Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real-world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial.

BACKGROUND: Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC). AIMS: To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial. METHODS: A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group). RESULTS: Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a. CONCLUSIONS: Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival.

[A Case of a Gastrointestinal Stromal Tumor of the Stomach with Lymph Node Metastasis].

A 87-year-old female was pointed out wall thickness in the upper part of gastric body for examination of anemia. The mass had a contrast effect, some of it protruded outside the wall, and the surrounding lymph nodes were enlarged. Upper endoscopy showed irregular ulcerative lesion with submucosal volume from posterior wall to the greater curvature in the upper part of gastric body. Biopsy was performed, and GIST of stomach was diagnosed. Surgery was performed for the GIST of the stomach. During open surgery, invasion of pancreatic tail was observed, therefore proximal gastrectomy with D1 lymph node dissection and distal pancreatectomy were performed. Pathologically, the tumor measured 95×78×65 mm with mitotic figures(38/50 high-power fields). Immunohistochemical analysis revealed that tumor cells expressed positive results for c-kit, α-SMA and CD34, and negative results for S-100 and desmin on the basis of the histology and immunostaining profile, the tumor was diagnosed as a GIST. The patient was classed as high risk according to Fletcher's risk classification. Tumor invades pancreatic tail, and lymph node metastasis was observed. She was discharged on the postoperative day 27 and alive without tumor recurrence at 6 months after surgery, not undergoing adjuvant chemotherapy.

Clinical usefulness of newly developed prognostic predictive score for atezolizumab plus bevacizumab for hepatocellular carcinoma.

AIMS: The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment. METHODS: A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c-index) and Akaike information criterion (AIC) results. RESULTS: Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring system. For IMABALI-De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p < .001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0, 1, and 2, OS was 26.11, 20.29, and 11.32 months, respectively (p < .001; AIC 2864.54, c-index 0.606). PFS periods for those IMABALI-De scores were 21.75, 12.89, 9.18, 8.0, 5.0, and 3.75 months, respectively (p < .001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores were 10.32, 7.68, and 3.57 months, respectively (p < .001; AIC 5246.61, c-index 0.574). As compared with CRAFITY score, IMABALI-De score had better AIC and c-index results for both OS and PFS. CONCLUSION: The present results indicated that the proposed IMABALI-De score may be favorable for predicting prognosis of uHCC patients receiving Atez/Bev therapy.

Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct-acting antiviral agents.

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development. METHODS: A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n = 1169) and post-DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed. RESULTS: Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 104/µL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P < 0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P < 0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P = 1.0). CONCLUSION: The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients.

[A Case of Resection of Leiomyosarcoma Suspected to Originate from the Right Ovarian Vein].

We present a 58-year-old female patient who underwent resection of a leiomyosarcoma arising from the right ovarian vein. She was referred to our hospital because of lower abdominal pain that had been present for 1 month prior to the visit. Ultrasound examination revealed a well-defined, smooth, lobulated, highly vascular mass(57 mm)adjacent to the distal portion of the duodenum. Contrast-enhanced computed tomography revealed the contrast enhancement mass (60 mm)located surround the right ovarian vein. In abdominal magnetic resonance image examination, the mass exhibited isointense signal on T1-weighted images, high signal on T2-weighted images, and restricted diffusion on diffusion- weighted images. We suspected primary leiomyosarcoma of the ovarian vein and proceeded with surgical intervention. On intraoperative findings, the mass was in contact with the duodenum and the inferior vena cava but dissection was easily achieved. We excised the mass together with the right ovarian vein. Pathological findings showed the mass was composed of proliferating spindle-shaped cells arranged in bundles. Some areas showed polygonal nuclear atypia and abnormal mitotic figures. Additional immunostaining showed positive for α-SMA, caldesmon, calponin, and negative for desmin, CD34, CKA1/AE3, S100. Based on the intraoperative findings, we diagnosed it as leiomyosarcoma arising of the right ovarian vein.

Straightforward Fabrication of Double Roughness Structures on a Microcrystalline Film of a Diarylethene Derivative.

