Clinical practice guidelines and real-life practice on hepatocellular carcinoma: the Hong Kong perspective

Hepatocellular carcinoma (HCC) is a major public health burden in Hong Kong, and chronic hepatitis B is the most common HCC etiology in our region. With the high case load, extensive local expertise on HCC has been accumulated. This article summarized local guidelines and real-life practice on HCC management in Hong Kong. For HCC surveillance, liver ultrasound and serum alpha-fetoprotein for periodic screening is recommended in viral hepatitis or cirrhotic patients, and this is adhered to in clinical practice. HCC diagnosis is not covered in local guidelines, yet our practice is in-line with regional guidelines, where diagnosis is usually achieved by cross-sectional imaging and without the need for histology. Our guidelines recommend using the Hong Kong Liver Cancer Staging for pre-treatment staging, yet we routinely use other widely-adopted systems such as the Barcelona Clinic Liver Cancer Staging and the Tumor-Node-Metastasis Staging as well. Our local guidelines have provided clear treatment algorithms for the whole range of HCC therapies, including resection, ablation, transplant, transarterial chemoembolization, transarterial radioembolization, stereotactic body radiation therapy, targeted therapy, and immunotherapy. Real-life treatment choices are largely in line with the guidelines, although treatment protocols are individualized, and availability of specific therapies can vary between centers. Overall, HCC guidelines in Hong Kong are tailored based on local expertise and our unique patient population. The guidelines are up-to-date and provide practical pathways to assist our routine practice. Regular updates of local guidelines are warranted to account for the rapidly evolving paradigm of HCC management

Efeitos do tratamento com captopril e losartan em ratos Wistar e ratos espontaneamente hipertensos submetidos a hipertensão arterial pulmonar com monocrotalina

A hipertensão arterial pulmonar (HAP) é uma doença que se inicia com o aumento da resistência das arteríolas pulmonares. Após a sua instalação, sucedem-se várias alterações sobre os sistemas cardiovascular, respiratório e autonômico. Apesar dos trabalhos disponíveis na literatura, o desenvolvimento desta doença em modelos experimentais de hipertensão arterial sistêmica permanece ainda por ser estudado, bem como os efeitos terapêuticos de bloqueadores do sistema renina-angiotensina na reversão desta doença. Os objetivos deste estudo foram avaliar os efeitos cardiovasculares, autonômicos e respiratórios promovidos pela HAP induzida pela monocrotalina (MCT) em ratos Wistar e SHR e os efeitos terapêuticos do tratamento crônico com captopril e losartan na reversão da HAP. Para tanto, foram utilizados ratos Wistar (150-180g) e SHR (150-180g), divididos nos seguintes grupos: Wistar controle tratado com salina ou MCT (WIS-CON-SAL e WIS-CON-MCT, respectivamente), SHR controle tratado com salina ou MCT (SHR-CON-SAL e SHR-CON-MCT, respectivamente), Wistar tratados com Captopril + salina ou MCT (WIS-CPT-SAL e WIS-CPT-MCT, respectivamente), SHR tratados com Captopril + salina ou MCT (SHR-CPT-SAL e SHR-MCT-CPT, respectivamente), Wistar tratados com Losartan + salina ou MCT (WIS-LOS-SAL e WIS-LOS-MCT, respectivamente), SHR tratados com Losartan + salina ou MCT (SHR-LOS-SAL e SHR-LOS-MCT, respectivamente). Os animais tratados com MCT receberam uma única injeção subcutânea (60 mg/Kg SC) e os controles receberam o mesmo volume de salina (~0,8 mL). Ao término da 3ª senama, quando os animais MCTs controle apresentaram HAP, foi feito o tratamento com captopril (100 mg/Kg/mL) ou losartan (30 mg/Kg/mL) na água de beber por 2 semanas no volume diário de 30 mL. Após o tratamento com captopril ou losartan, foram realizados os registros cardiovasculares, respiratórios, gasométricos e a histologia pulmonar. Os resultados mostraram um significativo aumento do Índice Pulmonar nos animais controles tratados com MCT (Wistar e SHR) quando comparados com seus respectivos controles. As pressões ventriculares (PSmáx, PDI e PDF) também foram significativamente aumentadas nos grupos MCTs, bem como os valores de pressão arterial sistólica and diastólica, frequência cardíaca, pressão de pulso e labilidade da pressão arterial média. O tratamento com captopril normalizou todos os parâmetros estudados, no entanto, o losartan se mostrou ineficiente em normalizar os parâmetros hemodinâmicos. As análises morfométricas mostraram um espessamento da camada média dos dos ramos distais da artéria pulmonar e uma diminuição do lúmen nos grupos tratados com MCT. O tratamento com captopril e losartan normalizou estes parâmetros, embora o grupo tratado com losartan tenha sido menos eficaz que o captopril, pois os tratamentos mostraram diferenças significativas entre si. Quanto a avaliação autonômica, os animais MCT mostraram aumento do tônus simpático cardíaco e redução do tônus parassimpático cardíaco. Novamente, o tratamento com captopril normalizou estes parâmetros, enquanto que o losartan foi ineficaz em normalizá-los. Quanto aos parâmetros respiratórios, observamos aumentos no volume corrente, na frequência respiratória, na ventilação minuto e na ventilação alveolar dos animais controles tratados com MCT. Apenas o tratamento com captopril normalizou estes parâmetros. A avaliação gasométrica mostrou que os grupos controles tratados com MCT apresentaram redução da pressão parcial de O2 (hipóxia), aumento da pressão parcial de CO2 (hipercapnia), queda da porcentagem de saturação da hemoglobina (% Hb), aumento do bicarbonato (HCO3-) e acidose. O tratamento com captopril normalizou todos os parâmetros gasométricos, enquanto que o mesmo não foi observado com o losartan para os animais SHR submetidos a HAP. Nossos resultados mostraram que a MCT induziu ao quadro de HAP nos animais Wistar e SHR, bem como importantes alterações cardiovasculares, autonômicas, respiratórias, gasométricas e morfológicas pulmonares. Os tratamentos com captopril e losartan foram capazes de reverter a HAP em animais Wistar e SHR, porém, o captopril se mostrou mais eficiente em normalizar esses parâmetros quando comparados ao losartan. Estes resultados sugerem que o uso de bloqueadores do sistema renina angiotensina pode ser uma opção terapêutica para o tratamento da HAP. Palavras chave: hipertensão arterial pulmonar; monocrotalina; SHR; captopril; losartan

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

Genome-Wide Association Study of Lung Adenocarcinoma in East Asia and Comparison With a European Population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

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Abstract Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array ), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, OR G-allele = 1.13, P meta = 1.60 × 10 −8 ). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers.

BackgroundLung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.MethodsPRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates.ResultsThe best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC = 0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI : 0.629,0.653) and odds ratio of 1.71 (95% CI : 1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier.ConclusionsMulti-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications