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1.
Artigo em Inglês | MEDLINE | ID: mdl-34981163

RESUMO

PURPOSE: The purpose of this study was to use the finite element method (FEM) to reproduce fracture lines that reach the lateral tibial plateau during open-wedge high tibial osteotomy (OWHTO) in patients with Type III lateral hinge fracture (LHF). It was hypothesized that the FEM could clarify biomechanical causes of Type III LHF, enabling prevention of adverse complications. METHODS: This study used the nonlinear FEM to analyze the data of eight knees in eight patients (two males and six females) with Type III LHF among 82 patients who underwent OWHTO, as well as the data of eight individuals with no LHF. To predict the onset of Type III LHF, simulation models were also developed in which posterior osteotomy sufficiency varied from 50% to perfect, the latter defined as osteotomy reaching the hinge point. RESULTS: Real-life instances of Type III LHF caused by insufficient posterior osteotomy were reproduced in all patient-specific FEM models, and these models accurately predicted fracture types and locations. During opening of the osteotomy gap, the fracture line reached the lateral tibial plateau, and extended vertically from the end of the insufficient posterior osteotomy, avoiding the rigid proximal tibiofibular joint. In contrast, sufficient posterior osteotomy resulted in a lack of LHF. Posterior osteotomy extension ≥ 70% of the width of the osteotomy plane was the cut-off value to prevent Type III LHF. CONCLUSION: Forced opening of insufficient posterior osteotomy was found to be a biomechanical cause of Type III LHF that extended perpendicularly to the lateral tibial plateau, avoiding the proximal tibiofibular joint. The clinical significance of this study is that sufficient posterior osteotomy during OWHTO, defined as at least 70% of the width of the osteotomy plane, can prevent Type III LHF.

2.
J Knee Surg ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991175

RESUMO

Tunnel position during anterior cruciate ligament (ACL) reconstruction is considered as an important factor to restore normal knee kinematics and to gain better clinical outcomes. It is still unknown where the optimal femoral and tibial tunnel position is located in single-bundle (SB) ACL reconstruction. The purposes of this study were to analyze the knee kinematics with various graft positions and to propose the optimal graft position during SB ACL reconstruction. A musculoskeletal computer simulation was used to analyze knee kinematics. Four attachments on the femoral side (anteromedial [AM], mid, posterolateral [PL], and over-the-top positions) and three attachments on the tibial side (AM, middle, and PL positions) were determined. The middle-bundle attachment was placed at the midpoint of the AM and PL bundle attachments for the femoral and tibial attachments. SB ACL reconstruction models were constructed to combine each of the four femoral attachments with each of three tibial attachments. Kinematic comparison was made among a double-bundle (DB) model and 12 SB reconstruction models during deep knee bend and stair descent activity. The tunnel position of the tibia had greater effect of knee kinematics than that of the femur. AM tibial attachment models showed similar medial and lateral anteroposterior positions to the DB model for both activities. Axial rotation in the AM tibial attachment models was similar to the DB model regardless of the femoral attachment, whereas greater maximum axial rotation was exhibited in the PL tibial attachment models, especially during stair descent activity. AM tibial attachment can represent normal knee kinematics, whereas the PL tibial attachment can induce residual rotational instability during high-demand activities. The AM tibial tunnel is recommended for SB ACL reconstruction.

