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Microvortices are emerging components that impart functionality to microchannels by exploiting inertia effects such as high shear stress, effective fluid diffusion, and large pressure loss. Exploring the dynamic generation of vortices further expands the scope of microfluidic applications, including cell stimulation, fluid mixing, and transport. Despite the crucial role of vortices' development within sub-millisecond timescales, previous studies in microfluidics did not explore the modulation of the Reynolds number (Re) in the range of several hundred. In this study, we modulated high-speed flows (54 < [Formula: see text] < 456) within sub-millisecond timescales using a piezo-driven on-chip membrane pump. By applying this method to microchannels with asymmetric geometries, we successfully controlled the spatiotemporal development of vortices, adjusting their behavior in response to oscillatory flow directions. These different vortices induced different pressure losses, imparting the microchannels with direction-dependent flow resistance, mimicking a diode-like behavior. Through precise control of vortex development, we managed to regulate this direction-dependent resistance, enabling the rectification of oscillatory flow resembling a diode and the ability to switch its rectification direction. This component facilitated bidirectional flow control without the need for mechanical valves. Moreover, we demonstrated its application in microfluidic cell pipetting, enabling the isolation of single cells. Consequently, based on modulating high-speed flow, our approach offers precise control over the spatiotemporal development of vortices in microstructures, thereby introducing innovative microfluidic functionalities.
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BACKGROUND: Primary analysis of the phase III AGEHA study suggested a favorable benefit-risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST) (Cohort 1) were included. OBJECTIVES: To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab. METHODS: For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.5 mg/kg once weekly from Day 8 onward. RESULTS: Twelve patients (Cohort 1) and 2 patients (Cohort 2) were enrolled. Duration of emicizumab treatment was 8-639 days (median: 44.5 days) in Cohort 1 and 64 and 450 days in Cohort 2. In both cohorts, no major bleeds were observed after initial emicizumab administration. Six patients started their first rehabilitation sessions during emicizumab treatment and no rehabilitation-related bleeds occurred. Twenty-three surgeries were performed under emicizumab prophylaxis and there were no bleeds related to surgeries. Although asymptomatic deep vein thrombosis was reported in 1 patient in the primary analysis, no other thrombotic events occurred thereafter. Two patients developed anti-emicizumab antibodies, 1 of whom showed accelerated emicizumab clearance. Tailored IST approaches (delayed initiation, no use, or reduced dose) were successfully executed in 3 patients undergoing emicizumab prophylaxis. CONCLUSIONS: These results suggest that emicizumab prophylaxis has a favorable benefit-risk profile in PwAHA regardless of eligibility for IST.
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A patient in Japan with HIV began antiretroviral therapy because of acute hepatitis B virus (HBV) 15 years ago, with low hepatitis B surface antibody, and experienced breakthrough HBV reactivation 4 months after switching from bictegravir/emtricitabine/tenofovir alafenamide to cabotegravir/rilpivirine. An immune escape mutation, E164V, was identified in the isolated HBV DNA.
