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1.
Gait Posture ; 112: 33-39, 2024 May 07.
Article En | MEDLINE | ID: mdl-38729081

BACKGROUND: Advanced varus ankle osteoarthritis is a debilitating disease that can present with limited physical function, severe pain, and diminished quality of life. Weightbearing computed tomography enables submillimeter 3-dimensional visualization, computational analyses, and enhanced diagnoses in reporting complex degenerative changes more accurately. RESEARCH QUESTION: This study set to compare static posture weightbearing joint angle differences in healthy and varus ankle osteoarthritis patients (compensated and non-compensated). METHODS: Our retrospective assessment included 70 individuals, 44 of whom were diagnosed with advanced varus ankle osteoarthritis, and the remaining 26 were healthy participants to serve as controls. An automatic anatomic coordinate system was applied to each patient's 3-dimensional talus and calcaneus bone reconstructions from weightbearing computed tomography scans. Subtalar and midtarsal joint angles were calculated using Euler angles. RESULTS: We report statistical differences between the healthy group and both advanced varus osteoarthritis groups for midtarsal inversion/eversion. Specifically, both osteoarthritis groups' midtarsal joints were more inverted and plantarflexed as compared to healthy participants. Compensated and non-compensated subtalar joints were statistically different with respect to inversion/eversion. Non-compensated ankles exhibited a similar mean to healthy ankles who were both less inverted than compensated ankles. SIGNIFICANCE: Our study helps physicians to better understand underlying mechanisms of peritalar compensation in varus ankle osteoarthritis. Patients featuring hindfoot compensation on average had a greater subtalar joint angle indicating greater inversion than healthy and non-compensated patients.

2.
J Gastroenterol ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38727822

BACKGROUND: This study aimed to clarify the morphological changes in esophageal varices after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) in patients with cirrhosis. METHODS: A total of 243 patients underwent esophagogastroduodenoscopy before DAA treatment and after achieving SVR. Morphological changes in esophageal varices were investigated using esophagogastroduodenoscopy. RESULTS: This study comprised 125 males and 118 females with a median age of 68 years. Esophageal varices at baseline were classified into no varix in 155 (63.8%), F1 in 59 (24.3%), F2 in 25 (10.3%) and F3 in 4 (1.6%) patients. The improvement, unchanged, and aggravation rates of esophageal varices after SVR were 11.9%, 73.3%, and 14.8%, respectively. High ALBI score at SVR12 was an independent factor associated with post-SVR esophageal varices aggravation (p = 0.045). Time-dependent receiver operating characteristic (ROC) curve analysis revealed a cut-off value of - 2.33 for ALBI score at SVR12 in predicting post-SVR esophageal varices aggravation. Of the 155 patients without esophageal varices at baseline, 17 developed de novo post-SVR esophageal varices. High ALBI score at SVR12 was a significant independent factor associated with de novo post-SVR esophageal varices (p = 0.046). ROC curve analysis revealed a cut-off value of - 2.65 for ALBI score at SVR12 in predicting de novo post-SVR esophageal varices. CONCLUSIONS: Patients with cirrhosis can experience esophageal varices aggravation or de novo esophageal varices, despite achieving SVR. In particular, patients with high ALBI score at SVR12 have a high likelihood of developing post-SVR esophageal varices aggravation or de novo post-SVR esophageal varices.

3.
J Gastroenterol ; 2024 May 13.
Article En | MEDLINE | ID: mdl-38739200

BACKGROUND: We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC). METHODS: The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24 weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR. RESULTS: Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI). CONCLUSIONS: The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.

