Publications by authors named "Yasuhito Tanaka"

748 Publications

Association of Cavovarus Foot Alignment With Peroneal Tendon Tears.

Foot Ankle Int 2021 Apr 13:1071100721990348. Epub 2021 Apr 13.

Orthopedic Associates of Dallas, Baylor University Medical Center, Dallas, TX, USA.

Background: Although it is a widely accepted clinical principle that cavovarus deformity predisposes to peroneal tendon problems, there are limited data to support that assumption. This study tested the hypothesis that cavovarus is associated with peroneal tendon tears and evaluated which radiographic measures correlated with that association.

Methods: A retrospective comparison of radiographic measures of cavovarus in 234 consecutive patients operatively treated for chronically symptomatic peroneal tendon tears was compared to a matched control group. Measures included calcaneal pitch, anteroposterior (AP) talometatarsal and talocalcaneal angles, and talonavicular coverage angle. A novel coordinate system analyzed midfoot and hindfoot components of cavovarus. Analysis of variance was used to compare cohorts, and a Tukey-Kramer test used to analyze 3 subgroups of brevis and longus tears, and concomitant tears.

Results: The distribution of tears was 73% peroneus brevis, 8% longus, and 19% both tendons. Compared with controls, the study group, and subgroups, had multiple measures of increased cavovarus, including greater calcaneal pitch ( = .0001), decreased AP talo-first metatarsal angle ( = .0001), and increased talonavicular coverage angle ( = .0001). Elevated medial longitudinal arch, and rotational changes in the radiographic profiles of the hindfoot were found with the coordinate system described by Yokokura.

Conclusion: This study found a statistically significant association of increased cavovarus deformity with peroneal tendon tears, compared to controls. It documented the relative incidence of tears of peroneus brevis, peroneus longus, and concomitant tears in a large surgical series. It demonstrated which simple radiographic angles and complex coordinate measurements of cavovarus deformity were significantly associated with peroneal tendon tears.

Level Of Evidence: Level III, retrospective comparative cohort study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1071100721990348DOI Listing
April 2021

Biomechanical comparison of arthroscopic and open lunate excisions in the cadaveric wrist.

Clin Biomech (Bristol, Avon) 2021 Mar 26;84:105343. Epub 2021 Mar 26.

Department of Orthopaedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan.

Background: In advanced Kienböck disease, unreconstructible lunate should be excised as a salvage procedure. There is a lack of information about the biomechanical approaches evaluating the carpal kinematics after lunate excision. We hypothesized that arthroscopic lunate excision would not break the ring structure of the proximal carpal row, preventing carpal instability. We aimed to investigate changes in carpal kinematics following arthroscopic and open lunate excisions.

Methods: We used upper extremities from five fresh cadavers and simulated arthroscopic and open lunate excisions. Arthroscopic lunate excision was performed to preserve the attachment sites of intrinsic and extrinsic carpal ligaments to the lunate. Open lunate excision was conducted with sectioning of the intrinsic and extrinsic carpal ligaments. Using a three-dimensional space electromagnetic tracking device, rotation angles of the scaphoid and triquetrum and the change of scaphotriquetrum distance were measured under axial loading. We compared the rotation angles and the change of scaphotriquetrum distance among intact wrists, open, and arthroscopic lunate excisions.

Findings: No Significant differences in the rotation angle of the scaphoid and triquetrum or the change of scaphotriquetrum distance were found between intact wrist and arthroscopic lunate excision. The triquetrum significantly dorsiflexed and supinated in wrists with open lunate excisions compared with intact wrists. Significant differences in the change of scaphotriquetrum distance were found between intact and openly excised wrists and between arthroscopic and open excisions.

Interpretation: Arthroscopic lunate excision potentially prevented kinematic change of the proximal carpal row under axial loading by maintaining the integrity of attachment sites of carpal ligaments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiomech.2021.105343DOI Listing
March 2021

Effect of Ankle Motion and Tensile Stress at the Achilles Tendon on the Contact Pressure Between the Achilles Tendon and the Calcaneus.

J Foot Ankle Surg 2021 Mar 6. Epub 2021 Mar 6.

Professor, Department of Orthopedic Surgery, Nara Medical University, Kashihara, Japan.

Impingement between the Achilles tendon and the posterosuperior prominence of the calcaneus is considered to be a cause of insertional Achilles tendinopathy. The corresponding treatment intends to reduce tensile stress from calf muscles and avoid hyper-dorsiflexion of the ankle joint for decreasing the contact pressure; however, no study has reported on whether these treatments can decrease impingement. Thus, this study investigated the hypothesis that the tensile stress of the Achilles tendon and ankle motion affect the contact pressure between the Achilles tendon and the posterosuperior prominence of the calcaneus. Six fresh-frozen cadaveric lower leg specimens were procured. Each specimen was set to a custom foot-loading frame and loaded with a ground reaction force of 40 N and a tensile load of 70 N along the Achilles tendon. The contact pressure between the Achilles tendon and the posterosuperior prominence of the calcaneus was measured using a miniature pressure sensor under different tensile loadings of the Achilles tendon at the neutral ankle position. Similarly, the contact pressures during the ankle motion from a neutral position to maximum dorsiflexion were measured. The tensile load of the Achilles tendon and ankle motion affected the contact pressure between the Achilles tendon and the posterosuperior prominence of the calcaneus. The contact pressure increased with tensile load or ankle dorsiflexion. Conditions with increasing the tensile load of the Achilles tendon or under ankle dorsiflexion increase the contact pressure between the Achilles tendon and the posterosuperior prominence of the calcaneus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.jfas.2021.02.008DOI Listing
March 2021

Clinical efficacy of a novel, high-sensitivity HBcrAg assay in the management of chronic hepatitis B and HBV reactivation.

J Hepatol 2021 Feb 26. Epub 2021 Feb 26.

Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan; Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. Electronic address:

Background & Aims: A fully automated, novel high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developed. We demonstrate the clinical utility of iTACT-HBcrAg for monitoring chronic hepatitis B (CHB) and early detection of hepatitis B virus (HBV) reactivation.

Methods: After fundamental assessments, the clinical performance of iTACT-HBcrAg was compared with other HBV markers. 1) Of our CHB patients, serial sera, available from 161 HBeAg-negative CHB patients with persistently undetectable HBV DNA, were measured by iTACT-HBcrAg and a conventional HBcrAg assay (G-HBcrAg). 2) Serial sera from 13 HBV-reactivated patients were measured by iTACT-HBcrAg and ultra-high-sensitivity hepatitis B surface antigen (HBsAg) immune complex transfer-chemiluminescent enzyme immunoassay (lower limit of detection; 0.0005 IU/mL, ICT-CLEIA) for comparison with HBV DNA detection. 3) To elucidate the various HBcrAg components iTACT-HBcrAg detected, OptiPrep density gradient centrifugation analysis was performed on sera obtained before and after HBV reactivation.

Results: The analytical performance of iTACT-HBcrAg was satisfactory. The sensitivity of iTACT-HBcrAg (2.1 Log U/mL) was approximately 10-fold greater than that of G-HBcrAg (2.8 Log U/mL). 1) HBcrAg was detectable in 97.5% (157/161) sera of CHB patients by iTACT-HBcrAg, of which 75.2% (121/161) had ≥2.8 Log U/mL HBcrAg; and 22.4% (36/161) had 2.1-2.8 Log U/mL HBcrAg, which was undetectable by G-HBcrAg. 2) Nine and 2 of 13 HBV-reactivated patients were HBcrAg-positive by iTACT-HBcrAg before and at HBV DNA positivity, respectively. Seven and 4 were HBcrAg-positive by iTACT-HBcrAg before and at being HBsAg-positive by ICT-CLEIA, respectively. 3) The HBcrAg detected before HBV reactivation by iTACT-HBcrAg was contained in empty particles (22-KDa precore protein).

Conclusions: iTACT-HBcrAg should be of increased benefit for monitoring novel anti-HBV treatments for HBeAg-negative patients and early detection of HBV reactivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.02.017DOI Listing
February 2021

Modified albumin-bilirubin grade to predict eligibility for second-line therapies at progression on sorafenib therapy in hepatocellular carcinoma patients.

Int J Clin Oncol 2021 Mar 17. Epub 2021 Mar 17.

Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto City, Kumamoto, 860-8556, Japan.

Background: Our aim is to evaluate the utility of liver function measured by modified albumin-bilirubin (mALBI) grade to predict eligibility for second-line therapies, including regorafenib and ramucirumab therapy, at initiation of sorafenib therapy for patients with hepatocellular carcinoma (HCC).

Methods: Participants in this retrospective, single-center study comprised 197 patients with sorafenib-treated HCC, Child-Pugh scores (CPs) 5-7 and performance status 0-1 treated between October 2009 and June 2019. The factors at initiation of sorafenib therapy, including mALBI grade and CPs, were analyzed with regard to second-line eligibility, regorafenib eligibility and ramucirumab eligibility, respectively.

Results: Proportions of eligibility for second-line therapies, regorafenib therapy and ramucirumab therapy were 48.7%, 35.5% and 18.3%. Modified ALBI grades 1 and 2a were contributing factors for second-line eligibility (odd ratios [OR] 16.7 and 5.6; 95% CI 6.5-43.3 and 2.6-12.2), regorafenib therapy (OR 13.9 and 6.9; 95% CI 5.6-34.4 and 2.9-16.2), and ramucirumab therapy (OR 9.5 and 4.8; 95% CI 2.9-30.8 and 1.6-14.4), with grade 2b defined as reference. Patients with mALBI grade 1 and CPs 5 exhibited especially high proportion of eligibility for regorafenib therapy (70.5%). In patients with mALBI grade 2b, those with CPs 5 displayed higher proportion of eligibility for second-line therapy and ramucirumab therapy (100% and 50%) than those with CPs 6 (31.8% and 11.4%).

Conclusions: Modified ALBI grade in combination with CPs at the initiation of sorafenib therapy would be useful to predict eligibility for second-line therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-020-01835-2DOI Listing
March 2021

Impacted intraarticular fragments of distal radius fractures: A radiographic characterization and analysis of reliability and diagnostic accuracy.

J Orthop Sci 2021 Mar 8. Epub 2021 Mar 8.

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, 634-8522, Japan.

Background: Reduction using ligamentotaxis may not be effective enough to treat impacted intraarticular fragments of distal radius fractures. Articular incongruence resulting from the loss of reduction is a risk factor for postoperative osteoarthritis and worse clinical outcome. This study aimed to analyze the radiographic characterization of the impacted intraarticular fragments of distal radius fractures using two/three-dimensional computed tomography (CT). Further, we assessed the reliability and diagnostic accuracy in detecting the fragments using plain radiographs.

Methods: We analyzed 167 three-dimensional CT images of the intraarticular distal radius fractures and selected 12 fractures with impacted intraarticular fragments. We recorded the location, size, and displacement of the fragment using CT images. In addition, six examiners evaluated 25 fractures including those 12 fractures having the fragments using plain radiographs for detecting the fragments and their displacements. Further, we evaluated the reliability and diagnostic accuracy of the plain radiographs in the detection of the fragment.

Results: Fifteen impacted intraarticular fragments were found in 12 wrists. The displacement of the scaphoid facet fragment was significantly larger than that of the lunate facet fragment in CT measurement (7.0 mm and 3.6 mm). Inter and intraobserver reliability of the diagnosis for the fragment in plain radiographs were poor and fair (κ: 0.14 and κ:0.27). Diagnostic accuracy in detecting the fragment in plain radiographs generated mean sensitivity: 0.4, mean specificity: 0.73, and mean accuracy: 0.58. The mean sensitivity in detecting a lunate facet fragment was lower than that of a scaphoid facet fragment in plain radiographs (0.24 and 0.44).

