The usefulness of contrast-enhanced subtraction magnetic resonance imaging for detecting endoleaks after endovascular aortic repair with prophylactic intraoperative sac embolization.

BACKGROUND: Metallic and hyperdense artifacts and T1-shortening substances in the abdominal aortic aneurysm (AAA) sac generated by embolic materials and lipiodol pose challenges in the identification of endoleaks on follow-up computed tomography (CT) or magnetic resonance imaging (MRI). PURPOSE: To evaluate the usefulness of contrast-enhanced subtraction MRI (CES-MRI) for detecting endoleaks after endovascular abdominal aortic aneurysm repair (EVAR) with intraoperative AAA sac embolization compared with CE-CT, this study was conducted. MATERIAL AND METHODS: In this study, 28 consecutive patients who underwent EVAR with prophylactic AAA sac embolization were included. All patients underwent CES-MRI and CE-CT to detect endoleaks. The definitive diagnosis of endoleaks was a consensus reading of CE-CT and CES-MRI by two certified radiologists, in addition to angiography or reproducible radiological findings in the observational examination. Analysis was performed to evaluate which examination was better for detecting endoleaks. RESULTS: The sensitivity, specificity, and area under the curve of CE-CT and CES-MRI according to observer 1 were 50%, 100%, and 0.813 (95% confidence interval [CI] = 0.625-1.00) and 100%, 95%, and 0.997 (95% CI = 0.984-1.00), respectively, and those according to observer 2 were 50%, 100%, and 0.750 (95% CI = 0.514-0.986) and 100%, 95%, and 0.969 (95% CI = 0.903-1.00), respectively. Intolerable artifacts were significantly observed on CE-CT. The severity of the artifacts did not depend on the stent graft on CT and MRI. CONCLUSION: Although no significant difference was observed, CES-MRI tended to have better accuracy for endoleak detection in EVAR with intraoperative AAA sac embolization than CE-CT.

Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome-Wide Association and Mendelian Randomization Study.

BACKGROUND: Observational studies have reported associations between primary aldosteronism (PA) and cardiovascular outcomes, including coronary artery diseases (CAD), congestive heart failure (CHF), and stroke. However, establishing causality remains a challenge due to the lack of randomized controlled trial data on this topic. We thus aimed to investigate the causal relationship between PA and the risk of developing CAD, CHF, and stroke. METHODS AND RESULTS: Cross-ancestry meta-analysis of genome-wide association studies combining East Asian and European ancestry (1560 PA cases and 742 139 controls) was conducted to identify single-nucleotide variants that are associated with PA. Then, using the identified genetic variants as instrumental variables, we conducted the 2-sample Mendelian randomization analysis to investigate the causal relationship between PA and incident CAD, CHF, and stroke among both East Asian and European ancestry. Summary association results were extracted from large genome-wide association studies consortia. Our cross-ancestry meta-analysis of East Asian and European populations identified 7 genetic loci significantly associated with the risk of PA, for which the genes nearest to the lead variants were CASZ1, WNT2B, HOTTIP, LSP1, TBX3, RXFP2, and NDP. Among the East Asian population, the pooled odds ratio estimates using these 7 genetic instruments of PA were 1.07 (95% CI, 1.03-1.11) for CAD, 1.10 (95% CI, 1.01-1.20) for CHF, and 1.13 (95% CI, 1.09-1.18) for stroke. The results were consistent among the European population. CONCLUSIONS: Our 2-sample Mendelian randomization study revealed that PA had increased risks of CAD, CHF, and stroke. These findings highlight that early and active screening of PA is critical to prevent future cardiovascular events.

Multi-institutional prospective observational study of radiotherapy for metastatic bone tumor.

Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming α/ß = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS ≥ 2). BED was <20 Gy (in 27%), 20-30 Gy (24%), 30-40 Gy (36%) and ≥ 40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4-5 toxicity was reported. Pain relief was achieved in 52% at 2 months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1-9.9) at 6 months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2-76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.

Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10-10; odds ratio [OR] = 1.51 [95% CI: 1.33-1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C*12:02, HLA-B*52:01, and HLA-DRB1*15:02 (P = 1.1 × 10-10, 1.5 × 10-10, and 1.2 × 10-9, respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10-10; OR = 0.65 [95% CI: 0.57-0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10-4; OR = 3.29 [95% CI: 1.78-5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology.

Genome-wide association study on meningioma risk in Japan: a multicenter prospective study.

PURPOSE: Although meningiomas are the most common primary intracranial tumors, their genetic etiologies have not been fully elucidated. To date, only two genome-wide association studies (GWASs) have focused on European ancestries, despite ethnic differences in the incidence of meningiomas. The aim of this study was to conduct the first GWAS of Japanese patients with meningiomas to identify the SNPs associated with meningioma susceptibility. METHODS: In this multicenter prospective case-control study, we studied 401 Japanese patients with meningioma admitted in five institutions in Japan, and 50,876 control participants of Japanese ancestry enrolled in Biobank Japan. RESULTS: The quality control process yielded 536,319 variants and imputation resulted in 8,224,735 variants on the autosomes and 224,820 variants on the X chromosomes. This GWAS eventually revealed no genetic variants with genome-wide significance (P < 5 × 10 - 8) and observed no significant association in the previously reported risk variants rs11012732 and rs2686876 due to low minor allele frequency in the Japanese population. CONCLUSION: This is the first GWAS of meningiomas in East Asian populations and is expected to contribute to the development of GWAS research for meningiomas.

Quantification of escape from X chromosome inactivation with single-cell omics data reveals heterogeneity across cell types and tissues.

Several X-linked genes escape from X chromosome inactivation (XCI), while differences in escape across cell types and tissues are still poorly characterized. Here, we developed scLinaX for directly quantifying relative gene expression from the inactivated X chromosome with droplet-based single-cell RNA sequencing (scRNA-seq) data. The scLinaX and differentially expressed gene analyses with large-scale blood scRNA-seq datasets consistently identified the stronger escape in lymphocytes than in myeloid cells. An extension of scLinaX to a 10x multiome dataset (scLinaX-multi) suggested a stronger escape in lymphocytes than in myeloid cells at the chromatin-accessibility level. The scLinaX analysis of human multiple-organ scRNA-seq datasets also identified the relatively strong degree of escape from XCI in lymphoid tissues and lymphocytes. Finally, effect size comparisons of genome-wide association studies between sexes suggested the underlying impact of escape on the genotype-phenotype association. Overall, scLinaX and the quantified escape catalog identified the heterogeneity of escape across cell types and tissues.

Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults.

Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk.

Body mass index stratification optimizes polygenic prediction of type 2 diabetes in cross-biobank analyses.

Type 2 diabetes (T2D) shows heterogeneous body mass index (BMI) sensitivity. Here, we performed stratification based on BMI to optimize predictions for BMI-related diseases. We obtained BMI-stratified datasets using data from more than 195,000 individuals (nT2D = 55,284) from BioBank Japan (BBJ) and UK Biobank. T2D heritability in the low-BMI group was greater than that in the high-BMI group. Polygenic predictions of T2D toward low-BMI targets had pseudo-R2 values that were more than 22% higher than BMI-unstratified targets. Polygenic risk scores (PRSs) from low-BMI discovery outperformed PRSs from high BMI, while PRSs from BMI-unstratified discovery performed best. Pathway-specific PRSs demonstrated the biological contributions of pathogenic pathways. Low-BMI T2D cases showed higher rates of neuropathy and retinopathy. Combining BMI stratification and a method integrating cross-population effects, T2D predictions showed greater than 37% improvements over unstratified-matched-population prediction. We replicated findings in the Tohoku Medical Megabank (n = 26,000) and the second BBJ cohort (n = 33,096). Our findings suggest that target stratification based on existing traits can improve the polygenic prediction of heterogeneous diseases.

Differentiation Between Ulcerative Colitis and Crohn's Disease Using Abdominal Computed Tomography in Patients With First-Time Inflammatory Bowel Disease.