4.
Hepatol Res ; 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38651670

The use of nucleos(t)ide analogs (NAs) is recommended for mothers with a high viral load of hepatitis B virus (HBV) during the second or third trimester of pregnancy. However, postpartum hepatitis flares can occur in some cases. We examined the efficacy of NA administration for the prevention of mother-to-child transmission of hepatitis B virus, and evaluated the risk of postpartum hepatitis flares in mothers after NA discontinuation. Nine pregnant women with a high viral load (HBV DNA ≥5.3 log IU/mL) received tenofovir disoproxil fumarate (TDF) at approximately 28 weeks of gestation, and TDF was discontinued at 4-10 weeks after delivery. We evaluated the virological and biochemical parameters in mothers after TDF discontinuation. Hepatitis flares in mothers were defined as alanine transaminase level ≥60 U/L. None of the infants developed any congenital anomaly or acquired HBV infection during infancy. Hepatitis flares occurred within 6 months after TDF discontinuation in five of seven cases, whereas two cases were lost to follow-up. Furthermore, three cases required the resumption of NA use. NA administration was highly effective against mother-to-child-transmission of HBV in pregnant women with high HBV DNA levels. However, hepatitis flares were commonly observed after NA discontinuation in the postpartum period. Patients should be followed up carefully after NA discontinuation, and NA resumption should be considered based on a comprehensive assessment of virological and biochemical parameters.

5.
Article En | MEDLINE | ID: mdl-38567863

OBJECTIVE: Economic feasibility of eliminating mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in highly endemic African countries remains uncertain. Prevention of MTCT (PMTCT) involves screening pregnant women for hepatitis B surface antigen (HBsAg), identifying those with high viral loads or hepatitis B e antigen (HBeAg), and administering tenofovir prophylaxis to high-risk women. We estimated the costs of integrating PMTCT services into antenatal care in Burkina Faso, based on four different strategies to select women for tenofovir prophylaxis: (1) HBV DNA (≥200 000 IU/mL), (2) HBeAg, (3) hepatitis B core-related antigen rapid diagnostic test (HBcrAg-RDT) and (4) all HBsAg-positive women. METHODS: Using a micro-costing approach, we estimated the incremental economic cost of integrating each strategy into routine antenatal care in 2024, compared to neonatal vaccination alone. Sensitivity analyses explored variations in prevalence, service coverage, test and tenofovir prices. RESULTS: HBcrAg-RDT strategy was the least expensive, with a total economic cost of US$3959689, compared to HBV DNA (US$6128875), HBeAg (US$4135233), and treat-all (US$4141206). The cost per pregnant woman receiving tenofovir prophylaxis varied from US$61.88 (Treat-all) to US$1071.05 (HBV DNA). The Treat-All strategy had the lowest marginal cost due to a higher number of women on tenofovir (66928) compared to HBV DNA (5722), HBeAg (10020), and HBcrAg-RDT (7234). In sensitivity analyses, the treat-all strategy became less expensive when the tenofovir price decreased. CONCLUSION: HBcrAg-RDT minimizes resource use and costs, representing 0.61% of Burkina Faso's 2022 health budget. This study highlights the potential economic feasibility of these strategies and provides valuable resources for conducting cost-effectiveness analyses.

6.
J Foot Ankle Res ; 17(2): e12007, 2024 Jun.
Article En | MEDLINE | ID: mdl-38632697

BACKGROUND: Factors associated with falls after total knee arthroplasty (TKA) have been rarely reported. The aim of this study was to identify factors that influence the incidence of falls after TKA, focusing on toe grip strength (TGS) in particular, which has been associated with falls in older adults. METHODS: 217 patients who underwent TKA were included and followed up for 1 year. Main study outcome measures were the presence or absence of falls within 1 year after TKA. Multiple logistic regression analysis was used with postoperative falls as the dependent variable and preoperative falls and postoperative TGS on the affected sides as independent variables. RESULTS: 170 (43 and 127 in the fall and non-fall groups) patients were included in the analysis. The presence of a preoperative falls history before TKA and a weak postoperative affected TGS indicated an increased susceptibility of the patient to fall postoperatively. CONCLUSIONS: Results of the current study revealed the association between postoperative TGS and postoperative falls. We highlight the importance of preoperative fall monitoring and postoperative TGS evaluation to prevent falls after TKA.


Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Humans , Aged , Arthroplasty, Replacement, Knee/methods , Accidental Falls/prevention & control , Hand Strength , Toes/surgery
7.
Curr Oncol ; 31(4): 2112-2132, 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38668060

Curettage is recommended for the treatment of Campanacci stages 1-2 giant cell tumor of bone (GCTB) in the extremities, pelvis, sacrum, and spine, without preoperative denosumab treatment. In the distal femur, bone chips and plate fixation are utilized to reduce damage to the subchondral bone and prevent pathological fracture, respectively. For local recurrence, re-curettage may be utilized when feasible. En bloc resection is an option for very aggressive Campanacci stage 3 GCTB in the extremities, pelvis, sacrum, and spine, combined with 1-3 doses of preoperative denosumab treatment. Denosumab monotherapy once every 3 months is currently the standard strategy for inoperable patients and those with metastatic GCTB. However, in case of tumor growth, a possible malignant transformation should be considered. Zoledronic acid appears to be as effective as denosumab; nevertheless, it is a more cost-effective option. Therefore, zoledronic acid may be an alternative treatment option, particularly in developing countries. Surgery is the mainstay treatment for malignant GCTB.


Bone Neoplasms , Giant Cell Tumor of Bone , Humans , Giant Cell Tumor of Bone/drug therapy , Bone Neoplasms/drug therapy , Denosumab/therapeutic use , Bone Density Conservation Agents/therapeutic use , Zoledronic Acid/therapeutic use
8.
Magn Reson Imaging ; 110: 210-217, 2024 Apr 27.
Article En | MEDLINE | ID: mdl-38679298

PURPOSE: We aimed to investigate the relationship between quantitative evaluation by compositional MRI, including T1ρ, and histological and macroscopic assessments, to verify the validity of compositional MRI, and examine the relationship between compositional MRI evaluation reconstructed in three dimensions (3D) and histological and visual assessments. METHOD: Twenty-seven patients with knee osteoarthritis underwent T1ρ and T2 magnetic resonance imaging (MRI). Histological and gross tissue evaluations were performed on the excised bone sections of total knee arthroplasty. Semi-quantitative histological evaluation of tissue changes were assessed by measuring the optical density of digitally captured safranin O-stained and Collagen type II antibody-stained paraffin sections. Macroscopic cartilage severity was determined on a 5-grade scale (G0-G5). T1ρ and T2 values (3D and 2D), and their correlation with each of these parameters were investigated. RESULTS: 3D T1 ρ is negatively correlated with histological evaluations and positively correlated with visual assessments. Only 3D T1ρ values correlated with histological quantitative evaluation (Safranin-O staining; r = -0.53, P = 0.014, Collagen type II antibody staining; r = -0.60, P = 0.019). 2D T1ρ and 3D, 2D T2 values did not correlate with histological evaluation results. Macroscopic cartilage severity grade correlated with all T1ρ and T2 values (3D T1ρ; r = 0.61, P < 0.001, 2D T1ρ; r = 0.52, P < 0.001, 3D T2; r = 0.33, P = 0.045, 2D T2; r = 0.41, P = 0.01). CONCLUSIONS: 3D T1ρ mapping reflects the changes in the molecular structure of the cartilage matrix that occur in arthropathic changes and may be an effective tool for detecting cartilage degeneration.

9.
In Vivo ; 38(3): 1465-1469, 2024.
Article En | MEDLINE | ID: mdl-38688629

BACKGROUND/AIM: The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding. CASE REPORT: A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia. CONCLUSION: Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control.