3.
J Knee Surg ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34891188

RESUMO

Several concepts may be used to restore normal knee kinematics after total knee arthroplasty. One is a kinematically aligned (KA) technique, which restores the native joint line and limb alignment, and the other is the use of a medial pivot knee (MPK) design, with a ball and socket joint in the medial compartment. This study aimed to compare motions, contact forces, and contact stress between mechanically aligned (MA) and KA (medial tilt 3° [KA3] and 5° [KA5]) models in MPK. An MPK design was virtually implanted with MA, KA3, and KA5 in a validated musculoskeletal computer model of a healthy knee, and the simulation of motion and contact forces was implemented. Anteroposterior (AP) positions, mediolateral positions, external rotation angles of the femoral component relative to the tibial insert, and tibiofemoral contact forces were evaluated at different knee flexion angles. Contact stresses on the tibial insert were calculated using finite element analysis. The AP position at the medial compartment was consistent for all models. From 0° to 120°, the femoral component in KA models showed larger posterior movement at the lateral compartment (0.3, 6.8, and 17.7 mm in MA, KA3, and KA5 models, respectively) and larger external rotation (4.2°, 12.0°, and 16.8° in the MA, KA3, and KA5 models, respectively) relative to the tibial component. Concerning the mediolateral position of the femoral component, the KA5 model was positioned more medially. The contact forces at the lateral compartment of all models were larger than those at the medial compartment at >60° of knee flexion. The peak contact stresses on the tibiofemoral joint at 90° and 120° of knee flexion were higher in the KA models. However, the peak contact stresses of the KA models at every flexion angle were <20 MPa. The KA technique in MPK can successfully achieve near-normal knee kinematics; however, there may be a concern for higher contact stresses on the tibial insert.

4.
Mod Rheumatol ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34910204

RESUMO

OBJECTIVES: This study aimed to elucidate the association between joint line tenderness (JLT) of the knee and knee joint structural changes evaluated with ultrasonography (US) for the early diagnosis of knee osteoarthritis (KOA). METHODS: This cross-sectional study included 121 participants (age 71.7 ± 5.8 years, 75 women) from a community-based population. Bilateral structural changes in the knee joint were evaluated with US, and the presence or absence of JLT was evaluated using a pressure algometer. Logistic regression analysis was performed to evaluate the odds ratios (ORs) of US findings for the presence of JLT. Moreover, when the analysis was limited to knees with pre-/early radiographic KOA, the ORs were also calculated using logistic regression analysis. RESULTS: Among the 242 knees, 38 had medial JLT, which was significantly associated with female sex (OR 11.87) and loss of cartilage thickness of the distal medial femoral condyle (CTh-MFC) (OR 0.12). Among 96 knees with Kellgren-Lawrence grade ≤ 2, 18 knees had medial JLT, which was also significantly associated with loss of CTh-MFC (OR 0.07) and medial osteophytes (OR 2.01). CONCLUSIONS: JLT is significantly associated with thinning of the femoral cartilage and larger osteophytes in elderly patients, even in those with pre-/early radiographic KOA.

5.
J Knee Surg ; 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34952552

RESUMO

The correlation between static and dynamic mediolateral (ML) tilts of the joint line in the coronal plane remains unknown after total knee arthroplasty (TKA). The purpose was to evaluate the ML tilt as measured by two-dimensional to three-dimensional registration during stair ascent in TKA patients, and to examine the correlation between the dynamic ML tilt and radiographic measurements of static indices. Thirty-two knees that underwent TKA using the mechanical alignment method were included. Continuous sagittal fluoroscopy was taken from before initial contact (IC) until after the toe-off (TO) phase during the stair ascent. The ML tilt of the tibial component relative to the ground was analyzed in terms of dynamic alignment using image-matching techniques, whereas static alignment was measured using standing long-leg radiographs. The correlation between static and dynamic ML tilts was evaluated. In the fluoroscopic analysis, the joint line was neutral (0.0 degree, standard deviation [SD] = 3.4 degrees) around IC phases, then was tilted valgus (5.5° valgus, SD = 2.6 degrees) in the mid-stance (MS) phase. After the TO phase, the joint line became almost neutral (0.4 degrees valgus, SD = 3.1 degrees). The dynamic ML tilt was significantly more varus during the IC phase and significantly more valgus in MS and TO phases than the static ML tilt (1.4 degrees valgus, SD = 2.0 degrees). No correlation was found between static and dynamic ML tilts in weight-bearing phases. During stair ascent, the static tilt had no correlation with the dynamic tilt in weight-bearing phases despite being in the same range. Static lower limb alignment does not reflect coronal alignment during motion. Further research should be conducted to determine whether the horizontal dynamic ML tilt can improve long-term durability and clinical outcomes after TKA.

