Real-world safety and effectiveness of lenvatinib in unresectable hepatocellular carcinoma in Korea: post-marketing study.

Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea.Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea.Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n = 511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration (p < 0.001).Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea.Clinical trial registration: ClinicalTrials.gov NCT05225207.

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Quantitative PCR for early detection of human cytomegalovirus end-organ disease in immunocompetent host: A retrospective single-center study.

BACKGROUND: Tissue-invasive end-organ disease (EOD) caused by cytomegalovirus (CMV) is less frequently reported in immunocompetent patients compared to immunocompromised patients. In this study, we investigated the association between CMV viremia and CMV end-organ disease in immunocompetent patients. METHODS: Adult patients (≥18 years old) with CMV viremia were screened from January 2010 to June 2022. The primary outcome was the presence of CMV EOD. Risk factors associated with CMV EOD were analyzed, and a receiver operating characteristic curve was plotted to determine the most accurate cutoff value of the CMV titer for the prediction of CMV EOD. RESULTS: Among the 106 immunocompetent patients with CMV viremia, 31 exhibited CMV EOD. Gastrointestinal tract disease was the most common. The log10 value of the CMV titer was significantly associated with the occurrence of CMV EOD in immunocompetent patients with CMV viremia. The optimal cut-off CMV titer for the prediction of CMV EOD was 749 IU/mL. CONCLUSIONS: Our study suggests the potential association between high CMV titers and the development of CMV end-organ diseases and describes the diagnostic performance and utility of quantitative PCR as a surrogate marker for predicting the occurrence of CMV EOD in immunocompetent patients.

Effects of MAFLD defined by fatty liver index or ultrasonography on kidney function decline in the general population.

This study aimed to investigate whether metabolic dysfunction-associated fatty liver disease (MAFLD) defined by the fatty liver index (FLI) affects the decline in kidney function and whether this relationship is still observed in MAFLD defined by ultrasonography (USG). A retrospective cohort study was conducted using de-identified data from participants who received health checkups at Samsung Changwon Hospital between 2002 and 2018. The primary and secondary exposures were the presence of FLI- and USG-defined MAFLD, respectively. The primary outcome was 5-years slope of eGFR. The secondary outcome was a rapid decline in kidney function, defined as a 5-years slope of estimated glomerular filtration rate (eGFR) of less than - 3 mL/min/1.73 m2 per year. A total of 37,500 participants were included in the analysis. Participants with FLI-defined MAFLD had a larger decline in 5-year eGFR slope than those without FLI-defined MAFLD (beta coefficients - 0.11; 95% CI - 0.14 to - 0.08). Participants with FLI-defined MAFLD had a higher risk of rapid kidney function decline than those without FLI-defined MAFLD (odds ratio 1.33; 95% confidence intervals (CIs) 1.05-1.69). However, USG-defined MAFLD was less related to kidney function decline. In conclusion, the presence of FLI-defined MAFLD was associated with larger and faster kidney function decline.

Prediction of the bone volume for sinus augmentation through 3-dimensional analysis.

Background/purpose: No consensus has been established regarding the exact amount of bone grafting in maxillary sinus augmentation. The aim of this study was to estimate the minimum bone volume for sinus augmentation and to investigate the factors that influence the augmentation volume (AV). Materials and methods: This study included patients with cone-beam computed tomography scanning. Dome-shaped sinus augmentation was performed virtually at vertical heights (VH) of 3, 5, 7, and 9 mm in Group A (without implantation) and Group B (with implantation). The augmentation angle (AA) and the sinus width (SW) were measured. The AV was measured using the three-dimensional image processing program 3D Slicer. Univariable and multivariable analyses were conducted. Results: This study included 30 patients (120 subjects). In Group A, the mean AVs were 0.062, 0.271, 0.642, and 1.287 cc at VHs of 3, 5, 7, and 9 mm, respectively, in Group B, the mean AVs were 0.037, 0.230, 0.594, and 1.230 cc. Univariable analysis indicated that factors significantly associated with the AV in both groups included SW, AA, and VH (P < 0.001). Multivariable analysis indicated that factors significantly associated with the AV in both groups included AA and VH (P < 0.01). Conclusion: Clinicians can predict the bone volume for sinus augmentation by measuring the augmentation height and angle.

Characteristics and biomarkers associated with mortality in COVID-19 patients presenting to the emergency department.