Adenomatous Polyps , Proton Pump Inhibitors , Humans , Male , Proton Pump Inhibitors/adverse effects , Middle Aged , Hyperplasia , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/diagnosis , Stomach Neoplasms/complications , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnosis , Polyps/pathology , Polyps/diagnosis , Polyps/chemically induced , Endoscopy, Digestive System
10.
Spine J ; 2024 Apr 27.
Article En | MEDLINE | ID: mdl-38679074

BACKGROUND CONTEXT: Transcranial electrical stimulation motor-evoked potentials (Tc-MEPs) are the current trend and are important in preventing intraoperative neurological deficits. Post-tetanic Tc-MEPs (p-MEP) can augment the amplitudes of compound muscle active potentials (CMAPs), especially in the case of insufficient conventional Tc-MEPs (c-MEP). PURPOSE: To retrospectively investigate pre- and intraoperative factors necessitating p-MEP monitoring and to examine changes in the success rates of baseline Tc-MEP monitoring before and after tetanic stimulation in patients with such factors. STUDY DESIGN: Retrospective observational study. PATIENT SAMPLE: Patients (n=184) who underwent spinal surgery with Tc-MEP monitoring in our department between August 2020 and July 2022. OUTCOME MEASURES: Manual muscle testing (MMT) scores were calculated to identify patients with preoperative motor deficits. c-MEP and p-MEP amplitudes were recorded from the defined muscles. METHODS: We compared preoperative and intraoperative factors between the c-MEP and p-MEP groups (study 1). In cases where the factors were identified, we investigated the success rate of the baseline MEP measurement of each muscle before and after tetanic stimulation (study 2). RESULTS: One hundred fifty-seven patients were included. Of those, 87 showed sufficient CMAPs with c-MEP. Meanwhile, 70 needed p-MEP because of insufficient CMAPs. In univariate analysis, cervical/thoracic surgery (p<.001), preoperative MMT 3 or below (p=.009), shorter duration of illness (p=.037), previous cerebrovascular disease (p=.014), and dialysis (p=.031) were significantly associated with p-MEP group. Preoperative MMT 3 or below was the only factor requiring p-MEP (odds ratio, 3.34; 95% confidence interval, 1.28-8.73, p=.014) in multivariate analysis. In the p-MEP group, 24 patients had preoperative motor deficits; 16 patients with complete data were included in the analysis (study 2). The success rates of MEP monitoring before and after tetanic stimulation of the entire lower-extremity muscles were 42.7 and 57.3%, respectively (p<.001). The success rates for each muscle before and after tetanic stimulation were abductor pollicis brevis: 81.3% and 96.9%, tibialis anterior: 34.4% and 50.0%, gastrocnemius: 25% and 40.6%, and abductor hallucis: 68.8% and 81.3%, respectively. No significant differences were observed in success rates for any of the muscles. CONCLUSIONS: Patients with preoperative MMT 3 or below highly needed p-MEP. The success rate of baseline MEP monitoring increased with tetanic stimulation, even in patients with preoperative motor deficits. We believe that p-MEP monitoring can result in reliable CMAP recording, especially in cases of preoperative motor deficits with MMT scores of 3 or below.

11.
Foot Ankle Int ; : 10711007241235674, 2024 Mar 16.
Article En | MEDLINE | ID: mdl-38491828

BACKGROUND: Although the incidence of os supranaviculare (OSSN) is generally low, symptomatic OSSN affects athletes. The aim of this study was to assess the variations of OSSN and the results of osteosynthesis between the OSSN and the navicular bone. METHODS: Eleven feet of 10 elite athletes with symptomatic OSSN were treated. There were 3 male and 7 female patients with an average age of 19 years. Eight feet exhibited navicular stress fracture (NSF). Operative treatment was performed in 9 feet of 8 patients and 2 conservatively. Seven OSSNs were fixed with 1 or 2 screw(s) according to their size, using an autologous bone graft. The accompanying NSF was also treated surgically in 4 feet. Foot condition was evaluated using the Japanese Society for Surgery of the Foot (JSSF) midfoot rating scale and sports activity score of the Self-Administered Foot Evaluation Questionnaire (SAFE-Q). RESULTS: The median OSSN was 12.7 mm in width, 5.6 mm in length, and 6.6 mm in height. The dorsal surface of the OSSN required at least 70 mm2 to be fixed using 2 screws. Seven OSSNs of 6 patients treated surgically successfully fused with the navicular. Two small OSSNs that were not stabilized with screws also fused after surgical treatment for NSF. However, one of the 2 OSSNs with NSF treated nonoperatively did not achieve fusion. The patients were followed up for 24-161 months. The median JSSF score improved from 87 to 97.7 postoperatively (P = .00312). The median postoperative SAFE-Q sports score was 84.8. All patients returned to their original activities. CONCLUSION: Our results suggest that osteosynthesis with autologous bone graft was effective for symptomatic OSSNs. Even when the OSSN was small and not suitable for internal fixation, treatment of NSF was effective for union of OSSNs. The OSSN possibly belongs to a part or subtype of NSF. LEVEL OF EVIDENCE: Level IV, retrospective case series.