7.
Oncology ; : 1-9, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844247

RESUMO

BACKGROUND/AIM: With the development of systemic treatment methods for unresectable hepatocellular carcinoma (uHCC), the concept of unsuitable for transcatheter arterial chemoembolization (TACE) has become important. This study aimed to establish a simple predictive scoring system for determining TACE unsuitable status. MATERIALS/METHODS: From 1998 to 2015, 196 patients with intermediate-stage uHCC with Child-Pugh A (score 5:6 = 108:88) and given TACE as the initial treatment were enrolled. At the baseline, tumor burden (Milan criteria-out, up-to-7 in/out, and up-to-11 in/out: 0-2 points) and modified albumin-bilirubin grade 1/2a or 2b (0-1 point) were added to determine the score for TACE unsuitable (CITRUS-MICAN score; low <2 and high ≥2). In addition, a previously reported tumor marker (TM) score, in which alpha-fetoprotein (AFP) was ≥100 ng/mL, fucosylated AFP ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL (each 1 point) (total 0, 1, or ≥2 points), was used for additionally evaluating tumor malignancy potential. Prognosis was retrospectively evaluated based on those scores. RESULTS: Median survival time (MST) was better for low compared to high CITRUS-MICAN score (42.0 vs. 26.4 months) (p = 0.002). A 2-step evaluation using the combination of CITRUS-MICAN and TM scores showed an MST of 43.2 months for low CITRUS-MICAN/TM score 0/1 (rank-A) and 39.6 months for low CITRUS-MICAN/TM score ≥2 (rank-B2), while it was 46.8 months for high CITRUS-MICAN/TM score 0 (rank-B1), 28.8 months for high CITRUS-MICAN/TM score 1 (rank-B2), and 22.8 months for high CITRUS-MICAN/TM score ≥2 (rank-C). For rank-A cases (n = 51), MST was 43.2 months, while it was 46.8 months for rank-B1 (n = 12), 31.2 months for rank-B2 (n = 82), and 22.8 months for rank-C (n = 51) (p = 0.001). CONCLUSION: The results showed that rank-C indicates absolute TACE unsuitable status. For rank-A patients, good prognosis with TACE can be expected, while TACE refractoriness status during the clinical course should be carefully evaluated so as to anticipate the appropriate timing for switching to systemic treatment in rank-B1 and -B2 patients.

8.
Knee ; 33: 298-304, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34739961

RESUMO

BACKGROUND: Total knee arthroplasty (TKA) is commonly performed to reduce knee pain and improve physical function. Compared with the values for healthy, age-matched women, previous studies have reported large deficits in functional ability, such as muscle strength and ambulatory ability, in women 1 year post-TKA. Ambulatory ability is to move around, particularly by walking and is clinically assessed by the timed up and go test (TUG). AIM: This study aimed to clarify the characteristics of knee functions in female patients whose ambulatory ability recovered to a normal level at 1 year after TKA. METHODS: This cross-sectional study included 151 female patients who underwent TKA. The muscle strength of the lower extremity was measured, and the 2011 Knee Society Scoring (2011 KSS) system was used postoperatively. The TUG was conducted to assess ambulatory ability after TKA; then the patients were classified into the fast and slow ambulation groups based on previously reported gait-speed values of healthy female individuals. Then, we identified significant indicators of ambulatory ability at 1 year after TKA. RESULTS: Forty-nine percent of patients after TKA achieved the level of ambulatory ability of a healthy female. Logistic regression analysis identified that the non-operative side knee extensor strength and the functional activity score, as assessed by the 2011 KSS, were variables significantly associated with the mid-term ambulatory ability after TKA. CONCLUSION: Female patients with high non-operative knee extensor strength and a functional activity score at 1 year postoperatively can achieve better ambulatory ability than those of healthy, age-matched females.