Background Ulcerative colitis (UC) and Crohn's disease (CD) are classified as inflammatory bowel diseases (IBDs). However, they have different pathogeneses and treatment strategies and need to be differentiated. Purpose To determine the feasibility of differentiating UC from CD in patients with first-time IBD based on simple abdominal computed tomography (CT) findings. Methods We conducted a retrospective study of patients diagnosed with IBD for the first time at our hospital between January and December 2021. Age, sex, white blood cell count, albumin concentration, C-reactive protein concentration, visceral fat area, subcutaneous fat area, and psoas major volume were extracted and used to differentiate the two groups. Results Forty-three patients were selected. Their mean age was 35.60 ± 17.19 years, and 32 were male, while 11 were female. The visceral fat cross-sectional area was 51.80 cm2 for UC and 21.10 cm2 for CD (p < 0.01). The subcutaneous fat cross-sectional area was 108.30 cm2 for UC and 66.30 cm2 for CD (p = 0.049). The total protein concentration was 6.15 g/L for UC and 6.60 g/L for CD (p = 0.012). Receiver operating characteristic curve analysis of the visceral and subcutaneous fat cross-sectional areas showed areas under the curve, 95% confidence intervals, sensitivities, and specificities of 0.750 and 0.675, 0.603-0.897 and 0.507-0.844, 0.810 and 1.00, and 0.591 and 0.409, respectively, at cutoffs of 26.53 and 36.6 cm2. Conclusions  The visceral and subcutaneous fat cross-sectional areas determined with simple abdominal CT can differentiate UC from CD in patients with first-time IBD.

A unified framework for estimating country-specific cumulative incidence for 18 diseases stratified by polygenic risk.

Polygenic scores (PGSs) offer the ability to predict genetic risk for complex diseases across the life course; a key benefit over short-term prediction models. To produce risk estimates relevant to clinical and public health decision-making, it is important to account for varying effects due to age and sex. Here, we develop a novel framework to estimate country-, age-, and sex-specific estimates of cumulative incidence stratified by PGS for 18 high-burden diseases. We integrate PGS associations from seven studies in four countries (N = 1,197,129) with disease incidences from the Global Burden of Disease. PGS has a significant sex-specific effect for asthma, hip osteoarthritis, gout, coronary heart disease and type 2 diabetes (T2D), with all but T2D exhibiting a larger effect in men. PGS has a larger effect in younger individuals for 13 diseases, with effects decreasing linearly with age. We show for breast cancer that, relative to individuals in the bottom 20% of polygenic risk, the top 5% attain an absolute risk for screening eligibility 16.3 years earlier. Our framework increases the generalizability of results from biobank studies and the accuracy of absolute risk estimates by appropriately accounting for age- and sex-specific PGS effects. Our results highlight the potential of PGS as a screening tool which may assist in the early prevention of common diseases.

Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci.

BACKGROUND AND AIMS: Brugada syndrome (BrS) is an inherited arrhythmia with a higher disease prevalence and more lethal arrhythmic events in Asians than in Europeans. Genome-wide association studies (GWAS) have revealed its polygenic architecture mainly in European populations. The aim of this study was to identify novel BrS-associated loci and to compare allelic effects across ancestries. METHODS: A GWAS was conducted in Japanese participants, involving 940 cases and 1634 controls, followed by a cross-ancestry meta-analysis of Japanese and European GWAS (total of 3760 cases and 11 635 controls). The novel loci were characterized by fine-mapping, gene expression, and splicing quantitative trait associations in the human heart. RESULTS: The Japanese-specific GWAS identified one novel locus near ZSCAN20 (P = 1.0 × 10-8), and the cross-ancestry meta-analysis identified 17 association signals, including six novel loci. The effect directions of the 17 lead variants were consistent (94.1%; P for sign test = 2.7 × 10-4), and their allelic effects were highly correlated across ancestries (Pearson's R = .91; P = 2.9 × 10-7). The genetic risk score derived from the BrS GWAS of European ancestry was significantly associated with the risk of BrS in the Japanese population [odds ratio 2.12 (95% confidence interval 1.94-2.31); P = 1.2 × 10-61], suggesting a shared genetic architecture across ancestries. Functional characterization revealed that a lead variant in CAMK2D promotes alternative splicing, resulting in an isoform switch of calmodulin kinase II-δ, favouring a pro-inflammatory/pro-death pathway. CONCLUSIONS: This study demonstrates novel susceptibility loci implicating potentially novel pathogenesis underlying BrS. Despite differences in clinical expressivity and epidemiology, the polygenic architecture of BrS was substantially shared across ancestries.

Functional dissection of complex and molecular trait variants at single nucleotide resolution.