12.
PLoS Comput Biol ; 20(3): e1011238, 2024 Mar.
Article En | MEDLINE | ID: mdl-38466770

Chronic infection with hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating the cccDNA remains challenging. Thus, quantifying and understanding the dynamics of cccDNA are essential for developing effective treatment strategies and new drugs. However, such study requires repeated liver biopsy to measure the intrahepatic cccDNA, which is basically not accepted because liver biopsy is potentially morbid and not common during hepatitis B treatment. We here aimed to develop a noninvasive method for quantifying cccDNA in the liver using surrogate markers in peripheral blood. We constructed a multiscale mathematical model that explicitly incorporates both intracellular and intercellular HBV infection processes. The model, based on age-structured partial differential equations, integrates experimental data from in vitro and in vivo investigations. By applying this model, we roughly predicted the amount and dynamics of intrahepatic cccDNA within a certain range using specific viral markers in serum samples, including HBV DNA, HBsAg, HBeAg, and HBcrAg. Our study represents a significant step towards advancing the understanding of chronic HBV infection. The noninvasive quantification of cccDNA using our proposed method holds promise for improving clinical analyses and treatment strategies. By comprehensively describing the interactions of all components involved in HBV infection, our multiscale mathematical model provides a valuable framework for further research and the development of targeted interventions.


Hepatitis B virus , Hepatitis B , Humans , Hepatitis B virus/genetics , Hepatitis B Surface Antigens/genetics , Hepatitis B e Antigens/genetics , DNA, Viral/genetics , Hepatitis B/drug therapy , Hepatitis B/pathology , Liver/pathology , DNA, Circular , Biomarkers , Antiviral Agents/therapeutic use
13.
Haemophilia ; 30(3): 780-790, 2024 May.
Article En | MEDLINE | ID: mdl-38507270

BACKGROUND: Joint damage in patients with haemophilia (PwH) is commonly assessed by imaging, but few reports have described how structural changes in joints, for example, haemophilic arthropathy (HA)-affect gait ability. OBJECTIVES: We evaluated gait function among PwH with HA, PwH without HA, and people without haemophilia (non-PwH) using a Zebris FDM-T treadmill (FDM-T), an easy-to-use gait assessment instrument with a force sensor matrix. METHODS: The following gait parameters were collected: centre of pressure trajectory intersection (COPi) anterior/posterior variability, COPi lateral variability, COPi anterior/posterior symmetry, COPi lateral symmetry, single-limb support line (SLSL) length, and SLSL variability. Participants walked at their typical gait speed. The physical function of the PwH was assessed by the Hemophilia Joint Health Score (HJHS). Parameters were compared among the three groups. RESULTS: Twelve PwH with HA, 28 PwH without HA, and 12 non-PwH were enrolled. Gait speed significantly differed between groups (non-PwH, 3.1 ± 0.7; PwH without HA, 2.0 ± 0.7; PwH with HA; 1.5 ± 0.4). The COPi anterior/posterior variability, COPi lateral variability, SLSL length, and SLSL variability were greater in the PwH groups than in the non-PwH group. The COPi lateral symmetry differed between PwH with HA and the other groups. The HJHS was not correlated with gait parameters among PwH with HA. CONCLUSIONS: Gait parameters and speed were abnormal in both PwH with HA and PwH without HA. The FDM-T can be used to identify early stages of physical dysfunction that cannot be detected by conventional functional assessments such as the HJHS.