This study aimed to investigate the diverse clinical manifestations and simple early biomarkers predicting mortality of COVID-19 patients admitted to the emergency department (ED). A total of 710 patients with COVID-19 were enrolled from 6,896 patients presenting to the ED between January 2022 and March 2022. During the study period, a total of 478 patients tested positive for COVID-19, among whom 222 (46.4%) presented with extrapulmonary manifestations of COVID-19; 49 (10.3%) patients displayed gastrointestinal manifestations, followed by neurological (n = 41; 8.6%) and cardiac manifestations (n = 31; 6.5%). In total, 54 (11.3%) patients died. A Cox proportional hazards model revealed that old age, acute kidney injury at presentation, increased total leukocyte counts, low platelet counts, decreased albumin levels, and increased LDH levels were the independent predictors of mortality. The albumin levels exhibited the highest area under the curve in receiver operating characteristic analysis, with a value of 0.860 (95% confidence interval, 0.796-0.875). The study showed the diverse clinical presentations and simple-to-measure prognostic markers in COVID-19 patients presenting to the ED. Serum albumin levels can serve as a novel and simple early biomarker to identify COVID-19 patients at high risk of death.

Clinical outcomes and treatment necessity in patients with toxin-negative Clostridioides difficile stool samples.

PURPOSE: The clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI. METHODS: All stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared. RESULTS: Among 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96-0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16-0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7-21 days without complication. CONCLUSION: Our study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.

Amine-Rich Hydrogels for Molecular Nanoarchitectonics of Photosystem II and Inverse Opal TiO2 toward Solar Water Oxidation.

Solar water oxidation is a crucial process in light-driven reductive synthesis, providing electrons and protons for various chemical reductions. Despite advances in light-harvesting materials and cocatalysts, achieving high efficiency and stability remains challenging. In this study, we present a simple yet effective strategy for immobilizing natural photosystems (PS) made of abundant and inexpensive elements, using amine-rich polyethylenimine (PEI) hydrogels, to fabricate organic/inorganic hybrid photoanodes. Natural PS II extracted from spinach was successfully immobilized on inverse opal TiO2 photoanodes in the presence of PEI hydrogels, leading to greatly enhanced solar water oxidation activity. Photoelectrochemical (PEC) analyses reveal that PS II can be immobilized in specific orientations through electrostatic interactions between the positively charged amine groups of PEI and the negatively charged stromal side of PS II. This specific orientation ensures efficient photogenerated charge separation and suppresses undesired side reactions such as the production of reactive oxygen species. Our study provides an effective immobilization platform and sheds light on the potential utilization of PS II in PEC water oxidation.

The impact of Renin-Angiotensin System Inhibitors on bone fracture risk: a nationwide nested case-control study.

BACKGROUND: The therapeutic efficacy of renin-angiotensin system inhibitors (RASi) in elderly patients with hypertension and at risk of fractures has been in the limelight because of accumulating evidence that localized RAS activation in bone tissue leads to osteoclastic bone resorption, resulting in osteoporosis. This study set out to investigate the association between RASi use and fracture incidence in a large cohort. METHODS: We employed a nested case-control design to investigate the association between RASi use and newly developed fractures. A case was defined as a patient newly diagnosed with a fracture between January 2004 and December 2015. We selected 1,049 cases and controls using 1:1 propensity score matching. Conditional logistic regression analysis was conducted to estimate the association between RASi exposure and fracture incidence. RESULTS: Overall, RASi usage was significantly associated with lower odds for fracture incidence (ever-users vs never-users: OR, 0.73; 95% CI, 0.59-0.91). We found that ARB-only users experienced fewer fractures than RASi-never users (OR, 0.65; 95% CI, 0.49-0.86), whereas ACEi-only users or ARB/ACEi-ever users did not. In subgroup analysis, RASi-ever users without cerebrovascular disease, those with a BMI exceeding 23, and statin exposure had significantly lower ORs. CONCLUSIONS: The present study established a significant association between RASi use and reduced fracture incidence, thus highlighting the potential clinical utility of RASi use as a preventive strategy in elderly patients at risk for osteoporotic fractures.

Greater Severity of Steatosis Is Associated with a Higher Risk of Incident Diabetes: A Retrospective Longitudinal Study.

