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Critically-ill surgical patients are at higher risk for sarcopenia, which is associated with worse survival. Sarcopenia may impair the respiratory musculature, which can subsequently influence the outcome of ventilator weaning. Although there are a variety of weaning parameters predictive of weaning outcomes, none have tried to incorporate \"muscle strength\" or \"sarcopenia\". The aim of the current study was to explore the association between sarcopenia and difficult-to-wean (DtW) in critically-ill surgical patients. The influence of sarcopenia on ICU mortality was also analyzed. Ninety-six patients undergoing mechanical ventilation in the surgical intensive care unit (ICU) were enrolled. Demographic data and weaning parameters were recorded from the prospectively collected database, and the total psoas muscle area (TPA) was determined at the level of the 3rd lumbar vertebra by computed tomography. Sarcopenia was defined by previously established cut-off points and its influence on clinical outcomes was examined. Receiver operating characteristic (ROC) curve analysis was conducted to investigate the predictive capability of TPA and weaning parameters for predicting weaning outcomes. The median age of the studied patients was 73 years. Thirty patients (31.3%) were sarcopenic and 30 (31.3%) were defined as DtW. Eighteen patients (18.8%) had ICU mortality. Multivariate logistic regression analyses revealed that sarcopenia was an independent risk factor for DtW and ICU mortality. The area under the ROC curve (AUC) of TPA for predicting successful weaning was 0.727 and 0.720 in female and male patients, respectively. After combining TPA and conventional weaning parameters, the AUC for DtW increased from 0.836 to 0.911 and from 0.835 to 0.922 in female and male patients, respectively. Sarcopenia is an independent risk factor for DtW and ICU mortality. TPA has predictive value when assessing weaning outcomes and can be used as an effective adjunct predictor along with conventional weaning parameters.

Background Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and safety in these two regimens are limited, we therefore conduct this study to investigate these issues. Methods We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance. Results A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.085[0.914–4.753], p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score. Conclusions The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC. This study provides real‐world experience of lenvatinib and A + B as firstline treatment for unresectable HCC. The data showed that compared survival, response rate, and adverse events between two regimens.

PurposeTo investigate the outcomes of radiofrequency ablation (RFA) following artificial ascites (AA) and artificial pleural effusion (AP) creation for hepatocellular carcinoma (HCC) in high-risk locations.Materials and methodsEligible patients were divided into 2 study periods (non-AAAP and AAAP groups) with AAAP performed in the latter period. Local tumor progression, primary technique effectiveness and complications were compared between patients with and without AAAP. Cumulative probability of local tumor progression and overall survival were estimated with Kaplan–Meier curves.ResultsOne hundred thirty-eight patients with 195 tumors were evaluated. AAAP was performed in 48 patients with 76 tumors. Local tumor progression rates at 12 and 24 months were 9.3% and 22.2% in the non-AAAP group versus 5.5% and 9% in the AAAP group (p < 0.0001). Primary technique effectiveness was achieved in 76.5% of the non-AAAP group versus 89.5% of the AAAP group (p = 0.046). Night (7.6%) major complications occurred in the non-AAAP group and 2 (2.6%) cases occurred in the AAAP group. Therapy-oriented severity grading system after RFA was lower in the AAAP group (p = 0.02). Overall survival rates at 12 and 24 months were 85.6% and 77.7% in the non-AAAP group versus 97.2% and 89.7% in the AAAP group (p = 0.033).ConclusionRFA following AA and AP for high-risk located HCC may improve outcomes.

Background: Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who achieved SVR through the DAA versus IFN regimens. Methods: A retrospective analysis was conducted on 4806 HCV patients, without coinfection nor prior HCC history, treated at the Chang Gung Memorial Hospital, Taiwan (DAA: 2825, IFN: 1981). Kaplan–Meier and Cox regression analyses with propensity score matching (PSM) were used to adjust for baseline differences. Results: DAA-treated patients exhibited a higher incidence of HCC than IFN-treated patients before and after PSM (after PSM: annual: 1% vs. 0.5%; 6-year: 6% vs. 3%, p = 0.01). Both DAA and IFN patients had a decreased HCC incidence during follow-up (>3 vs. <3 years from the end of treatment: DAA: 1.43% vs. 1.00% per year; IFN: 0.47% vs. 0.36% per year, both p < 0.05). HCC incidence was higher in the first three years post-SVR in DAA-treated ACLD patients and then decreased (3.26% vs. 1.39% per year, p < 0.01). In contrast, HCC incidence remained constant in the non-ACLD and IFN-treated groups. Multivariate Cox regression identified age ≥ 60, male sex, BMI, AFP ≥ 6 ng/mL, FIB-4, and ACLD status as independent risk factors for HCC, but antiviral regimens were not an independent factor for HCC. Conclusion: DAA treatment significantly affects HCC risk primarily within three years post-treatment, especially in younger HCV patients with ACLD. HCC incidence was reduced after three years in ACLD patients treated by DAA, but continued surveillance was still necessary. However, patients under 60 without advanced liver disease may require less intensive follow-up.