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Infections à VIH , Virus de l'hépatite B , Hépatite B , Activation virale , Humains , Infections à VIH/traitement médicamenteux , Infections à VIH/virologie , Virus de l'hépatite B/génétique , Virus de l'hépatite B/immunologie , Mâle , Hépatite B/virologie , Hépatite B/traitement médicamenteux , Pyridones/usage thérapeutique , Anticorps de l'hépatite B/sang , Anticorps de l'hépatite B/immunologie , Agents antiVIH/usage thérapeutique , Pyrimidines/usage thérapeutique , Adulte d'âge moyen , Antigènes de surface du virus de l'hépatite B/immunologie , Antigènes de surface du virus de l'hépatite B/sang , PipérazinedionesRÉSUMÉ
PURPOSE: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT. METHODS: The patients initially treated with SBRT for spine-targeted protocol treatment, or for areas adjacent to the spine, were enrolled. The second SBRT dose was 30 Gy delivered in five fractions; the spinal cord dose constraint was 15.5 Gy at the maximum point dose. The brachial or lumbosacral plexuses were dose-constrained to <30 Gy if the boundary between the nerves and tumors was detected. The primary endpoint was dose-limiting toxicity (DLT) (grade ≥ 3 severe radiation-related toxicity) within a year after the second SBRT. RESULTS: The second SBRT was administered to the same spinal level in 12 patients and to an adjacent spinal level in 8 patients. SBRT2 was performed for 14 painful lesions, 10 MESCC, and 6 oligometastases, with some lesions having multiple indications. The median interval between SBRT sessions was 21 months (range: 6-51 months). The median follow-up duration was 14 months. No radiation myelopathy or local failure was reported during the follow-up period. DLT was confirmed in two patients (10%) within a year, both of whom developed grade 3 lumbosacral plexopathy. These two patients received SBRT twice to the S1-2 and S1-5 vertebrae, respectively, and both experienced paralysis of the tibialis anterior muscle (L5 level). Grade 3 late adverse effects (including lumbosacral plexopathy and vertebral compression fracture) were observed in 25% of the patients throughout the entire follow-up period. CONCLUSIONS: The second spine SBRT achieved good local control without causing myelopathy. However, one-quarter of the patients experienced grade 3 late adverse effects, suggesting that the treatment protocol carries a risk of toxicity.
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BACKGROUND: Revascularization for extracranial vertebral artery dissection or vertebral artery atherosclerotic occlusive lesions caused by vertebrobasilar insufficiency or posterior circulation infarction is relatively rare. When bypassing the cervical external carotid artery (ECA) or common carotid artery (CCA) using a radial artery (RA) or saphenous vein (SV) graft, it is difficult to determine whether the recipient site should be the V2 or V3 portion. OBSERVATIONS: In case 1, cervical ECA-RA-V3 bypass was performed for bilateral extracranial vertebral artery dissection with the onset of ischemia, and cervical CCA-SV-V3 bypass was added 12 days later. Nine years after surgery, the bilateral vertebral artery dissection had improved, and the patient still had a patent bypass. In case 2, cervical ECA-RA-V2 bypass was performed for arteriosclerotic bilateral extracranial vertebral artery occlusion. The bypass was patent 5 years after surgery. The postoperative course was uneventful in both patients. LESSONS: The authors present cases of posterior fossa revascularization using the vertebral artery V3 and V2 portions via skull base surgery and note that it is important to consider each patient's individual characteristics when selecting the V3 or V2 portion.
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Purpose: Differences in the contours created during magnetic resonance imaging-guided online adaptive radiotherapy (MRgOART) affect dose distribution. This study evaluated the interobserver error in delineating the organs at risk (OARs) in patients with pancreatic cancer treated with MRgOART. Moreover, we explored the effectiveness of drugs that could suppress peristalsis in restraining intra-fractional motion by evaluating OAR visualization in multiple patients. Methods: This study enrolled three patients who underwent MRgOART for pancreatic cancer. The study cohort was classified into three conditions based on the MRI sequence and butylscopolamine administration (Buscopan): 1, T2 imaging without butylscopolamine administration; 2, T2 imaging with butylscopolamine administration; and 3, multi-contrast imaging with butylscopolamine administration. Four blinded observers visualized the OARs (stomach, duodenum, small intestine, and large intestine) on MR images acquired during the initial and final MRgOART sessions. The contour was delineated on a slice area of ±2 cm surrounding the planning target volume. The dice similarity coefficient (DSC) was used to evaluate the contour. Moreover, the OARs were visualized on both MR images acquired before and after the contour delineation process during MRgOART to evaluate whether peristalsis could be suppressed. The DSC was calculated for each OAR. Results: Interobserver errors in the OARs (stomach, duodenum, small intestine, large intestine) for the three conditions were 0.636, 0.418, 0.676, and 0.806; 0.725, 0.635, 0.762, and 0.821; and 0.841, 0.677, 0.762, and 0.807, respectively. The DSC was higher in all conditions with butylscopolamine administration compared with those without it, except for the stomach in condition 2, as observed in the last session of MR image. The DSCs for OARs (stomach, duodenum, small intestine, large intestine) extracted before and after contouring were 0.86, 0.78, 0.88, and 0.87; 0.97, 0.94, 0.90, and 0.94; and 0.94, 0.86, 0.89, and 0.91 for conditions 1, 2, and 3, respectively. Conclusion: Butylscopolamine effectively reduced interobserver error and intra-fractional motion during the MRgOART treatment.