Conclusion: Impacted intraarticular fragments were found in 7% of intraarticular distal radius fractures. We observed low reliability and sensitivity in detecting the fragment using plain radiographs. Preoperative recognition of the fragments using plain radiograph were difficult, even though the magnitude of step-off of the scaphoid facet fragment was large.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jos.2020.12.029DOI Listing
March 2021

Cytokines and Chemokines Involved in Hepatitis B Surface Antigen Loss in Human Immunodeficiency Virus/Hepatitis B Virus Coinfected Patients.

J Clin Med 2021 Feb 18;10(4). Epub 2021 Feb 18.

Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8602, Japan.

It has been reported that hepatic flare (HF), attributable to the development of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected patients, occurs frequently after the start of anti-retroviral therapy (ART). We have observed several cases of hepatitis B surface antigen (HBsAg) loss after IRIS. However, the factors leading to HBsAg clearance remain unknown. We measured CD4+ and CD8+ T cells, cytokines and chemokines in 16 patients coinfected HIV-1 and HBV with IRIS, and analyzed the factors leading to HBsAg clearance after IRIS. There was no significant difference in the CD4+ and CD8+ T cell counts between the HBsAg clearance and non-clearance groups, while the serum concentrations of almost all cytokines and chemokines in the HBsAg clearance group were higher than in the HBsAg non-clearance group at any time of observation. In particular, IP-10 at the ALT peak, GM-CSF and IL-12 one month after the ALT peak and TNF-α and GM-CSF after the ALT concentrations fell to within normal limits, were significantly higher in the HBsAg clearance group. It seems that HBsAg loss after IRIS requires continued immune responses against HBV, involving Th1 cytokines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10040833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922731PMC
February 2021

The Role of the Acromioclavicular Ligament in Acromioclavicular Joint Stability: A Cadaveric Biomechanical Study.

Orthop J Sports Med 2021 Feb 10;9(2):2325967120982947. Epub 2021 Feb 10.

Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan.

Background: Acromioclavicular (AC) joint dislocation is evaluated using the radiologically based Rockwood classification. The relationship between ligamentous injury and radiological assessment is still controversial.

Purpose/hypothesis: To investigate how the AC ligament and trapezoid ligament biomechanically contribute to the stability of the AC joint using cadaveric specimens. The hypothesis was that isolated sectioning of the AC ligament would result in increased instability in the superior direction and that displacement >50% of the AC joint would occur.

Study Design: Controlled laboratory study.

Methods: Six shoulders from 6 fresh-frozen cadavers were used in this study. Both the scapula and sternum were solidly fixed on a customized wooden jig with an external fixator. We simulated distal clavicular dislocation with sequential sectioning of the AC and coracoclavicular (CC) ligaments. Sectioning stages were defined as follows: stage 0, the AC ligament, CC ligament, and AC joint capsule were left intact; stage 1, the anteroinferior bundle of the AC ligament, joint capsule, and disk were sectioned; stage 2, the superoposterior bundle of the AC ligament was sectioned; and stage 3, the trapezoid ligament was sectioned. The distal clavicle was loaded with 70 N in the superior and posterior directions, and the magnitudes of displacement were measured.

Results: The amounts of superior displacement averaged 3.7 mm (stage 0), 3.8 mm (stage 1), 8.3 mm (stage 2), and 9.5 mm (stage 3). Superior displacement >50% of the AC joint was observed in stage 2 (4/6; 67%) and stage 3 (6/6; 100%). The magnitudes of posterior displacement were 3.7 mm (stage 0), 3.7 mm (stage 1), 5.6 mm (stage 2), and 9.8 mm (stage 3). Posterior displacement >50% of the AC joint was observed in stage 3 (1/6; 17%).

Conclusion: We found that the AC ligaments contribute significantly to AC joint stability, and superior displacement >50% of the AC joint can occur with AC ligament tears alone.

Clinical Relevance: The AC ligament plays an important role not only in horizontal stability but also in vertical stability of the AC joint.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2325967120982947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878954PMC
February 2021

Murine neonatal ketogenesis preserves mitochondrial energetics by preventing protein hyperacetylation.

Nat Metab 2021 02 18;3(2):196-210. Epub 2021 Feb 18.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Ketone bodies are generated in the liver and allow for the maintenance of systemic caloric and energy homeostasis during fasting and caloric restriction. It has previously been demonstrated that neonatal ketogenesis is activated independently of starvation. However, the role of ketogenesis during the perinatal period remains unclear. Here, we show that neonatal ketogenesis plays a protective role in mitochondrial function. We generated a mouse model of insufficient ketogenesis by disrupting the rate-limiting hydroxymethylglutaryl-CoA synthase 2 enzyme gene (Hmgcs2). Hmgcs2 knockout (KO) neonates develop microvesicular steatosis within a few days of birth. Electron microscopic analysis and metabolite profiling indicate a restricted energy production capacity and accumulation of acetyl-CoA in Hmgcs2 KO mice. Furthermore, acetylome analysis of Hmgcs2 KO cells revealed enhanced acetylation of mitochondrial proteins. These findings suggest that neonatal ketogenesis protects the energy-producing capacity of mitochondria by preventing the hyperacetylation of mitochondrial proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42255-021-00342-6DOI Listing
February 2021

Liver fibrosis improvement assessed by magnetic resonance elastography and Mac-2-binding protein glycosylation isomer in patients with hepatitis C virus infection receiving direct-acting antivirals.

Hepatol Res 2021 Feb 21. Epub 2021 Feb 21.

Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Aim: Fibrosis regression has been observed in patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antivirals. This study was aimed at evaluating dynamic changes of serum Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with HCV genotype 1 receiving elbasvir/grazoprevir.