Background Hepatocellular carcinoma (HCC) is an aggressive solid tumor. HCC occurred at younger and elder ages were considered driven by different oncogenic mechanisms, and they demonstrated distinct clinical courses. Methods A total of 382 HCC patients treated by surgical resections was analyzed. Results A univariate-multivariate analysis showed that viral etiology (chronic hepatitis B, C) and the UDP glucuronosyltransferase family 2 member B28 ( UGT2B28 ) genomic variant rs2132039 were independently associated with the age at presentation of HCC (all adjusted P  < 0.05). An extensive evaluations of clinicalpathological factors showed that the age (Odds ratio [OR], 1.016; 95% confidence interval [CI], 1.001–1.032; adjusted P  = 0.037) and ascites (OR, 3.505; CI, 1.358–9.048; adjusted P  = 0.010) were two independent factors associated with this genomic variant. The age was 54.1 ± 14.6 years for patients with the “TT” variant type, and 58.2 ± 13.7 years for those with the “Non-TT” variant type. The age disparity was most prominent in alcoholic patients (OR, 1.079; CI, 1.035–1.125; P  < 0.001, age of “TT”, 49.6 ± 12.2; age of “non-TT”, 59.3 ± 10.7). This genomic variant was also associated with age of recurrence ( P  = 0.025), distant metastasis ( P  = 0.024) and HCC-related death ( P  = 0.008) in non-censored patients. Conclusions An UGT2B28 genomic variant was indicative of the age of HCC presentation, recurrence, distant metastasis and death.

Objectives Radiofrequency ablation (RFA) of medium-sized (3–5 cm) hepatocellular carcinoma (HCC) is suboptimal. Switching monopolar RFA (SW-RFA) enlarges the ablative volume to better cover larger tumors. This study aims to compare the long-term outcomes of medium-sized HCC treated by either SW-RFA or single-monopolar RFA (S-RFA). Methods We retrospectively reviewed 139 cases (147 medium-size HCC) between 2008 and 2014. Under propensity score matching, a total of 43 paired patients with medium-size HCC and balanced clinical variables treated by either SW-RFA or S-RFA were selected for comparison. Results SW-RFA showed a higher rate of achieving an adequate safety margin ( p = 0.002). After a mean follow-up period of 40.4 months, SW-RFA produced significantly lower global RFA failure rates ( p < 0.001) and better overall survival ( p = 0.005) compared to S-RFA. SW-RFA was independently associated with a decreased risk of global RFA failure (hazard ratio [HR]: 0.136, 95% confidence interval [CI]: 0.030–0.607, p = 0.009) and improved overall survival (HR: 0.337, 95% CI: 0.152–0.747, p = 0.007). By last follow-up, the SW-RFA group maintained a superior tumor-free rate ( p = 0.010) and fewer progressions to Barcelona Clinic Liver Cancer stage C ( p = 0.011). Major complication rates were comparable in both groups (SW-RFA: 2.3% vs. S-RFA: 4.7%, p = 1.000). Conclusions The switching multi-monopolar ablation technique could be beneficial for patients with medium-sized HCCs given sustained control of larger tumors with better overall survival. Key Points • Switching monopolar ablation could provide a sustained local tumor control and better overall survival than single-monopolar ablation for the medium-sized hepatocellular carcinoma. • Compared to single-monopolar ablation, switching monopolar ablation could create a larger homogeneous coagulation volume by using a shorter total ablation time to achieve a higher rate of adequate safety margin for a medium-sized HCC. • Patients with medium-sized HCC can be maintained at a higher rate of tumor-free status and at a lower risk of progression into BCLC stage C in the follow-up period after ablation by switching monopolar than by single-monopolar ablation.

Purpose Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a dismal prognosis. Vascular invasion, among others, is the most robust indicator of postoperative recurrence and overall survival after liver resection for HCC. Few studies to date have attempted to search for effective markers to predict vascular invasion before the operation. The current study would examine the plasma metabolic profiling via 1 H-NMR of HCC patients undergoing liver resection and aim to search for potential biomarkers in the early detection of HCC with normal alpha-fetoprotein (AFP) and the diagnosis of vascular invasion preoperatively. Materials and methods HCC patients scheduled to receive liver resections for their HCC were recruited and divided into two separate groups, investigation cohort and validation cohort. Their preoperative blood samples were collected and subjected to a comprehensive metabolomic profiling using 1 H-nuclear magnetic resonance spectroscopy (NMR). Results There were 35 HCC patients in the investigation group and 22 patients in the validation group. Chronic hepatitis B remained the most common etiology of HCC, followed by chronic HCV infection. The two study cohorts were essentially comparable in terms of major clinicopathological variables. After 1 H-nuclear NMR analysis, we found in the investigation cohort that HCC with normal alpha-fetoprotein (AFP < 15 ng/mL) had significantly higher serum level of O-acetylcarnitine than those with higher AFP (AFP ≥ 15 ng/mL, P = 0.025). In addition, HCC with microscopic vascular invasion (VI) had significantly higher preoperative serum level of formate than HCC without microscopic VI ( P = 0.023). These findings were similar in the validation cohort. Conclusion A comprehensive metabolomic profiling of HCC demonstrated that serum metabolites may be utilized to assist the early diagnosis of AFP-negative HCC patients and recognition of microvascular invasion in order to facilitate preoperative surgical planning and postoperative follow-up. Further, larger scale prospective studies are warranted to consolidate our findings.

