Genetic and environmental determinants of bone quality: a cross-sectional analysis of the Hungarian Twin Registry.

There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80% additive genetic heritability. Adjustment for age, sex, BMI and smoking status improved model fit with 48.0% of total variance explained by independent variables. Furthermore, there was a strong dominant genetic effect (73.7%). In contrast, unadjusted and adjusted models for QUI showed an AE structure. Adjustments improved model fit and 25.7% of the total variance was explained by independent variables. Altogether 70-90% of the variance in QUI was related to additive genetic influences. We found a strong genetic heritability of bone quality in unadjusted models. Half of the variance of TBS was explained by age, sex and BMI. Furthermore, the adjusted model suggested that the genetic component of TBS could be dominant or an epistasis could be present. In contrast, independent variables explained only a quarter of the variance of QUI and the additive heritability explained more than half of all the variance.

The Population-Based Hungarian Twin Registry: An Update.

Between 2006 and 2021, the Hungarian Twin Registry (HTR) operated a volunteer twin registry of all age groups (50% monozygotic [MZ], 50% dizygotic [DZ], 70% female, average age 34 ± 22 years), including 1044 twin pairs, 24 triplets and one quadruplet set. In 2021, the HTR transformed from a volunteer registry into a population-based one, and it was established in the Medical Imaging Centre of Semmelweis University in Budapest. Semmelweis University's innovation fund supported the development of information technology, a phone bank and voicemail infrastructure, administrative materials, and a new website was established where twins and their relatives (parent, foster parent or caregiver) can register. The HTR's biobank was also established: 157,751 individuals with a likely twin-sibling living in Hungary (77,042 twins, 1194 triplets, 20 quadruplets, and one quintuplet) were contacted between February and March of 2021 via sealed letters. Until November 20, 2022, 12,001 twin individuals and their parents or guardians (6724 adult twins, 3009 parents/guardians and 5277 minor twins) registered, mostly online. Based on simple self-reports, 37.6% of the registered adults were MZ twins and 56.8% were DZ; 1.12% were triplets and 4.5% were unidentified. Of the registered children, 22.3% were MZ, 72.7% were DZ, 1.93% were triplets, and 3.05% were unidentified. Of the registered twins, 59.9% were female (including both the adult and minor twins). The registration questionnaire consists of eight parts, including socio-demographic and anthropometric data, smoking habits and medical questions (diseases, operations, therapies). Hungary's twin registry has become the sole and largest population-based twin registry in Central Eastern Europe. This new resource will facilitate performing world-class modern genetic research.

Imaging in the diagnosis and management of fibrosing interstitial lung diseases.

High-resolution computed tomography (HRCT) plays a pivotal role in the diagnosis and management of interstitial lung diseases (ILDs), particularly given the approval of antifibrotic agents for conditions like idiopathic pulmonary fibrosis and progressive pulmonary fibrosis. Diagnosing fibrotic pulmonary disorders through HRCT involves a detailed and methodical examination. The identification of specific lung tissue changes, including ground-glass opacities and reticulation, along with signs of fibrosis like honeycombing, traction bronchiectasis and lung volume loss, establishes clear HRCT patterns indicative of various ILDs. The reliability of these patterns in predicting pathological conditions depends largely on the clinical context. For instance, when a usual interstitial pneumonia pattern is present, the predictive value of this diagnosis is so high that a lung biopsy is considered to be redundant. This review intends to delineate the HRCT signs of fibrosis, elucidate the specific radiological patterns of fibrotic lung diseases, and identify the clinical circumstances under which these patterns emerge. Additionally, we introduce and discuss novel imaging techniques that hold promise for the diagnosis, screening and early detection of ILDs.

New developments in the imaging of lung cancer.

Radiological and nuclear medicine methods play a fundamental role in the diagnosis and staging of patients with lung cancer. Imaging is essential in the detection, characterisation, staging and follow-up of lung cancer. Due to the increasing evidence, low-dose chest computed tomography (CT) screening for the early detection of lung cancer is being introduced to the clinical routine in several countries. Radiomics and radiogenomics are emerging fields reliant on artificial intelligence to improve diagnosis and personalised risk stratification. Ultrasound- and CT-guided interventions are minimally invasive methods for the diagnosis and treatment of pulmonary malignancies. In this review, we put more emphasis on the new developments in the imaging of lung cancer.