9.
Hepatol Res ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799975

RESUMO

BACKGROUND/AIM: Although systemic therapy is recommended for patients with multiple intermediate stage unresectable hepatocellular carcinoma (u-HCC) classified as beyond the up-to-7 criteria (UT-7 out/multiple) as a transcatheter arterial chemoembolization (TACE) unsuitable condition, few reports have examined the therapeutic efficacy of atezolizumab plus bevacizumab combination therapy (Atez/Bev) in such cases. This study aimed to elucidate the therapeutic response of Atez/Bev in u-HCC patients classified as UT-7 out/multiple. MATERIAL/METHODS: From September 2020 to September 2021, 95 u-HCC Japanese patients classified as UT-7 out/multiple/Child-Pugh A were enrolled from 21 institutions (median age 76 years, males 73, Child-Pugh 5:6 = 68:27, TNM stage II:III = 17:78). Therapeutic response was retrospectively evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1 and modified RECIST (mRECIST). RESULTS: Atez/Bev was given as first-line treatment to 52 (54.7%). Objective response rate (ORR)/disease control rate (DCR) at six weeks of RECIST and mRECIST were 17.7%/84.7% and 42.5%/86.2%, respectively. Median PFS was 8.0 months (median observation period: 6.0 months). Child-Pugh A/modified Albumin-bilirubin grade (mALBI) 1 and 2a at baseline, 3, 6, and 9 weeks, were 100%/69.4%, 89.8%/57.3%, 94.8%/65.3%, and 91.4%/60.0%, respectively. Among adverse events (any-grade, >10%) during the present observation period, general fatigue was most frequent (23.2%), followed by urine protein (21.1%), appetite loss (20.0%), and hypertension (13.7%). CONCLUSION: Atez/Bev treatment showed favorable therapeutic response with less influence on hepatic function, suggesting it as a useful therapeutic option for patients with such condition.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34779926

RESUMO

PURPOSE: This study evaluated whether patients with particular lower limb morphological factors have femoral and tibial component malpositioning during mechanically aligned total knee arthroplasty (TKA) and lower postoperative satisfaction. METHODS: This study included 146 knees in 117 Asian patients undergoing TKA for medial osteoarthritis. Preoperative bony morphological factors such as the angle between the femoral mechanical and anatomical axes (MA-AA angle), angle between the anatomical axes of the proximal and distal femur (lateral bowing femoral angle, LBFA), mechanical lateral distal femoral angle, medial proximal tibial angle, and % anatomical axis of the tibia were evaluated, as well as preoperative and 1-year postoperative 2011 Knee Society scores (KSSs). RESULTS: MA-AA angle and LBFA were significantly larger in knees with varus femoral component alignment versus neutral alignment. Preoperative MA-AA angle was underestimated in patients with larger MA-AA angle or LBFA, especially by inexperienced surgeons. Tibial morphological factors did not affect tibial component alignment. Changes in 2011 KSSs were similar among groups by lower limb alignment or femoral and tibial component alignment. CONCLUSION: Femoral bowing affects varus femoral component alignment by obscuring preoperative planning, but it had little impact on patient satisfaction when mechanical alignment is targeted during TKA.