Identifying the causal variants and mechanisms that drive complex traits and diseases remains a core problem in human genetics. The majority of these variants have individually weak effects and lie in non-coding gene-regulatory elements where we lack a complete understanding of how single nucleotide alterations modulate transcriptional processes to affect human phenotypes. To address this, we measured the activity of 221,412 trait-associated variants that had been statistically fine-mapped using a Massively Parallel Reporter Assay (MPRA) in 5 diverse cell-types. We show that MPRA is able to discriminate between likely causal variants and controls, identifying 12,025 regulatory variants with high precision. Although the effects of these variants largely agree with orthogonal measures of function, only 69% can plausibly be explained by the disruption of a known transcription factor (TF) binding motif. We dissect the mechanisms of 136 variants using saturation mutagenesis and assign impacted TFs for 91% of variants without a clear canonical mechanism. Finally, we provide evidence that epistasis is prevalent for variants in close proximity and identify multiple functional variants on the same haplotype at a small, but important, subset of trait-associated loci. Overall, our study provides a systematic functional characterization of likely causal common variants underlying complex and molecular human traits, enabling new insights into the regulatory grammar underlying disease risk.

Prognostic significance of chronic kidney disease and impaired renal function in Japanese patients with COVID-19.

BACKGROUND: Renal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes. METHODS: This retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression. RESULTS: The prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03-1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36-2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64-4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08-3.23, P = 0.025) only. CONCLUSIONS: Clinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19.

Association between PET-CT accumulation in the hypothalamic/pituitary regions and neuron-specific enolase/primary tumor in limited-stage small cell lung cancer: a case-controlled retrospective study.

BACKGROUND: Research on the relationship between neuron-specific enolase (NSE) levels and normal organs, particularly the central nervous system, in small cell lung cancer is limited. Therefore, this study aimed to investigate the relationship between positron emission tomography-computed tomography (PET-CT) accumulation at hypothalamic/pituitary regions, tumor activity, and NSE level in limited-stage small cell lung cancer. We retrospectively analyzed patients who were diagnosed with limited-stage small cell lung cancer at Tokyo Medical University Hospital between July 1, 2019, and May 31, 2023, and were treated with chemoradiotherapy or radiotherapy. Leukocytes, erythrocytes, hemoglobin, platelets, total protein, albumin, NSE, and carcinoembryonic antigen were measured in blood samples obtained before treatment initiation. The maximum standardized uptake value (SUVmax), volume, and total lesion glycolysis (TLG) of each hypothalamic /pituitary region, primary tumor, and lymph node metastases were extracted from PET-CT images. The total tumor volume (primary tumor volume plus lymph node metastases volume) and total TLG (primary tumor TLG plus lymph node metastases TLG) were calculated. RESULTS: This study included 19 patients (mean age, 70.1 ± 8.8 years; 13 men and 6 women); the pathology in all patients was small cell lung cancer. Patients were classified into two groups according to the NSE reference value (16.3 ng/mL): six patients having NSE level below the reference value and 13 having NSE level above the reference value. The SUVmax in the hypothalamic/pituitary region was 2.95 in the NSE < 16.3 ng/mL group and 4.10 in the NSE > 16.3 ng/mL group, with a statistically significant difference (p = 0.03). The total tumor volume was 17.8 mL in the NSE < 16.3 ng/mL group and 98.9 mL in the NSE > 16.3 ng/mL group, with a statistically significant difference (p < 0.01). A correlation coefficient of r = 0.458 (p = 0.0486) was observed between SUVmax in the hypothalamus/pituitary and NSE level. A correlation coefficient of r = 0.647 (p < 0.01) was also observed between total tumor volume and NSE level. Finally, a correlation coefficient of r = 0.53 (p = 0.01) was observed between hypothalamic/pituitary TLG and primary tumor TLG. CONCLUSIONS: The findings demonstrated a correlation between hypothalamic/pituitary activity and tumor activity, suggesting the prognostic significance of NSE.

Diagnostic accuracy of a novel ultrasound imaging index for knee osteoarthritis: Evaluation of sensitivity, specificity, and predictive values.