Photon-counting computed tomography in the assessment of rheumatoid arthritis-associated interstitial lung disease: an initial experience

PURPOSE: Interstitial lung disease (ILD) accounts for a significant proportion of mortality and morbidity in patients with rheumatoid arthritis (RA). The aim of this cross-sectional study is to evaluate the performance of novel photon-counting detector computed tomography (PCD-CT) in the detection of pulmonary parenchymal involvement. METHODS: Sixty-one patients with RA without a previous definitive diagnosis of ILD underwent high-resolution (HR) (0.4 mm slice thickness) and ultra-high-resolution (UHR) (0.2 mm slice thickness) PCDCT examination. The extent of interstitial abnormalities [ground-glass opacity (GGO), reticulation, bronchiectasis, and honeycombing] were scored in each lobe using a Likert-type scale. Total ILD scores were calculated as the sum of scores from all lobes. RESULTS: Reticulation and bronchiectasis scores were higher in the UHR measurements taken compared with the HR protocol [median (quartile 1, quartile 3): 2 (0, 3.5) vs. 0 (0, 3), P < 0.001 and 2 (0, 2) vs. 0 (0, 2), P < 0.001, respectively]; however, GGO and honeycombing scores did not differ [2 (2, 4) vs. 2 (2, 4), P = 0.944 and 0 (0, 0) vs. 0 (0, 0), P = 0.641, respectively]. Total ILD scores from both HR and UHR scans showed a mild negative correlation in diffusion capacity for carbon monoxide (HR: r = -0.297, P = 0.034; UHR: r = -0.294, P = 0.036). The pattern of lung parenchymal involvement did not differ significantly between the two protocols. The HR protocol had significantly lower volume CT dose index [0.67 (0.69, 1.06) mGy], total dose length product [29 (24.48, 33.2) mGy*cm] compared with UHR scans [8.18 (6.80, 9.23) mGy, P < 0.001 and 250 (218, 305) mGy*cm, P < 0.001]. CONCLUSION: UHR PCD-CT provides more detailed information on ILD in patients with RA than low-dose HR PCDCT. HR PCD-CT image acquisition with a low effective radiation dose may serve as a valuable, low-radiation screening tool in the selection of patients for further, higher-dose UHR PCD-CT screening.

Strong Genetic Effects on Bone Mineral Density in Multiple Locations with Two Different Techniques: Results from a Cross-Sectional Twin Study.

Background and Objectives: Previous studies have demonstrated that risk of hip fracture is at least partly heritable. The aim of this study was to determine the magnitude of the genetic component of bone mineral density (BMD), using both X-ray and ultrasound assessment at multiple sites. Materials and Methods: 216 adult, healthy Hungarian twins (124 monozygotic, MZ, 92 dizygotic, DZ; mean age 54.2 ± 14.3 years), recruited from the Hungarian Twin Registry with no history of oncologic disease underwent cross-sectional BMD studies. We measured BMD, T- and Z-scores with dual energy X-ray absorptiometry (DEXA) at multiple sites (lumbar spine, femoral neck, total hip and radius). Quantitative bone ultrasound (QUS) was also performed, resulting in a calculated value of estimated bone mineral density (eBMD) in the heel bone. Heritability was calculated using the univariate ACE model. Results: Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.613 to 0.838 in the total sample. Lumbar BMD and calcaneus eBMD had major genetic components with estimates of 0.828 and 0.838 respectively, and least heritable (0.653) at the total hip. BMD of the radius had also a strong genetic component with an estimate of 0.806. No common environmental effect was found. The remaining variance was influenced by unique environment (0.162 to 0.387). In females only, slightly higher additive genetic estimates were found, especially in the case of the femoral neck and total hip. Conclusion: Bone mineral density is strongly heritable, especially in females at all locations using both DEXA and QUS, which may explain the importance of family history as a risk factor for bone fractures. Unshared environmental effects account for the rest of the variance with slight differences in magnitude across various bone regions, supporting the role of lifestyle in preventing osteoporotic fractures with various efficacy in different bone regions.