Gait Analysis , Gait , Hemophilia A , Humans , Hemophilia A/complications , Hemophilia A/physiopathology , Gait Analysis/methods , Male , Adult , Gait/physiology , Young Adult , Joint Diseases/physiopathology , Joint Diseases/diagnosis , Female , Middle Aged , Adolescent
14.
J Gastroenterol ; 59(4): 315-328, 2024 Apr.
Article En | MEDLINE | ID: mdl-38315437

BACKGROUND: Currently, standard treatments for chronic hepatitis B such as nucleos(t)ide analogs (NAs), effectively reduce hepatitis B virus (HBV) loads but rarely result in a functional cure (defined as sustained HBsAg loss). We report the discovery of a novel, 4-pyridone compound, SAG-524, a potent and orally bioavailable small molecule inhibitor of HBV replication. METHODS: The antiviral characteristics and selectivity of SAG-524 and its derivative compound against HBV were evaluated in HBV-infection assays and HBV-infected chimeric urokinase-type plasminogen activator/severe combined immunodeficiency mice with humanized livers (PXB mice), alone or in combination with entecavir. Toxicity studies were conducted in mice and monkeys. RESULTS: SAG-524 reduced HBV-DNA (IC50 = 0.92 nM) and HBsAg (IC50 = 1.4 nM) in the supernatant of the HepG2.2.15 cells. SAG-524 selectively destabilized HBV-RNA via PAPD5, but not GAPDH or albumin mRNA, by shortening the poly(A) tail. PAPD5 may also be involved in HBV regulation via ELAVL1. In a study of HBV-infected PXB mice, SAG-524 produced potent reductions of serum HBsAg and HBcrAg, and the minimum effective dose was estimated to be 6 mg/kg/day. The combination therapy with entecavir greatly reduced HBsAg and cccDNA in the liver due to reduction of human hepatocytes with good tolerability. Administration of SAG-524 to monkeys, up to 1000 mg/kg/day for two weeks, led to no significant toxicity, as determined by blood tests and pathological images. CONCLUSIONS: We have identified SAG-524 as novel and orally bioavailable HBV-RNA destabilizers which can reduce HBsAg and HBV-DNA levels, and possibly contribute a functional cure.


Hepatitis B virus , Hepatitis B, Chronic , Humans , Mice , Animals , Hepatitis B virus/genetics , Hepatitis B Surface Antigens , DNA, Viral , Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , RNA
15.
Article En | MEDLINE | ID: mdl-38421093

BACKGROUND AND AIM: The 10-mm self-expandable metal stent (SEMS) is the standard for endoscopic transpapillary biliary drainage before pancreatic cancer surgery. However, the efficacy of stents thinner than 10 mm has not been adequately validated. Therefore, we aimed to evaluate the safety of a 6-mm fully covered SEMS (FCSEMS) for distal malignant biliary obstruction (DMBO) during preoperative chemotherapy for pancreatic cancer. METHODS: This was a single-arm, multicenter, prospective phase II study of endoscopic transpapillary initial biliary drainage for DMBO before pancreatic cancer surgery. The primary endpoint was stent-related adverse events, and the key secondary endpoint was the non-recurrent biliary obstruction (non-RBO) rate during the observation period for both resectable (R) and borderline resectable (BR) pancreatic cancers. RESULTS: The study enrolled 33 patients, among whom 32 received the study treatment. There were 23 and 9 cases of R and BR pancreatic cancers, respectively. The technical and clinical success rates were 97.0% and 90.1%, respectively. The stent-related adverse event rate was 3.1% (n = 1, acute pancreatitis) (95% confidential interval, 0.00-16.2), which met the criteria to be considered safe. The overall non-RBO rate during the observation period (median 96 days) was 78.1% (82.6% and 66.7% for R and BR pancreatic cancer cases, respectively). CONCLUSIONS: The 6-mm FCSEMS is an extremely safe metallic stent with a low stent-related adverse event rate of 3.1% for preoperative biliary drainage in pancreatic cancer. It is considered the optimal stent for preoperative biliary drainage in terms of the non-RBO rate. UMIN Clinical Trial Registry (UMIN-CTR 000041704).