PURPOSE: We aimed to develop and validate a new ultrasonography (US) index for the diagnosis of primary medial-type knee osteoarthritis (OA). METHODS: In total, 156 patients (203 limbs) underwent standing knee radiography and the US for suspected knee OA. Total osteophyte height (TOH) and distance between bones (DBB) aided diagnosis. Logistic regression identified optimal cutoff values. Thresholds from logistic regression informed recipient operating characteristic curve (ROC) analysis, balancing sensitivity and specificity. These thresholds were then applied in the differential thermal analysis (DTA) to construct a 2 × 2 table. RESULTS: The TOH-DBB index showed that a DBB of 5.6 mm or less was required to diagnose primary medial-type knee arthropathy. The results in the 2 × 2 table were 41 true-positive (TP), 10 false negative (FN), 22 true-negative (TN), and 7 false positive (FP). A DBB of 5.6 mm or less and TOH of 4.7 mm or more were necessary to diagnose severe deformity. The results in the 2 × 2 table were 10 TP, 4 FN, 23 TN, and 4 FP. CONCLUSION: The TOH-DBB index was confirmed to capture changes in primary medial-type knee OA across various stages.

CT-derived vertebral bone mineral density is a useful biomarker to predict COVID-19 outcome.

The low vertebral bone computed tomography (CT) Hounsfield unit values measured on CT scans reflect low bone mineral density (BMD) and are known as diagnostic indicators for osteoporosis. The potential prognostic significance of low BMD defined by vertebral bone CT values for the coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to assess the impact of BMD on the clinical outcome in Japanese patients with COVID-19 and evaluate the association between BMD and critical outcomes, such as high-flow nasal cannula, non-invasive and invasive positive pressure ventilation, extracorporeal membrane oxygenation, or death. We examined the effects of COVID-19 severity on the change of BMD over time. This multicenter retrospective cohort study enrolled 1132 inpatients with COVID-19 from the Japan COVID-19 Task Force database between February 2020 and September 2022. The bone CT values of the 4th, 7th, and 10th thoracic vertebrae were measured from chest CT images. The average of these values was defined as BMD. Furthermore, a comparative analysis was conducted between the BMD on admission and its value 3 months later. The low BMD group had a higher proportion of critical outcomes than did the high BMD group. In a subanalysis stratifying patients by epidemic wave according to onset time, critical outcomes were higher in the low BMD group in the 1st-4th waves. Multivariable logistic analysis of previously reported factors associated with COVID-19 severity revealed that low BMD, chronic kidney disease, and diabetes were independently associated with critical outcomes. At 3 months post-infection, patients with oxygen demand during hospitalization showed markedly decreased BMD than did those on admission. Low BMD in patients with COVID-19 may help predict severe disease after the disease onset. BMD may decrease over time in patients with severe COVID-19, and the impact on sequelae symptoms should be investigated in the future.

PET/CT findings and dose distribution during radiotherapy in T1N0M0-T2N0M0 glottic cancer.

OBJECTIVE: To investigate the positron emission tomography/computed tomography (PET/CT) findings of T1/T2N0M0 glottic cancer (hereafter referred to as T1/T2) and dose distribution in radiotherapy. SUBJECTS AND METHODS: We retrospectively collected data from patients diagnosed with T1/T2N0M0 glottic cancer who received radiotherapy. The extent of fluorine-18-fluorodeoxyglucose (18F-FDG) accumulation in primary tumors, maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), tumor volume of primary tumors on PET/CT were compared. Furthermore, the tumor identified on PET/CT was incorporated into the radiotherapy plans. A dummy plan (radiation field 6x6cm, prescription point facing the vertebral body, maximum dose ≤107%, T1/T2 66Gy/33 fractions) was developed for three-dimensional conformal radiotherapy, and the dose distribution of primary tumors was calculated. RESULTS: Twenty-nine patients (27 men and two women) were included; their mean age was 67.2±15.0 years. Increased 18F-FDG accumulation in primary tumors was observed on PET/CT in 22/29 (78.5%; T1: 14/21 [67%], T2: 8/8 [100%]) patients. The median SUVmax, TLG, and primary tumor volume were significantly different between T1 and T2 (SUVmax, T1: 4.56 vs. T2: 8.43, P=0.035; TLG, T1: 1.01 vs. T2: 3.71 SUVxmL, P<0.01; primary tumor volume, T1: 0.38mL vs. T2: 0.80mL, P=0.01). At a TLG cut-off value of 3.470, the area under the curve was 0.875, sensitivity was 0.875, and specificity was 0.929 for T1-T2 differentiation. In 20 patients with 18F-FDG accumulation, the minimum radiation dose was significantly different between T1 and T2 (66Gy vs. 64Gy, P<0.01) at the same 66Gy prescription. The minimum radiation dose and primary tumor volume show the correlation value (r=-0.516, P=0.02). CONCLUSION: In glottic cancer, T1 and T2 can be differentiated by the extent of 18F-FDG accumulation in primary tumors on PET/CT. The minimum radiation dose rate decreases as volume increases.

