Factors associated with perioperative deep vein thrombosis in arthroscopic anterior cruciate ligament reconstruction.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) is reportedly associated with a higher incidence of deep vein thrombosis (DVT) incidence than other arthroscopic surgical procedures. The aim of this study is to retrospectively investigate the incidence and type of DVT and evaluate the relationship between DVT and risk factors among all patients who underwent ACLR under uniform conditions consisting of mechanical prophylaxis, no medical prophylaxis, and preoperative and postoperative lower extremity venous ultrasonography. METHODS: Of the 114 patients who underwent arthroscopic primary ACLR at our hospital who did not have a compound ligament injury or revision surgery, 112 patients were included. Two patients were not examined. DVT evaluation consisted of whole-leg ultrasonography at 1 week after surgery. We evaluated age, sex, body mass index, comorbidities, operative time, tourniquet time, presence of concurrent surgery (meniscus repair/resection or osteochondral column grafting), and non-weight-bearing status at 1 week after surgery as risk factors for DVT. RESULTS: DVT was found in 33 (29.5%) of 112 patients. Of these, 22 (19.6%) had distal DVT and 11 (9.8%) had proximal DVT. Non-weight-bearing status at 1 week after surgery was a statistically significant risk factor for proximal DVT (P = .034). CONCLUSIONS: Non-weight-bearing status is an independent risk factor for DVT, suggesting that early weight bearing may reduce the occurrence of DVT.

Blood pressure and coeliac artery blood flow responses during increased inspiratory muscle work in healthy males.

NEW FINDINGS: What is the central question of this study? Increased work of breathing and the accumulation of metabolites have neural and cardiovascular consequences through a respiratory muscle-induced metaboreflex. The influence of the respiratory muscle-induced metaboreflex on splanchnic blood flow in humans remains unknown. What is the main finding and its importance? Coeliac artery blood flow decreased gradually during inspiratory resistive breathing, accompanied by a progressive increase in arterial blood pressure. It is possible that the respiratory muscle-induced metaboreflex contributes to splanchnic blood flow regulation. ABSTRACT: The purpose of this study was to clarify the effect of increasing inspiratory muscle work on coeliac artery blood flow. Eleven healthy young males completed the study. The subjects performed voluntary hyperventilation with or without inspiratory resistance (loading or non-loading trial; tidal volume of 40% of vital capacity and breathing frequency of 20 breaths/min). The loading trial was conducted with inspiratory resistance (40% of maximal inspiratory pressure) and was terminated when the subjects could no longer maintain the target tidal volume or breathing frequency. The non-loading trial was conducted without inspiratory resistance and was of the same duration as the loading trial. Arterial blood pressure was recorded using finger photoplethysmography, and coeliac artery blood flow was measured using Doppler ultrasound. Mean arterial blood pressure increased gradually during the loading trial (mean ± SD; from 89.0 ± 10.8 to 103.9 ± 17.3 mmHg) but not in the non-loading trial (from 88.7 ± 5.9 to 90.4 ± 9.9 mmHg). Coeliac artery blood flow and coeliac vascular conductance decreased gradually during the loading trial (from 601.2 ± 155.7 to 482.6 ± 149.5 mL/min and from 6.9 ± 2.2 to 4.8 ± 1.7 mL/min/mmHg, respectively) but were unchanged in the non-loading trial (from 630.7 ± 157.1 to 635.6 ± 195.7 mL/min and from 7.1 ± 1.8 to 7.2 ± 2.9 mL/min/mmHg, respectively). These results show that increasing inspiratory muscle work affects splanchnic blood flow regulation, and we suggest that this might be mediated by the inspiratory muscle-induced metaboreflex.

Clinical Significance of Serum Zinc Levels on the Development of Sarcopenia in Cirrhotic Patients.

Background/Aim: Sarcopenia increases the mortality in patients with cirrhosis. Approximately 60% of zinc is accumulated in skeletal muscle. We aimed to determine the role of subclinical zinc deficiency on sarcopenia development in patients with cirrhosis. Patients and Methods: We enrolled 151 patients with cirrhosis and divided them into the group with normal serum zinc levels (Group N: 80-130 µg/dl; n=38) and group with subclinical zinc deficiency (Group D: <80 µg/dl; n=113). The risk factors for sarcopenia were then investigated. Results: Group D had more sarcopenia cases than Group N (31.0% vs. 13.2%). In group D, HGS exhibited a weakly positive but significant correlation with serum zinc levels (R=0.287, p=0.00212), serum zinc levels negatively correlated with both ammonia and myostatin levels (R=-0.254, p=0.0078; R=-0.33, p<0.01), and low zinc levels were independently associated with sarcopenia development. Conclusion: Patients with cirrhosis showing subclinical zinc deficiency have a significantly higher risk of developing sarcopenia.

Total knee arthroplasty in the past three decades: Trends in patient characteristics and implant survivorship.

OBJECTIVE: To explore the trends in patient characteristics and implant survivorship (IS) for primary total knee arthroplasty (TKA) over the past three decades. METHODS: This retrospective study enrolled a total of 635 knees who underwent TKA from 1985 to 2014. They were divided into three groups: group A, 125 knees in 1985-1994; group B, 203 knees in 1995-2004; and group C, 307 knees A in 2005-2014. The patient characteristics and IS were compared. RESULTS: The mean age of patients undergoing TKA was getting older: 65.3 ± 9.7, 69.1 ± 10.0, and 74.6 ± 8.4 years, in groups A, B, and C, respectively (p = .001). The proportion of patients <60 years old with RA decreased (p < .001), whereas that of patients ≥ 80 years old with OA increased dramatically, it was 7.0%, 14.5%, and 32.0% in groups A, B, and C, respectively (p < .001). The IS free from infection was over 98% in all groups. Alternatively, the IS free from aseptic loosening become better, it was 83.7%, 95.2%, and 98.2% in groups A, B, and C, respectively (p = .014). CONCLUSIONS: From these trends, we can estimate that the number of patients undergoing TKA will further increase in the future in an aging society.

The Combination of Albumin-Bilirubin Score and Prothrombin Time Is a Useful Tool for Predicting Liver Dysfunction after Transcatheter Arterial Chemoembolization in Child-Pugh Class A Patients with Hepatocellular Carcinoma within Up-to-Seven Criteria.

Mortality and recurrence rates of hepatocellular carcinoma (HCC) are high. Recent studies show that for patients with HCC beyond up-to-seven criteria, treatment with molecular-targeted agents (MTAs) is recommended because the treatment efficiency of transcatheter arterial chemoembolization (TACE) is poor; further, TACE increases decline in liver function. However, the relationship between TACE and liver function decline in patients with HCC within up-to-seven criteria has not been clarified. Hence, we aimed to investigate this relationship. This retrospective observational study included 189 HCC tumors within up-to-seven criteria in 114 Child-Pugh class A patients. Twenty-four (12.7%) tumors were changed from Child-Pugh class A to B after TACE, and 116 (61.4%) tumors exhibited recurrence within 6 months after TACE. Prothrombin time (PT) and albumin-bilirubin (ALBI) score before TACE were significantly associated with liver dysfunction from Child-Pugh class A to B. The combination of PT and ALBI score before TACE had high predictive ability for liver dysfunction from Child-Pugh class A to B after TACE (specificity = 100%, sensitivity = 91.7%). The combined use of pre-TACE PT and ALBI score has a high predictive ability for liver dysfunction after TACE for Child-Pugh class A patients with HCC within up-to-seven criteria.

Enhanced liver fibrosis score as a surrogate of liver-related complications and mortality in primary biliary cholangitis.

ABSTRACT: The presence of bridging fibrosis predicts survival of primary biliary cholangitis (PBC). This study aimed to compare serum parameters for the estimation of liver fibrosis and prediction of clinical outcomes in PBC.Out of 392 patients with PBC, 102 who underwent liver biopsy and in whom fibrosis indices, platelet count, hyaluronic acid, type IV collagen 7 second domain, procollagen type III amino-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer, N-terminal type III collagen propeptide levels; fibrosis index based on 4 factors, aspartate aminotransferase-to-platelet ratio index, and enhanced liver fibrosis (ELF) score were determined, were included. The correlation of histological stages based on both Scheuer and Nakanuma classifications with fibrosis indices was investigated. The Nakanuma system comprises grading for liver fibrosis and bile duct loss. Diagnostic performances of 10 fibrosis indices were evaluated to identify patients with poor prognosis. Moreover, correlations of those with PBC clinical manifestation and survival were also investigated.Enhances liver fibrosis (ELF) score had the highest correlation coefficient for liver fibrosis evaluated according to either the Scheuer or Nakanuma classification among 10 serum fibrosis indices. It also had the highest diagnostic performance in estimating Scheuer stage III and Nakanuma fibrosis score 2, both of which represent portal-bridging fibrosis. Patients with an ELF score of ≥10.0 had shorter survival and presented more frequently clinical complications than those with an ELF score of <10.0.ELF score determines the severity of liver fibrosis and predicts the occurrence of complications and survival in patients with PBC.

The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects.

Molecular targeted therapy with lenvatinib is commonly offered to advanced hepatocellular carcinoma (HCC) patients, although it is often interrupted by adverse effects which require a reduction in the initial dose. Thus, an alternative lenvatinib-based therapy to compensate for dose reduction is anticipated. This study aimed to assess the effect of combination of low-dose of lenvatinib and the angiotensin-II (AT-II) receptor blocker losartan on human HCC cell growth. In vitro studies found that losartan suppressed the proliferation by inducing G1 arrest and caused apoptosis as indicated by the cleavage of caspase-3 in AT-II-stimulated HCC cell lines (Huh-7, HLE, and JHH-6). Losartan attenuated the AT-II-stimulated production of vascular endothelial growth factor-A (VEGF-A) and interleukin-8 and suppressed lenvatinib-mediated autocrine VEGF-A production in HCC cells. Moreover, it directly inhibited VEGF-mediated endothelial cell growth. Notably, the combination of lenvatinib and losartan augmented the cytostatic and angiostatic effects of the former at a low-dose, reaching those achieved with a conventional dose. Correspondingly, a HCC tumor xenograft assay showed that the oral administration of losartan combined with lenvatinib reduced the subcutaneous tumor burden and intratumor vascularization in BALB/c nude mice. These findings support that this regimen could be a viable option for patients intolerant to standard lenvatinib dosage.

Sulforaphane ameliorates ethanol plus carbon tetrachloride-induced liver fibrosis in mice through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway.

Alcoholic liver disease (ALD)-related fibrosis results from a variety of mechanisms including the accumulation of acetaldehyde, reactive oxygen species, and hepatic overload of endogenous lipopolysaccharide (LPS). Alcohol cessation is the therapeutic mainstay for patients with all stages of ALD, whereas pharmacological strategies for liver fibrosis have not been established. Sulforaphane, a phytochemical found in cruciferous vegetables, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts anticancer, antidiabetic, and antimicrobial effects; however, few studies investigated its efficacy in the development of ALD-related fibrosis. Herein, we investigated the effect of sulforaphane on acetaldehyde metabolism and liver fibrosis in HepaRG and LX-2 cells, human hepatoma and hepatic stellate cell lines, respectively, as well as in a mouse model of alcoholic liver fibrosis induced by ethanol plus carbon tetrachloride (EtOH/CCl4). Sulforaphane treatment induced the activity of acetaldehyde-metabolizing mitochondrial aldehyde dehydrogenase in HepaRG cells and suppressed the acetaldehyde-induced proliferation and profibrogenic activity in LX-2 cells with upregulation of Nrf2-regulated antioxidant genes, including HMOX1, NQO1, and GSTM3. Moreover, sulforaphane attenuated the LPS/toll-like receptor 4-mediated sensitization to transforming growth factor-ß with downregulation of NADPH oxidase 1 (NOX1) and NOX4. In EtOH/CCl4-treated mice, oral sulforaphane administration augmented hepatic acetaldehyde metabolism. Additionally, sulforaphane significantly inhibited Kupffer cell infiltration and fibrosis, decreased fat accumulation and lipid peroxidation, and induced Nrf2-regulated antioxidant response genes in EtOH/CCl4-treated mice. Furthermore, sulforaphane treatment blunted hepatic exposure of gut-derived LPS and suppressed hepatic toll-like receptor 4 signaling pathway. Taken together, these results suggest sulforaphane as a novel therapeutic strategy in ALD-related liver fibrosis.

A Simple Method to Reduce the Incidence of Cyclops Lesion after Anterior Cruciate Ligament Reconstruction.