BACKGRUOUND: Fatty liver is associated with increased risk of developing type 2 diabetes. We aimed to evaluate whether the severity of hepatic steatosis is associated with incident diabetes. METHODS: We conducted a longitudinal analysis using data from 1,798 participants who underwent a comprehensive health checkup and abdominal computed tomography (CT). We assessed the association between baseline liver attenuation value on non-contrast CT images and risk of incident diabetes. All the participants were categorized into three groups based on the baseline liver attenuation value on non-contrast CT images: without hepatic steatosis (>57 Hounsfield unit [HU]), mild hepatic steatosis (41-57 HU), and moderate to severe hepatic steatosis (≤40 HU). RESULTS: During a median follow-up period of 5 years, 6.0% of the study participants progressed to diabetes. The incidence of diabetes was 17.3% in the moderate to severe hepatic steatosis group, 9.0% in the mild steatosis group, and 2.9% in those without hepatic steatosis. In a multivariate adjustment model, as compared with participants without hepatic steatosis, those with moderate to severe steatosis had a hazard ratio (HR) of 3.24 (95% confidence interval [CI], 1.64 to 4.2) for the development of diabetes, and those in the mild steatosis group had a HR of 2.33 (95% CI, 1.42 to 3.80). One standard deviation decrease in mean CT attenuation values of the liver was associated with a 40% increase in the development of diabetes (multivariate adjusted HR, 1.40; 95% CI, 1.2 to 1.63). CONCLUSION: We found a positive association between severity of hepatic steatosis and risk of incident diabetes. Greater severity of steatosis was associated with a higher risk of incident diabetes.

Efficacy and Safety of Chemotherapy in Elderly Patients with Unresectable Pancreatic Cancer.

BACKGROUND/AIMS: The incidence of pancreatic cancer (PC) is gradually increasing among elderly individuals, but there are insufficient clinical data on elderly individuals. To determine the efficacy and safety of chemotherapy, we compared the. the outcomes of elderly patients with unresectable PC. METHODS: We enrolled patients aged 75 years or older diagnosed with PC from 1 January 2010 to 30 November 2021. Propensity score matching (PSM) was used to reduce the heterogeneity of the study population. For efficacy evaluation, the median overall survival (OS) was estimated for the chemotherapy and nonchemotherapy groups. Chemotherapy tolerability evaluations were also investigated. RESULTS: The study included 115 patients, 47 of whom received chemotherapy and 68 who did not. After PSM, compared with the nonchemotherapy group, the chemotherapy group had more myocardial infarctions (14.6 vs. 0.0%, p < 0.001) and chronic obstructive pulmonary disease (4.4 vs. 0.0%, p = 0.043). The primary endpoint, median OS, was significantly different in the with vs. without chemotherapy groups (203 vs. 106 days, p = 0.013). In the chemotherapy group, 10 patients (21.3%) discontinued treatment due to adverse events. However, there were no reports of death due to severe adverse events. CONCLUSIONS: This study demonstrated that chemotherapy improved median OS among elderly patients. These data could support the use of chemotherapy for elderly patients with unresectable PC.

Clinical Outcomes and Validation of Ursodeoxycholic Acid Response Scores in Patients with Korean Primary Biliary Cholangitis: A Multicenter Cohort Study.

Background/Aims: The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. Methods: A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. Results: After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCA response rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41 (n=97). The area under the receiver operating characteristic curve of URS in predicting UDCA response was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5 years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed according to the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005). Conclusions: URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.

Efficacy and safety of glecaprevir/pibrentasvir treatment in Koreans with chronic hepatitis C: A retrospective study.

BACKGROUND AND STUDY AIMS: The introduction of direct-acting antiviral (DAA) drugs has dramatically improved chronic hepatitis C (CHC) treatment. The pangenotype DAA therapy glecaprevir/pibrentasvir (G/P) was recently recommended for treating CHC in Korea. Unfortunately, given its recent introduction, little real-world data from a Korean population exists. We examined the effectiveness and safety of G/P treatment in Koreans with CHC. PATIENTS AND METHODS: We analyzed CHC patients at Samsung Changwon Hospital from June 2018 to December 2020. Sustained virologic response at 12 weeks posttreatment (SVR 12) was evaluated after treatment, and the associated factors were analyzed. Furthermore, the degree of liver fibrosis before and after treatment was compared to determine whether liver fibrosis improved. RESULTS: In total, 102 patients were enrolled; 35.3 % had compensated liver cirrhosis (LC), and 11.8 % had received previous treatment. Of the 102 patients, 99 (97.1 %) reached SVR 12. Of the 81 patients who completed 8 weeks of G/P treatment, 80 (98.8 %) reached SVR 12, while 19 of the 21 (90.5 %) patients in the 12- or 16-week group reached SVR 12, with no significant difference between the two groups (P = 0.107). As a secondary endpoint, liver fibrosis before and after treatment was also compared. The Fibrosis-4 index (FIB-4) (3.3 vs 2.8, P = 0.010), aspartate transaminase (AST)-platelet ratio index (APRI) (1.3 vs 1.0, P < 0.001), and liver stiffness measurements (LSM) (9.5 vs 4.6, P < 0.001) were significantly different after G/P treatment. CONCLUSIONS: Regardless of genotype, G/P treatment for Koreans with CHC is safe, highly effective, and can improve liver fibrosis.

