Clinical application of whole-genome sequencing of solid tumors for precision oncology.

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Clinical Implications for the Comprehensive Interpretation of Radiologic and Immunodiagnostic Tests in Patients Suspected of Parasitic Hepatic Cyst, a Rare Case in Korea.

Cystic echinococcosis (CE) is a representative neglected tropical disease (NTD) with increased morbidity and mortality but is ignored and overlooked in developed countries. Serological and radiographic findings are helpful in distinguishing these parasites; however, conflicting results of these can make it difficult to diagnose if medical knowledge of hepatic parasitic disease, including the etiology, features of imaging, and immunodiagnostic test, is not acquired. We report the case of a male patient with dyspepsia and right epigastric pain who had positive results for cysticercosis antibodies on immunodiagnostic examination. Abdominal ultrasonography revealed two huge communicating cystic lesions measuring 8-11 cm. Further evaluations for cysticercosis of the brain (neurocysticercosis) and eyes (intraocular cysticercosis) were unremarkable throughout the brain imaging test and fundus examination. A laparoscopic right hemi-hepatectomy was performed for diagnosis and treatment. On histopathological examination, diverse stages of Echinococcus granulosus were identified. Albendazole was administered postoperatively, and the patient was also followed up. We should be aware of the etiologies that have been prevalent in parasite infection thought to be the cause of hepatic cysts. Moreover, we make an effort to ascertain the patient's nationality, past travel experiences, and immediate environment, including any animals and pets. We present the case of a patient who was worried about the possibility of liver invasion of cysticercus due to the positivity of the cysticercosis antibody and was ultimately diagnosed with CE.

Prognostic Impact of Myosteatosis on Mortality in Hospitalized Patients with COVID-19.

Body composition, including sarcopenia, adipose tissue, and myosteatosis, is associated with unfavorable clinical outcomes in patients with coronavirus disease (COVID-19). However, few studies have identified the impact of body composition, including pre-existing risk factors, on COVID-19 mortality. Therefore, this study aimed to evaluate the effect of body composition, including pre-existing risk factors, on mortality in hospitalized patients with COVID-19. This two-center retrospective study included 127 hospitalized patients with COVID-19 who underwent unenhanced chest computed tomography (CT) between February and April 2020. Using the cross-sectional CT images at the L2 vertebra level, we analyzed the body composition, including skeletal muscle mass, visceral to subcutaneous adipose tissue ratio (VSR), and muscle density using the Hounsfield unit (HU). Of 127 patients with COVID-19, 16 (12.6%) died. Compared with survivors, non-survivors had low muscle density (41.9 vs. 32.2 HU, p < 0.001) and high proportion of myosteatosis (4.5 vs. 62.5%, p < 0.001). Cox regression analyses revealed diabetes (hazard ratio [HR], 3.587), myosteatosis (HR, 3.667), and a high fibrosis-4 index (HR, 1.213) as significant risk factors for mortality in patients with COVID-19. Myosteatosis was associated with mortality in hospitalized patients with COVID-19, independent of pre-existing prognostic factors.

Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration.

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

Association between Fasting Ketonuria and Advanced Liver Fibrosis in Non-Alcoholic Fatty Liver Disease Patients without Prediabetes and Diabetes Mellitus.

Ketone body production, an alternative fuel upon low glucose availability, reduces hepatic fat accumulation. However, its clinical implications have not been established in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the association between spontaneous fasting ketonuria and liver fibrosis in patients with NAFLD without prediabetes and diabetes mellitus (DM). A total of 6202 patients with ultrasound confirmed NAFLD without prediabetes and DM were enrolled in the study. Using low cut off values of NAFLD fibrosis score (NFS) and fibrosis-4, liver fibrosis was defined as an intermediate-high probability of advanced liver fibrosis. Of the 6202 NAFLD patients, 360 (5.8%) had ketonuria. Compared to the patients without ketonuria, patients with ketonuria were younger (41.1 vs. 44.6 years, p < 0.001), had lower levels of glucose (87.2 vs. 91.0 mg/dL, p < 0.001), and homeostatic model assessment for insulin resistance (1.0 vs. 1.5, p < 0.001). The presence of ketonuria had an inverse association with liver fibrosis, assessed using both NFS (final adjusted odds ratio [aOR], 0.67; 95% confidence interval [CI], 0.45-1.01) and fibrosis-4 (aOR, 0.58; 95% CI, 0.40-0.84). The presence of ketonuria in NAFLD patients without prediabetes and DM may have favorable metabolic effects compared to the absence of ketonuria, independent of traditional metabolic factors.

