Pirfenidone and nintedanib exert additive antifibrotic effects by the SPP1-AKT pathway in macrophages and fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality rates. It has been shown that pirfenidone (PFD) and nintedanib (Ofev) can slow down the decline in lung function of IPF patients, but their efficacy remains suboptimal. Some studies have suggested that the combination of PFD and Ofev may yield promising results. However, there is a lack of research on the combined application of these two medications in the treatment of IPF. A mouse model of bleomycin-induced (BLM) pulmonary fibrosis was established to investigate the impact of combination therapy on pulmonary fibrosis of mice. The findings demonstrated a significant reduction in lung tissue damage in mice treated with the combination therapy. Subsequent transcriptome analysis identified the differential gene secreted phosphoprotein 1 (SPP1), which was found to be associated with macrophages and fibroblasts based on multiple immunofluorescence staining results. Analysis of a phosphorylated protein microarray indicated that SPP1 plays a regulatory role in macrophages and fibroblasts via the AKT pathway. Consequently, the regulation of macrophages and fibroblasts in pulmonary fibrosis by the combination of PFD and Ofev is mediated by SPP1 through the AKT pathway, potentially offering a novel therapeutic option for IPF patients. Further investigation into the targeting of SPP1 for the treatment of pulmonary fibrosis is warranted.

Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference-A Case Study.

BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

Perioperative Management in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Minor Bleeding Risk Procedure: Rationale and Protocol for the PERIXa Study.

Background: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks. Objective: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk. Methods: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events. Conclusion: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk. Trial Registration: Clinicaltrials.gov: NCT05801068.

Safety and efficacy of apixaban versus vitamin K antagonists in patients undergoing dialysis: a systematic review and meta-analysis.

BACKGROUND: This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis. METHODS: All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible. RESULTS: Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; I2 = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, I2 = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, I2 = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, I2 = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, I2 = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, I2 = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, I2 = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes. CONCLUSIONS: Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results.

Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL'HIV open-label, factorial randomised controlled trial.

BACKGROUND: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences. MATERIALS AND METHODS: The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales. RESULTS: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48. CONCLUSIONS: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03160105.

Comparative Effectiveness of Baloxavir Marboxil and Oseltamivir Treatment in Reducing Household Transmission of Influenza: A Post Hoc Analysis of the BLOCKSTONE Trial.

BACKGROUND: The transmission of influenza virus in households, especially by children, is a major route of infection. Prior studies suggest that timely antiviral treatment of ill cases may reduce infection in household contacts. The aim of the study was to compare the effects of oseltamivir (OTV) and baloxavir marboxil (BXM) treatment of index cases on the secondary attack rate (SAR) of influenza within household. METHODS: A post hoc analysis was done in BLOCKSTONE trial-a placebo-controlled, double-blinded post-exposure prophylaxis of BXM. Data were derived from the laboratory-confirmed index cases' household contacts who received placebo in the trial and also from household members who did not participate in the trial but completed illness questionnaires. To assess the SAR of household members, multivariate analyses adjusted for factors including age, vaccination status, and household size were performed and compared between contacts of index cases treated with BXM or OTV. RESULTS: In total, 185 index cases (116 treated with BXM and 69 treated with OTV) and 410 household contacts (201 from trial, 209 by questionnaire) were included. The Poisson regression modeling showed that the SAR in household contacts of index cases treated with BXM and OTV was 10.8% and 18.5%, respectively; the adjusted relative reduction in SAR was 41.8% (95% confidence interval: 1.0%-65.7%, p = 0.0456) greater with BXM than OTV. Similar reductions were found in contacts from the trial and those included by questionnaire. CONCLUSION: BXM treatment of index cases appeared to result in a greater reduction in secondary household transmission than OTV treatment.

Large-vessel vasculitis possibly induced by BRAF and MEK inhibitors for BRAF V600E positive lung adenocarcinoma.