The purpose of this study is to determine the influence of debridement in and around the bone tunnels on the prevalence of cyclops lesion (CL), after anterior cruciate ligament reconstruction (ACLR) with hamstring grafts. Our hypothesis was that bone tunnel debridement during ACLR would reduce the prevalence of CL. Methods for debridement in and around the bone tunnels after tunnel drilling were standardized and applied to 38 knees undergoing double-bundle ACLR between 2011 and 2014, Group A (debridement group). Group B (nondebridement group) included 56 knees in which bone tunnel debridement was not performed. Postoperative MRI was performed to evaluate the presence of CL and the following three criteria: (1) the intercondylar site of CL (grade 1-3), depending on its anterior extent along the femoral condyle; (2) posterior bowing of the ACL graft; and (3) the positional relationship between the frontmost fiber of ACL graft and Blumensaat's line. If CL caused loss of extension or pain or discomfort during knee extension, it was defined as symptomatic CL (SCL). CL was detected in 8 cases (21.1%) in Group A and 26 cases (46.4%) in Group B. The prevalence of CL was significantly lower in Group A than in Group B (p = 0.010), and the risk ratio of CL was 0.31 (95% confidence interval: 0.12-0.79). Furthermore, 10 patients in Group B had SCL, compared with none in Group A (p = 0.004). In Group A, the intercondylar site of CL was grade 1 in all cases, while in Group B, the CL grades were 1 (n = 17), 2 (n = 7), 3 (n = 2) (p = 0.008). There were no cases of posterior bowing of the ACL in Group A, but six cases in Group B (p = 0.023). Debridement in and around the bone tunnel is a simple and effective method of preventing CL and SCL after ACLR. The level of evidence for the study is 3.

Association between ADAMTS13 activity-VWF antigen imbalance and the therapeutic effect of HAIC in patients with hepatocellular carcinoma.

BACKGROUND: Prediction of HAIC treatment response is important for improving the prognosis in patients with hepatocellular carcinoma (HCC). The progression of HCC is related to hypercoagulability and angiogenesis. It is known that ADAMTS13 and von Willebrand factor (VWF) are related to hypercoagulability. In addition, previous study reported that the association between ADAMTS13 and VWF, and angiogenesis via vascular endothelial growth factor (VEGF). Recently, ADAMTS13 and VWF have been associated with the prognosis in patients with various kinds of cancer undergoing chemotherapy. AIM: To investigate whether ADAMTS13 and VWF become useful biomarkers of treatment response in HCC patients before the initiation of HAIC treatment. METHODS: Seventy-two patients were enrolled in this study. ADAMTS13 activity (ADAMTS13:AC), VWF antigen (VWF:Ag) and VEGF levels were determined via enzyme-linked immunosorbent assay. Univariable and multivariable analyses were performed to determine the predictive factors of treatment response in patients with HCC undergoing HAIC treatment. RESULTS: ADAMTS13:AC levels in HCC patients with stable disease (SD) + partial response (PR) of HAIC treatment were significantly higher than those with progressive disease (PD) (P < 0.05). In contrast, VWF:Ag/ADAMTS13:AC ratio and VEGF levels in HCC patients with SD + PR were significantly lower than those with PD (both P < 0.05). Patients with high VWF:Ag/ADAMTS13:AC ratio (> 2.7) had higher VEGF levels than those with low ratio (≤ 2.7). Multivariable analysis revealed that VWF:Ag/ADAMTS13:AC ratio was a predictive factor of HAIC treatment response. CONCLUSION: VWF:Ag/ADAMTS13:AC ratio may become a useful biomarker of treatment response in HCC patients before the initiation of HAIC treatment.

Estimation of individual thigh muscle volumes from a single-slice muscle cross-sectional area and muscle thickness using magnetic resonance imaging in patients with knee osteoarthritis.

PURPOSE: This study aimed to identify the best single-slice anatomical muscle cross-sectional area (CSA) and muscle thickness (MT) on magnetic resonance imaging (MRI) to estimate the overall individual muscle volumes (MVs) of knee extensors and flexors in patients with knee osteoarthritis (KOA). METHODS: Twelve patients (24 legs; 4 men and 8 women) with KOA underwent a 1.5-Tesla axial MRI scan in the femoral region of interest (ROI), between the lesser trochanter and rectus femoris tendon. Individual MVs were calculated by numerical integration based on individual CSAs analyzed at the ROI. The best slice was determined as follows: coefficient of determination ( R2) between MVs measured and those estimated from the femoral length (FL) × CSAs or FL × MTs measured at each 10% interval level of the ROI. These estimation equations were applied for a cross-validation group (24 KOA patients: 12 men and 12 women). RESULTS: Estimated individual MVs of knee extensors and flexors, based on the CSAs at the distal 10% level, significantly correlated with each of the measured individual MVs ( R2: 0.79-0.96, p < 0.05 for all). Similarly, estimated individual knee extensor MVs, based on MTs at the mid-slice, significantly correlated with each of the measured individual MVs ( R2: 0.77-0.84, p < 0.05 for all). The application of the developed regression equation to the cross-validation group did not exhibit any systematic bias. CONCLUSION: These simple methods could be applied in prospective research with a larger number of patients with KOA.

