A comparison of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for the treatment of hepatitis C infection among people who inject drugs.

Background: To eliminate hepatitis C (HCV) infection as a public health concern by 2030, there is a need to develop comprehensive programs among key populations such as people who use drugs (PWUD). Two highly effective regimens are available for initial therapy: glecaprevir/pibrentasvir (G/P) given as 3 tablets/day for 8 weeks and sofosbuvir/velpatasvir (S/V) given as 1 tablet/day for 12 weeks. Data evaluating the safety and efficacy comparing one regimen over another in a population of PWUD is limited. Methods: Patients were identified through outreach events. Viremic patients were offered HCV treatment within a multidisciplinary program. This retrospective comparison analysis focuses on the first 120 sequential individuals who chose either treatment and in whom a definitive outcome of treatment was available between March 1, 2019 and February 29, 2024. The primary outcomes of the analysis were cure of HCV infection and its corelates, as well as safety of the individual regimens. Results: We successfully identified 120 within each of the G/P and S/V treatment groups. Of those on G/P, we note 28.3 % female, 20.9 % Indigenous, 70.8 % using fentanyl, and 51.3 % with unstable housing. Of those on S/V, we note 25.8 % female, 20.8 % Indigenous, and 75 % using fentanyl and 56.7 % with unstable housing. Overall, 118 and 115 patients completed therapy on G/P and S/V, respectively. A total of 118 and 115 completed therapy on G/P and S/V, with virologic relapse documented in 3 and 2 participants on G/P and S/V, respectively. The ITT/mITT cure rates for G/P and S/V were 95.0 %/97.4 % and 94.2 %/98.3 %, respectively. There were 5 drug overdose deaths among those who initiated treatment, one on G/P and 4 on S/V. Conclusion: We have evaluated two highly effective regimens in a group of inner-city PWUD, with comparable success rates well in excess of 90 %. Our data supports the offer of both options for the treatment of PWUD with HCV infection.

Long-term risk of HCC in a DAA-treated national hepatitis C cohort, and a proposed risk score.

BACKGROUND: The risk of hepatocellular carcinoma (HCC) remains elevated in cirrhotic hepatitis C patients with sustained virological response (SVR) after DAA treatment. We assessed long-term HCC risk stratified by pretreatment liver stiffness measurement (LSM) and developed a risk score algorithm. METHODS: This register-based nationwide cohort study of 7,227 DAA-treated patients with SVR evaluated annual HCC incidence rates (IRs) and cumulative incidences stratified by pretreatment LSM. The association between LSM and HCC risk was analyzed using multivariate Cox regression. A risk score algorithm was developed and internally validated in 2,664 individuals with LSM >9.5 kPa, assigning each patient a score based on risk factors, proportionally weighted by the association with HCC risk. RESULTS: During a median follow-up of 1.8 years (3.2 years for LSM ≥12.5 kPa), 92 patients (1.3%) developed HCC. The IRs for LSM 9.5-12.4, 12.5-19.9 and ≥20 kPa were 0.21, 0.99 and 2.20 HCC/100 PY, respectively, with no significant risk reduction during follow-up. The HRs (and 95% CI) for LSM 9.5-12.5, 12.5-19.9 and ≥20 kPa are 1.19 (0.43-3.28), 4.66 (2.17-10.01) and 10.53 (5.26-21.08), respectively. Risk score models including FIB-4, alcohol, diabetes, age and LSM effectively stratified patients with LSM >9.5 kPa into low-, intermediate- and high-risk groups, with a Harrell's C of 0.799. Notably, 48% with LSM ≥9.5 kPa and 27% ≥12.5 kPa were classified as low-risk. CONCLUSION: Pretreatment LSM is associated with HCC risk, which remains stable during the initial five years post-SVR. The HCC risk score algorithm effectively identifies low-risk patients, who may not require HCC surveillance.

The Inhibitory Impact of a Co-Assembly Gel with Natural Carrier-Free Binary Small Molecules, as Used in Traditional Chinese Medicine, on the Viability of SW1990 Cells.