The Role of Soluble Low-Density Lipoprotein Receptor-Related Protein-1 in Obstructive Sleep Apnoea.

Intermittent hypoxia in obstructive sleep apnoea (OSA) is related to inflammation and metabolic abnormalities. Soluble low-density lipoprotein receptor-related protein-1 (sLRP-1) is involved in anti-inflammatory and metabolic processes. However, its ligand, calreticulin (CALR) promotes pro-inflammatory responses and apoptosis. Our aim was to analyse the levels of these biomarkers in OSA. We recruited 46 patients with OSA and 30 control subjects. Inpatient sleep study was performed and fasting plasma samples were collected. Triglyceride glucose index (TyG) and atherogenic index of plasma (AIP) were calculated. Plasma sLRP-1 levels were significantly lower in the OSA group compared to the controls (1.67 (0.90-2.11) mg/L vs. 1.99 (1.53-3.51) mg/L; p = 0.04) after adjustment for age, gender, BMI and lipid profile. Plasma sLRP-1 concentrations were inversely related to age (r = -0.29), BMI (r = -0.35), cigarette pack years (r = -0.31), LDL-C (r = -0.34) and triglyceride levels (r = -0.27), TyG (r = -0.37) and AIP (r = -0.27) as well as to the oxygen desaturation index (ODI, r = -0.24; all p < 0.05). BMI (p = 0.01) and ODI (p = 0.04) were independent predictors for low sLRP-1 levels. CALR did not differ significantly between the two groups (0.23 (0.17-0.34) ng/mL vs. 0.24 (0.20-0.36) ng/mL p = 0.76). We detected lower sLRP-1 levels in subjects with OSA which could contribute to metabolic abnormalities associated with this disease.

Delayed contrast enhancement of hepatic parenchyma after intravenous sonographic contrast agent: unusual phenomenon. Case report and review of literature.

AIM: A case of heterogeneous late-phase hepatic enhancement (HLHE) using contrast-enhanced ultrasound (CEUS) with SonoVue is presented, where HLHE lasted after 50 min of injection. METHODS: This study aims to review prior literature on this topic, to characterize the features of HLHE in the liver, and to find possible and reliable explanations for this phenomenon. RESULTS: From literature, thus far five publications discuss this phenomenon with a total of 21 patients. CONCLUSION: We suggest that phagocytosis of contrast agent microbubbles by macrophages, and lymphocytosis of peripheral blood due to stress conditions of the patients might be in the background of HLHE.

Autoimmune Progressive Fibrosing Interstitial Lung Disease: Predictors of Fast Decline.

A subset of interstitial lung diseases (ILDs) with autoimmune traits-including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)-develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) changes in autoimmune PF-ILD patients in a real-world setting. All ILD cases with confirmed or suspected autoimmunity discussed by a multidisciplinary team (MDT) between January 2017 and June 2019 (n = 511) were reviewed, including 63 CTD-ILD and 44 IPAF patients. Detailed medical history, LF test, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), blood gas analysis (BGA), and high-resolution computer tomography (HRCT) were performed. Longitudinal follow-up for functional parameters was at least 2 years. Women were overrepresented (70.1%), and the age of the IPAF group was significantly higher as compared to the CTD-ILD group (p < 0.001). Dyspnea, crackles, and weight loss were significantly more common in the IPAF group as compared to the CTD-ILD group (84.1% vs. 58.7%, p = 0.006; 72.7% vs. 49.2%, p = 0.017; 29.6% vs. 4.8%, p = 0.001). Forced vital capacity (FVC) yearly decline was more pronounced in IPAF (53.1 ± 0.3 vs. 16.7 ± 0.2 ml; p = 0.294), while the majority of patients (IPAF: 68% and CTD-ILD 82%) did not deteriorate. Factors influencing progression included malignancy as a comorbidity, anti-SS-A antibodies, and post-exercise pulse increase at 6MWT. Antifibrotic therapy was administered significantly more often in IPAF as compared to CTD-ILD patients (n = 13, 29.5% vs. n = 5, 7.9%; p = 0.007), and importantly, this treatment reduced lung function decline when compared to non-treated patients. Majority of patients improved or were stable regarding lung function, and autoimmune-associated PF-ILD was more common in patients having IPAF. Functional decline predictors were anti-SS-A antibodies and marked post-exercise pulse increase at 6MWT. Antifibrotic treatments reduced progression in progressive fibrosing CTD-ILD and IPAF, emphasizing the need for guidelines including optimal treatment start and combination therapies in this special patient group.