The combination therapy of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors is approved for treating patients with BRAF V600E-positive tumours, including melanoma and lung cancer. Several case reports indicated autoimmune side effects associated with the use of BRAF and MEK inhibitors. Still, the effects of these drugs on the immune system were not fully elucidated. Here, we report a patient with large-vessel vasculitis diagnosed after initiation of treatment with dabrafenib and trametinib for BRAF V600E-positive metastatic lung adenocarcinoma. She was a never-smoker woman in her early 70s who presented with a chronic cough and was diagnosed with BRAF V600E-positive metastatic lung adenocarcinoma by transbronchial lung biopsy. She was successfully treated with prednisolone and methotrexate while BRAF and MEK inhibitors were continued. We should be careful about autoimmune diseases using BRAF and MEK inhibitors.

Targeted treatment in complex lymphatic anomaly: a case of synergistic efficacy of trametinib and sirolimus.

Repurposing anticancer drugs to vascular malformations has significantly improved patient outcomes. Complex Lymphatic Anomalies (CLA) are part of the spectrum of lymphatic malformations (LMs) that share similar oncogenic mutations to cancer. We report the case of a young patient with highly symptomatic CLA who was initially treated with sirolimus, due to the frequent involvement of the PI3K-AKT-mTOR pathway in CLA pathogenesis. Despite an initial reduction in symptoms, sirolimus progressively lost its effectiveness. After an unsuccessful attempt with trametinib alone, sirolimus was added to trametinib and resulted in a significant, rapid and sustained improvement in symptoms. This suggests that, contrary to current dogmas, combination therapy using sub-therapeutic doses targeting both the PI3K and RAS pathways retains efficacy without generating the toxicity known for combination therapies, and is beneficial in the management of CLAs and potentially other vascular anomalies.

PRESTIGIO RING "a 59-year-old man with multidrug resistant HIV-1 infection failing a regimen including dolutegravir, rilpivirine, atazanavir/cobicistat: successful treatment tailoring based on genotypic and phenotypic resistance tests".

Management of virological failure in heavily treatment-experienced people with multidrug-resistant (MDR) HIV infection is a serious clinical challenge. New drugs with novel mechanisms of action have recently been approved, and their use has improved the outcome of subjects with limited treatment options (LTO). In this setting, the choice of antiretroviral therapy (ART) should be tailored based on the pattern of resistance, treatment history and patients' individual characteristics. While genotypic resistance testing is the reference method for analysing residual drug susceptibility, phenotypic resistance testing can provide additional support when facing LTO. Herein, we present the case of a patient with MDR HIV-1 infection on virological failure enrolled in the PRESTIGIO Registry. The salvage ART regimen, which included drugs with novel mechanisms of action (MoA), was tailored to the patient's clinical characteristics and on the resistance pattern explored with genotypic and phenotypic investigation, allowing the achievement of viro-immunological success. The use of recently approved drugs with novel MoA, combined with an optimized background regimen, may also achieve virological suppression in people with LTO.

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. OBJECTIVE: To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. METHODS: This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. RESULTS: Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). CONCLUSIONS: Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Racial and Ethnic Disparities in Initiation of Direct Oral Anticoagulants Among Medicare Beneficiaries.

Importance: The influence of race and ethnicity on initiation of direct oral anticoagulants (DOACs) is relatively understudied in Medicare data. Objective: To investigate disparities in the initiation of DOACs compared with warfarin by race, ethnicity, and social vulnerability. Design, Setting, and Participants: This retrospective cohort study used a 50% sample of Medicare fee-for-service data from January 1, 2010, to December 31, 2019 (mean patient enrollment duration, 7.7 years). Analysis took place between January 2023 and February 2024. A cohort of older adults (aged ≥65 years) with atrial fibrillation who newly initiated warfarin or DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) was identified. Exposure: Patients were classified as non-Hispanic White, non-Hispanic Black, and Hispanic. Main Outcomes and Measures: The likelihood of starting use of DOACs compared with warfarin was modeled, adjusting for race, ethnicity, age, sex, county-level social vulnerability, and other clinical factors. Results: Among 950 698 anticoagulation initiations, consisting of 680 974 DOAC users and 269 724 warfarin users (mean [SD] age, 78.5 [7.6] years; 52.6% female), 5.2% were Black, 4.3% were Hispanic, and 86.7% were White. During the 10-year study period, DOAC use increased for all demographic groups. After adjustment, compared with White patients, Black patients were 23% less likely (adjusted odds ratio [AOR, 0.77; 95% CI, 0.75-0.79) and Hispanic patients were 13% less likely (AOR, 0.87; 95% CI, 0.85-0.89) to initiate DOAC use. Disparities in DOAC initiation were greatest among Black patients in the earlier years but attenuated during the study period. For instance, in 2010, the OR of Black patients initiating DOACs was 0.54 (95% CI, 0.50-0.57), attenuating linearly over time to 0.69 by 2013 (95% CI, 0.65-0.74) and 0.83 (95% CI, 0.78-0.89) by 2017. By 2019, these differences became nonsignificant (OR, 1.08; 95% CI, 0.99-1.18). Conclusions and Relevance: In this cohort study of Medicare patients with atrial fibrillation, Black and Hispanic patients were less likely to initiate DOACs for atrial fibrillation, although these differences diminished over time. Identifying the factors behind these early disparities is crucial for ensuring equitable access to novel therapies as they emerge for Black and Hispanic populations.