Methods: M2BPGi were serially measured at baseline, during and after therapy. Its diagnostic performance at baseline and sustained virological response at 24 weeks after treatment (SVR24) were compared with transient elastography (TE) and the aspartate aminotransferase/platelet ratio index (APRI) using magnetic resonance elastography (MRE) as a reference.

Results: Overall, 60 HCV mono-infected and 36 HCV/HIV co-infected patients were included with SVR24 rates of 93.3% and 97.2%, respectively. At baseline, TE, M2BPGi and APRI were correlated with MRE (r = 0.788, r = 0.703 and r = 0.564, respectively, p < 0.001). The area under the receiver operator characteristics curves for TE, M2BPGi and APRI in differentiating significant fibrosis were 0.88 (95% confidence interval; 0.81-0.95, p < 0.001), 0.86 (0.79-0.94, p < 0.001) and 0.74 (0.64-0.83, p < 0.001), respectively. The corresponding figures for cirrhosis were 0.95 (0.90-1.00, p < 0.001), 0.96 (0.92-1.00, p < 0.001) and 0.88 (0.79-0.97, p < 0.001), respectively. Compared with baseline, all fibrosis markers significantly declined after achieving SVR24. The correlations of TE, M2BPGi and APRI with MRE at time of SVR24 were r = 0.587 (p < 0.001), r = 0.457 (p < 0.001) and r = 0.293 (p = 0.004), respectively. In multivariate analysis, high baseline alanine aminotransferase level, HCV mono-infection and advanced fibrosis were factors associated with M2BPGi reduction.

Conclusions: HCV eradication is associated with liver fibrosis improvement. M2BPGi has a better performance than APRI in monitoring liver fibrosis in patients treated with direct-acting antivirals. This marker is applicable in resource-limited settings where imaging-based modalities are not widely accessible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.13630DOI Listing
February 2021

Soft-tissue reconstruction after soft-tissue sarcoma resection: the clinical outcomes of 24 patients.

Eur J Orthop Surg Traumatol 2021 Feb 20. Epub 2021 Feb 20.

Department of Orthopaedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.

Purpose: Pedicle or free-flap reconstruction is important in surgical sarcoma management. Free flaps are indicated only when pedicle flaps are considered inadequate; however, they are associated with a higher risk of flap failure, longer surgical times, and technical difficulty. To determine the skin defect size that can be covered by a pedicle flap, we investigated the clinical outcomes and complications of reconstruction using pedicle flaps vs. free flaps after sarcoma resection.

Methods: We retrospectively studied the medical records of 24 patients with soft-tissue sarcomas who underwent reconstruction using a pedicle (n = 20) or free flap (n = 4) following wide tumour resection.

Results: All skin defects of the knee, lower leg, and ankle were reconstructed using a pedicle flap. Skin defects of the knee, lower leg, and ankle were covered by up to 525 cm, 325 cm, and 234 cm, respectively. The amount of blood loss was significantly greater in the free-flap group than in the pedicle flap group (p = 0.011). Surgical time was significantly shorter in the pedicle flap group than in the free-flap group (p = 0.006). Total necrosis was observed in one (25%) patient in the free-flap group; no case of total necrosis was observed in the pedicle flap group.

Conclusion: Less blood loss, shorter surgical time, and lower risk of total flap necrosis are notable advantages of pedicle flaps over free flaps. Most skin defects, even large ones, of the lower extremities following sarcoma resection can be covered using a single pedicle flap or multiple pedicle flaps.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00590-021-02901-9DOI Listing
February 2021

Improvement of Gut Diversity and Composition after Direct-Acting Antivirals in HCV-Infected Patients with or without HIV Coinfection.

J Infect Dis 2021 Feb 17. Epub 2021 Feb 17.

Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)-infected patients with or without human immunodeficiency virus (HIV) is unclear.

Methods: We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir/grazoprevir from a clinical trial. Fecal specimens collected at pre-treatment and 12 weeks post-treatment were analyzed using amplicon-based 16S rRNA sequencing.

Results: Sustained virological response (SVR12) rates in the mono- and co-infection groups were similar (98.4%vs.95.8%). Pre-treatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha-diversity but displayed declined Firmicutes/Bacteroidetes ratio. The improvement of microbial dysbiosis was observed in responders achieving SVR12 across fibrosis stages but was not found in non-responders. Responders with low degree of fibrosis exhibited a recovery in alpha-diversity to level comparable with healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders.

Conclusions: This study indicates short-term effect of DAAs in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might potentially contribute towards the reduction of HCV-related complications among infected individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiab094DOI Listing
February 2021

Prophylactic antiviral therapy for hepatitis B virus surface antigen-positive patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy.

Cancer Sci 2021 Feb 12. Epub 2021 Feb 12.

Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti-HBV prophylactic therapy: no nucleos(t)ide analogue (non-NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P = .081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P < .001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non-NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non-NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14846DOI Listing
February 2021

Analysis of Hepatitis B Virus Genotype D in Greenland Suggests the Presence of a Novel Quasi-Subgenotype.

Front Microbiol 2020 15;11:602296. Epub 2021 Jan 15.

Department of Medicine, University of California San Diego, San Diego, CA, United States.

A disproportionate number of Greenland's Inuit population are chronically infected with Hepatitis B virus (HBV; 5-10%). HBV genotypes B and D are most prevalent in the circumpolar Arctic. Here, we report 39 novel HBV/D sequences from individuals residing in southwestern Greenland. We performed phylodynamic analyses with ancient HBV DNA calibrators to investigate the origin and relationship of these taxa to other HBV sequences. We inferred a substitution rate of 1.4 × 10 [95% HPD 8.8 × 10, 2.0 × 10] and a time to the most recent common ancestor of 629 CE [95% HPD 37-1138 CE]. The Greenland taxa form a sister clade to HBV/D2 sequences, specifically New Caledonian and Indigenous Taiwanese sequences. The Greenland sequences share amino acid signatures with subgenotypes D1 and D2 and ~97% sequence identity. Our results suggest the classification of these novel sequences does not fit within the current nomenclature. Thus, we propose these taxa be considered a novel quasi-subgenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.602296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843931PMC
January 2021

Usefulness of an artificial intelligence system for the detection of esophageal squamous cell carcinoma evaluated with videos simulating overlooking situation.