Chinese herbs are a huge treasure trove of natural products and an important source of many active molecules. The theory of traditional Chinese medicine compatibility (TCMC) is widely applied in clinical practice, but its mechanism is still ambiguous. This study aims to open a new window for this predicament by studying the interaction between the main active ingredients from a drug pair. Carrier-free assembly of natural products improves the shortcomings of traditional nanodelivery systems and opens a new path for the development of new nanomaterials. The drug pair "Pueraria and Hedyotis diffusa" has been commonly used in clinical practice, with a predominant therapeutic effect. This study is devoted to the study of the binary small molecule co-assembly of the main active molecules from the drug pair. In this study, we introduce a carrier-free composite gel, formed by the co-assembly of puerarin (PUE) and deacetylasperulosidic acid (DAA) via non-covalent bonds including π-π packing, intermolecular hydrogen bonding, and C=O π interactions. With a strain point 7-fold higher than that of P gel, the P - D gel exhibited favorable rheological properties. The survival rate of SW1990 cells in the P - D group was only 21.39% when the concentration of administration reached 200 µM. It thus demonstrated activity in inhibiting SW1990 cells' survival, suggesting potential in combating pancreatic cancer. Furthermore, this research offers a valuable concept for enhancing the mechanical properties and bioactivity of hydrogel materials through the utilization of a multi-component natural small molecule co-assembly approach. More importantly, this provides new ideas and methods for the treatment of pancreatic cancer and the analysis of traditional Chinese medicine compatibility theory.

"Heterotopic ossification after total hip arthroplasty through direct anterior approach without a dedicated orthopaedic table or direct lateral approach: a quasi-randomized single-center study".

INTRODUCTION: Heterotopic ossifications (HO) are common after total hip arthroplasty (THA). The invasiveness of surgical approaches plays a relevant role in HO development. The aims of this study were to assess the development of HO 6 months after THA through direct lateral approach (DLA) or direct anterior approach (DAA) without a dedicated orthopaedic table and to assess the clinical impact of HO. METHODS: This is a single-center IRB-approved, quasi-randomized prospective cohort, observational imaging study. Fifty patients underwent primary THA through DLA and 50 through DAA. Age, sex, BMI and side of the affected hip were collected. At the 6 post-operative month the Harris Hip Score (HHS) and the presence of HO (scored through the Brooker classification system) were assessed. RESULTS: There was no significant difference in the demographic data between groups. Operative time was significantly higher in the DAA group (72 ± 10 min vs. 58 ± 8 min: p < 0.03). At 6 post-operative months the incidence of HO was 14% in the DAA group and 32% in the DLA group (p = 0.02). Severe HO (Brooker 3-4) were significantly more common in the DLA group (p = 0.04). There was no significant difference in the HHS of patients with HO between the DAA and DLA groups. There was no association between poorer clinical outcomes and the severity of HO. CONCLUSION: The DAA without a dedicated orthopaedic table is associated with a significant lower incidence of HO than the DLA 6 months after elective THA. Except for the surgical approach, no other factors correlated with the occurrence of HO. Even though a lower HHS was found with severe HO, the correlation between severity of HO and clinical outcomes did not reach statistical significance.

Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C Shows Liver Fibrosis Regression on Three Noninvasive Tests: A Puerto Rican Cohort.

OBJECTIVE: Direct-acting antiviral (DAA) drugs have resulted in high rates of virological cure in chronic hepatitis C (CHC)-infected patients. We used noninvasive tests to assess fibrosis in subjects who had been cured with DAA. METHODS: Retrospective data collection (2014-2019) from the medical record of CHC patients at the hepatology clinic was performed. Subjects co-infected with HIV and hepatitis B, post-liver transplant, and lost to follow-up were excluded. We evaluated fibrosis at baseline and 1 year after completing therapy using vibration-controlled transient elastography (VCTE), fibrosis-4 (FIB-4), and aspartate aminotransferase-toplatelet ratio index (APRI) scores. RESULTS: With 210 medical records reviewed, 41 were included. The mean age was 62.8 years; 61% were men. Significant fibrosis regression was observed 1-year post-treatment using 3 noninvasive methods: VCTE, APRI, and FIB-4 score. Prior to treatment, 46% of the patients had advanced fibrosis compared to 25% 1 year after treatment. The VCTE scores of 4 subjects (with body mass indices [BMIs] > 30) indicated a worsening of fibrosis. We did not find a statistically significant association between BMI and VCTE, FIB-4, or APRI score. CONCLUSION: In most CHC patients, DAA therapy leads to liver fibrosis regression. Obesity may play an important role in the worsening of hepatic fibrosis or the absence of fibrosis regression.