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Objective Frailty is common in patients with heart failure (HF). Given that gardening demands regular physical activity and offers therapeutic relaxation benefits, this activity may reduce frailty. We investigated the association between gardening activities and frailty in patients with HF. Methods, patients, or materials Between August 2022 and March 2023, we surveyed patients at risk of HF and those with HF who regularly attended a cardiology outpatient clinic. Gardening activities were defined as the ongoing cultivation of flowers, vegetables, or fruits for more than a year. The questionnaire assessed the presence or absence of gardening activities as well as the frequency, duration per session, years of experience, and scale of such activities. We calculated the frailty index. Frailty was defined as a frailty index of 0.25 or greater. Results Of the 1,277 respondents, 69% engaged in gardening and 35% were frail. After adjusting for multiple confounding factors, gardening activities showed an inverse association with frailty [odds ratio = 0.723, 95% confidence interval (0.533-0.981)]. Moreover, frailty and the frailty index showed an inverse association with more extended and large-scale gardening activities. Conclusion Gardening activities were thus found to be associated with a low prevalence of frailty in patients with HF.
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The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne® CDx assay at the Keio PleSSision Group (19 hospitals in Japan). A scoring system was developed to identify potentially actionable genomic alterations of biological significance and actionable genomic alterations. The detection rates for potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer, were analyzed. Among the 1587 patients, 547 had digestive cancer. The detection rates of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx were 99.5%, 62.5%, and 11.5%, respectively. APC, KRAS, and CDKN2A alterations were frequently observed in colorectal, pancreatic, and biliary cancers, respectively. Most digestive cancers, except esophageal cancer, were adenocarcinomas. Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.
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Tricuspid annular enlargement in patients with atrial fibrillation (AF) can induce tricuspid regurgitation (TR). However, risk factors associated with TR progression in patients with AF have not been defined. This study aimed to clarify an association between tricuspid annular diameter (TAD) and TR progression in patients with longstanding persistent AF. We retrospectively analyzed data from 228 patients who had longstanding persistent AF for > 1 year and mild or less TR on baseline echocardiograms. We defined significant TR as moderate or greater TR, graded according to the jet area and vena contracta. The optimal cut-off value of the TAD index (TADI), based on body surface area for predicting progression to significant TR, was estimated using receiver operating characteristic (ROC) curves. The independence and incremental value of the TADI were evaluated using multivariate Cox proportional hazard regression analysis and likelihood ratio tests. Over a median follow-up of 3.7 years, 55 (24.1%) patients developed significant TR. The optimal cut-off value of 21.1 mm/m2 for the TADI at baseline and ROC curves predicted TR progression with 70.4% sensitivity and 86% specificity. Furthermore, TADI was an independent predictor of TR progression (hazard ratio, 1.32; 95% confidence interval, 1.17-1.49, P < 0.001) and had a significant incremental value that exceeded that of models constructed using clinical parameters. In conclusion, TADI was significantly associated with TR progression and was an independent predictor of TR progression in longstanding persistent AF.