Comparison of Fixed Versus Weight-Based Prothrombin Complex Concentrate Dosing Strategies for Factor Xa Inhibitor Reversal.

Background: Our institution introduced fixed-dose prothrombin complex concentrate (PCC) to streamline order verification and medication administration. Previous studies using fixed-dose PCC for vitamin K antagonist reversal showed comparable efficacy to weight-based dosing. Objective: To compare fixed versus weight-based PCC dosing for reversal of Factor Xa Inhibitor (FXaI) effects. Methods: Retrospective cohort study conducted at a tertiary care academic medical center. Patients who received PCC to reverse the effects of apixaban or rivaroxaban were eligible. Subjects in the fixed-dose group (5000 units or 2000 units) were compared to weight-based PCC (50 units/kg). The primary outcome was time between order entry and medication administration. Secondary outcomes included: average PCC dose, postadministration procedures, achieved hemostasis, 30-day mortality, hospital length of stay, and adverse drug events. Results: 72 patients received fixed-dose PCC and 101 received weight-based PCC. Median time between order entry and administration was 4.5 min shorter in the fixed-dose group compared to weight-based (34.5 vs 39 min, P = .10). In patients who received fixed-dose, 79.2% achieved hemostasis versus 71.3% in the weight-based group (RR = 1.11, 95% CI = 0.94-1.32). There was no difference in the number of subsequent hemorrhage-related surgeries (29.2% vs 36.7%, RR = 0.80, 95% CI = 0.51-1.24) or mortality rate (26.4% vs 35.6%, RR = 0.73, 95% CI = 0.46-1.17). There were zero adverse drug events reported. Rates of thrombosis were 2.8% and < 1% (P = .57) in the fixed and weight-based groups, respectively. Conclusion and Relevance: The fixed-dosing strategy did not reduce time to PCC administration nor impact hemostasis or mortality. These data support that the fixed-dosing method is a viable option.

Genetics-guided therapy in neuroendocrine carcinoma: response to BRAF- and MEK-inhibitors.

Background: Metastatic neuroendocrine carcinoma (NEC) is associated with short survival. Other than platinum-based chemotherapy, there is no clear standard regimen. Current guidelines suggest that combination treatment with BRAF-inhibitors should be considered for patients with BRAF V600E-mutated NEC. However, since only eight such patients have been reported in the literature, our object was to confirm the validity of this recommendation. Methods: This was a single-center retrospective cohort study conducted at Uppsala University Hospital. The included patients 1) had a histopathologically confirmed diagnosis of NEC, 2) were diagnosed between January 1st, 2018 and December 31st, 2023, 3) had tumor tissue genetically screened by a broad next-generation sequencing (NGS) panel, and 4) showed a tumor mutation for which there is a currently available targeted therapy. Results: We screened 48 patients diagnosed with NEC between January 1st, 2018 and December 31st, 2023. Twelve had been analyzed with a broad NGS-panel, and two had a targetable mutation. Both these patients harbored a BRAF V600E-mutated colon-NEC and were treated with BRAF- and MEK-inhibitors dabrafenib and trametinib in second-line. At first radiological evaluation (RECIST 1.1), both patients had a reduction of tumor size, which decreased by 31 and 40%. Both had short response periods, and their overall survival was 12 and 9 months. Conclusions: BRAF-mutated NEC is sensitive to treatment with BRAF- and MEK-inhibitor combination. These results further support that DNA sequencing should be considered as standard of care in NECs to screen for potential treatment targets.

Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial.

BACKGROUND: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. METHODS: In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. DISCUSSION: Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. TRIAL REGISTRATION: ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.

Impact of switching to injectables cabotegravir and rilpivirine on sleep disturbances in a cohort of people living with HIV.

BACKGROUND: Recently, injectable cabotegravir/rilpivirine (ICAB/RPV) became available for HIV treatment. However, there are no real-life data on the impact of switching to ICAB/RPV on sleep disturbances (SD). Therefore, we aimed at assessing and investigating this aspect in our cohort. METHODS: A SD multidimensional assessment (Epworth Sleepiness scale, Insomnia severity Index, Berlin Questionnaire, and Pittsburg Sleep Quality Index, PSQI) was performed to all people who consented before starting ICAB/RPV and 12 wk after the switch. Demographics, life-style habits, laboratory, and clinical data were collected from medical health records. RESULTS: To June 2023, 46 people were included, 76.1% males, with a median age of 48.5 (IQR: 41-57), 50% had multimorbidity, 13% was on polypharmacy. Median age with HIV and CD4 + T cell count nadir were 10 (5-19.5) years and 360 (205-500) cell/mm3, respectively. The reason to start a long-acting strategy was person's choice in all cases. Baseline antiretroviral regimens were mostly: tenofovir alafenamide/emtricitabine/rilpivirine (39.1%) and dolutegravir/lamivudine (32.6%). No significant changes were observed in any of the scores for each questionnaire, but for a worsening PSQI. 37% people reported a subjectively improved sleep quality, even if statistically significant changes were not observed in almost all the sleep parameters. CONCLUSIONS: To the best of our knowledge, this is the first study exploring impact of switching to ICAB/RPV on SD. Despite integrase inhibitor have been associated with SD, we did not observed a negative impact on sleep quality after the switch to ICAB/RPV. More studies and with larger number of people are necessary to confirm our results.

Effective Apixaban removal using hemoadsorption during emergent open-heart surgery: a case report and narrative literature review.

BACKGROUND: The management of hemostasis in patients medicated with apixaban (Eliquis) undergoing emergency cardiac surgery is exceedingly difficult. The body's natural elimination pathways for apixaban prove ineffective in emergency situations, and the impact of hemodialysis is limited. The application of Cytosorb® may attenuate the concentration of apixaban, thereby facilitating the stabilization of these patients. CASE PRESENTATION: An 84-year-old man treated with apixaban, underwent emergency ascending aorta replacement surgery due to an acute type A aortic dissection. To address the challenges induced by apixaban, we integrated Cytosorb® cartridge into the Cardiopulmonary bypass circuit. There was a 63.7% decrease in perioperative apixaban-specific anti-factor Xa activity. The patient's postoperative course was favourable. CONCLUSION: Hemoadsorption with Cytosorb® may offers a safe and feasible approach for reducing apixaban concentration in emergency cardiac surgery, thereby mitigating the risk of hemorrhagic complications.

Revolutionizing the Treatment of Idiopathic Pulmonary Fibrosis: From Conventional Therapies to Advanced Drug Delivery Systems.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease that has been well-reported in the medical literature. Its incidence has risen, particularly in light of the recent COVID-19 pandemic. Conventionally, IPF is treated with antifibrotic drugs-pirfenidone and nintedanib-along with other drugs for symptomatic treatments, including corticosteroids, immunosuppressants, and bronchodilators based on individual requirements. Several drugs and biologicals such as fluorofenidone, thymoquinone, amikacin, paclitaxel nifuroxazide, STAT3, and siRNA have recently been evaluated for IPF treatment that reduces collagen formation and cell proliferation in the lung. There has been a great deal of research into various treatment options for pulmonary fibrosis using advanced delivery systems such as liposomal-based nanocarriers, chitosan nanoparticles, PLGA nanoparticles, solid lipid nanocarriers, and other nanoformulations such as metal nanoparticles, nanocrystals, cubosomes, magnetic nanospheres, and polymeric micelles. Several clinical trials are also ongoing for advanced IPF treatments. This article elaborates on the pathophysiology of IPF, its risk factors, and different advanced drug delivery systems for treating IPF. Although extensive preclinical data is available for these delivery systems, the clinical performance and scale-up studies would decide their commercial translation.