Background: Atezolizumab plus bevacizumab is the standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). Immune-related liver injury (IrLI) is common; however, the association between IrLI severity and patient outcomes remains unknown. This study aimed to investigate the prognostic value of irLI in such patients. Methods: One hundred and sixteen patients who fulfilled the IMBrave150 inclusion criteria were enrolled. IrLI was defined as an increase in serum ALT and/or AST levels attributed to treatment and was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: A total of 61 patients (52.6%) developed any grade of irLI, with a median onset time of 1.7 months. Multivariate analysis revealed that grade II ALBI (hazard ratio [HR] = 2.003, p = 0.028) and BCLC stage C (HR = 3.876, p = 0.016) were associated with worse OS and PFS (HR = 1.327, p = 0.044 and HR = 1.790, p = 0.039, respectively), whereas grade 2 irLI was associated with better OS (HR = 0.223, p = 0.046) and PFS (HR = 0.244, p = 0.011). Patients with grade 2 irLI showed better median OS (not reached) than those without irLI (16.7 months), those with grade 1 (17.5 months), and those with grade ≥ 3 (7.3 months) (overall log-rank p = 0.037). Furthermore, patients with grade 2 irLI demonstrated significantly enhanced PFS (not reached) compared to those without irLI (5.7 months), grade 1 (4.6 months), or grade ≥ 3 (2.3 months), with an overall log-rank p = 0.010. In addition, patients with grade 2 irLI had the highest disease control rate (overall p = 0.053). Conclusion: In patients with uHCC treated with Ate/Bev, moderate elevation of liver enzymes (grade 2 irLI) was associated with significantly improved survival and tumor control.

Background: The combination of anti-angiogenic therapy and immune checkpoint inhibitors has revolutionized the management of unresectable hepatocellular carcinoma (uHCC). While an early-phase study demonstrated promising outcomes for lenvatinib plus pembrolizumab (L+P) in treating uHCC, the LEAP-002 trial did not meet its primary endpoint. However, the comparative efficacy between L+P and atezolizumab plus bevacizumab (A+B) as first-line treatment remains a topic of uncertainty. This study aimed to assess the effectiveness and safety of L+P in contrast to A+B among patients diagnosed with uHCC. Methods: We conducted a retrospective analysis of enrolled patients with uHCC who received L+P or A+B as initial systemic treatment at Chang Gung Memorial Hospital from June 2019 to December 2022. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by modified RECIST were compared. Results: 121 patients were recruited, with 37 receiving L+P and 84 receiving A+B. Among them, 95 (78.5%) patients were BCLC stage C, and 99 (81.8%) patients had viral etiology for HCC, predominantly chronic HBV (68.6%). Both the L+P and the A+B groups demonstrated comparable OS (18.2 months versus 14.6 months, p = 0.35) and PFS (7.3 months versus 8.9 months, p = 0.75). The ORR and DCR were similar. After propensity score matching, the results remained consistent between the matched patients. Treatment-related adverse events of any grade occurred in 30 (81.1%) in the L+P group and 62 (73.8%) in the A+B group. Conclusions: Our findings suggest that L+P and A+B exhibit comparable efficacy and safety profiles in real-world settings.

Hepatic decompensation is a severe on-treatment adverse event for chronic hepatitis C treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Till now, few papers regarding on-treatment hepatic decompensation have been reported. The study aims to analyze the general feature and predictive factors of on-treatment hepatic decompensation in hepatitis C virus (HCV) genotype 1b-infected patients with advanced fibrosis and compensated cirrhosis who receive treatment with PrOD. A real-word cohort enrolled 189 HCV genotype 1b patients with advanced fibrosis and compensated cirrhosis treated with 12-week PrOD. Clinical and laboratory data were analyzed between patients with and without on-treatment hepatic decompensation. The sustained virologic response rate at 12 weeks after treatment was 97.3% in HCV subtype 1b patients with advanced fibrosis and cirrhosis. On-treatment hyperbilirubinemia (total bilirubin >2 mg/dL) occurred in 27 (14.3%) patients, and the incidence of the increase of total and direct form bilirubin was significantly different during treatment between patients with Child-Turcotte-Pugh score 5 and score 6. Five (18.5%) hyperbilirubinemia patients progressed to hepatic decompensation. Older age (adjusted OR: 1.2, 95% CI: 1.0-1.4) and albumin ≤3.6 g/dL (adjusted OR: 10.4, 95% CI: 1.3-81.2) may be two predictors for on-treatment hepatic decompensation by multivariate analysis. PrOD is an effective direct-acting antiviral agent for antiviral therapy in HCV genotype 1b patients with advanced fibrosis and cirrhosis. Hyperbilirubinemia is possibly the early warning feature of on-treatment hepatic decompensation. This serious adverse event of on-treatment hepatic decompensation is not common. Older age and low baseline albumin level may be predictive factors.