Dig Endosc 2021 Jan 27. Epub 2021 Jan 27.

AI Medical Service Inc, Tokyo, Japan.

Objectives: Artificial intelligence (AI) systems have shown favorable performance in the detection of esophageal squamous cell carcinoma (ESCC). However, previous studies were limited by the quality of their validation methods. In this study, we evaluated the performance of an AI system with videos simulating situations in which ESCC has been overlooked.

Methods: We used 17,336 images from 1376 superficial ESCCs and 1461 images from 196 noncancerous and normal esophagi to construct the AI system. To record validation videos, the endoscope was passed through the esophagus at a constant speed without focusing on the lesion to simulate situations in which ESCC has been missed. Validation videos were evaluated by the AI system and 21 endoscopists.

Results: We prepared 100 video datasets, including 50 superficial ESCCs, 22 noncancerous lesions, and 28 normal esophagi. The AI system had sensitivity of 85.7% (54 of 63 ESCCs) and specificity of 40%. Initial evaluation by endoscopists conducted with plain video (without AI support) had average sensitivity of 75.0% (47.3 of 63 ESCC) and specificity of 91.4%. Subsequent evaluation by endoscopists was conducted with AI assistance, which improved their sensitivity to 77.7% (P = 0.00696) without changing their specificity (91.6%, P = 0.756).

Conclusions: Our AI system had high sensitivity for the detection of ESCC. As a support tool, the system has the potential to enhance detection of ESCC without reducing specificity. (UMIN000039645).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/den.13934DOI Listing
January 2021

Risk stratification for advanced colorectal neoplasia based on the findings of the index and first surveillance colonoscopies.

PLoS One 2021 22;16(1):e0245211. Epub 2021 Jan 22.

Department of Gastroenterology and Hepatology, Kumamoto University Hospital, Kumamoto, Japan.

Risk stratification by index colonoscopy is well established for first surveillance endoscopy, but whether the previous two colonoscopies affect the subsequent advanced neoplasias has not been established. Therefore, the subsequent risk based on the findings of the index and first surveillance colonoscopies were investigated. This retrospective, cohort study was conducted in two clinics and included participants who had undergone two or more colonoscopies after index colonoscopy. High-risk was defined as advanced adenoma (≥ 1 cm, or tubulovillous or villous histology, or high-grade dysplasia). Based on the findings of the index and first surveillance colonoscopies, patients were classified into four categories: category A (both colonoscopy findings were normal), category B (no high-risk findings both times), category C (one time high-risk finding), and category D (high-risk findings both times). The incidence of subsequent advanced neoplasia was examined in each category. A total of 13,426 subjects were included and surveyed during the study periods. The subjects in category D had the highest risk of advanced neoplasia (27.4%, n = 32/117). The subjects in category A had the lowest risk (4.0%, n = 225/5,583). The hazard ratio for advanced neoplasia of category D compared to category A was 9.90 (95% Confidence interval 6.82-14.35, P<0.001). Classification based on the findings of index and first surveillance colonoscopies more effectively stratifies the risk of subsequent advanced neoplasia, resulting in more proper allocation of colonoscopy resources after two consecutive colonoscopies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245211PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822265PMC
January 2021

Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma.

Oncotarget 2020 Dec 29;11(52):4803-4812. Epub 2020 Dec 29.

Department of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.

Genome-wide analysis is widely applied to detect molecular alterations during oncogenesis and tumor progression. We analyzed DNA methylation profiles of hepatocellular carcinoma (HCC), and investigated the clinical role of most heypermethylated of tumor, encodes T-box 15 (TBX15), which was originally involved in mesodermal differentiation. We conducted a genome-wide analysis of DNA methylation of tumor and non-tumor tissue of 15 patients with HCC, and revealed was the most hypermethylated gene of tumor (Beta-value in tumor tissue = 0.52 compared with non-tumor tissue). Another validation set, which comprised 58 HCC with radical resection, was analyzed to investigate the relationships between tumor phenotype and mRNA expression. mRNA levels in tumor tissues were significantly lower compared with those of nontumor tissues ( < 0.0001). When we assigned a cutoff value = 0.5-fold, the overall survival 5-year survival rates of the low-expression group ( = 17) were significantly shorter compared with those of the high-expression group ( = 41) (43.3% vs. 86.2%, = 0.001). Multivariate analysis identified low expression as an independent prognostic factor for overall and disease-free survival. Therefore, genome-wide DNA methylation profiling indicates that hypermethylation and reduced expression of in tumor tissue represents a potential biomarker for predicting poor survival of patients with HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.27852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779253PMC
December 2020

Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients.

Sci Rep 2021 Jan 13;11(1):960. Epub 2021 Jan 13.

Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.

In HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-80247-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806981PMC
January 2021

Narrow-band imaging with magnification in perianal Paget disease.

Gastrointest Endosc 2021 Jan 6. Epub 2021 Jan 6.

Department of Gastroenterology and Hepatology, Kumamoto University Hospital, Kumamoto, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2020.12.044DOI Listing
January 2021

Tetanic stimulation of the peripheral nerve augments motor evoked potentials by re-exciting spinal anterior horn cells.

J Clin Monit Comput 2021 Jan 9. Epub 2021 Jan 9.

Department of Orthopaedic Surgery, Nara Medical University, Shijocho 840, Kashihara, Nara, 634-8521, Japan.