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea.

Biological functions of hyaluronic acid (HA) depend on its molecular size. High-molecular weight HA (HMW-HA) is an important component of the endothelial wall and has anti-inflammatory and antioxidant properties. Under inflammation or hypoxia, HMW-HA is degraded by hyaluronidases, such as HYAL-1 resulting in pro-inflammatory low-molecular weight fragments. Obstructive sleep apnoea (OSA) is characterised by intermittent hypoxia and systemic inflammation. Our aim was to evaluate circulating HMW-HA and HYAL-1 in OSA. We recruited 68 patients with OSA and 40 control volunteers. After full-night sleep study blood samples were taken for HMW-HA and HYAL-1 measurements. HYAL-1 levels were significantly higher in patients with OSA compared to controls (0.59/0.31-0.88/ng/mL vs. 0.31/0.31-0.58/ng/mL; p = 0.005) after adjustment for gender, age, BMI and smoking. There was a trend for reduced HMW-HA concentrations in OSA (31.63/18.11-59.25/ng/mL vs. 46.83/25.41-89.95/ng/mL; p = 0.068). Significant correlation was detected between circulating HMW-HA and apnoea-hypopnoea-index (r = - 0.195, p = 0.043), HYAL-1 and apnoea-hypopnoea-index (r = 0.30, p < 0.01) as well as oxygen desaturation index (r = 0.26, p < 0.01). Our results suggest that chronic hypoxia is associated with increased plasma HYAL-1 concentration and accelerated HMW-HA degradation. Altered hyaluronan metabolism may be involved in the inflammatory cascade potentially leading to endothelial dysfunction in OSA.

Impact of interstitial lung disease and simultaneous lung cancer on therapeutic possibilities and survival.

BACKGROUND: Fibrosing interstitial lung diseases (ILDs) are associated with poor survival and an increased risk of developing lung cancer (LC). Patient and LC characteristics, therapeutic possibilities and survival in this rare patient population are not well established. METHODS: Fibrosing ILD patients treated at the Department of Pulmonology Semmelweis University were reviewed retrospectively between 2012-2018 (N = 160). All patients with concomitant LC (N = 23) underwent detailed pulmonary evaluation. Cancer characteristics including driver mutation data, as well as therapy and survival were analyzed. RESULTS: ILD-LC patients (56% men, mean age 73 ± 6 years) had mild-moderate lung functional impairment (forced vital capacity [FVC]: 80 ± 24%ref., forced expiratory volume in one second [FEV1]: 76 ± 27%ref.; transfer factor of the lung for carbon monoxide [TLCO]: 62 ± 25% reference). In 56% of cases histology confirmed adenocarcinoma followed by squamous cell carcinoma in 26%. Lobectomy could only be performed in one case; driver mutation was present in one patient. Chemotherapy was most commonly administered; however, 26% could only receive supportive palliative care. Four idiopathic pulmonary fibrosis patients received concomitant nintedanib to their LC treatment. Median survival of ILD-LC patients was only 321 days. CONCLUSIONS: Diagnosis and therapy of ILD-LC is challenging and patients have a very limited survival. A significant proportion of patients could only receive palliative care indicating the need for better management strategies in this special patient population. The evaluation of the effect of cotreatment with antifibrotics needs further study. KEY POINTS: Interstitial lung diseases are often associated with lung cancer Diagnosis is challenging and therapy often limited due to underlying lung disease. Patients received platinum based chemotherapy or only supportive care.