Intraoperative fluoroscopic confirmation of the knee improves the accuracy of stem anteversion in total hip arthroplasty with direct anterior approach using traction table.

BACKGROUND: Stem anteversion (SA) in total hip arthroplasty (THA) is crucial for postoperative outcomes, affecting dislocation risk and hip function. Accurate SA placement is challenged by intraoperative estimation methods, with discrepancies reported between predicted and true SA. This study investigates the effect of conventional methods and intraoperative fluoroscopic confirmation on SA accuracy in THA performed with a direct anterior approach using a traction table. METHODS: This involves 200 patients undergoing primary THA from August 2019 to January 2023, divided into a conventional group (n = 100) and a fluoroscopic group (n = 100). Postoperative SA measurements were conducted using computed tomography scans. Statistical analysis focused on comparing the SA angles and the prevalence of excessive SA (≥>35° and ≥>40°) between the groups. RESULTS: The fluoroscopic group showed a lower average SA angle (24.3° ± 8.3°) compared to the conventional group (30.0° ± 11.3°), with a statistically significant difference (p < 0.01). Excessive SA (≥>40°) was found in 17% of the conventional group, significantly reduced to 5% in the fluoroscopic group (p < 0.01). Similarly, SA exceeding 35° was present in 39% of the conventional group, compared to only 11% in the fluoroscopic group (p < 0.01), indicating a substantial reduction in excessive SA placements with fluoroscopic guidance. DISCUSSION: The study demonstrates that intraoperative fluoroscopic guidance significantly enhances the accuracy of SA placement in THA, reducing the variability and proportion of excessive SA. This suggests a critical reevaluation of conventional estimation methods in favor of fluoroscopic confirmation to improve surgical outcomes. CONCLUSION: Intraoperative fluoroscopic confirmation of knee external rotation angle markedly decreases the proportion of excessive SA and enhances the precision of stem placement in THA with a direct anterior approach. This technique represents a significant advancement in surgical practice, offering a simple and effective method to achieve optimal postoperative results.

Effect of immunogenetics polymorphism and expression on direct-acting antiviral drug response in chronic hepatitis C.

The prevalence of HCV infection in Egypt has decreased following the introduction of direct-acting antiviral therapy. However, treatment response is influenced by various factors, particularly host immunogenetics such as IL-28B and FOXP3 polymorphisms. The current study examined the impact of SNPs in the FOXP3 gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved 99 HCV patients who achieved SVR12 after a 12 week DAA treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, FOXP3 rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and FOXP3 were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T > C (P = 0.013) and FOXP3 rs2232365 A > G polymorphisms (P = 0.008) were found to significantly increase the risk of non-response. Responders had higher IL28B serum levels (P = 0.046) and lower FOXP3 levels (P < 0.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and FOXP3 rs2232365 with treatment response, independent of age and gender. A predictive model was developed with 76.2% sensitivity and 91.9% specificity for estimating DAAs response in HCV patients.Our findings confirmed the IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. Our results may lead to new insights into DAA responsiveness contributing to personalized medicine and improving therapeutic decision-making for HCV patients.

Should we be concerned when the anterior approach to the hip goes accidentally medial? A retrospective study.

BACKGROUND: The direct anterior approach is increasingly used for primary total hip arthroplasty (THA) due to its minimally invasive nature and rapid recovery time. Difficulties in identifying the correct intermuscular interval can arise during the procedure, sometimes resulting in excessive medial exposure. This study aimed to evaluate demographics and risk factors, outcomes, and potential complications in those THA patients in which a medialized approach was performed. METHODS: We retrospectively reviewed cases of anterior THA to identify cases where the surgical approach to the hip was more medial than the standard interval. Demographic data, operative time, blood loss, intraoperative and postoperative complications, radiographic findings were collected and compared with a control group of 50 THA performed using the standard anterior intermuscular interval. RESULTS: In a series of 1,450 anterior total hip arthroplasty (THA) procedures performed between January 2018 and December 2021, with an average follow-up of 33 ± 22.3 months, six patients (0.4%) had a medialized surgical interval. In one case the superficial layer was medial to the sartorious muscle while in the other five cases, the interval was lateral to the sartorius superficially, and medial to the rectus femoris deeply. Four out of 6 patients (66.6%) showed neuropraxia affecting the femoral nerve, and 3 out of 6 (50%) had involvement of the lateral femoral cutaneous nerve. In 6 out of 6 patients (100%), surgery was performed during the learning curve of DAA. No patients in the control group developed femoral nerve neuropraxia, and 2 out of 50 patients (4%) showed involvement of the lateral femoral cutaneous nerve. DISCUSSION AND CONCLUSION: The anterior approach can rarely result in excessive medial exposure to the hip joint, especially during the learning curve. In our study cohort, an increased rate of neurological complications and reduced outcomes were observed, thereby rendering this event of particular clinical significance. To avoid unconventional intermuscular intervals, patient positioning and correct identification of the muscle bellies by recognizing the orientation of the muscle fibers are useful, together with the identification and ligation of the circumflex vessels, to ensure the identification of the correct intermuscular interval.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