Lung volume measurement using chest CT in COVID-19 patients: a cohort study in Japan.

OBJECTIVE: This study aimed to investigate the utility of CT quantification of lung volume for predicting critical outcomes in COVID-19 patients. METHODS: This retrospective cohort study included 1200 hospitalised patients with COVID-19 from 4 hospitals. Lung fields were extracted using artificial intelligence-based segmentation, and the percentage of the predicted (%pred) total lung volume (TLC (%pred)) was calculated. The incidence of critical outcomes and posthospitalisation complications was compared between patients with low and high CT lung volumes classified based on the median percentage of predicted TLCct (n=600 for each). Prognostic factors for residual lung volume loss were investigated in 208 patients with COVID-19 via a follow-up CT after 3 months. RESULTS: The incidence of critical outcomes was higher in the low TLCct (%pred) group than in the high TLCct (%pred) group (14.2% vs 3.3%, p<0.0001). Multivariable analysis of previously reported factors (age, sex, body mass index and comorbidities) demonstrated that CT-derived lung volume was significantly associated with critical outcomes. The low TLCct (%pred) group exhibited a higher incidence of bacterial infection, heart failure, thromboembolism, liver dysfunction and renal dysfunction than the high TLCct (%pred) group. TLCct (%pred) at 3 months was similarly divided into two groups at the median (71.8%). Among patients with follow-up CT scans, lung volumes showed a recovery trend from the time of admission to 3 months but remained lower in critical cases at 3 months. CONCLUSION: Lower CT lung volume was associated with critical outcomes, posthospitalisation complications and slower improvement of clinical conditions in COVID-19 patients.

Poor accuracy and sustainability of the first-step FIB4 EASL pathway for stratifying steatotic liver disease risk in the general population.

BACKGROUND AND AIMS: The European Association for the Study of the Liver introduced a clinical pathway (EASL CP) for screening significant/advanced fibrosis in people at risk of steatotic liver disease (SLD). We assessed the performance of the first-step FIB4 EASL CP in the general population across different SLD risk groups (MASLD, Met-ALD and ALD) and various age classes. METHODS: We analysed a total of 3372 individuals at risk of SLD from the 2017-2018 National Health and Nutrition Examination Survey (NHANES17-18), projected to 152.3 million U.S. adults, 300,329 from the UK Biobank (UKBB) and 57,644 from the Biobank Japan (BBJ). We assessed liver stiffness measurement (LSM) ≥8 kPa and liver-related events occurring within 3 and 10 years (3/10 year-LREs) as outcomes. We defined MASLD, MetALD, and ALD according to recent international recommendations. RESULTS: FIB4 sensitivity for LSM ≥ 8 kPa was low (27.7%), but it ranged approximately 80%-90% for 3-year LREs. Using FIB4, 22%-57% of subjects across the three cohorts were identified as candidates for vibration-controlled transient elastography (VCTE), which was mostly avoidable (positive predictive value of FIB4 ≥ 1.3 for LSM ≥ 8 kPa ranging 9.5%-13% across different SLD categories). Sensitivity for LSM ≥ 8 kPa and LREs increased with increasing alcohol intake (ALD>MetALD>MASLD) and age classes. For individuals aged ≥65 years, using the recommended age-adjusted FIB4 cut-off (≥2) substantially reduced sensitivity for LSM ≥ 8 kPa and LREs. CONCLUSIONS: The first-step FIB4 EASL CP is poorly accurate and feasible for individuals at risk of SLD in the general population. It is crucial to enhance the screening strategy with a first-step approach able to reduce unnecessary VCTEs and optimise their yield.