Double roughness structure mimicking the surface of a lotus leaf was prepared using a newly synthesized diarylethene having a six-membered perfluorocyclohexene ring. The cubic-shaped crystals of the open-ring isomer, with sizes of approximately 7 µm, appeared immediately following solution casting. Upon UV irradiation, each cubic crystal was covered with needle-shaped crystals of the closed-ring isomer to form double roughness structures within 1 h. This structure could bear the continuous impact of water droplets.

Postoperative function of patients with rheumatoid arthritis after total knee arthroplasty in the last decade was comparable in the unadjusted cohort but inferior in the propensity score matched cohort with that of patients with osteoarthritis.

BACKGROUND: The perioperative pain and function of total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) approach those in patients with osteoarthritis (OA). This study aimed to evaluate whether the clinical outcomes, especially functions, of patients with RA reached those of OA, utilizing a background-matched cohort. METHODS: Patients who underwent TKA between 2013 and 2021 were enrolled. Preoperative and minimum 2-year postoperative scores, specifically the Original Knee Society Score (OKSS) and New Knee Society Score (2011KSS), between RA and OA were compared. Clinical assessments were performed on unadjusted and propensity-score matched cohorts, ensuring age, sex, body mass index, and valgus deformity rate parity. RESULTS: In an unadjusted cohort involving 98 patients with RA and 560 patients with OA, patients with RA demonstrated inferior preoperative OKSS-Function Score (FS) but similar postoperative functional scores to OA patients. In the matched cohort of 83, patients with RA displayed lower preoperative OKSS- FS (median difference: 20, P < 0.001) and 2011KSS functional activities (difference: 9, P = 0.01) beyond minimum clinically important differences than patients with OA. Patients with RA improved more in OKSS-FS, yielding no postoperative difference compared with patients with OA. However, postoperative 2011KSS functional activities remained lower in patients with RA (difference: 9.5, P = 0.03), especially in advanced functions, than in those with OA. CONCLUSION: Postoperative function showed no difference between patients with RA and OA in the unadjusted cohort; within the background-matched cohort, postoperative function, especially advanced function, was inferior in patients with RA to those with OA.

mADRES predicts hepatocellular carcinoma development in patients with hepatitis C virus who achieved sustained virological response.

BACKGROUND AND AIM: The study aims to develop a novel predictive model including the fibrosis (FIB)-3 index for hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) who achieved sustained virological response (SVR) with direct-acting antiviral (DAA) therapy. METHODS: This study included 2529 patients in whom HCV was eradicated with DAA therapy. The after DAA recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used to predict HCC development. We developed a modified ADRES (mADRES) score, in which the FIB-4 index was replaced by the FIB-3 index, and evaluated its usefulness in predicting HCC development compared with the ADRES score. RESULTS: In the training set (n = 1770), multivariate analysis with Cox proportional hazards modeling showed that male sex (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.48-3.01), FIB-3 index (HR, 1.36; 95% CI, 1.28-1.45), and α-fetoprotein (HR, 1.05; 95% CI, 1.03-1.07) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES or mADRES score in multiple comparisons. Univariate Cox proportional hazards models showed that compared with the mADRES score 0 group, the HR for HCC development was 2.07 (95% CI, 1.02-4.19) for the mADRES score 1 group, 11.37 (95% CI, 5.80-22.27) for the mADRES score 2 group, and 21.95 (95% CI, 10.17-47.38) for the mADRES score 3 group. Similar results were obtained for mADRES score but not for ADRES score in the validation set (n = 759). CONCLUSION: The mADRES score is useful for predicting HCC development after SVR.

Anterior Position of the Femoral Condyle During Mid-Flexion Worsens Knee Activity After Cruciate-Retaining Total Knee Arthroplasty.

