence further patient therapy as well as the outcome. DECT delayed myocardial enhancement can be an important complementary tool for distinguishing true versus false LV aneurysms. Moreover, it can provide additional information for making complex diagnose. Adding DECT delayed myocardial enhancement to CCTA can replace cardiac magnetic resonance imaging evaluation in certain settings.

RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients.

RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia. Many non-p.R4810K rare variants of RNF213 have been identified in white moyamoya disease patients, although the ethnic mutations have not been investigated in this population. In the present study, we screened for RNF213 variants in 19 Slovakian and Czech moyamoya disease patients. A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic. We previously reported one proband harboring RNF213 p.D4013N. Results from the present study identified four rare variants other than p.D4013N (p.R4019C, p.E4042K, p.V4146A, and p.W4677L) in four of the patients. P.V4146A was determined to be a novel de novo mutation, and p.R4019C and p.E4042K were identified as double mutations inherited on the same allele. P.W4677L, found in two moyamoya disease patients and an unaffected subject in the same pedigree, was a rare single nucleotide polymorphism. Functional analysis showed that RNF213 p.D4013N, p.R4019C and p.V4146A-transfected human umbilical vein endothelial cells displayed significant lowered migration, and RNF213 p.V4146A significantly reduced tube formation, indicating that these are disease-causing mutations. Results from the present study identified RNF213 rare variants in 22.2% (4/18 probands) of Slovakian and Czech moyamoya disease patients, confirming that RNF213 may also be a major causative gene in a relative large population of white patients.