Obstructive sleep apnea and hypertriglyceridaemia share common genetic background: Results of a twin study.

Obstructive sleep apnea is associated with an increased risk of hypertension, diabetes and dyslipidaemia. Both obstructive sleep apnea and its comorbidities are at least partly heritable, suggesting a common genetic background. Our aim was to analyse the heritability of the relationship between obstructive sleep apnea and its comorbidities using a twin study. Forty-seven monozygotic and 22 dizygotic adult twin pairs recruited from the Hungarian Twin Registry (mean age 51 ± 15 years) attended an overnight diagnostic sleep study. A medical history was taken, blood pressure was measured, and blood samples were taken for fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a). To evaluate the heritability of obstructive sleep apnea and its comorbidities bivariate analysis was performed with an adjustment for age, gender, body mass index (BMI) and smoking after false discovery rate correction and following exclusion of patients on lipid-lowering and antidiabetic medications. There was a significant correlation between indices of obstructive sleep apnea severity, such as the apnea-hypopnea index, oxygen desaturation index and percentage of sleep time spent with oxygen saturation below 90%, as well as blood pressure, serum triglyceride, lipoprotein (a) and glucose levels (all p < .05). The bivariate analysis revealed a common genetic background for the correlations between serum triglyceride and the oxygen desaturation index (r = .63, p = .03), as well as percentage of sleep time spent with oxygen saturation below 90% (r = .58, p = .03). None of the other correlations were significantly genetically or environmentally determined. This twin study demonstrates that the co-occurrence of obstructive sleep apnea with hypertriglyceridaemia has a genetic influence and heritable factors play an important role in the pathogenesis of dyslipidaemia in obstructive sleep apnea.

Exhaled carbon monoxide levels in obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterised by chronic intermittent hypoxia, which enhances airway inflammation and oxidative stress. Exhaled carbon monoxide (eCO), a marker for oxidative stress, has been investigated in OSA. However, previous studies could be biased as they did not differentiate patients with OSA based on smoking history, a known factor influencing eCO levels. The aim of this study to investigate eCO levels in patients with OSA and non-OSA controls and compare evening to morning results. METHODS: Exhaled carbon monoxide concentration was measured in the evening and in the morning following an in-hospital cardiorespiratory polygraphy in 60 never-smoker OSA patients, 14 ex-smoker OSA patients, 39 current-smoker OSA patients, 10 never-smoker asthmatic patients with OSA, 16 COPD patients with OSA and 20 never-smoker non-OSA controls. OSA was diagnosed based on the apnoea-hypopnoea index (AHI > 5/h). RESULTS: There was no difference between the never-smoker controls and never-smoker patients with OSA either in the evening (1.98 ± 1.00 ppm versus 1.95 ± 1.28 ppm, p = 0.57, OSA versus controls, respectively) or morning (1.95 ± 0.96 ppm versus 1.80 ± 0.95 ppm, p = 0.42), however there was a weak correlation between eCO and AHI in the evening (r = 0.31, p = 0.01). Accordingly, patients with severe OSA had higher eCO levels in the evening (2.43 ± 1.12 ppm) compared to mild OSA patients (1.57 ± 0.87 ppm, p < 0.01). Ex-smoker (3.07 ± 2.23 ppm), current-smoker (13.13 ± 11.35 ppm), asthmatic (2.70 ± 1.16 ppm) and COPD (18.25 ± 18.60 ppm) patients with OSA had higher levels of eCO compared to the non-smoker OSA group. CONCLUSION: Exhaled carbon monoxide is elevated only in severe never-smoker OSA suggesting accelerated oxidative stress. Previous smoking history is a major influencing factor which may explain differences between our findings and those of previous studies. Although our results show some impact of OSA on eCO measurements, the bias is small, and it does not significantly affect the clinical utility of eCO to monitor smoking cessation.

