A role for the nucleoporin Nup170p in chromatin structure and gene silencing.

Embedded in the nuclear envelope, nuclear pore complexes (NPCs) not only regulate nuclear transport but also interface with transcriptionally active euchromatin, largely silenced heterochromatin, as well as the boundaries between these regions. It is unclear what functional role NPCs play in establishing or maintaining these distinct chromatin domains. We report that the yeast NPC protein Nup170p interacts with regions of the genome that contain ribosomal protein and subtelomeric genes, where it functions in nucleosome positioning and as a repressor of transcription. We show that the role of Nup170p in subtelomeric gene silencing is linked to its association with the RSC chromatin-remodeling complex and the silencing factor Sir4p, and that the binding of Nup170p and Sir4p to subtelomeric chromatin is cooperative and necessary for the association of telomeres with the nuclear envelope. Our results establish the NPC as an active participant in silencing and the formation of peripheral heterochromatin.

A therapeutic dose and its pharmacokinetics of ropeginterferon Alfa-2b for hepatitis C treatment.

AIM: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous clinical studies. This trial evaluates the pharmacokinetics of 400 µg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 µg. METHODS: Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 µg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed. RESULTS: Tmax was 154.003 h and T1/2 was 114.273 h. The Cmax was 29.823 ng mL-1. AUClast was 9364.292 h∗ng mL-1 and AUCinf was 11084.317 h∗ng mL-1. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL-1. CONCLUSION: Ropeginterferon alfa-2b at 400 µg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 µg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications.

Age-adjusted Charlson Comorbidity Index as an effective tool for the choice between simultaneous or staged bilateral total knee arthroplasty.

INTRODUCTION: The choice between simultaneous and staged bilateral total knee arthroplasty (BTKA) remains controversial. Age-adjusted Charlson Comorbidity Index(CCI) is a promising tool for risk-stratification. We aimed to compare the outcomes between patients who underwent simultaneous and staged BTKA, stratified by age-adjusted CCI scores. MATERIALS AND METHODS: We conducted this retrospective, single-surgeon case series from 2010 to 2020. This study consisted of 1558 simultaneous BTKA and 786 staged BTKA procedures. The outcome domains included 30-day and 90-day readmission and 1-year reoperation events. We performed multivariate regression analysis to compare the risk of readmission and reoperation following simultaneous and staged BTKA. Other factors included age, sex, body mass index, diabetes mellitus, rheumatoid arthritis, smoking, receiving thromboprophylaxis and blood transfusion. RESULTS: The rates of 30-day, 90-day readmission and 1-year reoperation following simultaneous BTKA was 1.99%, 2.70% and 0.71%, respectively. The rates of 30-day, 90-day readmission and 1-year reoperation following staged BTKA was 0.89%, 1.78% and 0.89%, respectively. For patients with age-adjusted CCI ≥ 4 points, simultaneous BTKA was associated with a higher risk of 30-day (aOR:3.369, 95% CI:0.990-11.466) and 90-day readmission (aOR:2.310, 95% CI:0.942-5.668). In patients with age-adjusted CCI ≤ 3 points, the risk of readmission and reoperation was not different between simultaneous or staged BTKA. CONCLUSION: Simultaneous BTKA was associated with an increased risk of short-term readmissions in patients with age-adjusted CCI ≥ 4 points but not in those with age-adjusted CCI ≤ 3 points. Age-adjusted CCI can be an effective index for the choice between simultaneous and staged BTKA procedures.

The cementless taper wedge vs. fit-and-fill stem in primary total hip arthroplasty: risk of stem-related complication differs across Dorr types.