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Fibrillation auriculaire , Évolution de la maladie , Insuffisance tricuspide , Valve atrioventriculaire droite , Humains , Fibrillation auriculaire/physiopathologie , Fibrillation auriculaire/diagnostic , Fibrillation auriculaire/complications , Mâle , Femelle , Insuffisance tricuspide/physiopathologie , Insuffisance tricuspide/diagnostic , Insuffisance tricuspide/étiologie , Insuffisance tricuspide/complications , Études rétrospectives , Valve atrioventriculaire droite/imagerie diagnostique , Valve atrioventriculaire droite/physiopathologie , Sujet âgé , Adulte d'âge moyen , Courbe ROC , Facteurs de risque , Facteurs temps , Échocardiographie , Études de suivi , Valeur prédictive des testsRÉSUMÉ
Missense mutations in certain small envelope proteins diminish the efficacy of antibodies. Consequently, tracking the incidence and types of vaccine-escape mutations (VEMs) was crucial both before and after the introduction of universal hepatitis B vaccination in Japan in 2016. In this study, we isolated hepatitis B virus (HBV) DNA from 58 of 169 hepatitis B surface antigen (HBsAg)-positive blood samples from Japanese blood donors and determined the nucleotide sequence encoding the small envelope protein. DNA from six (10%) of the samples had VEMs, but no missense mutations, such as G145R, were detected. Complete HBV genome sequences were obtained from 29 of the 58 samples; the viral genotype was A1 in one (3%), A2 in three (10%), B1 in nine (31%), B2 in five (17%), B4 in one (3%), and C2 in 10 (34%) samples. Tenofovir-resistance mutations were detected in two (7%) samples. In addition, several core promoter mutations, such as 1762A>T and 1764G>A, and a precore nonsense mutation, 1986G>A, which are risk factors for HBV-related chronic liver disease, were detected. These findings provide a baseline for future research and highlight the importance of ongoing monitoring of VEMs and drug resistance mutations in HBV DNA from HBsAg-positive blood donors without HBV antibodies.
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Hépatite B chronique , Hépatite B , Humains , Virus de l'hépatite B/génétique , Antigènes de surface du virus de l'hépatite B/génétique , Japon , Donneurs de sang , ADN viral/génétique , Mutation , GénotypeRÉSUMÉ
Capillary samples offer practical benefits compared with venous samples for the measurement of drug concentrations, but the relationship between the two measures varies between different drugs. We measured the concentrations of lumefantrine, mefloquine, piperaquine in 270 pairs of venous plasma and concurrent capillary plasma samples collected from 270 pregnant women with uncomplicated falciparum or vivax malaria. The median and range of venous plasma concentrations included in this study were 447.5 ng/mL (8.81-3,370) for lumefantrine (day 7, n = 76, median total dose received 96.0 mg/kg), 17.9 ng/mL (1.72-181) for desbutyl-lumefantrine, 1,885 ng/mL (762-4,830) for mefloquine (days 3-21, n = 90, median total dose 24.9 mg/kg), 641 ng/mL (79.9-1,950) for carboxy-mefloquine, and 51.8 ng/mL (3.57-851) for piperaquine (days 3-21, n = 89, median total dose 52.2 mg/kg). Although venous and capillary plasma concentrations showed a high correlation (Pearson's correlation coefficient: 0.90-0.99) for all antimalarials and their primary metabolites, they were not directly interchangeable. Using the concurrent capillary plasma concentrations and other variables, the proportions of venous plasma samples predicted within a ±10% precision range was 34% (26/76) for lumefantrine, 36% (32/89) for desbutyl-lumefantrine, 74% (67/90) for mefloquine, 82% (74/90) for carboxy-mefloquine, and 24% (21/89) for piperaquine. Venous plasma concentrations of mefloquine, but not lumefantrine and piperaquine, could be predicted by capillary plasma samples with an acceptable level of agreement. Capillary plasma samples can be utilized for pharmacokinetic and clinical studies, but caution surrounding cut-off values is required at the individual level.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT01054248.