Muscle atrophy and recovery of individual thigh muscles as measured by magnetic resonance imaging scan during treatment with cast for ankle or foot fracture.

PURPOSE: We aimed to longitudinally investigate individual thigh muscle changes using magnetic resonance imaging (MRI) during treatment with cast of ankle or foot fracture. Moreover, we aimed to demonstrate whether measurements of muscle cross-sectional area (CSA) are sensitive to muscle changes, contributing to simpler methods in clinical application . METHODS: Ten patients undergoing treatment with cast of acute ankle or foot fractures were studied. Axial MRI (1.5 T) was conducted around the affected mid-thigh region after the injury (Pre), after maintaining a nonweight-bearing (NWB) period (approximately 28 days), and after finishing rehabilitation (recovery). Regarding individual thigh muscles, the total CSAs corresponding to 40% of the femoral length (FL) and the CSAs at 5% interval of the FL were longitudinally measured. Standardized response means (SRMs) were accessed for sensitivity in the muscle changes. RESULTS: The total CSAs at NWB were significantly lower than those at Pre in vastus lateralis (10.9% ± 5.4%), vastus intermedius (8.4% ± 6.7%), and vastus medialis (11.2% ± 6.9%) ( p < 0.01 for all). In contrast, at recovery, the only significant muscle atrophy relative to that at Pre was observed in the semitendinosus of the proximal 15% and 10% CSAs ( p < 0.01 and p = 0.01, respectively). In all muscles, SRM using a single-slice CSA at or near the muscle belly was high. CONCLUSION: Thigh muscle changes differ according to the variations in individual muscles. CSA measurements at or near the muscle belly are simple methods and sensitive indicators of these muscle changes.

Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation.

Ly49Q, a type II C-type lectin expressed on mouse plasmacytoid DC (pDC), contains a single carbohydrate recognition domain in its extracellular region and an ITIM in its cytoplasmic domain. We have identified the MHC class I molecule H-2K(b) as a Ly49Q ligand, confirming prior reports. Although H-2K(b) is expressed on essentially all hematopoietic cells, we found that only CpG-stimulated B cells were able to activate Ly49Q. This discovery correlated with our finding that although H-2K(b) forms clusters on CpG-activated B cells, it is diffusely expressed on resting B cells. Furthermore, CpG-stimulated, but not resting, B cells up-regulated co-stimulatory molecules on pDC. This finding was confirmed by the fact that binding by anti-Ly49Q mAb to Ly49Q led to pDC maturation in vitro. Our results suggest that clustered H-2K(b) on activated B cells act as ligands for Ly49Q and induce pDC maturation in vitro.

Cell adhesion aside from integrin system can abrogate anoikis in rat liver cells by down-regulation of FasL expression, not by activation of PI-3K/Akt and ERK signaling pathway.

Epithelial cells require contact with extracellular matrix (ECM) to inhibit detachment-induced apoptosis (anoikis). The ERK and PI-3K/Akt signaling pathways have been identified to inhibit anoikis. We present here a different story. An adult rat liver cell line, ARLJ301-3, underwent apoptosis within 4h under suspension conditions even with active forms of Akt and ERK1/2. Once ARLJ301-3 cells are plated on tissue culture plates coated with synthetic polymer, such as poly-(N-p-vinyl benzyl-O-beta-D-galactopyranosyl-D-gluconamide) (PVLA), poly-L-lysine or polystyrene, instead of functional ECM such as fibronectin, they could survive and proliferate without activation of Akt and ERK1/2. The expression of Fas receptor ligand (FasL) is specifically detected in cells under suspension conditions or treated with cytochalasin-D. We present here the first report that FasL expression is up-regulated by the cytoskeletal disruption directed by cytochalasin-D treatment or cell detachment from ECM.