INTRODUCTION: The choice between a cementless taper wedge stem and a fit-and-fill stem in total Hip arthroplasty (THA) for various proximal femoral morphological types has not been thoroughly evaluated. This study aimed to compare the risk of stem-related complications between these two stem types in Dorr type A, B, and C femurs. MATERIALS AND METHODS: From January 2015 through April 2021, we retrospectively reviewed 1995 cementless THA procedures. We stratified all procedures into three groups: Dorr type A (N = 360, 18.0%), B (N = 1489, 74.7%) and C (N = 146, 7.3%). The primary outcome domain was stem-related complications, including stem subsidence ≥ 3 mm, intraoperative fracture, periprosthetic fracture and aseptic stem loosening. We performed multivariate regression analysis to compare the risk of stem-related complication between the two stem types. Other factors included age, sex, body mass index, diagnosis, age-adjusted Charlson comorbidity index, stem alignment and canal fill ratio. RESULTS: The incidence of stem-related complications in the taper wedge and fit-and-fill stem groups was 4.4% (N = 15) and 6.5% (N = 107), respectively. Fit-and-fill stems showed an increased risk of stem-related complications (aOR: 9.903, 95% CI: 1.567-62.597) only in Dorr type C femurs. No significant difference in risk was observed in Dorr type A and B femurs. Furthermore, the canal fill ratio at the lesser trochanter, 2 cm and 7 cm below the lesser trochanter, did not exhibit an association with stem-related complications in any Dorr type. CONCLUSIONS: Concerning the risk of stem-related complications, the taper wedge stem was a better choice in Dorr type C femurs. However, there was no difference in risk between the taper wedge stem and fit-and-fill stem in Dorr type A and B femurs.

Synthesis, biological activity and mechanism of action of novel allosecurinine derivatives as potential antitumor agents.

Cancer with low survival rates is the second main cause of death among all diseases in the world and consequently, effective antineoplastic agents are urgently needed. Allosecurinine is a plant-derived indolicidine securinega alkaloid shown bioactivity. The object of this study is to investigate synthetic allosecurinine derivatives with considerable anticancer capacity against nine human cancer cell lines as well as mechanism of action. We synthesized twenty-three novel allosecurinine derivatives and evaluated their antitumor activity against nine cancer cell lines for 72 h by MTT and CCK8 assays. FCM was applied to analyze the apoptosis, mitochondrial membrane potential, DNA content, ROS production, CD11b expression. Western blot was selected to analyze the protein expression. Structure-activity relationships were established and potential anticancer lead BA-3 which induced differentiation of leukemia cells towards granulocytosis at low concentration and apoptosis at high concentration was identified. Mechanism studies showed that mitochondrial pathway mediated apoptosis within cancer cells with cell cycle blocking was induced by BA-3. In addition, western blot assays revealed that BA-3 induced expression of the proapoptotic factor Bax, p21 and reduced the levels of antiapoptotic protein such as Bcl-2, XIAP, YAP1, PARP, STAT3, p-STAT3, and c-Myc. Collectively, BA-3 was a lead compound for oncotherapy at least in part, through the STAT3 pathway. These results were an important step in further studies on allosecurinine-based antitumor agent development.

Effect of Ultrasonic Treatment on Structure, Antibacterial Activity of Sugarcane Leaf Polysaccharides.

This study investigated the impact of ultrasonic extraction (UE) on the structure and in vitro antibacterial activity of polysaccharides from sugarcane leaves (SLW). Native sugarcane leaf polysaccharides were treated with ultrasound (480 W) for 3 h to yield sugarcane leaf polysaccharides (SLU). Compared to SLW (33.59 kDa), the molecular weight of SLU (13.08 kDa) was significantly decreased, while the monosaccharide composition of SLU was unchanged. The results of SEM and XRD indicated that UE significantly changed the surface morphology of SLW and destroyed its inner crystalline structure. In vitro experiments showed that SLU had stronger antibacterial activity. These findings revealed that UE treatment could alter the tertiary structure of SLW but had no impact on its primary structure. Furthermore, the antibacterial activity of SLW could be greatly enhanced after UE treatment. As a bioactive additive, SLU has great application potential in functional foods, cosmetics, and pharmaceuticals.

A Functional Polymorphism Downstream of Vitamin A Regulator Gene CYP26B1 Is Associated with Hand Osteoarthritis.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10-7-7.31 × 10-6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10-7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10-6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D' = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

Is there a role for cementless primary stem in hip arthroplasty for early or late fixation failures of intertrochanteric fractures?