BACKGROUND: The effects of kinematics on patient-reported outcome measures (PROMs) after cruciate-retaining (CR) total knee arthroplasty (TKA) remain unclear. This study investigated the effects of kinematic patterns after CR-TKA on PROMs. METHODS: We examined 35 knees (27 patients) undergoing primary CR-TKA. Knee kinematics and 2011 Knee Society Score were evaluated at a mean follow-up of 72.4 (± 28.2) months. Knee kinematics was analyzed using fluoroscopy, and the femoral antero-posterior position relative to the tibial component was assessed separately for medial and lateral compartments during a squat. The correlations between kinematics and PROMs were evaluated. RESULTS: The average amount of posterior femoral translation from full extension to maximum flexion was 0.2 (± 2.6) mm for the medial femoral condyle and 4.1 (± 2.9) mm for the lateral condyle. Medial pivot motion was observed in 24 knees (68.6%) with a low rate (14.3%) of paradoxical anterior translation. The anterior position of the medial femoral condyle at 60° had a negative impact on discretionary activities (ρ = -0.37; P = .039), and at maximum flexion, had a negative impact on total functional activities (ρ = -0.46; P = .005), advanced activities (ρ = -0.45; P = .006), and discretionary activities (ρ = -0.63; P < .001). Anterior position of the lateral femoral condyle at 30° had a negative impact on total functional activities (ρ = -0.48; P = .005), walking and standing (ρ = -0.56; P < .001), and advanced activities (ρ = -0.49; P = .004), and at 60° had a negative impact on walking and standing (ρ = -0.45; P = .010). CONCLUSIONS: The anterior positions of the medial and lateral femoral condyles at mid-flexion and maximum flexion had negative impacts on PROMs. Soft tissue conditions should be carefully managed to achieve medial knee joint stability, which can improve PROMs.

Small medial proximal tibial angle is a radiographic finding strongly associated with less coronal alignment correction under valgus stress in medial knee osteoarthritis.

PURPOSE: The degree to which varus knees can be corrected manually is important when considering total versus unicompartmental knee arthroplasty (UKA). The primary aim was to clarify the relationship between the degree of coronal alignment correction and radiographic parameters involved in UKA prognosis using preoperative full-length lower extremity valgus stress radiography. The secondary aim was to identify the factors affecting alignment correction. METHODS: This retrospective observational study included 115 knees with medial osteoarthritis that underwent knee osteotomy or arthroplasty. Percent mechanical axis without valgus stress (%MA: neutral, 50%; varus, <50% and valgus, >50%), mechanical lateral distal femoral angle, lateral bowing femoral angle, medial proximal tibial angle (MPTA), joint line convergence angle, medial and lateral joint space width (LJSW) and medial femoral and tibial joint osteophyte size were measured using preoperative full-length weight-bearing radiographs. Correlation and multiple linear regression analyses were used to assess associations between parameters and %MA with valgus stress or amount of %MA change (%MA with valgus stress minus %MA without valgus stress). RESULTS: %MA with valgus stress was correlated with all radiographic parameters. %MA change was correlated with parameters except for MPTA and LJSW. Multiple regression analyses showed that %MA without valgus stress and MPTA were associated with both %MA with valgus stress and %MA change. When %MA with valgus stress was set at 30%, 40% and 50%, MPTA cutoff values were 81.6°, 83.5° and 84.9°, and cutoffs for %MA without valgus stress were 10.7%, 17.1% and 25.1%, respectively. CONCLUSION: Small MPTA is strongly associated with less alignment correction under valgus stress in varus knees. The finding is useful in surgical planning, especially to avoid undercorrection with UKA when valgus stress radiographs are unavailable. LEVEL OF EVIDENCE: Level III.

The predictors for the knee extension strength at 2 years after total knee arthroplasty using regression tree analysis.