16.
Spine Surg Relat Res ; 8(1): 51-57, 2024 Jan 27.
Article En | MEDLINE | ID: mdl-38343413

Introduction: Posterior lumbar interbody fusion (PLIF) is a common treatment for nerve root disease associated with lumbar foraminal stenosis or lumbar spondylolisthesis. At our institution, PLIF is usually performed with high-angle cages and posterior column osteotomy (PLIF with HAP). However, not all patients achieve sufficient segmental lumbar lordosis (SLL). This study determined whether the location of PLIF cages affect local lumbar lordosis formation. Methods: A total of 59 patients who underwent L4/5 PLIF with HAP at our hospital, using the same titanium control cage model, were enrolled in this cohort study. The mean ratio of the distance from the posterior edge of the cage to the posterior wall of the vertebral body/vertebral length (RDCV) immediately after surgery was 16.5%. The patients were divided into two groups according to RDCV <16.5% (group P) and ≥16.5% (group G). The preoperative and 6-month postoperative slip rate (%slip), SLL, local disk angle (LDA), ratio of disk height/vertebral height (RDV), 6-month postoperative RDCV, ratio of cage length/vertebral length (RCVL), and ratio of posterior disk height/anterior disk height at the fixed level (RPA) were evaluated via simple lumbar spine X-ray. The preoperative and 6-month postoperative Japanese Orthopedic Association (JOA) and low back pain visual analog scale (VAS) scores were also evaluated. Results: Groups G and P included 31 and 28 patients, respectively. The preoperative %slip, SLL, LDA, RDV, JOA score, and low back pain VAS score were not significantly different between the groups. In groups G and P, 6-month postoperative %slip, SLL, LDA, RDV, RDCV, RCVL, and RPA were 3.3% and 7.9%, 18.6° and 15.4°, 9.7° and 8.0°, 36.6% and 40.3%, 21.1% and 10.1%, 71.4% and 77.0%, and 56.1% and 67.7%, respectively. The 6-month postoperative SLL, LDA, RDV, RDCV, RCVL, and RPA significantly differed (p=0.03, 0.02, 0.02, <0.001, <0.001, and <0.001, respectively). Conclusions: Anterior PLIF cage placement relative to the vertebral body is necessary for good SLL in PLIF.

17.
Eur J Orthop Surg Traumatol ; 34(3): 1627-1634, 2024 Apr.
Article En | MEDLINE | ID: mdl-38367186

PURPOSE: This study aimed to describe the reposition flap for reconstructing fingertip amputation when replantation is not possible. METHODS: This study retrospectively reviewed the records of patients with reposition flap transfers and investigated postoperative clinical outcomes and patient satisfaction. Sixteen patients with fingertip amputations treated with a reposition flap from 2016 to 2020. The mean age at injury was 46 years (range, 26-70 years). Ten cases were treated with oblique triangular advancement flaps, 3 with retrograde-flow digital artery flaps, and 3 with thumb palmar advancement flaps. Postoperative outcomes, including wound healing period and the IP/PIP extension angle, and the presence of grafted bone absorption and patient satisfaction were evaluated as of 3 years after surgery. RESULTS: The average reduction in passive extension angle of the IP/PIP joint was 19°. The average time for complete wound healing was 28 days (range, 18-41 days). The reduction in passive extension angle of the IP/PIP joint was significantly correlated with the wound healing period (r = 0.66, p = 0.01). The absorption of the grafted bone was observed in 3 cases. In these cases, the distal tip of the flap became thin due to flap retraction and an insufficient flap volume. All patients were highly or fairly satisfied with the results of surgery. CONCLUSION: Our findings show that IP/PIP flexion contracture can occur due to delayed wound healing after reposition flap transfer, but the patient satisfaction level was generally high. Therefore, reconstruction using a reposition flap gives acceptable clinical outcomes and high patient satisfaction as a result of medium to long-term.