BACKGROUND: The choice of femur stems during the hip arthroplasty procedures for patients with treatment failure of intertrochanteric fractures (ITF) remains controversial. We aimed to compare the surgical complication and reoperation rates between cementless primary and revision stems in the early (≤3 months) and late (> 3 months) fixation failures of ITF. METHODS: This was a retrospective, cohort study conducted in a single, tertiary referral hospital of Taipei, Taiwan. We included hip arthroplasty procedures for failed ITF using cementless primary or revision stems. There were 40 and 35 patients who had early and late fixation failure of ITF, respectively. The patient demographics, time to fixation failure, surgical complications and medical complications were recorded for analysis. RESULTS: We included 75 patients that underwent hip arthroplasty procedure for failed ITF using cementless primary (n = 38) or revision (n = 37) stems. The mean age was 79.3 years and 56% of the patients were female. In the early fixation failure group, the complication rate was similar between the primary and revision stems (44% vs. 29%, p = 0.343). However, there was a trend toward a higher reoperation rate (31% vs. 8%, p = 0.061) of using the primary stem, compared with the revision stem. In the late fixation failure group, the rate of complication and reoperation was similar between the two stem types. CONCLUSION: For early fixation failures of ITFs, we caution against the use of cementless primary stems due to a trend towards an increased risk of reoperations compared to the use of cementless revision stems. However, in late fixation failures of ITFs, there is a role for cementless primary stems. LEVEL OF EVIDENCE: III, retrospective cohort study.

Accuracy of the Application of 3-Dimensional Printing Models in Orbital Blowout Fractures-A Preliminary Study.

BACKGROUND: Application of 3-dimensional (3D) printing technology has grown in the medical field over the past 2 decades. In managing orbital blowout fractures, 3D printed models can be used as intraoperative navigators and could shorten the operational time by facilitating prebending or shaping of the mesh preoperatively. However, a comparison of the accuracy of computed tomography (CT) images and printed 3D models is lacking. MATERIAL AND METHODS: This is a single-center retrospective study. Patients with unilateral orbital blowout fracture and signed up for customized 3D printing model were included. Reference points for the 2D distance were defined (intersupraorbital notch distance, transverse horizontal, sagittal vertical, and anteroposterior axes for orbital cavity) and measured directly on 3D printing models and on corresponding CT images. The difference and correlation analysis were conducted. RESULTS: In total, 9 patients were reviewed from June 2017 to December 2020. The mean difference in the intersupraorbital notch measurement between the 2 modules was -0.14 mm (P = 0.67). The mean difference in the distance measured from the modules in the horizontal, vertical, and anteroposterior axes of the traumatic orbits was 0.06 mm (P = 0.85), -0.23 mm (P = 0.47), and 0.51 mm (P = 0.32), whereas that of the unaffected orbits was 0.16 mm (P = 0.44), 0.34 mm (P = 0.24), and 0.1 mm (P = 0.88), respectively. Although 2D parameter differences (<1 mm) between 3D printing models and CT images were discovered, they were not statistically significant. CONCLUSIONS: Three-dimensional printing models showed high identity and correlation to CT image. Therefore, personalized models might be a reliable tool of virtual surgery or as a guide in realistic surgical scenarios for orbital blowout fractures.

Community-based screening by Anti-HCV reflex HCV Ag test and accessible post-screening care toward elimination of hepatitis C in two hyperendemic townships.

BACKGROUND: Hyperendemic townships of hepatitis C virus (HCV) infection should devote extra efforts to eliminate HCV. We aimed to evaluate efficacy of the screening and linkage to care in two HCV hyperendemic townships. METHODS: Village-to-village HCV screening using anti-HCV reflex HCV Ag test was conducted in two HCV hyperendemic rural townships (Lioujiao and Yijhu). All residents aged 30 years or older were invited. Those patients detected as infected were referred to nearby hospitals or clinics in Lioujiao and to an accessible outreach hepatology clinic in Yijhu. RESULTS: The populations of Lioujiao and Yijhu townships at time of survey were 18,389 and 14,787 with 6086 (33.1%) and 4604 (31.1%) having ever been previously screened, and 1517 and 1071 responded to this screening respectively. Their crude screening coverage rates were 41.5% and 38.5%, and adjusted screening coverage rates were 54.3% and 94.6% respectively. The prevalence rates of anti-HCV and HCV Ag were 17.9% and 11.9% in Lioujiao, and 9.2% and 5.6% in Yijhu respectively, with their rates of antigenemia (HCV Ag/anti-HCV) being 62.1% and 60.6% respectively. Numbers needed to test (NNT) to find a candidate for anti-viral treatment were 9 and 18. For linkage to care, treatment rate by referral (Lioujiao) was slightly lower than by accessible outreach hepatology clinic (Yijhu) (84.9% vs. 93.3%, p = 0.093). Overall successful sustained virological response rate at week 12 was 98.2% (161/164) in outreach hepatology clinic. CONCLUSION: Since NNT was low, it was worthwhile conducting intensive screening in these hyperendemic townships. For high treatment rate, accessible outreach hepatology clinic is feasible especially in areas without adequate medical resources.