OBJECTIVE: To clarify the interactive combinations of clinical factors associated with knee extension strength (KES) 2 years after TKA. DESIGN: A retrospective cohort study was conducted on 264 patients who underwent TKA. KES was assessed preoperatively, 3 weeks, and 2 years after TKA. Physical functions were measured with 10 m walking test (10MWT), Timed-up and Go test (TUG), one-leg standing time, isometric knee flexion strength, knee joint stability, knee pain, femora-tibial angle, and passive knee extension and flexion angle before surgery as a baseline and 3 weeks after TKA as acute phase. Regression tree analysis was conducted to clarify the interactive combinations that accurately predict the KES 2 years after TKA. RESULTS: Operational side KES (> 1.00 Nm/kg) at acute phase was the primal predictor for the highest KES at 2 years after TKA. Acute phase TUG (≤ 10.13 seconds) and baseline 10MWT (≤ 11.72 seconds) was the second predictor. Acute phase non-operative side KES (> 0.90 Nm/kg) was also selected as the predictor. CONCLUSION: This study demonstrated that KES or TUG in the acute phase and 10MWT before TKA are useful for estimating the KES after TKA. The results will help determine specific postoperative rehabilitation goals and training options.

Comparison of prognostic impact of atezolizumab plus bevacizumab versus lenvatinib in patients with intermediate-stage hepatocellular carcinoma.

BACKGROUND & AIMS: The study goal was to compare the outcomes of patients with intermediate-stage (Barcelona Clinic Liver Cancer [BCLC]-B) hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first-line systemic therapy. METHODS: A total of 358 patients with BCLC-B HCC treated with Atezo/Bev (n = 177) or LEN (n = 181) as first-line systemic therapy were included. RESULTS: The median progression-free survival (PFS) times in the Atezo/Bev and LEN groups were 10.8 months (95% confidence interval [CI], 7.8-12.6) and 7.3 months (95% CI, 6.3-8.5), respectively (p = .019). In the propensity score-matched cohort, the median PFS times in the Atezo/Bev (n = 151) and LEN (n = 151) groups were 10.2 months (95% CI, 7.0-12.3) and 6.9 months (95% CI, 5.9-8.1), respectively (p = .020). Restricted mean survival times of PFS were significantly higher in the Atezo/Bev group than in the LEN group at landmarks of 12 and 18 months (p = .031 and .012, respectively). In a subgroup analysis of patients with HCC beyond the up-to-seven criteria, the median PFS times in the Atezo/Bev (n = 134) and LEN (n = 117) groups were 10.5 months (95% CI, 7.0-11.8) and 6.3 months (95% CI, 5.5-7.3), respectively (p = .044). CONCLUSIONS: The use of Atezo/Bev as first-line systemic therapy in patients with BCLC-B HCC is expected to result in good PFS.

Comparative analysis of the therapeutic outcomes of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma patients aged 80 years and older: Multicenter study.

AIM: Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older. METHODS: From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first-line treatment, respectively, were retrospectively analyzed. RESULTS: The median ages of the Atez/Bev and LEN groups were 83.0 (8.01-86.0) and 83.0 (82.0-86.0) years (p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group (p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively (p = 1.0). The median progression-free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different (p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant (p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group. CONCLUSIONS: Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first-line treatment even for elderly HCC patients.

Preoperative radiographs underdiagnose the severity of lateral femoral and medial trochlear cartilage damage in varus osteoarthritis knees.

OBJECTIVE: This study evaluated whether preoperative radiographs accurately predicted intra-articular cartilage damage in varus knees. METHODS: The study assessed 181 knees in 156 patients who underwent total knee arthroplasty. Cartilage damage was graded by two examiners with the International Cartilage Repair Society (ICRS) classification; one used knee radiographs and the other used intraoperative photographs. It was then determined if this radiographic cartilage assessment over- or underestimated the actual damage severity. Knee morphological characteristics affecting radiographic misestimation of damage severity were also identified. RESULTS: The concordance rate between radiographic and intraoperative assessments of the medial femoral condyle was high, at around 0.7. Large discrepancies were found for the lateral femoral condyle and medial trochlear groove. Radiographic assessment underestimated cartilage damage on the medial side of the lateral femoral condyle due to a large lateral tibiofemoral joint opening and severe varus alignment (both r = -0.43). Medial trochlear damage was also underdiagnosed, in cases of residual medial tibiofemoral cartilage and shallow medial tibial slope (r = -0.25 and -0.21, respectively). CONCLUSIONS: Radiographic evaluation of knee osteoarthritis was moderately practical using ICRS grades. Lateral femoral and medial trochlear cartilage damage tended to be misestimated, but considering morphologic factors might improve the diagnostic rate.