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Multi-Strain Synbiotic in Patients with Functional Diarrhea and High Fecal Calprotectin Levels: A Pilot Study.

Synbiotics, including probiotics and prebiotics, are useful for patients with functional bowel disorders. However, which synbiotics are beneficial for patients with which diseases, especially those with functional diarrhea (FDr) with high fecal calprotectin levels, is currently unknown. FDr is an extension of irritable bowel syndrome with diarrhea (IBS-D). Although fewer studies have been conducted on FDr compared to IBS-D, its importance is increasing as its prevalence increases. The aim of this study was to evaluate the effects of a synbiotic containing a mixture of Lactobacillus and Bifidobacterium and its substrate, fructooligosaccharide, on bowel symptoms, fecal calprotectin levels, fecal microbiota, and safety in FDr patients with high fecal calprotectin levels. Forty patients were randomly assigned to either a synbiotic group or a placebo group. A total of 20 subjects in the synbiotic group and 19 subjects in the placebo group completed the study (8 weeks). Changes in FDr symptoms, fecal calprotectin levels, and gut microbiota were assessed during the intervention period. At 4 and 8 weeks, the number of bowel movements tended to increase in the synbiotic group, with a significant increase in the number of formed stools rather than loose stools (p < 0.05). Bowel movement satisfaction was significantly increased in the synbiotic group, but not in the placebo group. Intestinal flora analysis revealed that Lactobacillales at the order level was increased only in the synbiotic group at the end of the intervention. In contrast, at week 8 of the intervention, log-transformed fecal calprotectin levels were significantly decreased in the synbiotic group, although the change was not significantly different from that of the placebo group. These findings suggest that the intake of a multi-strain-containing synbiotic for 8 weeks could improve gut symptoms and the intestinal microenvironment of FDr patients with high fecal calprotectin levels.

Usefulness of Hounsfield Units and the Serum Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Patients with Breast Cancer.

Breast cancer is a leading cause of death worldwide. Tumor vascularity and immune disturbances are hallmarks of cancer. This study aimed to investigate the reciprocal effect of tumor vascularity, assessed by the tumor-to-aorta ratio (TAR) of Hounsfield units (HU) on computed tomography (CT), and host immunity, represented by the serum neutrophil-to-lymphocyte ratio (NLR) from peripheral, complete blood cell counts and its impact on patient survival. Female patients with breast cancer who received primary treatment between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. The final cohort included 740 patients with a mean age of 54.3 ± 11.3 (22−89) years. The TAR was 0.347 ± 0.108 (range, 0.062−1.114) and the NLR was 2.29 ± 1.53 (0.61−10.47). The cut-off value for the TAR and NLR were 0.27 and 1.61, respectively. The patients with a TAR > 0.27 showed a poor recurrence free-interval (RFI) only when their NLR was larger than 1.61, and vice versa. The patients showed worse RFI when they had both high TAR and NLR. Our results suggest a dynamic reciprocal communication between tumor vascularity and systemic immunity.

A Review of Flow Characterization of Metallic Materials in the Cold Forming Temperature Range and Its Major Issues.

We focus on the importance of accurately describing the flow behaviors of metallic materials to be cold formed; we refer to several valuable examples. We review the typical experimental methods by which flow curves are obtained, in addition to several combined experimental-numerical methods. The characteristics of four fundamental flow models including the Ludwik, Voce, Hollomon, and Swift models are explored in detail. We classify all flow models in the literature into three groups, including the Ludwik and Voce families, and blends thereof. We review the experimental and numerical methods used to optimize the flow curves. Representative flow models are compared via tensile testing, with a focus on the necking point and pre- or post-necking strain hardening. Several closed-form function models employed for the non-isothermal analyses of cold metal forming are also examined. The traditional bilinear C-m model and derivatives thereof are used to describe the complicated flow behaviors of metallic materials at cold forming temperatures, particularly in terms of their applications to metal forming simulations and process optimization.