Analyzing BMP2, FGFR, and TGF Beta Expressions in High-Grade Osteosarcoma Untreated and Treated Autografts Using Proteomic Analysis.

In the last few decades, biological reconstruction techniques have improved greatly for treating high-grade osteosarcoma patients. To conserve the limb, and its function the affected tumor-bearing bones have been treated using liquid nitrogen and irradiation processes that enable the removal of entire tumors from the bone, and these treated autografts can be reconstructed for the patients. Here, we focus on the expressions of the growth factor family proteins from the untreated and treated autografts that play a crucial role in bone union, remodeling, and regeneration. In this proteomic study, we identify several important cytoskeletal, transcriptional, and growth factor family proteins that showed substantially low levels in untreated autografts. Interestingly, these protein expressions were elevated after treating the tumor-bearing bones using liquid nitrogen and irradiation. Therefore, from our preliminary findings, we chose to determine the expressions of BMP2, TGF-Beta, and FGFR proteins by the target proteomics approach. Using a newly recruited validation set, we successfully validate the expressions of the selected proteins. Furthermore, the increased growth factor protein expression after treatment with liquid nitrogen may contribute to bone regeneration healing, assist in faster recovery, and reduce local recurrence and metastatic spread in high-grade sarcoma patients.

IL-1b in the Secretomes of MSCs Seeded on Human Decellularized Allogeneic Bone Promotes Angiogenesis.

Angiogenesis plays an important role in the development of bone and bone regeneration to provide the required molecules. Mesenchymal stem cells (MSCs) are pluripotent, self-renewing, and spindle-shaped cells, which can differentiate into multiple lineages such as chondrocytes, osteocytes, and adipocytes. MSCs derived from bone marrow (BMMSCs), adipose tissue (ADMSCs), and Wharton's jelly (UCMSCs) are popular in the field of tissue regeneration. MSCs have been proposed that can promote bone regeneration by enhancing vascularization. In this study, the angiogenic potential of secretomes of undifferentiated and osteo-differentiated BMMSCs, ADMSCs, and UCMSCs seeded on human decellularized allogeneic bone were compared. Human umbilical vein endothelial cells (HUVECs) were treated with MSC secretomes. Cell growth, cell migration, and angiogenesis of HUVECs were analyzed by MTT, wound healing, and tube formation assays. Angiogenic gene expression levels of MSCs were evaluated using real-time quantitative PCR. Antibody neutralization was performed to validate the candidate target. Our study demonstrates that the angiogenic gene expression profile is tissue-dependent and the angiogenic ability of secretomes is independent of the state of differentiation. We also explore that IL-1b is important for MSC angiogenic potential. Taken together, this study proves that IL-1b in the secretomes plays a vital role in angiogenesis.

Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019.

BACKGROUND & AIMS: Acute viral hepatitis (AVH) represents an important global health problem; however, the progress in understanding AVH is limited because of the priority of combating persistent HBV and HCV infections. Therefore, an improved understanding of the burden of AVH is required to help design strategies for global intervention. METHODS: Data on 4 major AVH types, including acute hepatitis A, B, C, and E, excluding D, were collected by the Global Burden of Disease (GBD) 2019 database. Age-standardized incidence rates and disability-adjusted life year (DALY) rates for AVH were extracted from GBD 2019 and stratified by sex, level of socio-demographic index (SDI), country, and territory. The association between the burden of AVH and socioeconomic development status, as represented by the SDI, was described. RESULTS: In 2019, there was an age-standardized incidence rate of 3,615.9 (95% CI 3,360.5-3,888.3) and an age-standardized DALY rate of 58.0 (47.3-70.0) per 100,000 person-years for the 4 major types of AVH. Among the major AVH types, acute hepatitis A caused the heaviest burden. There was a significant downward trend in age-standardized DALY rates caused by major incidences of AVH between 1990 and 2019. In 2019, regions or countries located in West and East Africa exhibited the highest age-standardized incidence rates of the 4 major AVH types. These rates were stratified by SDI: high SDI and high-middle SDI locations recorded the lowest incidence and DALY rates of AVH, whereas the low-middle SDI and low SDI locations showed the highest burden of AVH. CONCLUSIONS: The socioeconomic development status and burden of AVH are associated. Therefore, the GBD 2019 data should be used by policymakers to guide cost-effective interventions for AVH. LAY SUMMARY: We identified a negative association between socioeconomic development status and the burden of acute viral hepatitis. The lowest burden of acute viral hepatitis was noted for rich countries, whereas the highest burden of acute viral hepatitis was noted for poor countries.