Amputation, Traumatic , Finger Injuries , Humans , Adult , Middle Aged , Aged , Amputation, Traumatic/surgery , Retrospective Studies , Finger Injuries/surgery , Surgical Flaps , Amputation, Surgical , Treatment Outcome
18.
Hip Int ; : 11207000241227399, 2024 Feb 19.
Article En | MEDLINE | ID: mdl-38372085

BACKGROUND: Nerve injury is one of the most serious complications of total hip arthroplasty (THA). It is suspected to be a result from nerve compression or direct injury caused by an acetabular retractor. The anatomical relationship between the acetabular rim and the femoral and sciatic nerves, including hip motion, has not been investigated. This study aimed to identify the optimal position for retractor insertion during THA to prevent nerve damage. METHODS: A total of 28 hip joints from 14 freshly frozen cadavers were used. Using an anterolateral approach, each cadaver was immobilised in the lateral decubitus position and deployed to measure the distance between the nerves and the acetabular rim, while the hip joint was changed to the extension, neutral, and flexion positions. RESULTS: Three femoral nerves were closest to the anterior margin of the acetabulum at 90° and 120° of extension and farthest away at 30° of flexion. The sciatic nerve was closest to the posterior margin of the acetabulum at 90° and 120° of flexion and farthest away at 30° and 150° of extension compared with the other points. CONCLUSIONS: To prevent nerve damage during THA, we suggest that the retractor be inserted at the points where the nerves are the farthest away, such as at 30° and 150°. The femoral and sciatic nerves vary in their movements depending on the hip position. Therefore, the safe insertion of a retractor is recommended for hip flexion of the femoral nerve and extension of the sciatic nerve. Additionally, it is important to carefully insert the retractor along the acetabular margin without penetrating the joint capsule. Overall, this study provides valuable insights into the anatomical location and movement of the femoral and sciatic nerves in relation to hip motion and can help inform surgical techniques for safer THA.

19.
Int J Cancer ; 2024 Feb 21.
Article En | MEDLINE | ID: mdl-38380807

The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre- and post-surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non-cirrhotic or single-tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long-term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4-week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p = .022). In conclusion, serum MYCN holds promise for biomarker-based precision medicine for the prevention of HCC, long-term prognosis of early-stage HCC, and identification of high-response subgroups for ACR-based treatment.

20.
Plast Reconstr Surg Glob Open ; 12(2): e5611, 2024 Feb.
Article En | MEDLINE | ID: mdl-38348463

Background: The anterolateral thigh (ALT) flap, which is nourished by perforators from the descending branch of the lateral femoral circumflex artery (P), is one of the most commonly used flaps in soft tissue reconstruction. With the growing use of ALT flaps, attention toward donor-site morbidity has increased in recent years. Damage to the motor nerve branches of the vastus lateralis muscle (N) is one of the causes of donor-site morbidity, particularly muscle weakness. This study investigated the anatomical locations of the P and N in fresh-frozen cadaveric specimens. Methods: This study included 43 cadaver limbs. A silicone rubber compound (30 mL) was injected into the femoral artery to visualize the vessel. The locations of the P and motor points of N were measured to assess the risk of N injury during ALT flap harvesting. Results: There were one to six (mean, 2.7) P and two to seven (mean, 4) N. When the two most proximal perforators were used for flap harvesting, an average of 1.5 motor nerve branches (42%) was damaged because transection of the motor nerve branches was required for flap harvesting. In 33% of the limbs, only one motor nerve branch remained after the flap harvest. However, there were no cases where all motor nerve branches were severed. Conclusion: When an ALT flap with two perforators is harvested, weakness of the vastus lateralis muscle may occur in cases with a small number of motor nerve branches.

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