Tetanic stimulation of the peripheral nerve, immediately prior to conducting transcranial electrical stimulation motor evoked potential (TES-MEP), increases MEP amplitudes in both innervated and uninnervated muscles by the stimulated peripheral nerve; this is known as the remote augmentation of MEPs. Nevertheless, the mechanisms underlying the remote augmentation of MEPs remain unclear. Although one hypothesis was that remote augmentation of MEPs results from increased motoneuronal excitability at the spinal cord level, the effect of spinal anterior horn cells has not yet been investigated. We aimed to investigate the effect of tetanic stimulation of the peripheral nerve on spinal cord anterior horn cells by analyzing the F-wave. We included 34 patients who underwent elective spinal surgeries and compared the changes in F-waves and TES-MEPs pre- and post-tetanic stimulation of the median nerve. F-wave analyses were recorded by stimulating the median and tibial nerves. TES-MEPs and F-wave analyses were compared between baseline and post-tetanic stimulation time periods using Wilcoxon signed-rank tests. A significant augmentation of MEPs, independent of the level corresponding to the median nerve, was demonstrated. Furthermore, F-wave persistence was significantly increased not only in the median nerve but also in the tibial nerve after tetanic stimulation of the median nerve. The increased F-wave persistence indicates an increase of re-excited motor units in spinal anterior horn cells. These results confirm the hypothesis that tetanic stimulation of the peripheral nerve may cause remote augmentation of MEPs, primarily by increasing the excitability of the anterior horn cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10877-020-00647-zDOI Listing
January 2021

An infected aneurysm of the vertebral artery following cervical pyogenic spondylitis: a case report and literature review.

BMC Musculoskelet Disord 2021 Jan 6;22(1):22. Epub 2021 Jan 6.

Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara City, 6348522, Nara, Japan.

Background: An important complication of pyogenic spondylitis is aneurysms in the adjacent arteries. There are reports of abdominal aortic or iliac aneurysms, but there are few reports describing infected aneurysms of the vertebral artery. Furthermore, there are no reports describing infected aneurysms of the vertebral arteries following cervical pyogenic spondylitis. We report a rare case of an infected aneurysm of the vertebral artery as a complication of cervical pyogenic spondylitis, which was successfully treated by endovascular treatment.

Case Presentation: Cervical magnetic resonance imaging (MRI) of a 59-year-old man who complained of severe neck pain showed pyogenic spondylitis. Although he was treated extensively by antibiotic therapy, his neck pain did not improve. Follow-up MRI showed the presence of a cyst, which was initially considered an abscess, and therefore, treatment initially included guided tapping and suction under ultrasonography. However, under ultrasonographic examination an aneurysm was detected. The contrast-enhanced computed tomography (CT) scan showed an aneurysm of the vertebral artery. Following endovascular treatment (parent artery occlusion: PAO), the patient's neck pain disappeared completely.

Conclusion: Although there are several reports of infected aneurysms of the vertebral arteries, this is the first report describing an infected aneurysm of the vertebral artery as a result of cervical pyogenic spondylitis. Whenever a paraspinal cyst exist at the site of infection, we recommend that clinicians use not only X-ray, conventional CT, and MRI to examine the cyst, but ultrasonography and contrast-enhanced CT as well because of the possibility of an aneurysms in neighboring blood vessels. It is necessary to evaluate the morphology of the aneurysm to determine the treatment required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12891-020-03881-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786991PMC
January 2021

Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.

BMC Musculoskelet Disord 2021 Jan 5;22(1):12. Epub 2021 Jan 5.

Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136, Bologna, Italy.

Background: This study compared the clinical and functional outcomes of patients initially treated with observation or medical treatment with those of patients treated with local treatment (surgery alone or surgery with adjuvant radiotherapy) to confirm whether observation or medical treatment is an appropriate first-line management approach for patients with desmoid tumors.

Methods: We retrospectively reviewed the medical records of 99 patients with histologically confirmed primary desmoid tumors treated between 1978 and 2018. The median follow-up period was 57 months. We evaluated event-free survival, defined as the time interval from the date of initial diagnosis to the date of specific change in treatment strategy or recurrence or the last follow-up.

Results: An event (specific change in treatment strategy or recurrence) occurred in 28 patients (28.3%). No significant difference in event-free survival was found between the first-line observation/medical treatment and local treatment groups (p = 0.509). The median Musculoskeletal Tumor Society score of the patients treated with first-line local treatment was 29 (interquartile range [IQR], 23-30), whereas that of the patients managed with first-line observation or medical treatment was 21 (IQR, 19-29.5). First-line observation or medical treatment was more frequently chosen for larger tumors (p = 0.045). In the patients treated with local treatment, local recurrence was not related to the surgical margin (p = 0.976).

Conclusion: Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12891-020-03897-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784367PMC
January 2021

Restoration of type I interferon signaling in intrahepatically primed CD8+ T cells promotes functional differentiation.

JCI Insight 2021 Feb 8;6(3). Epub 2021 Feb 8.

Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Hepatitis B virus-specific (HBV-specific) CD8+ T cells fail to acquire effector functions after priming in the liver, but the molecular basis for the dysfunction is poorly understood. By comparing the gene expression profile of intrahepatically primed, dysfunctional HBV-specific CD8+ T cells with that of systemically primed, functional effector counterparts, we found that the expression of interferon-stimulated genes (ISGs) is selectively suppressed in the dysfunctional CD8+ T cells. The ISG suppression was associated with impaired phosphorylation of STAT1 in response to IFN-α treatment. Importantly, a strong induction of type I interferons (IFN-Is) in the liver facilitated the functional differentiation of intrahepatically primed HBV-specific CD8+ T cells in association with the restoration of ISGs' expression in the T cells. These results suggest that intrahepatic priming suppresses IFN-I signaling in CD8+ T cells, which may contribute to the dysfunction. The data also suggest a therapeutic value of the robust induction of intrahepatic IFN-Is for the treatment of chronic HBV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.145761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934883PMC
February 2021

Ultrasonographic test for detecting the chiasma plantare formation between the flexor hallucis longus and flexor digitorum longus.