12.
Cancer Med ; 10(21): 7673-7682, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34655175

RESUMO

BACKGROUND: In the JCOG1108/WJOG7312G trial, a combination (FLTAX) of 5-fluorouracil (FU) /leucovorin (FL) and paclitaxel (PTX) did not show superiority in overall survival (OS) to FL in untreated patients with severe peritoneal metastasis of gastric cancer (GC-SPM), some of whom received second-line chemotherapy with PTX after FL. This post hoc study aimed to investigate the clinical implications of using both FU and PTX either sequentially or in combination for patients with GC-SPM. METHODS: A total of 94 patients were enrolled and categorized into the following three subgroups: patients treated with (1) FL followed by PTX (FL/PTX, N = 25), (2) FL followed by best supportive care (BSC) (FL/BSC, N = 21), and (3) FLTAX (N = 48). OS was compared between the subgroups. By comparing baseline factors between the FL/PTX and FL/BSC subgroups, factors preventing the sequential use of PTX (SUP) were explored using logistic regression model. The efficacy of FL and FLTAX was compared according to the presence of risk factors preventing SUP. RESULTS: The FL/PTX subgroup showed better and equivalent OS compared to the FL/BSC (median 7.8 vs. 2.0 months, p < 0.01) and FLTAX (median 7.8 vs. 8.0, p = 0.49) subgroups, respectively. Glasgow Prognostic Score 2 and initially unresectable disease were identified as risk factors preventing SUP. Absence of both risks predicted SUP with a sensitivity of 13% and a specificity of 100%, whereas absence of any risks predicted SUP with a sensitivity of 67% and a specificity of 62%. FLTAX showed better OS than FL in patients with one or two of these risks but worse OS in those with none. CONCLUSIONS: Although sequential use of FU and PTX showed equivalent survival to FLTAX in patients with GC-SPM, FLTAX might be preferable given the difficulty in selecting patients likely to receive sequential use at the initiation of first-line chemotherapy.

13.
Hepatol Commun ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676692

RESUMO

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum-based risk model that could identify patients with low-risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma-glutamyl transferase < 28 IU/L, alpha-fetoprotein < 4.0 ng/mL, and Fibrosis-4 Index < 4.28) were classified as low-risk and others were classified as high-risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low-risk patients (0.5-1.1 per 100 person-years in the derivation cohort and 0.9-1.1 per 100 person-years in the validation cohort) than in high-risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high-risk to low-risk (HCC incidence: 0.6 per 100 person-years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person-years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.

14.
Chem Sci ; 12(34): 11585-11592, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34567506

RESUMO

Here, we present single crystalline capsules of a photoresponsive molecule produced by simple recrystallization from organic solutions without direct human processing. During the crystal growth process, a movie was taken of the capsule taking in the organic solution. The capsules responded rapidly (<1 s) to the UV light stimuli and released the captured solution or solute. In principle, they can take in any substance dissolved in organic solvents, and their size can be controlled. Moreover, the capsule can be broken by multi-photon excitation using a near-infrared laser within the biological window. Furthermore, because the molecular packing in the crystal is unidirectional, the response can be controlled by the polarization of the light. This study shows the new potential of photoresponsive molecules.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34347628

RESUMO

OBJECTIVE: Patients with shoulder disorders show altered periscapular muscle activity [e.g., decreased serratus anterior (SA) and increased upper trapezius (UT) activities]. We herein devised a novel method for strengthening SA without excessive UT activation, named Squeezing Ball exercise (SB-ex) in which patients squeezed a ball between both elbows with maximum voluntary isometric contraction in the horizontal adduction direction with the arms elevated at a 45° angle. The present study aimed to investigate if the SB-ex could produce high muscle activity in the SA in patients with frozen shoulder and subacromial impingement syndrome (SAIS) before the rehabilitation intervention. DESIGN: This is a proof-of-concept study. SA and UT activities during SB-ex were evaluated using electromyography (EMG) in 16 patients with frozen shoulders and SAIS. EMG signals were normalized using maximal voluntary isometric contraction (MVIC), and the muscle balance ratios (UT/SA) were calculated. RESULTS: The average SA and UT activity was 69.9% ± 30.8% and 10.2% ± 6.3% MVIC during the SB-ex, respectively, whereas the UT/SA ratio of the affected side was 0.15 ± 0.07. CONCLUSION: The high SA activation and low UT/SA ratio during SB-ex could be attributed to the limb position where shortened SA exerts itself without painful subacromial impingement. SB-ex could be a novel rehabilitation tool for patients with frozen shoulders and SAIS.

