Bal kamrai deformáció cardialis könnyűlánc-amyloidosisban és hypereosinophilia-szindrómában. Eredmények a MAGYAR-Path Tanulmányból = Left ventricular deformation in cardiac light-chain amyloidosis and hypereosinophilic syndrome Results from the MAGYAR-Path Study

Absztrakt: Bevezetés: A hypereosinophilia-szindróma (HES) és az immunglobulinkönnyűlánc-amyloidosis (ALA) két ritka hematológiai betegség, melyek cardialis eltérésekkel járnak együtt. Célkitűzés: A jelen vizsgálat célja a HES- és ALA-betegek bal kamrai (BK-i) deformációs paramétereinek összehasonlító vizsgálata volt háromdimenziós speckle-tracking echokardiográfia (3DSTE) segítségével. Módszer: A vizsgálatok során 10 HES-beteg (átlagos életkor: 60,9 ± 14,7 év) és 19 ALA-ban szenvedő páciens (átlagos életkor: 63,4 ± 7,8 év, 13 férfi) eredményeit elemeztük. Kontrollcsoportként 13, korban és nemben egyeztetett, egészséges felnőtt szolgált (átlagos életkor: 59,2 ± 4,3 év, 5 férfi). Valamennyi esetben teljes körű kétdimenziós Doppler-echokardiográfiás vizsgálat készült 3DSTE-vel kiegészítve. Eredmények: A kontrollcsoporthoz képest az ALA-betegcsoportban mért valamennyi basalis szegmentális BK-i strain szignifikánsan alacsonyabbnak mutatkozott. Az ALA-betegek globális és átlagolt szegmentális BK-i longitudinális strain (LS) értékei az egészséges kontrollcsoporthoz hasonlítva szignifikánsan alacsonyabbnak bizonyultak. A HES-betegcsoport és az egészséges kontrollok összehasonlítása során szignifikáns különbséget tapasztaltunk a globális BK-LS tekintetében, míg a szegmentális basalis BK-LS is szignifikánsan alacsonyabbnak bizonyult a HES-betegekben. A HES- és az ALA-betegcsoport értékeit összehasonlítva a basalis BK-i radiális és 3D strain mutatott szignifikáns eltérést. Következtetések: A 3DSTE alkalmas módszer a HES- és az ALA-betegcsoportban a BK-i deformációs mechanika részletes vizsgálatára. Mindkét betegcsoportban jelentős deformációs eltérések tapasztalhatók, ALA fennállása esetén az eltérések kifejezettebbek. Orv Hetil. 2020; 161(5): 169–176. | Abstract: Introduction: Hypereosinophilic syndrome (HES) and immunoglobulin light-chain amyloidosis (ALA) are two, rare haematological disorders associated with cardiac alterations. Aim: The goal of the present study was a comparative assessment of left ventricular (LV) deformational parameters in HES and ALA patients using three-dimensional speckle-tracking echocardiography (3DSTE). Method: In the present study, results of 10 HES patients (mean age: 60.9 ± 14.7 years) and 19 ALA patients (mean age: 63.4 ± 7.8 years, 13 males) were analysed. The control group contained 13 age- and gender-matched healthy adults (mean age: 59.2 ± 4.3 years, 5 males). All patients underwent a complete two-dimensional Doppler echocardiography followed by 3DSTE. Results: All basal segmental LV strains were significantly reduced in ALA patients as compared to the control group. Global and mean segmental LV longitudinal strain (LS) values of ALA patients proved to be significantly decreased as compared to those of the healthy control group. During comparison of HES patients and healthy controls, significant difference could be detected in global LV-LS, while segmental basal LV-LS was also significantly reduced in HES patients. Basal LV radial and 3D strains showed significant differences when parameters of HES and ALA patient groups were compared. Conclusion: 3DSTE is a feasible tool for the detailed assessment of LV deformation in HES and ALA patients. Significant LV deformational abnormalities could be detected in both groups. In the case of ALA, these abnormalities are more prominent. Orv Hetil. 2020; 161(5): 169–176

The relationship between atherosclerosis and gut microbiome in patients with obstructive sleep apnoea

Background: Obstructive sleep apnoea (OSA) and gut dysbiosis are known risk factors for atherosclerosis. However, only very few studies have been focused on the relationship between OSA, atherosclerosis, and the intestinal microbiome, all in animal models. Methods: Twenty-two patients with OSA, 16 with and 6 without carotid atherosclerosis were involved in the study. After a diagnostic sleep examination, the intima media thickness (IMT) was measured and plaques were found using carotid ultrasound. Blood was also drawn for metabolic profile, and a stool sample was provided for 16S ribosomal RNA microbiome investigation. Results: An increased maximal common carotid artery (CCA) IMT was significantly associated with decreased phylum-level diversity. The level of Peptostreptococcaceae was significantly lower in atherosclerotic subjects. Some other candidate microbes appeared in the two groups at the genus level as well: Bilophila, Romboutsia, Slackia, and Veillonella in the non-atherosclerotic group; and Escherichia-Shigella, Prevotella, and Ruminococcaceae in the atherosclerotic group. Conclusions: This is the first pilot research to analyze the association between the gut microbiome and atherosclerosis in adult patients with OSA with and without carotid atherosclerosis. Dysbiosis and individual bacteria may contribute to the development of carotid atherosclerosis in patients with OSA. Further investigations are necessary to reveal a more precise background in a larger sample

Overlapping Genetic Background of Coronary Artery and Carotid/Femoral Atherosclerotic Calcification

Background and objectives: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries’ atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet. Materials and Methods: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries. Results: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 [95% CI: 0.37–1] and 0.69 [95% CI: 0.38–1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0–0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 [95% CI: 0.30–0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42–1]. Conclusions: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization

Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy

Background: Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy. Methods: 505 Caucasian stage III-IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed. Results: Among 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS (P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status (P = 0.018). Importantly, however, G12V KRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes (P = 0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P = 0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233 days; versus 175 days in the G12x group; P = 0.145). Conclusions: While KRAS mutation status per se is neither prognostic nor predictive in stage III-IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions. © 2014 The Authors