Hepatitis C Elimination in Egypt: Story of Success.

Egypt has long been overwhelmed by the hepatitis C virus (HCV) infection, and it used to be the country with the world's highest prevalence rates. The disease had been a significant public health problem, affecting millions of Egyptians and posing severe economic and social challenges. By the early 2000s, it was estimated that around 10% of the Egyptian population was infected with HCV. However, in recent years, with the availability of direct-acting antiviral therapies, the country has made enormous steps in combating this public health threat. The combination of innovative health strategies and political will enabled Egypt to establish a successful model of care for HCV management and to be the first country to eliminate hepatitis C, setting a model for the rest of the world. In 2023, Egypt became the first country to fulfill the World Health Organization's set programmatic criteria of reduction of hepatitis C incidence and mortalities to levels close to elimination of disease or achieve the "gold tier" status on the path to disease elimination.

Functional Outcome after Direct Anterior Approach Total Hip Arthroplasty (DAA-THA) for Coxa Profunda and Protrusio Acetabuli-A Retrospective Study.

Objective: The direct anterior approach (DAA) is a recognized technique for total hip arthroplasty (THA) that spares soft tissue. Functional and clinical outcomes following THA via the DAA in patients with complex acetabular deformities, specifically coxa profunda (CP) and protrusio acetabuli (PA), have yet to be determined. Methods: A retrospective analysis was conducted on 188 primary THA cases, including 100 CP hips and 88 PA hips, performed via the DAA. Functional and clinical outcomes were evaluated by means of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Harris Hip Score (HHS) preoperatively and at a mean follow-up of 46 ± 14 months. Furthermore, potential complications were assessed. Results: From the preoperative to the latest postoperative visit, a significant improvement in the WOMAC total score was observed (CP: -34.89 ± 20.66; PA: -40.38 ± 21.11). The length of stay (LOS) was the only parameter predictive of the postoperative WOMAC total score, with each day of LOS increasing the postoperative WOMAC by a mean of 1.77 points (p < 0.01). The HHS improved by 38.37 ± 14.23 (PA-group) and 32.79 ± 14.89 points (CP-group). No significant difference in the patient-reported outcome measures (PROMs) between the CP- and PA-group was found. The survival rate for any revision was 97.70% (PA-group) and 92.80% (CP-group). Conclusion: The results of this study indicate that the minimally invasive DAA was not predictive of the functional and clinical outcome following DAA-THA in patients with CP and PA. Improvements in the mean WOMAC and HHS scores were above or within the reported MCID. Additionally, revision rates were well below those reported in the literature for short and intermediate follow-up periods.

Changes in the Lipid Asset of HIV/HCV Patients after a Successful Course of Direct-Acting Antivirals.