Modified FOLFIRINOX as a Second-Line Treatment for Patients with Gemcitabine-Failed Advanced Biliary Tract Cancer: A Prospective Multicenter Phase II Study.

BACKGROUND: After the publication of the ABC-02 trial, gemcitabine and cisplatin combination therapy (GP) became the standard first-line treatment for advanced biliary tract cancer (BTC). Despite GP therapy, most patients suffer from disease progression. The ABC-06 trial recommended FOLFOX as a second-line treatment, but its efficacy was modest. In this phase II study, we looked at the efficacy and safety of a second-line modified dose of FOLFIRINOX (mFOLFIRINOX) for patients who had failed first-line gemcitabine-based treatment. METHODS: From January 2020 to January 2021, 34 patients with advanced BTC who failed first-line gemcitabine-based chemotherapy were enrolled. We evaluated the clinical efficacy and safety outcomes of mFOLFIRINOX. RESULTS: With a median follow-up duration of 13.4 months, the median progression-free survival and overall survival was 2.8 months (95% confidence interval (CI): 1.6-4.0 months) and 6.2 months (95% CI: 5.0-7.4 months), respectively. The objective response rate was 14.7% with no complete response. The disease control rate was 61.7%, with a disease control duration of 4.2 months. Due to the rapid progression of the disease, approximately half of all patients received less than three cycles of treatment. The most common type of adverse event (AEs) was hematopoietic AEs. The incidence of non-hematopoietic AEs was relatively low. CONCLUSIONS: The efficacy of mFOLFIRINOX as a second-line treatment in advanced BTC patients after the failure of gemcitabine-based first-line treatment was replicated, albeit with slightly shorter survival results compared to previous studies. Long-term administration of mFOLFIRINOX with toxicity management might offer a survival benefit.

Patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy for localized prostate cancer: a single-center retrospective study.

BACKGROUND: Several studies have reported patient-related risk factors for late rectal bleeding following conventionally fractionated radiotherapy for prostate cancer. We investigated patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy. METHODS: A total of 231 patients with local or locally advanced prostate cancer treated with hypofractionated radiotherapy (70 or 67.2 Gy in 28 fractions) were evaluated retrospectively. All patients received intensity-modulated radiotherapy with daily image guidance. The relationships between late rectal bleeding and risk factors like diabetes, hypertension, cirrhosis, and anticoagulant use were analyzed. RESULTS: During a median follow-up of 23 months, the crude rates of grade ≥ 1, grade ≥ 2, and grade ≥ 3 late rectal bleeding were 23.8%, 16.9%, and 9.5%, respectively. Cirrhosis and anticoagulant use predicted an increased risk of grade ≥ 3 rectal bleeding in multivariable analyses (hazard ratio [HR] 14.37, 95% confidence interval [CI] 3.09-66.87, P = 0.001, and HR 2.93, 95% CI 1.14-7.55, P = 0.026, respectively). The non-anticoagulant group had a significantly superior 5-year freedom from grade ≥ 3 bleeding compared to the anticoagulant group in a propensity-weighted log-rank analysis (88.0% vs. 76.7%, P = 0.041). A receiver operating characteristic curve analysis revealed that rectal bleeding was minimized in the anticoagulant group if the equivalent dose at fractionation of 2 Gy (EQD2) V77 Gy of the rectum was < 4.5% or if the EQD2 V8.2 Gy was < 71.0%. CONCLUSIONS: Patients taking anticoagulants or those with cirrhosis had a significantly higher risk of severe late rectal bleeding than other patients after hypofractionated radiotherapy for prostate cancer in the present study. The bleeding risk could be lowered by minimizing hotspots in patients taking anticoagulants.

Incidence and risk factors for development of hepatocellular carcinoma at young age in patients with chronic hepatitis B.