Surg Radiol Anat 2021 Jan 4. Epub 2021 Jan 4.

Graduate School of Medicine, Musculoskeletal Reconstructive Surgery, Nara Medical University, Kashihara, Nara, Japan.

Purpose: Flexor hallucis longus (FHL) and flexor digitorum longus (FDL) tendons are frequently used in surgery. Therefore, it is necessary to evaluate the chiasma plantare formation preoperatively. The development of ultrasonography (US) may help the chiasma plantare formation evaluation. The purpose of this study is to prove the usefulness of the US method using cadavers.

Methods: Eleven cases (twenty-two ankles) were obtained from Asian adult cadavers. At first, we evaluated and compared the chiasma plantare formation using US. Later, we evaluated that using the findings after dissection as type A (connection from FHL to FDL of the second toe), type B (connection from FHL to the second and third toes), type C (connection from FHL to the second through fourth toes), or type D (connection from FHL to all lesser toes).

Results: Chiasma plantare formation was classified as types A and B in fifteen and seven ankles, respectively. After dissection, chiasma plantare formation was classified as types A, B, and C in fourteen, six, and two ankles, respectively. Therefore, there was an 86% similarity between the two methods.

Conclusions: Chiasma plantare formation can be reliably and noninvasively evaluated using US. This may be useful for preoperative rehabilitation or surgical procedure planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00276-020-02630-4DOI Listing
January 2021

Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients.

Hepatol Int 2021 Feb 4;15(1):71-81. Epub 2021 Jan 4.

Division of Gastroenterology and Hepatology, Stanford University Medical Center, 780 Welch Road, CJ250K, Palo Alto, CA, 94304, USA.

Background: Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization's goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions.

Methods: We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan-Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria.

Results: Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03-1.57% among noncirrhotic males and 2.57-6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment.

Conclusion: Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-020-10113-2DOI Listing
February 2021

Identification of a novel long-acting 4'-modified nucleoside reverse transcriptase inhibitor against HBV.

J Hepatol 2020 Dec 15. Epub 2020 Dec 15.

Department of Refractory Viral Infections, National Center for Global Health & Medicine Research Institute, Tokyo, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Clinical Sciences, Kumamoto University Hospital, Kumamoto, Japan. Electronic address:

Background & Aims: While certain nucleos(t)ide reverse transcriptase inhibitors (NRTIs) are efficacious in treating HBV infection, their effects are yet to be optimized and the emergence of NRTI-resistant HBV variants is an issue because of the requirement for lifelong treatment. The development of agents that more profoundly suppress wild-type and drug-resistant HBVs, and that have a long-acting effect, are crucial to improve patient outcomes.

Methods: Herein, we synthesized a novel long-acting 4'-modified NRTI termed E-CFCP. We tested its anti-HBV activity in vitro, before evaluating its anti-HBV activity in HBV-infected human-liver-chimeric mice (PXB-mice). E-CFCP's long-acting features and E-CFCP-triphosphate's interactions with the HBV reverse transcriptase (HBV-RT) were examined.

Results: E-CFCP potently blocked HBV production (IC1.8 nM) in HepG2.2.15 cells and HBV (IC=0.7 nM), entecavir (ETV)-resistant HBV (IC=77.5 nM), and adefovir-resistant HBV production (IC=14.1 nM) in Huh7 cells. E-CFCP profoundly inhibited intracellular HBV DNA production to below the detection limit, but ETV and tenofovir alafenamide (TAF) failed to do so. E-CFCP also showed less toxicity than ETV and TAF. E-CFCP better penetrated hepatocytes and was better tri-phosphorylated; E-CFCP-triphosphate persisted intracellularly for longer than ETV-triphosphate. Once-daily peroral E-CFCP administration over 2 weeks (0.02~0.2 mg/kg/day) reduced HBV-viremia by 2-3 logs in PXB-mice without significant toxicities and the reduction persisted over 1-3 weeks following treatment cessation, suggesting once-weekly dosing capabilities. E-CFCP also reduced HBV-viremia by 2 logs over 2 weeks, while ETV completely failed to reduce HBV-viremia. E-CFCP's 4'-cyano and fluorine interact with both HBV-RT and HBV -RT via Van der Waals and polar forces, being important for E-CFCP-triphosphate's interactions and anti-HBV potency.

Conclusion: E-CFCP represents the first reported potential long-acting NRTI with potent activity against wild-type and treatment-resistant HBV.

Lay Summary: Although there are currently effective treatment options for HBV, treatment-resistant variants and the need for lifelong therapy pose a significant challenge. Therefore, the development of new treatment options is crucial to improve outcomes and quality of life. Herein, we report preclinical evidence showing that the anti-HBV agent, E-CFCP, has potent activity against wild-type and treatment-resistant variants. In addition, once-weekly oral dosing may be possible, which is preferrable to the current daily dosing regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2020.12.006DOI Listing
December 2020

Establishment of a novel hepatitis B virus culture system using immortalized human hepatocytes.

Sci Rep 2020 12 10;10(1):21718. Epub 2020 Dec 10.

Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.

Recent development of hepatitis B virus (HBV) culture systems has made it possible to analyze the almost all steps of the viral life cycle. However, the reproducibility of interaction between HBV and host cells seemed inaccurate in those systems because of utilization of cancer cell lines with a difference from hepatocytes in the majority of cases. In this study, in order to resolve this point, a novel HBV culture system using non-cancer-derived immortalized human hepatocytes derived cell lines, producing exogenous human sodium taurocholate cotransporting polypeptide, was developed. One of the cell clones, E/NtG8 cells, was permissive to both blood-borne HBV (HBVbb) and culture-derived recombinant HBV when cultured in the three-dimensional condition. Furthermore, the production of infectious HBV particles, which showed the similar physicochemical properties to HBVbb, was observed for about a month after HBVbb infection in this system, suggesting that it may reproduce whole steps of the HBV lifecycle under the condition analogous to human liver cells infected with HBV. This system seemed to contribute not only to find novel interactions between HBV and host cells but also to understand mechanism of HBV pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-78655-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729873PMC
December 2020

Anti-Stem Cell Property of Pterostilbene in Gastrointestinal Cancer Cells.