Sofosbuvir/velpatasvir is an effective treatment for patients with hepatitis C and advanced fibrosis or cirrhosis in a real-world setting in Taiwan.

INTRODUCTION: Real-world data regarding the impact of hepatic fibrosis on the effectiveness of sofosbuvir/velpatasvir (SOF/VEL) treatment is limited in the Asian population. METHODS: We analyzed data for all 823 patients with hepatitis C virus treated with SOF/VEL from June 2019 to September 2020 at Chang Gung Memorial Hospital in Chiayi, Taiwan. The degree of fibrosis was determined using the fibrosis-4 (FIB-4) index, with advanced fibrosis or cirrhosis defined as a FIB-4 score of > 3.25. The primary treatment outcome was the rate of sustained virologic response 12 weeks after treatment cessation (SVR). Adverse events (AEs) were also evaluated. RESULTS: SVR rates did not significantly differ (p > 0.05) between patients with FIB-4 scores of ≤ 3.25 and those with scores of > 3.25. In the per protocol analysis, 99.2% (593/598) of the FIB-4 ≤ 3.25 group and 100% (172/172) of the FIB-4 > 3.25 group achieved SVR; in the evaluable population analysis, 93.4% (593/635) of the FIB-4 ≤ 3.25 group and 91.5% (172/188) of the FIB-4 > 3.25 group achieved SVR. Five patients with FIB-4 scores of ≤ 3.25 did not attain SVR: two relapsed and three had no response. The most common AEs were comparable (p > 0.05) for the FIB-4 ≤ 3.25 group and the FIB-4 > 3.25 group and included abdominal discomfort (4.4% vs. 5.9%), fatigue (4.1% vs. 5.9%), and skin itching (3.6% vs. 3.2%). Laboratory abnormalities were more common in the FIB-4 > 3.25 group (p < 0.001). Six patients with FIB-4 scores of > 3.25 had total bilirubin elevation > 3 × the upper normal limit (UNL). Alanine transaminase elevation > 5 × the UNL was observed in two patients with FIB-4 scores of ≤ 3.25 and one patient with a FIB-4 score of > 3.25. No AEs resulted in treatment discontinuation. CONCLUSIONS: SOF/VEL treatment is well tolerated and achieves high SVR rates for patients of Taiwanese ethnicity with HCV, regardless of cirrhosis status.

Pangenotypic direct-acting antiviral agents for mixed genotype hepatitis C infection: A real-world effectiveness analysis.

BACKGROUND: Pangenotypic direct-acting antiviral agents (DAAs) glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL) are effective against all hepatitis C virus (HCV) genotype infections. However, data on pangenotypic DAA treatment for mixed genotype HCV infection are sparse. METHODS: This is a retrospective, single site cohort study analyzing all patients with mixed HCV genotype infections treated with GLE/PIB or SOF/VEL from August 2018 to August 2020 in Chiayi Chang Gung Memorial Hospital, Taiwan. The primary study endpoint was sustained virologic response (SVR) 12 weeks after treatment cessation. We also reported adverse events (AEs). RESULTS: A total of 108 patients with mixed infections of any two or three genotypes of 1a, 1b, 2, 3, and 6 received pangenotypic DAAs during the study period. A total of 67 patients received GLE/PIB and 41 received SOF/VEL. The evaluable population analysis revealed SVR rates of 94% (63/67) and 95.1% (39/41) for GLE/PIB and SOF/VEL therapy, respectively, and the per-protocol analysis revealed an SVR of 100% for both regimens. Four patients in the GLE/PIB group and two patients in the SOF/VEL were lost to follow-up. The most common AEs for GLE/PIB versus SOF/VEL therapy included pruritus (14.9% vs 2.4%), fatigue (6.0% vs 7.3%), abdominal discomfort (4.5% vs 7.3%), and acid reflux (3.0% vs 4.9%). DAA-related significant laboratory abnormalities occurred in three patients with > 1.5 × elevated bilirubin level in the GLE/PIB group. None of the above AEs resulted in DAA discontinuation. CONCLUSIONS: Pangenotypic DAAs are well tolerated by and yield high SVR rates in patients with mixed genotype HCV infection.