Background: Highly Active Antiretroviral Therapy (HAART) for HIV infection and Direct-Acting Antivirals (DAA) for HCV infection currently represent the main treatment options for HIV/HCV co-infected patients. However, HAART has been associated with increased lipids. This study aimed to evaluate lipid profile changes after the DAA cycle in HIV/HCV co-infected patients undergoing HAART/DAA therapy. Methods: A prospective, longitudinal, observational study among HIV/HCV co-infected patients undergoing HAART/DAA treatment was conducted at the Infectious Diseases Unit of the University Hospital of Salerno. Inclusion criteria were age > 18 years, written informed consent, completion of the DAA cycle, and virologic suppression on HAART. Changes in the lipid profile were analyzed from baseline during and after DAA therapy at 12, 24, and 48 weeks after the sustained virologic response (SVR). A t-test was used to compare continuous variables. An analysis of variance was performed for each antiretroviral drug and genotype. Results: Fifty-four HIV/HCV patients (men/women n. 34/20 [68/32%], median age 56 years), all naïve to HCV therapy, were enrolled. HCV infection was caused by genotype 1 in 55% of cases and by genotype 3 in 29%. An increase in total cholesterol was recorded after the DAA treatment (from 165.03 ± 46.5 to 184.7 ± 44.9 mg/dL, p < 0.0001), after 12, 24, and 48 weeks, and in LDL-C at 24 weeks follow-up (at baseline 86.7 ± 34 mg/dL to 103.4 ± 41.38 mg/dL, p < 0.0001). Conclusions: Changes in the lipid profile after combined DAA/HAART treatment represent an important prognostic index. Further evaluation of cardiovascular-associated risk is necessary to implement appropriate prevention strategies.

The Era of DAAs: Assessing the Patients' Characteristics, Clinical Impact, and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals.

Objective: To determine whether HIV-infected individuals versus individuals with HIV/HCV coinfection, in the era of interferon-free therapies, exhibit an increased incidence of comorbidities and non-AIDS-related events. Methods: A retrospective analysis was conducted by collecting data from clinical records of Spanish patients at a tertiary hospital involving HIV/HCV-coinfected and HIV-infected patients, all with effectively controlled HIV. Coinfected patients underwent HCV clearance using direct-acting antivirals (DAAs) and had no history of interferon treatment. The incidences of hypertension, diabetes mellitus, cardiovascular disease, kidney disease, liver disease, non-AIDS cancer, and death were compared between the groups. Multivariate adjustments for all factors potentially impacting outcomes were used to assess the risk of clinical event onset. Propensity score (PS) analyses were also conducted to support the multivariate model results. Results: Data were available from 229 HIV/HCV-coinfected patients and 229 HIV-infected patients. Both cohorts were comparable in terms of age, gender distribution, follow-up, and HIV-related characteristics. Multivariate models and PS showed that previous exposure to HCV was not associated with the onset of any clinical events studied. Significant differences between HIV/HCV-coinfected and HIV-infected were not found for survival according to the log-rank test (p = 0.402). Conclusions: Successful HCV elimination using DAAs improved the outlook regarding comorbidities and survival across HIV/HCV-coinfected cohorts. Early HCV detection and DAA therapy could enhance clinical results. These findings provide an optimistic perspective for those living with HIV/HCV coinfection and underscore the importance of continuing efforts toward early detection and DAA treatment initiation.

Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study.

Background and Aims: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. Methods: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. Results: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. Conclusions: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

After the Storm: Persistent Molecular Alterations Following HCV Cure.

The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management of this pathology, as their use allows viral elimination in a large majority of patients. Nonetheless, HCV remains a major public health problem due to the multiple challenges associated with its diagnosis, treatment availability and development of a prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk of developing hepatic complications such as hepatocellular carcinoma. In the present review, we aim to summarize the impact that HCV infection has on a wide variety of peripheral and intrahepatic cell populations, the alterations that remain following DAA treatment and the potential molecular mechanisms implicated in their long-term persistence. Finally, we consider how recent developments in single-cell multiomics could refine our understanding of this disease in each specific intrahepatic cell population and drive the field to explore new directions for the development of chemo-preventive strategies.

The Effect of Conjugated Nitrile Structures as Acceptor Moieties on the Photovoltaic Properties of Dye-Sensitized Solar Cells: DFT and TD-DFT Investigation.