Genetic and Environmental Effects on the Abdominal Aortic Diameter Development / Efeitos Genéticos e Ambientais no Desenvolvimento do Diâmetro da Aorta Abdominal

Abstract Background: Configuration of the abdominal aorta is related to healthy aging and a variety of disorders. Objectives: We aimed to assess heritable and environmental effects on the abdominal aortic diameter. Methods: 114 adult (69 monozygotic, 45 same-sex dizygotic) twin pairs (mean age 43.6 ± 16.3 years) underwent abdominal ultrasound with Esaote MyLab 70X ultrasound machine to visualize the abdominal aorta below the level of the origin of the renal arteries and 1-3 cm above the bifurcation. Results: Age- and sex-adjusted heritability of the abdominal aortic diameter below the level of the origin of the renal arteries was 40% [95% confidence interval (CI), 14 to 67%] and 55% above the aortic bifurcation (95% CI, 45 to 70%). None of the aortic diameters showed common environmental effects, but unshared environmental effects were responsible for 60% and 45% of the traits, respectively. Conclusions: Our analysis documents the moderate heritability and its segment-specific difference of the abdominal aortic diameter. The moderate part of variance was explained by unshared environmental components, emphasizing the importance of lifestyle factors in primary prevention. Further studies in this field may guide future gene-mapping efforts and investigate specific lifestyle factors to prevent abdominal aortic dilatation and its complications.

Resumo Fundamento: A configuração da aorta abdominal relaciona-se com o envelhecimento saudável e uma série de distúrbios. Objetivos: Avaliar efeitos herdáveis e ambientais no diâmetro da aorta abdominal. Métodos: 114 pares de gêmeos adultos (69 monozigóticos e 45 dizigóticos do mesmo sexo), com idade média de 43,6 ± 16,3 anos, foram submetidos a ultrassonografia abdominal com o aparelho Esaote MyLab 70X para visualização da aorta abdominal abaixo da origem das artérias renais e 1-3 cm acima da bifurcação aórtica. Resultados: A herdabilidade ajustada para idade e sexo do diâmetro da aorta abdominal abaixo da origem das artérias renais foi 40% [intervalo de confiança (IC) 95%, 14 – 67%] e acima da bifurcação, 55% (IC 95%, 45 – 70%). Nenhum dos diâmetros aórticos apresentou efeitos ambientais comuns, mas os efeitos ambientais não compartilhados foram responsáveis por 60% e 45% dos traços, respectivamente. Conclusões: Nossa análise mostrou herdabilidade moderada e diferença do diâmetro da aorta abdominal com especificidade de segmento. A parte moderada da variância foi explicada pelo componente ambiental não compartilhado, enfatizando a importância do estilo de vida na prevenção primária. Estudos adicionais nesse campo poderão guiar futuros esforços de mapeamento genético e investigar fatores específicos de estilo de vida para prevenir dilatação da aorta abdominal e suas complicações.

Pattern of Tumour Spread of Common Primary Tumours as Seen on Magnetic Resonance Imaging.

Although some reports with computed tomography and bone scintigraphy are available in the literature, the distinct epidemiologic description of skeletal metastatic pattern of various tumors is still lacking. This study uses a novel approach to identify skeletal metastases from magnetic resonance imaging (MRI) data to describe metastatic pattern in common malignancies. A retrospective analysis of 130 cancer patients (42 lung, 56 breast, 11 prostate cancers; 21 multiple myeloma) with vertebral metastases and without disseminated disease, and whom underwent a whole body 3Tesla MRI investigation (Discovery MR750w), was carried out. Multiple myeloma had the most commonly disseminated metastatic disease (95%) compared to lung (28%), breast (44%) and prostate (71%) cancers. Lung cancer was related to more frequent pedicle involvement compared to breast or prostate cancer (29, 9 and 0%, p < 0.05). Pathologic fracture was mainly associated with multiple myeloma (43%). The prevalence of lung cancer metastases was more frequent in the lumbal spine (81%), as well as particular in C7, D7, D8, D9 and L1, compared to breast cancers. Most differences among tumors were detected in the extravertebral osseous metastatic pattern (p < 0.05). The highest frequency of extravertebral skeletal metastases was present in multiple myeloma (28 to 76%). Brain metastasis was more frequent in lung cancer compared to breast cancers (35% vs. 17%, p < 0.05). Significant differences in the skeletal metastatic pattern among common malignancies were demonstrated with MRI.