Comparison of antiplatelet antibody profiles between hepatitis C virus-associated immune thrombocytopenia and primary immune thrombocytopenia.

Hepatitis C virus-associated immune thrombocytopenia (HCV-ITP) has been assumed to be one of secondary ITP and associated with antiplatelet antibodies. This study was to clarify the antibody profile in HCV-ITP compared with primary ITP. We enrolled 55 HCV-ITP, 30 primary ITP, 11 Helicobacter pylori-ITP, 21 HCV control, and 16 healthy volunteers. We reviewed their blood cell counts, autoimmune markers, and spleen size. We used enzyme-linked immunosorbent assay kit to detect the specific antibody to glycoproteins IIb/IIIa, Ia/IIa, Ib/IX, IV, and human leukocyte antigen (HLA) class I. Compared with primary ITP patients, HCV-ITP patients had an older age, lower white blood cell (WBC) count and fewer presented with severe thrombocytopenia. The rate of positive antibody detection was 63.6% for the HCV-ITP group higher than the rate of 40% for the primary ITP. In the HCV control, antiplatelet antibodies were detected in 38.1% patients and no one had more than two types of antibodies. The antiplatelet antibodies correlated to severer thrombocytopenia. An HLA class I antibody was associated with lower WBCs and larger spleen. In conclusion, HCV-ITP patients had a high rate of positive antiplatelet antibody. The antibodies were associated with not only lower platelets but also leukopenia and splenomegaly.

Cementation of the highly cross-linked polyethylene liner into a well-fixed acetabular shell to treat patients with recurrent dislocation after total hip arthroplasty.

Cementation of a highly cross-linked polyethylene liner into a well-fixed acetabular shell provided a good durability for liner wear. However, its efficacy in treating recurrent instability due to malposition cup is less reported. The aim of this study is to evaluate the outcome of this surgical technique to treat hip instability. From 2009 to 2019, we have identified 38 patients who had been surgically treated for recurrent instability, including cementation liner (N = 20) and revision cup (N = 18) procedures. Patients were followed for a mean of 45.66 months. We have recorded and analyzed all causes of implant failure including recurrent instability. Clinical outcomes were assessed including complication and Harris Hip Score (HHS) preoperatively and at the latest follow-up. Revision-free survivorship for any cause was 95.0% at 1 year, and 84.4% at 5 years in cementation liner group and 88.9% at 1 year and 5 years in revision cup group. Mean Harris hip score improved from 48.3 points preoperatively to 79.5 points at the last follow-up in cementation liner group and mean HHS improved from 43.3 points preoperatively to 77.2 points in revision cup group. There were two implant failures in each group, including one is due to persistent hip instability and the other is due to periprosthetic joint infection in the cementation liner group and two implant failure are due to persistent hip instability in the revision cup group. Functional scores and implant survival were similar in both groups. We demonstrated that orientation correction via the cementation of the polyethylene liner into well-fixed acetabular shell is a promising option to treat and prevent instability. Level of Evidence: Therapeutic Level IV.

Significantly reducing blood loss via a peri-articular injection of tranexamic acid during total knee arthroplasty: a retrospective study.

BACKGROUND: The administration of an intra-articular injection (IAI) of tranexamic acid (TXA) has been demonstrated to be effective in reducing both blood loss and transfusion rate during total knee arthroplasty (TKA); however, few studies have reported the efficiency of a peri-articular injection (PAI) of TXA. We studied the efficiency of a PAI of TXA in reducing blood loss during TKA. METHODS: Fifty patients undergoing primary simultaneous bilateral TKA were enrolled in this retrospective study. The right knee received a PAI of 1 g of TXA (Group I), and the left knee received an IAI of 1 g of TXA (Group II). The clinical outcome measures were a change in blood loss from Hemovac drains and surgical time. RESULTS: The decrease in blood loss from the Hemovac was significantly lower in Group I (460.1 ± 36.79 vs. 576.0 ± 34.01, P < 0.001) than in Group II, and no significant difference in surgical times was observed. The blood transfusion rate in the present study was 16 %. CONCLUSIONS: A PAI of TXA may reduce blood loss more efficiently than an IAI of TXA during TKA without increased complications such as surgical site infection, poor wound healing, skin necrosis, pulmonary embolism, and deep vein thrombosis.