Clinical Outcomes of Next-Generation Microwave Thermosphere Ablation for Hepatocellular Carcinoma with Primarily Hepatitis-Related Etiology.

BACKGROUND AND AIM: We investigated the clinical outcomes of patients with hepatocellular carcinoma (HCC) who underwent next-generation microwave thermosphere ablation (MTA). METHODS: A total of 429 patients with 607 HCCs (maximum tumor diameter ≤40 mm) were included. We defined the following areas of the liver as those where MTA therapy is difficult to perform: caudate lobe and areas near the primary and secondary branches of the intrahepatic portal vein, inferior vena cava, gallbladder, heart, duodenum, abdominal esophagus, collateral veins around the liver, and spleen. Factors which predisposed patients to local tumor recurrence in the context of tumor location and complications were examined. RESULTS: The primary etiologies of HCC were hepatitis-related: 259 (60.4%) cases of HCV, 31 (7.3%) cases of HBV, and two instances of both. Median maximum tumor diameter was 15.0 (interquartile range, 10.0-21.0) mm. There were 86 tumors in areas of the liver where MTA is difficult. The most common area was near the primary and secondary branches of the intrahepatic portal vein (26 nodules). The cumulative local tumor recurrence rates at 1, 2, and 3 years were 4.4%, 8.0%, and 8.5%, respectively. The cumulative local tumor recurrence rate differed significantly by tumor size group: 6.6%, 13.8%, and 29.4% at three years in the ≤20 mm group (n = 483), 20-30 mm group (n = 107), and ≥30 mm group (n = 17), respectively (p < 0.001). The cumulative local tumor recurrence rate was similar despite difficult-to-treat status (p = 0.169). In the multivariable analysis, tumor size (>15 mm) (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.11-4.16; p = 0.023) and ablative margin (<3 mm) (HR, 2.94; 95% CI, 1.52-5.71; p = 0.001) were significantly associated with local tumor recurrence. Only tumor size (>15 mm) (odds ratio, 3.41 95% CI, 1.53-7.84; p = 0.026) was significantly associated with complications. CONCLUSIONS: MTA is a safe and effective local ablation therapy for HCC, even for tumors located in areas of the liver where local ablation therapy is difficult.

Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach.

AIM: This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma. METHODS: We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity-score-matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed-effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow-up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups. RESULTS: Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were -2.41 ± 0.40 and -2.44 ± 0.42 at baseline, and -2.17 ± 0.56 and -2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN-treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev. CONCLUSIONS: Using a nonlinear mixed-effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN-treated patients with BCLC advanced stage or those receiving the full dose of LEN.

Comparison of knee kinematics and ligament forces in single and multi-radius cruciate-retaining total knee arthroplasty: A computer simulation study.

BACKGROUND: The single-radius design in total knee arthroplasty has been designed to develop a more fixed flexion-extension axis without mid-flexion instability compared with the multi-radius design. It remains unclear whether differences between the multi-radius and single-radius designs can affect kinematics and collateral ligament forces. This study aimed to simulate knee kinematics and kinetics between single-radius and multi-radius models using a musculoskeletal computer model. METHODS: The single-radius and multi-radius femoral components were virtually implanted in a computer simulation using the same tibial insert. The effects of implant design on kinematics and medial collateral ligament forces during squatting and gait activities were analyzed. RESULTS: During squatting, the multi-radius model exhibited paradoxical anterior translation on both the medial and lateral flexion facet center where peak anterior translation was 2.4 mm for medial flexion facet center and 2.2 mm for the lateral flexion facet center, while the peak anterior translation of the single-radius model was less than 1 mm at early flexion. A rapid decrease in medial collateral ligament tension was observed in the early flexion phase in the multi-radius model, which occurred simultaneously with paradoxical anterior translation, whereas the relatively constant medial collateral ligament tension was observed in the single-radius model. During gait activity, the single-radius model exhibited a more posterior position than the multi-radius model. CONCLUSION: These suggest that abrupt changes in the medial collateral ligament force influence anterior sliding of the femur, and that the single-radius design is a reasonable choice for prevention of mid-flexion instability.