BACKGROUND: Some young adults with chronic hepatitis B virus (HBV) infection might be at high risk for hepatocellular carcinoma (HCC), enough to justify regular HCC surveillance despite the young age of the patients. However, ways to identify at-risk individuals who may benefit from HCC surveillance need further evaluations. METHODS: A hospital-based retrospective cohort of 2757 chronic HBV mono-infected young adults (median age: 34 years, males 66%) were analyzed. The primary outcome was young-onset HCC, defined as a diagnosis made under 40 years of age. We calculated the HCC incidence/1000 person-years in the overall cohort and pre-defined subgroups of patients assessed the independent risk factors that can be used to identify surveillance targets. RESULTS: The HCC incidence was low (2.55/1000 person-years) in the overall cohort. However, the HCC incidence varied widely according to baseline characteristics: lowest among young adults with FIB-4 ≤ 0.70 (0.17/1000 person-years) and highest in young adults with radiological cirrhosis (30.7/1000 person-years). In multivariable analysis, radiological cirrhosis, the FIB-4 index, and serum HBV DNA level were independent factors associated with HCC development at a young age. Performance for prediction of young-onset HCC in radiological cirrhotic patients showed the highest specificity but sensitivity was <70%. Combination with FIB-4 index and HBV DNA levels increased sensitivity to 90%. CONCLUSION: Risk stratification using FIB-4 index, HBV DNA levels, and either combining radiological cirrhosis or gender and AFP levels would be helpful to stratify young patients who would and would not benefit from regular HCC surveillance.

Neutrophil to Lymphocyte Ratio after Treatment Completion as a Potential Predictor of Survival in Patients with Triple-Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has been associated with worse prognosis, and biomarkers are needed to identify high-risk patients who may benefit from clinical trials or escalated treatment after completion of standard treatment. We aimed to assess whether the post-treatment neutrophil-to-lymphocyte ratio (NLR) can reflect patient prognosis and determine the follow-up period that can provide the most feasible data. METHODS: In this retrospective analysis involving patients with TNBC, clinicopathological data, including those on peripheral complete blood cell count, were collected. The prognostic powers of serial NLRs obtained at baseline and after treatment completion were compared. Kaplan-Meier curves were generated to compare the overall survival (OS) and distant disease-free survival (DDFS). RESULTS: In total, 210 patients were enrolled. Forty-three (20.5%) events were detected. Two-thirds of the events (29/43) were related to breast cancer. Most recurrent breast cancer-related diseases (27/29) were detected within 5 years of the initial diagnosis. In contrast, half of the events due to secondary malignancies or non-breast-related diseases (7/14) occurred 5 years after the initial diagnosis. Comparison of the prognostic performance of NLRs at baseline and at 6, 12, and 24 months after treatment completion revealed the strongest prognostic performance at 6 months after treatment completion (area under the curve = 0.745). The high NLR group (NLR >2.47) showed worse OS (p = 0.006) and DDFS (p < 0.001) than low NLR group. CONCLUSION: Elevated post-treatment NLR was significantly associated with worse survival in patients with TNBC. We believe that it can be a useful surrogate marker for identifying high-risk patients with TNBC.

Prevalence, risk factors, and short-term outcomes of postparacentesis acute kidney injury using revised criteria of the international club of ascites.

ABSTRACT: Acute kidney injury (AKI) can become complicated after paracentesis due to extrarenal fluid loss and inadequate blood flow to the kidneys. The objective of this study was to explore the incidence and clinical implications of postparacentesis AKI.A retrospective cohort of 137 liver cirrhosis patients (mean age: 61.3 ±â€Š11.8 years, male: 100 [73.0%], viral hepatitis: 93 [67.9%]) who underwent paracentesis was analyzed. The incidence of AKI as defined by the international club of ascites (ICA) criteria, the risk factors, and its impact on early mortality were all assessed.Thirty two patients (23.4%) developed AKI after paracentesis. In multivariate analysis, the Model for end-stage liver disease (MELD)-Na score was an independent factor associated with AKI development (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.07-1.23) after paracentesis. The incidence of early mortality was significantly higher for those with AKI than without AKI (71.9% [23/32 patients] vs 11.4% [12/105 patients], P < .001). AKI (hazard ratio [HR], 7.56; 95% CI, 3.40-16.8) and MELD-Na score (HR, 1.08; 95% CI, 1.02-1.14) were independent factors associated with early mortality. In subgroup analysis, AKI after paracentesis was associated with significantly higher early mortality in both MELD-Na groups, that is, patients with a MELD-Na score >26 (87.5% vs 22.2%, P < .001) and those with a MELD-Na score ≤26 (56.3% vs 9.2%, P < .001).Postparacentesis AKI occurred frequently in cirrhotic patients. Furthermore, it was associated with early mortality. Baseline MELD-Na score was associated with AKI, indicating that careful attention is required for those with a higher MELD-Na score who are being considered for therapeutic paracentesis.