Risk factors and modes of failure in the modern dual mobility implant. A systematic review and meta-analysis.

BACKGROUND: The aims of this meta-analysis were to: (1) validate the outcome of modern dual mobility (DM) designs in patients who had undergone primary and revision total hip arthroplasty (THA) procedures and (2) to identify factors that affect the outcome. METHODS: We searched for studies that assessed the outcome of modern DM-THA in primary and revision procedures that were conducted between January, 2000 to August, 2020 on PubMed, MEDLINE, Cochrane Reviews and Embase. The pooled incidence of the most common failure modes and patient reported outcomes were evaluated in patients who have received: (1) primary THA, (2) revision THA for all causes or (3) for recurrent dislocation. A meta-regression analysis was performed for each parameter to determine the association with the outcome. The study design of each study was assessed for potential bias and flaws by using the quality assessment tool for case series studies. RESULTS: A total of 119 studies (N= 30016 DM-THAs) were included for analysis. The mean follow-up duration was 47.3 months. The overall implant failure rate was 4.2% (primary: 2.3%, revision for all causes: 5.5%, recurrent dislocation: 6.0%). The most common failure modes were aseptic loosening (primary: 0.9%, revision for all causes: 2.2%, recurrent dislocation: 2.4%), septic loosening (primary:0.8%, revision for all causes: 2.3%, recurrent dislocation: 2.5%), extra-articular dislocation (primary:0.6%, revision for all causes:1.3%, recurrent dislocation:2.5%), intra-prosthetic dislocation (primary:0.8%, revision for all causes:1.0%, recurrent dislocation:1.6%) and periprosthetic fracture (primary:0.9%, revision for all causes:0.9%, recurrent dislocation:1.3%). The multi-regression analysis identified younger age (ß=-0.04, 95% CI -0.07 - -0.02) and female patients (ß=3.34, 95% CI 0.91-5.78) were correlated with higher implant failure rate. Age, gender, posterolateral approach and body mass index (BMI) were not risk factors for extra-articular or intra-prosthetic dislocation in this cohort. The overall Harris hip score and Merle d'Aubigné score were 84.87 and 16.36, respectively. Level of evidence of this meta-analysis was IV. CONCLUSION: Modern dual-mobility designs provide satisfactory mid-term implant survival and clinical performance. Younger age and female patients might impact the outcome after DM-THA. Future research directions should focus on, (1) long-term outcome of modern dual-mobility design, including specific concerns such as intra-prosthetic dislocation and elevated metal ion, and (2) cost-effectiveness analysis of dual-mobility implant as an alternative to conventional THA for patients who are at high risk of dislocation.

Future outcomes and health needs of chronic hepatitis C patients after receiving antiviral therapy.

AIMS: To study the future outcomes and health needs of chronic hepatitis C (CHC) patients after receiving direct-acting antiviral (DAA) therapy based on the health promotion perspectives and cardiometabolic risks in a rural setting. DESIGN: This cross-sectional study was conducted from May to December 2019 in coastal western and southern Taiwan. METHODS: We included CHC patients who were diagnosed and transferred by the gastroenterologist and hepatologist in outpatient clinics and completed DAA treatments. Data on demographic characteristics, health-related behaviours and physiological biomarkers were collected through one-on-one interview using a questionnaire and from medical records obtained from a teaching hospital. RESULTS: In total, 124 participants were enrolled. Most participants (87.1%) had no side effects and 79.8% felt satisfied after treatment. However, 62.1% had metabolic syndrome, 48.4% had hypertension and 37.9% had diabetes. Furthermore, 71.8% patients were considered to have medium-to-high risk based on Framingham risk scores. In the multiple regression model, after adjusting for education level, other chronic diseases were negatively associated with health-promoting behaviours in participants. CONCLUSIONS: Although there were few side effects and most patients were satisfied after treatment, there was a high prevalence of cardiometabolic risk factors and cardiometabolic diseases and less adoption of healthy behaviours in CHC patients. Despite the small sample size, the study suggests that clinicians can reduce the burden of the aforementioned comorbidities by providing adequate treatment and individualized lifestyle modification. IMPACT: This study highlights that primary healthcare providers should consider the health needs of CHC patients after DAA treatment since many patients have high cardiometabolic risks, but only a few adopt a healthy lifestyle. Further studies are needed to initiate health-promoting programs for these patients to reduce further injury to vital organs.