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Antipaludiques , Luméfantrine , Paludisme à Plasmodium falciparum , Paludisme à Plasmodium vivax , Méfloquine , Pipérazines , Quinoléines , Humains , Femelle , Méfloquine/sang , Méfloquine/usage thérapeutique , Méfloquine/pharmacocinétique , Antipaludiques/sang , Antipaludiques/usage thérapeutique , Antipaludiques/pharmacocinétique , Grossesse , Quinoléines/sang , Quinoléines/pharmacocinétique , Quinoléines/usage thérapeutique , Luméfantrine/usage thérapeutique , Luméfantrine/sang , Paludisme à Plasmodium falciparum/traitement médicamenteux , Paludisme à Plasmodium falciparum/sang , Adulte , Paludisme à Plasmodium vivax/traitement médicamenteux , Paludisme à Plasmodium vivax/sang , Jeune adulte , Éthanolamines/sang , Éthanolamines/pharmacocinétique , Éthanolamines/usage thérapeutique , Fluorènes/sang , Fluorènes/usage thérapeutique , Fluorènes/pharmacocinétique , AdolescentRÉSUMÉ
It has been suggested that the effect of coronavirus disease 2019 (COVID-19) booster vaccination in patients with B-cell non-Hodgkin's lymphoma (B-NHL) is inferior to that in healthy individuals. However, differences according to histological subtype or treatment status are unclear. In addition, there has been less research on patients who subsequently develop breakthrough infections. We investigated the effects of the first COVID-19 booster vaccination for patients with B-NHL and the clinical features of breakthrough infections in the Omicron variant era. In this study, B-NHL was classified into two histological subtypes: aggressive lymphoma and indolent lymphoma. Next, patients were subdivided according to treatment with anticancer drugs at the start of the first vaccination. We also examined the clinical characteristics and outcomes of patients who had breakthrough infections after a booster vaccination. The booster effect of the COVID-19 mRNA vaccine in patients with B-NHL varied considerably depending on treatment status at the initial vaccination. In the patient group at more than 1 year after the last anticancer drug treatment, regardless of the histological subtype, the booster effect was comparable to that in the healthy control group. In contrast, the booster effect was significantly poorer in the other patient groups. However, of the 213 patients who received the booster vaccine, 22 patients (10.3%) were infected with COVID-19, and 18 patients (81.8%) had mild disease; these cases included the patients who remained seronegative. Thus, we believe that booster vaccinations may help in reducing the severity of Omicron variant COVID-19 infection in patients with B-NHL.
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COVID-19 , Lymphome malin non hodgkinien , Lymphomes , Humains , Vaccins contre la COVID-19 , COVID-19/prévention et contrôle , Vaccins à ARNm , Réinfections , Études de cohortes , SARS-CoV-2/génétique , ARN messager , Lymphome malin non hodgkinien/traitement médicamenteux , Vaccination , Anticorps antivirauxRÉSUMÉ
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of dormant JC polyomavirus (JCPyV). PML was mainly observed in immunocompromised individuals, such as HIV-positive patients, autoimmune disease patients, and cancer patients. Given that the presence of anti-JCPyV antibodies in serum is a risk indicator for PML development, it is essential to monitor anti-JCPyV antibody levels. In the present study, we established reporter-based single-infection neutralization assays for JCPyV and the genetically similar BK polyoma virus (BKPyV). We then confirmed the lack of cross-reactivity between the two viruses using test sera obtained from mice immunized with plasmids encoding the JCPyV or BKPyV capsid. Next, we compared neutralization antibody titers in sera from healthy donors, patients with multiple sclerosis (MS), and HIV-positive patients using an in-house enzyme-linked immunosorbent assay (ELISA) with JCPyV-like particles (virus-like particles; VLPs). A positive correlation was demonstrated between the neutralization titer (75% infectious concentration; IC75) against JCPyV and the antibody titer obtained by VLP-based JCPyV ELISA. This assay system may be applied to detect antibodies against other PyVs by generation of pseudoviruses using the respective capsid expression plasmids, and is expected to contribute to the surveillance of PyV as well as basic research on these viruses.