Catastrophic Mid-Flexion Instability After Avulsion Fractures of the Articular Capsule of the Femur and Tibia in a Patient With Posterior-Stabilized Total Knee Arthroplasty: A Case Report.

Mid-flexion instability can be caused by patient-related, implant-related, or technique-specific factors and impairs the activities of daily living after total knee arthroplasty (TKA). In this study, we report a rare case of a patient with severe mid-flexion instability following tibial and femoral avulsion fractures after posterior-stabilized (PS) TKA for knee osteoarthritis. An 82-year-old female with bilateral knee osteoarthritis underwent staged bilateral TKA with a posterior-stabilized prosthesis. The course of the early postoperative period was good, and the patient was able to walk independently with a cane. Two months postoperatively, the patient fell and then experienced left knee pain and instability in the mid-flexion range. Radiographic images showed avulsion fractures of the articular capsule of the femur and tibia, and fluoroscopic examination showed severe posterior subluxation of the tibia between 40° and 60° of flexion. Conservative treatment with a functional knee brace and quadriceps training was initiated due to the patient's hesitation to undergo a second surgery; however, no improvement was observed. Eventually, revision surgery was planned three months after the fall incident (five months after the left primary TKA). At revision surgery, osteosynthesis of the tibial avulsion fracture and thickening of the PS insert did not sufficiently stabilize the instability, and revision TKA with a rotating-hinge prosthesis was needed. The postoperative course was uneventful, and she was able to walk with a cane within two weeks after revision TKA with no complaints of instability. Two years postoperatively, the patient recovered well and had no recurrence of instability, pain, or dysfunction. This case report shows that loss of support by the joint capsules due to avulsion fractures may cause significant anteroposterior instability in the mid-flexion position after posterior-stabilized TKA. In such a case, conservative treatment failed, and the revision of the rotating-hinge prosthesis provided stability and good improvement.

Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. METHODS: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098. FINDINGS: The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab. INTERPRETATION: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully. FUNDING: F Hoffmann-La Roche/Genentech.

Surgical versus conservative treatment of greater trochanteric fractures with occult intertrochanteric fractures: Retrospective cohort study.

BACKGROUND: Greater trochanter (GT) fractures are rare and frequently associated with occult intertrochanteric (IT) fractures. No consensus has been reached regarding whether surgical or conservative treatment is preferred for such fractures. The purpose of this study was to evaluate the clinical outcomes of surgical versus conservative treatment for coexistent GT and occult IT fractures. MATERIALS AND METHODS: Between January 2006 and December 2021, we enrolled patients who were diagnosed with GT fracture on radiography or CT and underwent MRI to reveal occult IT fracture. Eligible patients were divided into two treatment groups: surgical and conservative treatment. The characteristics and outcomes of the patients were compared between the two groups. RESULTS: Fifty patients were included in this study. There were 29 patients (3 male, 26 female; mean age: 84.45 ± 10.68 years) in the surgical treatment group and 21 patients (3 male, 18 female; mean age: 83.33 ± 9.34 years) in the conservative group, respectively. The demographic and clinical characteristics of the two groups were comparable, including sex, age, body mass index (BMI), percentage of extension into the IT area, days from injury to diagnosis, and activities of daily living (ADL) before injury. All 50 patients healed without displaced fractures, regardless of the percentage of extension into the IT area. There were no significant differences in the modified functional ambulation category scores between the two groups at one week, one month, and three months following the start of the treatment intervention (P = 0.653, 0.923, and 0.577, respectively). The length of hospital stay was 48.4 ± 5.97 days in the surgical treatment group and 50.6 ± 7.55 days in the conservative treatment group (P = 0.422). There was no significant difference in one-year mortality between surgical and conservative treatments (P = 0.219). CONCLUSIONS: There were no significant differences in any outcome between the surgical and nonsurgical treatment groups. The results of the study suggested that coexistent GT and occult IT fractures may be managed conservatively without developing complete fractures, regardless of extension into the IT area.