A major challenge in improving the overall efficiency of dye-sensitized solar cells is improving the optoelectronic properties of small molecule acceptors. This work primarily investigated the effects of conjugation in nitriles incorporated as acceptor moieties into a newly designed series of D-A-A dyes. Density functional theory was employed to specifically study how single-double and single-triple conjugation in nitriles alters the optical and electronic properties of these dyes. The Cy-4c dye with a highly conjugated nitrile unit attained the smallest band gap (1.80 eV), even smaller than that of the strong cyanacrylic anchor group (2.07 eV). The dyes lacking conjugation in nitrile groups did not contribute to the LUMO, while LUMOs extended from donors to conjugated nitrile components, facilitating intramolecular charge transfer and causing a strong bind to the film surface. Density of state analysis revealed a considerable impact of conjugated nitrile on the electronic properties of dyes through an effective contribution in the LUMO, exceeding the role of the well-known strong 2,1,3-benzothiadiazole acceptor unit. The excited state properties and the absorption spectra were investigated using time-dependent density functional theory (TD-DFT). Conjugation in the nitrile unit caused the absorption band to broaden, strengthen, and shift toward the near-infrared region. The proposed dyes also showed optimum photovoltaic properties; all dyes possess high light-harvesting efficiency (LHE) values, specifically 96% for the dyes Cy-3b and Cy-4c, which had the most conjugated nitrile moieties. The dyes with higher degrees of conjugation had longer excitation lifetime values, which promote charge transfer by causing steady charge recombination at the interface. These findings may provide new insights into the structure of conjugated nitriles and their function as acceptor moieties in DSSCS, which may lead to the development of extremely effective photosensitizers for solar cells.

Indirect comparisons of traction table versus standard table in total hip arthroplasty through direct anterior approach: a systematic review and frequentist network meta-analysis.

BACKGROUND: It remains unclear whether the use of an orthopaedic traction table (TT) in direct anterior approach (DAA) total hip arthroplasty (THA) results in better outcomes. The aim of this systematic review and network meta-analysis was to compare the THA outcomes through DAA on a standard operating table and the THA outcomes through DAA on a TT. METHODS: PubMed, Epistemonikos, and Google Scholar were searched for relevant randomized controlled trials (RCTs) up to 01 January 2024. An indirect comparison in network meta-analysis was performed to assess treatment effects between DAA on a TT and DAA on a standard table, using fixed-effects and random-effects models estimated with frequentist approach and consistency assumption. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated for continuous variables and odds ratios (ORs) with 95% CIs were estimated for binary variables. RESULTS: The systematic review of the literature identified 43 RCTs with a total of 2,258 patients. DAA with TT had a 102.3 mL higher intraoperative blood loss and a 0.6 mmol/L lower Hb 3 days postoperatively compared with DAA without TT (SMD = 102.33, 95% CI 47.62 to 157.04; SMD = - 0.60, 95% CI - 1.19 to - 0.00). DAA with TT had a 0.15 lower periprosthetic fracture OR compared with DAA without TT (OR 0.15, 95% CI 0.03 to 0.86). There were no further significant differences in surgical, radiological, functional outcomes and in complication rates. CONCLUSION: Based on our findings and taking into account the limitations, we recommend that particular attention be paid to the risk of periprosthetic fracture in DAA on a standard operating table and blood loss in DAA with TT. Since numerous other surgical, radiological, functional outcome parameters and other complication rates studied showed no significant difference between DAA on a standard operating table and DAA with TT, no recommendation for a change in surgical technique seems justified. LEVEL OF EVIDENCE: Level I evidence, because this is a systematic review and meta-analysis of randomized controlled trials.

Hepatitis C epidemiology and treatment outcomes in Italy: Impact of the DAA era and the COVID-19 pandemic.

HCV infection poses a global health threat, with significant morbidity and mortality. This study examines HCV trends in a large Italian region from 2015 to 2022, considering demographic changes, evolving clinical profiles, treatment regimens and outcomes, including the impact of the COVID-19 pandemic. This multicentre retrospective study analysed demographics, clinical histories and risk factors in 6882 HCV patients. The study spanned before and after the direct-acting antiviral (DAA) era, and the COVID-19 period, focusing on treatment outcomes (SVR12, non-SVR12 and patients lost to follow-up). Statistical methods included ANOVA, multinomial logistic regression, Kruskal-Wallis test and chi-square analysis, and were conducted adhering to the intention-to-treat (ITT) principle. The cohort, mainly Italian males (average age 58.88), showed Genotype 1 dominance (56.6%) and a high SVR12 rate (97.5%). The pandemic increased follow-up losses, yet SVR12 rates remained stable, influenced by factors like age, gender, cirrhosis and comorbidities. Despite COVID-19 challenges, the region sustained high SVR12 rates in HCV care, emphasising the importance of sustained efforts in HCV care. Continuous screening and targeted interventions in high-risk populations are crucial for achieving WHO elimination targets. The study highlights the resilience of HCV care during the pandemic and provides insights for future public health strategies.