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AIMS: As part of the Toon Health Study, which is an ongoing population-based cohort study, we aimed to develop a prediction model for N-terminal pro-brain natriuretic peptide (NT-proBNP) in a general Japanese population. We sought to explore the influence of various demographic and clinical factors on NT-proBNP levels and assess the model's performance. In addition, our objectives included internal validation and investigation of the diagnostic potential of the observed-to-predicted NT-proBNP ratio (OPR) at baseline for predicting the risk of heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: In this prospective cohort study, participants were recruited from Toon City, Japan, as part of the larger Toon Health Study, focusing on cardiovascular risk factors. We measured the NT-proBNP levels and used linear regression with penalization (ridge regression) to develop the model. The model incorporated 10 prespecified predictors (age, gender, body mass index, diastolic blood pressure, heart rate, haemoglobin, albumin, total cholesterol, haemoglobin A1c, and estimated glomerular filtration rate) and underwent assessment using R2 and root mean squared error (RMSE). Internal validation was conducted through bootstrapping. In a post hoc analysis, we explored the OPR's diagnostic potential using 5 year follow-up data (n = 636) to predict the elevation of NT-proBNP > 125 pg/mL at the 5 year follow-up as the risk of HFpEF. A total of 2505 participants (age: 60.4 ± 12.9 years, men: 35%) were enrolled in this study. There was a linear relationship between the observed and predicted values of NT-proBNP in which the logarithm of observed NT-proBNP was <6, which corresponds to 403 pg/mL in NT-proBNP. The prediction model demonstrated satisfactory performance (R2: 0.291, RMSE: 0.688), with age identified as a dominant predictor. The stability of the model was underscored by the internal validation. The OPR at baseline predicted NT-proBNP > 125 pg/mL at the 5 year follow-up with an area under the curve of 0.793. CONCLUSIONS: This study introduces the first prediction model for NT-proBNP in a general Japanese population. Although the model has acceptable performance, ongoing refinement is essential. Our transparent approach to model development, alongside a web-based interactive tool, lays the groundwork for further improvements and external validation. The OPR holds potential for predicting the future risk of HFpEF. This research contributes to understanding the nuanced influence of patient backgrounds on levels of NT-proBNP in asymptomatic individuals within the context of a broader population-based cohort study.
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Marqueurs biologiques , Défaillance cardiaque , Peptide natriurétique cérébral , Fragments peptidiques , Débit systolique , Humains , Peptide natriurétique cérébral/sang , Fragments peptidiques/sang , Mâle , Femelle , Japon/épidémiologie , Études prospectives , Marqueurs biologiques/sang , Sujet âgé , Défaillance cardiaque/sang , Défaillance cardiaque/épidémiologie , Adulte d'âge moyen , Débit systolique/physiologie , Études de suivi , Appréciation des risques/méthodes , Surveillance de la population , Pronostic , Facteurs de risque , Valeur prédictive des tests , Peuples d'Asie de l'EstRÉSUMÉ
BACKGROUND: People who inject drugs (PWID) are at increased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB), but little is known about clinical outcomes of CA-SAB in PWID compared with the wider population of patients with CA-SAB. METHODS: Three national datasets were linked to provide clinical and mortality data on patients hospitalized with CA-SAB in England between 1 January 2017 and 31 December 2020. PWID were identified using the International Classification of Diseases, Tenth Revision code for "mental health and behavioral disorder due to opioid use" (F11). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for associations of PWID with 30-day all-cause mortality and 90-day hospital readmission. RESULTS: In 10 045 cases of CA-SAB, 1612 (16.0%) were PWID. Overall, 796 (7.9%) patients died within 30 days of CA-SAB admission and 1189 (11.8%) patients were readmitted to hospital within 90 days of CA-SAB. In those without infective endocarditis, there was strong evidence of lower odds of mortality among PWID compared with non-PWID (aOR, 0.47 [95% confidence interval {CI}: .33-.68]; P < .001), whereas there was no association in CA-SAB case fatality with endocarditis (aOR, 1.40 [95% CI: .87-2.25]; P = .163). PWID were less likely to be readmitted within 90 days of CA-SAB (aOR, 0.79 [95% CI: .65-.95]; P = .011). CONCLUSIONS: In this large cohort study of patients with CA-SAB in England, PWID had lower odds of death in the absence of endocarditis and lower odds of readmission within 90 days compared to non-PWID patients. This study highlights the overrepresentation of PWID among patients with CA-SAB nationally.