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study

Objectives Decreased thyroid volume has been related to increased prevalence of thyroid cancer. Subjects and methods One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63). Results Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%). Conclusions Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects.

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study.

OBJECTIVES: Decreased thyroid volume has been related to increased prevalence of thyroid cancer. SUBJECTS AND METHODS: One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63). RESULTS: Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%). CONCLUSIONS: Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects.

Modest genetic influence on bronchodilator response: a study in healthy twins.

AIM: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. METHODS: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 µg salbutamol). Univariate quantitative genetic modeling was performed. RESULTS: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P<0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1-adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). CONCLUSION: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

Clinical value of whole-body magnetic resonance imaging in health screening of general adult population.

BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) and angiography (WB-MRA) has become increasingly popular in population-based research. We evaluated retrospectively the frequency of potentially relevant incidental findings throughout the body. MATERIALS AND METHODS: 22 highly health-conscious managers (18 men, mean age 47±9 years) underwent WB-MRI and WB-MRA between March 2012 and September 2013 on a Discovery MR750w wide bore 3 Tesla device (GE Healthcare) using T1 weighted, short tau inversion recovery (STIR) and diffusion weighted imaging (DWI) acquisitions according to a standardized protocol. RESULTS: A suspicious (pararectal) malignancy was detected in one patient which was confirmed by an endorectal sonography. Incidental findings were described in 20 subjects, including hydrocele (11 patients), benign bony lesion (7 patients) and non-specific lymph nodes (5 patients). Further investigations were recommended in 68% (ultrasound: 36%, computed tomography: 28%, mammography: 9%, additional MRI: 9%). WB-MRA were negative in 16 subjects. Vascular normal variations were reported in 23%, and a 40% left proximal common carotid artery stenosis were described in one subject. CONCLUSIONS: WB-MRI and MRA lead to the detection of clinically relevant diseases and unexpected findings in a cohort of healthy adults that require further imaging or surveillance in 68%. WB-MR imaging may play a paramount role in health screening, especially in the future generation of (epi)genetic based screening of malignant and atherosclerotic disorders. Our study is the first which involved a highly selected patient group using a high field 3-T wide bore magnet system with T1, STIR, MRA and whole-body DWI acquisitions as well.

Transmission of second-hand smoke sensitivity and smoking attitude in a family.

INTRODUCTION AND OBJECTIVE: The role of genetic factors in nicotine dependence is well understood, but no information is available on the inheritability of second-hand smoke (SHS) exposure sensitivity and their co-variance. MATERIALS AND METHODS: 186 adult same-gender pairs of twin (146 monozygotic, 40 dizygotic; 44±17 years±SD) completed a questionnaire. RESULTS: The model showed a significant role of unshared environmental factors influencing the co-variance between smoking habit and SHS sensitivity (re=-0.191, 95% CI, -0.316 to -0.056, or the total phenotypic correlation of rph=-0.406, p<0.001) without evidence for genetic covariation. Age, gender and country-adjusted analysis indicated 51.5% heritability for smoking habit (95% confidence interval/CI/, 6.2 to 89.8%), 49.7% for SHS sensitivity (95%CI, 19.1-72.0%), 35.5% for general opinions on SHS exposure in restaurants/cafés (95%CI, 10.7-58.6%), and 16.9% in pubs/bars (95%CI, 0.0-49.0%). CONCLUSIONS: The co-variance between SHS sensitivity and smoking habits is driven mainly by the unshared environment. SHS sensitivity is moderately inheritable. The considerable influence of environmental factors on general opinions on SHS exposure in designated indoor public venues emphasizes the importance of smoking bans and health behaviour interventions at the individual level in developing an anti-smoking attitude.