Effect of self-efficacy among persons who inject drugs treated with direct-acting antivirals on Hepatitis C treatment initiation, duration, completion, adherence, and cure.

BACKGROUND: Self-efficacy, a patient-level factor, has been shown to facilitate patient engagement in treatment and optimize treatment-related outcomes in various health contexts. Research on interventions supporting hepatitis C virus (HCV) direct-acting antiviral (DAA) treatment uptake and adherence among persons who inject drugs (PWID) is needed, but whether self-efficacy factors influence DAA treatment cascade outcomes in this population has been less studied. METHODS: Using the HERO study data, we analyzed a subset of participants with any general health self-efficacy data (n=708) measured at baseline and end-of-treatment time points using a 5-items instrument (facets: 'goal setting', 'goal attainment', 'having a positive effect', 'being in control', and 'working to improve'). The cascade outcomes included DAA treatment initiation, duration, adherence, completion, and sustained virologic response (SVR). The effect of baseline and change (Δ) scores for composite and item-level self-efficacy on the cascade outcomes was assessed using logistic regression and generalized linear models. RESULTS: Higher baseline composite self-efficacy [adjusted odds ratio (95 % confidence interval) =1.57 (1.07, 2.29)], 'goal attainment' [1.31 (1.03, 1.67)] and 'having a positive effect' [1.33 (1.03, 1.74)] were associated with greater likelihood of treatment initiation. 'Δ Goal attainment' was significantly associated with SVR [1.63 (1.04, 2.53)]. 'Δ Being in control' and 'Δ working to improve' were associated with treatment adherence and duration, respectively. CONCLUSIONS: General health self-efficacy positively influences DAA treatment initiation among PWID. 'Goal attainment' facilitates the achievement of DAA treatment-related outcomes. Further studies should assess the effect of self-efficacy related to performing healthcare tasks specific to DAAs on the treatment-related outcomes.

Designing cities for everyday nature.

The motivations for incorporating nature into the design of cities have never been more compelling. Creating experiences with nature that occur every day (everyday nature) in cities could help reverse the fate of many threatened species and connect people with nature and living cultural traditions. However, this requires more than just urban greening; it involves ensuring daily doses of nature in a way that also supports nonhuman organisms. A major shift in the way nature is conceived of and is made part of the design of cities is required. Principles include reconsidering nature as a development opportunity rather than a constraint and eliminating offsetting of biodiversity site values. Processes include using biodiversity-sensitive design frameworks and establishing meaningful professional engagement among ecologists, planners, and designers. Challenges include design obstacles, conflicts between nature and people (e.g., safety, disease, and noise) that require careful management, and socioeconomic and political considerations (e.g., Global North vs. Global South). Research to interrogate the multiple benefits of nature in cities can complement experimental interventions, ultimately supporting better urban design and creating much more resiliently built environments for people and nature.

Diseño de ciudades para la naturaleza cotidiana Resumen Los motivos para incorporar a la naturaleza dentro del diseño urbano jamás habían sido tan convincentes. La creación en las ciudades de experiencias con la naturaleza que ocurren a diario (naturaleza cotidiana) podría ayudar a cambiar el destino de muchas especies amenazadas y conectar a las personas con la naturaleza y las tradiciones culturales vivientes. Lo anterior requiere más que reverdecimiento urbano ya que involucra dosis diarias de naturaleza de manera que también mantengan a los organismos no humanos. Se necesita de un cambio mayor en la manera en la que se concibe a la naturaleza y cómo se le hace parte del diseño urbano. Los principios incluyen reconsiderar a la naturaleza como una oportunidad de desarrollo en lugar de una limitación y eliminar la compensación del valor de los sitios de biodiversidad. Los procesos incluyen el uso de marcos de diseños sensibles con la biodiversidad y el establecimiento de una participación profesional significativa entre los ecologistas, los planeadores y los diseñadores. Los retos incluyen los obstáculos del diseño, conflictos entre la naturaleza y las personas (seguridad, enfermedades y ruido) que requieren de un manejo cuidadoso y consideraciones políticas (Norte Global versus Sur Global). La investigación para interrogar los múltiples beneficios de la naturaleza en las ciudades puede complementar a las intervenciones, a la larga respaldando un mejor diseño urbano y creando ambientes para las personas y la naturaleza construidos con mayor resiliencia.