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Bactériémie , Infections communautaires , Infections à staphylocoques , Staphylococcus aureus , Toxicomanie intraveineuse , Humains , Mâle , Infections à staphylocoques/épidémiologie , Infections à staphylocoques/mortalité , Femelle , Angleterre/épidémiologie , Bactériémie/épidémiologie , Bactériémie/mortalité , Adulte , Adulte d'âge moyen , Toxicomanie intraveineuse/complications , Toxicomanie intraveineuse/épidémiologie , Infections communautaires/épidémiologie , Infections communautaires/microbiologie , Infections communautaires/mortalité , Études de cohortes , Réadmission du patient/statistiques et données numériques , Sujet âgé , Jeune adulte , Facteurs de risqueRÉSUMÉ
We assessed whether the impact of cabotegravir plus rilpivirine on inflammation reduction differs from that of oral antiretrovirals, using real-world data. Inflammatory biomarkers and lipid profiles were followed from baseline to 8 months after switching. Seventy-eight participants were analyzed. The CD4/CD8 ratio and C-reactive protein did not change. There were transient decreases in CD8 and CD4 counts in the group that switched from the dolutegravir-based regimen, but not in the tenofovir alafenamide-based regimen group. High-density lipoprotein (HDL) cholesterol increased, resulting in a decrease in the total-cholesterol to HDL cholesterol ratio, whereas there was no significant change in low-density lipoprotein cholesterol.
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Agents antiVIH , Infections à VIH , Humains , Rilpivirine/usage thérapeutique , Infections à VIH/traitement médicamenteux , Antirétroviraux/usage thérapeutique , Marqueurs biologiques , Cholestérol/usage thérapeutique , Lipides , Agents antiVIH/usage thérapeutiqueRÉSUMÉ
INTRODUCTION: Epidemiological evidence regarding the relationship between smoking and secondhand smoke (SHS) exposure and carotid intima-media thickness (CIMT) has been limited in Asian populations. Employing baseline data from the Aidai Cohort Study, Japan, we evaluated the evidence in this cross-sectional study. METHODS: Study subjects were 727 men aged 35-88 years and 1297 women aged 34-85 years. Information on smoking, SHS exposure, and confounders was obtained through a self-administered questionnaire. An automated carotid ultrasonography device was used to measure the right and left CIMT. The greatest CIMT measurement in the left or right common carotid artery was considered the maximum CIMT, and a maximum CIMT >1.0 mm was indicative of carotid wall thickening. Age, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, body mass index, waist circumference, employment, and education level were adjusted at one time. RESULTS: The prevalence of carotid wall thickening was 13.0%. The prevalence of never smoking was 30.5% in men and 90.1% in women. Among those who had never smoked, the prevalence of never SHS exposure at home and work was 74.3% and 48.2% in men and 38.3% and 56.3% in women, respectively. Active smoking and pack-years of smoking were independently positively related to carotid wall thickening regardless of sex, although the association with current smoking in women was not significant. Independent positive relationships were shown between former smoking and pack-years of smoking and maximum CIMT in men but not in women. No significant relationships were found between SHS exposure at home and work and carotid wall thickening or maximum CIMT in either men or women. CONCLUSIONS: Active smoking, especially pack-years of smoking, was positively associated with carotid wall thickening in both sexes. Such positive associations with maximum CIMT were found only in men; however, interactions between smoking and sex were not significant.