Int J Mol Sci 2020 Dec 8;21(24). Epub 2020 Dec 8.

Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan.

Pterostilbene (PTE) is a natural sterbenoid contained in blueberries that has an antioxidant effect. In contrast, PTE also generates oxidative stress in cancer cells and provides an antitumor effect. Here, we examined the potential mechanism of this contrasting effect of PTE using three gastrointestinal cancer cell lines, namely CT26, HT29, and MKN74. PTE showed a dose-dependent inhibition of cell proliferation, sphere-forming ability, and stem cell marker expression in all three cell lines. Furthermore, the cells treated with PTE showed an increase in mitochondrial membrane potential and an increase in mitochondrial oxidative stress and lipid peroxide. Upon concurrent treatment with vitamin E, N-acetyl-L-cysteine, and PTE, the PTE-induced mitochondrial oxidative stress and growth inhibition were suppressed. These findings indicate that PTE induces oxidative stress in cancer cells, suppresses stemness, and inhibits proliferation. These antitumor effects of PTE are considered to be useful in cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21249347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762551PMC
December 2020

Application of a Customized Total Talar Prosthesis for Revision Total Ankle Arthroplasty.

JB JS Open Access 2020 Oct-Dec;5(4). Epub 2020 Oct 28.

Department of Orthopedic Surgery, Nara Medical University, Nara, Japan.

Background: The rate of revision surgery for total ankle arthroplasty (TAA) is higher than for hip and knee arthroplasties. Tibiotalocalcaneal arthrodesis is widely used; however, it requires a large allograft. Thus, the use of a customized total talar prosthesis in combination with the tibial component of TAA (combined TAA) may be an effective strategy for talar component subsidence. This study aimed to evaluate the clinical and radiographic effectiveness of the combined TAA in such revision cases.

Methods: Between 2000 and 2015, 10 patients (10 women; 10 ankles) were treated using the combined TAA for revision after standard TAA or combined procedures that included the use of a talar body prosthesis. In 6 patients, the tibial component was concurrently replaced. The median follow-up period was 49 months (interquartile range [IQR], 24.5 to 90 months). The Japanese Society for Surgery of the Foot (JSSF) ankle-hindfoot scale score, a numerical rating scale (NRS) pain score, passive range of motion of the ankle, and the presence of osteophytes and degenerative changes in the adjacent joints were assessed preoperatively and at final postoperative follow-up.

Results: The median NRS pain score improved significantly, from 7 (IQR, 6.25 to 8.75) to 2 (IQR, 1 to 3). The median JSSF ankle-hindfoot scale total score improved significantly, from 64 (IQR, 56.25 to 71.5) to 88.5 (IQR, 79.75 to 96). In the subcategories of this scale, the median pain score improved from 20 (IQR, 20 to 27.5) to 35 (IQR, 30 to 40), and the median function score improved from 34 (IQR, 26.5 to 37) to 43.5 (IQR, 39.75 to 46). The median range of motion improved from 29° (IQR, 25.5° to 35°) to 35° (IQR, 31.25° to 43.75°). No significant difference in osteophyte formation was found. Degenerative changes in the adjacent joint were found only in the talonavicular joint.

Conclusions: The combined TAA, used in revision for postoperative complications after standard TAA or combined procedures including the use of a talar body prosthesis, was associated with improved objective JSSF ankle-hindfoot scale scores, subjective pain assessment, and range of motion in the ankle.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2106/JBJS.OA.20.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593043PMC
October 2020

HCC risk post-SVR with DAAs in East Asians: findings from the REAL-C cohort.

Hepatol Int 2020 Dec 4;14(6):1023-1033. Epub 2020 Dec 4.

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 780 Welch Road, Palo Alto, CA, 94304, USA.

Background: Despite HCV cure, patients remain at risk for HCC, but risk factor data for HCC following SVR are limited for Asian patients.

Methods: To address this gap, we analyzed 5814 patients (5646 SVR, 168 non-SVR) from the Real-World Evidence from the Asia Liver Consortium for HCV (REAL-C) who did not have HCC or a history of HCC at baseline (pre-DAA treatment) and did not develop HCC within 6 months of baseline. To assess the effect of SVR on HCC incidence, we used 1:4 propensity score matching [(PSM), age, sex, baseline cirrhosis, and baseline AFP] to balance the SVR and non-SVR groups.

Results: In the PSM cohort (160 non-SVR and 612 SVR), the HCC incidence rate per 100 person years was higher in the non-SVR compared to the SVR group (5.26 vs. 1.94, p < 0.001). Achieving SVR was independently associated with decreased HCC risk (adjusted HR [aHR]: 0.41, p = 0.002). Next, we stratified the SVR cohort of 5646 patients to cirrhotic and noncirrhotic subgroups. Among cirrhotic SVR patients, aged ≥ 60, having an albumin bilirubin grade (ALBI) of 2 or 3 (aHR: 2.5, p < 0.001), and baseline AFP ≥ 10 ng/mL (aHR: 1.6, p = 0.001) were associated with higher HCC risk, while among the non-cirrhotic SVR group, only baseline AFP ≥ 10 ng/mL was significant (aHR: 4.26, p = 0.005).

Conclusions: Achieving SVR decreases HCC risk; however, among East Asians, patients with elevated pretreatment AFP remained at risk. Pretreatment AFP, an easily obtained serum marker, may provide both prognostic and surveillance value for HCC in East Asian patients who obtained SVR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-020-10105-2DOI Listing
December 2020