Association of Skeletal Muscle and Adipose Tissue Distribution with Histologic Severity of Non-Alcoholic Fatty Liver.

Adipose tissue and skeletal muscle is associated with non-alcoholic fatty liver disease (NAFLD). This study evaluates the association between body composition and histologic severity in patients with NAFLD. Using the cross-sectional CT images at the level of L3 vertebra and the histologic findings of 178 patients with biopsy-proven NAFLD, we analyzed the correlation of the histologic findings to the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI), which is defined as the body composition area (cm2) by height squared (m2). The clinical and laboratory features with body composition were analyzed to determine the risk factors for advanced fibrosis. The VATI significantly increased in severe non-alcoholic steatohepatitis (NASH) or advanced fibrosis. In addition, the VATI was correlated with the NAFLD activity score (NAS) and the fibrosis stage. In multivariate analyses, age (odds ratio (OR), 1.09; 95% confidence interval (CI), 1.02-1.19; p = 0.025), severe NASH (OR, 8.66; 95% CI, 2.13-46.40; p = 0.005), and visceral adiposity (OR, 6.77; 95% CI, 1.81-29.90; p = 0.007) were independently associated with advanced fibrosis in patients with NAFLD. Visceral adiposity is correlated with the histologic severity of NAFLD, which is independently associated with advanced fibrosis.

Low Skeletal Muscle Mass Is a Risk Factor for Subclinical Atherosclerosis in Patients with Nonalcoholic Fatty Liver Disease.

Sarcopenia and nonalcoholic fatty liver disease (NAFLD) are associated with subclinical atherosclerosis. We aimed to investigate the association between low skeletal muscle mass (LSMM) and subclinical atherosclerosis in patients with NAFLD. A total of 683 patients with ultrasound-confirmed NAFLD who underwent carotid ultrasonography were enrolled retrospectively. The appendicular skeletal muscle mass divided by the body mass index was used to define LSMM. Using carotid ultrasound, increased carotid intima-media thickness (cIMT, >1 mm) and the presence of carotid plaques were measured. Of the 683 patients, 75 (11.0%) had LSMM. In multivariate analyses, LSMM was associated with increased cIMT (odds ratios (ORs) = 2.26 to 2.95, all p < 0.05) and carotid plaques (ORs = 2.05 to 2.90, all p < 0.05). The proportion of increased cIMT and carotid plaques was significantly higher in obese NAFLD patients with LSMM than in those without LSMM (33.3% vs. 17.6% for cIMT and 12.7% vs. 5.7% for carotid plaques, respectively; p < 0.001). Furthermore, LSMM was independently associated with increased cIMT (ORs = 2.44 to 3.30, all p < 0.05) and carotid plaques (ORs = 2.56 to 3.54, all p < 0.05) in obese NAFLD patients. LSMM is associated with subclinical atherosclerosis in patients with NAFLD.

Isolated double-chambered right ventricle in a young adult.

Double-chambered right ventricle (DCRV) is a rare congenital heart disorder in which the right ventricle is divided by an anomalous muscle bundle into a high pressure inlet portion and a low pressure outlet portion. We report a case of isolated DCRV without symptoms in adulthood, diagnosed through echocardiography, cardiac catheterization and cardiac magnetic resonance imaging.