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Long-acting cabotegravir plus rilpivirine has revolutionized the concept of antiretroviral therapy, but as the causes of virological failure and satisfaction can depend on patient background, real-world data are needed. In this single-center study, we reviewed clinical records of people with HIV (PWH) who received injectable cabotegravir plus rilpivirine between June 2022 and January 2023. We assessed virological and safety outcomes, including injection site reactions (ISRs) and changes in serum creatinine and cystatin C. Seventy-four patients were included. There were no virological failures. Approximately 80% of individuals achieved HIV-RNA undetectable in all visits up to 14 months (median 13 months) after switching. Pain upon injection was significantly more common at the rilpivirine injection site, while delayed pain was significantly more common at the cabotegravir injection site. The serum creatinine (mean difference -0.12 mg/dL, p < .0001) and the cystatin C (mean difference -0.077 mg/dL, p < .0001) decreased significantly after switching, and in multivariable regression analysis, baseline characteristics did not affect the decrease in these renal function markers. Long-acting cabotegravir plus rilpivirine showed excellent antiviral efficacy and safety in PWH in Japan. ISRs were characterized differently at the cabotegravir and rilpivirine injection sites. Although cystatin C showed decrease after the regimen switch, further confirmation is needed whether cabotegravir plus rilpivirine can improve renal function.
Sujet(s)
Agents antiVIH , Pipérazinediones , Infections à VIH , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Pyridones , Humains , Agents antiVIH/effets indésirables , Antirétroviraux/usage thérapeutique , Asiatiques , Créatinine , Cystatine C , Infections à VIH/traitement médicamenteux , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/génétique , Réaction au site d'injection/traitement médicamenteux , Rein , Douleur/traitement médicamenteux , Rilpivirine/effets indésirables , Études rétrospectives , JaponRÉSUMÉ
AIM: Hepatitis A (HA) is a vaccine-preventable disease. In regions with good sanitation, men who have sex with men (MSM) are the key affected populations. During the 2018-2019 HA outbreak among MSM in Japan, we actively vaccinated MSM living with HIV (MSM-LWHIV) with Aimmugen. As previously reported, their antibody seroconversion rate due to vaccination was lower than that of healthy individuals. However, the durability of Aimmugen in people living with HIV has not yet been reported. We evaluated attenuation after the one-series vaccination (comprising three inoculations) and the factors associated with attenuation. METHODS: We retrospectively examined anti-HA immunoglobulin G (anti-HA-IgG) titers and other clinical data from our hospital's medical records. Patients with no history of vaccination or HA infection (i.e., negative HA-IgG titers) who received one series of Aimmugen, achieved seropositivity, and anti-HA-IgG antibodies were tested ≥2 years after three doses were included. Fisher's exact test and the Mann-Whitney U-test were performed. p < 0.05 was considered statistically significant. RESULTS: Fifty-one MSM-LWHIV were included. All were seropositive after the third dose with a median HA-IgG titer of 10.1 (interquartile range, 7.2-12.2) (sample/cut-off values [s/co]). In 45 (40-49) months, seropositivity decreased to 90% (46/51) and was attenuated to a median of 4.4 (2.3-6.5) s/co. Lower baseline B cell counts (p = 0.049), lower anti-HA-IgG levels after the second dose (p = 0.002), and lower anti-HA-IgG levels after the third dose (p = 0.003) were associated with seronegativity. CONCLUSIONS: Anti-HA-IgG titers of vaccinated MSM-LWHIV may be attenuated; thus, additional immunizations should be considered.
RÉSUMÉ
Frustules, whose length spans from a few micrometers to more than a hundred micrometers, have been the subject of various modifications to improve their physical properties because of their complex porous silica structure. However, three-dimensional measurements of these changes can be challenging because of the complex 3D architecture and limitations of known methods. In this study, we present a new method that applies digital holographic microscopy (DHM) to analyze controlled etched frustules and observe real-time degradation of frustules at the single-cell level. Frustules obtained from Craspedostauros sp. diatoms were etched in 1 N NaOH for 5 min at 25 and 60 °C, respectively, and the frustule's valve was analyzed using DHM. DHM uses a combination of holography and tomography to reconstruct a 3D refractive index image of the frustule. Measurements of the width, volume, and surface area are achieved. Results showed that at 60 °C of etching, a significant difference with the unetched frustule was observed for all measurements but with high fluctuation values. Finally, real-time observation of the degradation of the frustule is observed when immersed in a high concentration of NaOH. This is the first time the real-time etching of the frustule is observed at the single-cell level. This research provides an easy estimation of the 3D measurements of frustules that may provide new fundamental information and applications.