16.
Sci Rep ; 11(1): 16673, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404826

RESUMO

This study aimed to perform a comparative analysis of postoperative results between lumbar degenerative spondylolisthesis (LDS) treated with oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) from the Chiba spine surgery registry database. Sixty-five patients who underwent single-level OLIF (O group) for LDS with ≥ 3 years' follow-up were retrospectively reviewed. The control group comprised 78 patients who underwent single-level TLIF (T group). The analyzed variables included global alignment, radiological parameters of fused segments, asymptomatic and symptomatic ASD incidence, clinical outcomes at 3 years postoperatively using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire data, visual analogue scale scores for low back pain, lower extremity pain, and lower extremity numbness. There was no significant change in global alignment between the two groups. The rate of improvement in anterior intervertebral disc height was not significantly different between the groups at 1-month postoperatively. However, at the final evaluation, the anterior intervertebral disc height and incidence of asymptomatic ASD were significantly higher in the O group. There was no significant difference in symptomatic ASD, reoperation cases, or clinical results between groups. Thus, single-level OLIF can maintain the corrected disc height, but as it has no effect on global alignment, its benefit is limited.


Assuntos
Vértebras Lombares/cirurgia , Espondilolistese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fusão Vertebral/métodos , Resultado do Tratamento
17.
Sci Rep ; 11(1): 16663, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404856

RESUMO

It was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child-Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Estudos Retrospectivos
18.
Liver Int ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34250737

RESUMO

BACKGROUND AND AIM: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. METHODS: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). RESULTS: The appearance of arterial hypertension G ≥ 2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, P = .0188], whereas decreased appetite G ≥ 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, P = .0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, P = .0149), whereas decreased appetite G ≥ 2 predicted decreased PFS (HR 1.36, 95% CI 1.04-1.77, P = .0277). CONCLUSIONS: Our main findings are that the occurrence of arterial hypertension G ≥ 2 is a predictor of longer survival, whereas decreased appetite G ≥ 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients' quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.

19.
Sci Rep ; 11(1): 14474, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262065

RESUMO

We investigated the impact on survival of modified albumin-bilirubin (mALBI) grade versus Child-Pugh classification in patients with hepatocellular carcinoma (HCC) who received lenvatinib. A total of 524 patients with HCC who received lenvatinib were included. Univariate analysis showed that mALBI grade 2b/3 and Child-Pugh class B/C were significantly associated with survival [hazard ratio (HR), 2.471; 95% confidence interval (CI), 1.944-3.141 and HR, 2.178; 95%CI, 1.591-2.982]. In patients with a Child-Pugh score of 5, multivariate analysis showed that mALBI grade 2b/3 was independently associated with survival (HR, 1.814; 95%CI, 1.083-3.037). Conversely, among patients with mALBI grade 1/2a, there was no difference in survival between those with a Child-Pugh class of 5 or 6 (p = 0.735). Time-dependent receiver operating characteristic analysis showed that the ALBI score predicted survival better than the Child-Pugh score. The optimal cut-off value of the ALBI score for predicting survival was nearly the same as the value separating mALBI grades 2a and 2b. In conclusion, the mALBI grade was a better predictor of survival than the Child-Pugh classification in patients with unresectable HCC who received lenvatinib therapy.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Albumina Sérica Humana/análise , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Curva ROC , Taxa de Sobrevida
20.
J Phys Chem A ; 125(27): 5895-5902, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34196175

RESUMO

The difference in the quantum yields of the cyclization reaction of two isomers of dye-attached diarylethene via the triplet state observed in the experiment [J. Phys. Chem. C 2009, 113, 11623-11627] was theoretically examined by quantum chemical calculations. By evaluating the spin-orbit couplings, we found that the ratio of the rate constants from the S1 state to the T2 state between two isomers agreed with that of the experimental quantum yield of the cyclization reaction. The difference in the spin-orbit couplings is due to the difference in the delocalization of the orbitals between diarylethene and dye. We further found that after the intersystem crossing took place the cyclization reaction via the triplet state occurred in the experiment due to the low energy barrier (∼10 kcal/mol) for the reaction.

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