SEARCH · PubMed Health

Results for “injection”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

No Efficacy of Dexamethasone Injections for Acute Sciatica: A Double-Blind Randomized Study Versus Saline.

BACKGROUND: The efficacy of caudal injections for patients with acute sciatica remains controversial. The DEXHIA study was designed to evaluate whether ultrasound-guided caudal injection of dexamethasone provides superior clinical outcomes compared with saline placebo. METHODS: This prospective, randomized, placebo-controlled, double-blind trial included adult patients with sciatica secondary to lumbar disc herniation of less than 3 months' duration. Participants were randomly assigned in a 1:1 ratio to receive either 16 mg of dexamethasone (4 mL) diluted with 16 mL of saline (DEXA group) or 20 mL of saline alone (PLACEBO group), administered by ultrasound-guided caudal epidural injection. The primary outcome was the change in the Oswestry Disability Index (ODI) at 3 weeks. Secondary outcomes included leg pain and low back pain assessed by visual analogue scale (VAS), health-related quality of life (SF-36), need for repeat epidural injection, and need for lumbar surgery. Clinical assessments were performed at 3 weeks, 3 months, and 6 months. RESULTS: A total of 106 patients were randomized, with 53 participants assigned to each treatment group. The primary endpoint was not met, as the improvement in ODI at 3 weeks did not differ significantly between groups (mean change: -9.5 ± 4.4 in the DEXA group versus -13.8 ± 4.4 in the PLACEBO group; p = 0.18). No significant differences were observed for any relevant secondary outcome at any follow-up time point. During the 6-month follow-up, 34 patients in the DEXA group and 30 patients in the PLACEBO group underwent a second, non-blinded injection of dexamethasone (ns). Lumbar surgery was performed in 10 patients in the DEXA group and nine patients in the PLACEBO group (ns). Injection-related adverse events were mild and transient but occurred more frequently in the DEXA group. CONCLUSIONS: Caudal injection of soluble dexamethasone conferred no clinical benefit over saline placebo in patients with acute sciatica. SIGNIFICANCE STATEMENT: Epidural injections are widely used worldwide for the treatment of resistant sciatica and have been extensively studied in multiple meta-analyses. However, their clinical value remains debated due to the limited methodological quality of most available studies. We conducted a methodologically rigorous randomized, placebo-controlled trial, which yielded negative results. These findings question the efficacy of caudal epidural injection of a non-particulate corticosteroid administered via a remote (sacrococcygeal) approach for disc-related sciatica. TRIAL REGISTRATION: The trial was registered under European Clinical Trials No. 2021-001571-17 and ClinicalTrials.gov identifier NCT05000658.

Adult↗

PubMed2026

Cryostick pre-cooling reduces pain during intra-articular knee injections: a randomized, contralateral-controlled trial.

BACKGROUND: Intra-articular knee injections are essential for osteoarthritis management but often limited by "needle phobia" and procedural pain. The cryostick, a high-thermal-conductivity device, is a potential analgesic; however, evidence regarding its efficacy in reducing pain and bleeding is limited. The purpose of the study was to evaluate whether cryostick application reduces procedural pain, reduces bleeding, and improves patient satisfaction during intra-articular knee injections. METHODS: This randomized, contralateral-controlled trial included 50 patients (100 knees) with bilateral knee osteoarthritis. One knee received a 20-s cryostick protocol (-20°C) immediately before injection; the contralateral knee received a standard injection. Primary outcome was pain intensity (100-mm VAS) during needle penetration and at 5-min post-injection. Secondary outcomes included bleeding area (mm2) and satisfaction (1-5 Likert scale). RESULTS: Cryostick application significantly reduced pain during needle penetration (Mean Difference [MD] -24.8 mm; 95% CI -29.9 to -19.7; P < 0.001) and at 5-min post-injection (MD -20.8 mm; 95% CI -26.8 to -14.8; P < 0.001). The Number Needed to Treat (NNT) to achieve the Minimal Clinically Important Difference (13 mm) was 1.28 (95% CI 1.15-1.54) during penetration and 1.79 (95% CI 1.45-2.36) at 5-min post-injection. The bleeding area was significantly smaller with cryostick (MD -4.82 mm2; P = 0.014). Patients reported significantly higher satisfaction scores with the cryostick (4.10 vs 2.96; P < 0.001). CONCLUSIONS: A 20-s cryostick application is a safe, well-tolerated, and effective adjunct for attenuating pain and bleeding during knee injections. This technically simple approach requires minimal complexity, offering an efficient, non-pharmacological tool to enhance patient comfort.

Humans↗

PubMed2026

Higher Rates of PASS and SCB After Arthroscopic Subspine Decompression Are Associated With a Positive Diagnostic AIIS Injection: A Propensity Score-Matched Cohort Study.

BACKGROUND: Hip arthroscopy effectively treats femoroacetabular impingement syndrome (FAIS), but persistent pain may be related to concomitant extra-articular pathology such as subspine impingement syndrome (SSI). Standard diagnosis of SSI often relies on 3-dimensional computed tomography (3D-CT) morphology (Hetsroni type II/III), although this morphology is common in individuals who are asymptomatic and correlates poorly with symptoms. PURPOSE: To compare minimum 2-year clinical outcomes after arthroscopic subspine decompression in patients with concurrent FAIS and type II/III anterior inferior iliac spine (AIIS) morphology, stratified by diagnostic method: 3D-CT morphology alone versus 3D-CT morphology plus a positive ultrasound-guided diagnostic injection. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included patients aged 18 to 55 years with type II/III AIIS morphology who underwent primary hip arthroscopy for FAIS and SSI between January 2021 and November 2023 and had minimum 2-year follow-up. Patients diagnosed by CT morphology alone (CT classification group) were propensity score matched 1:1 to patients with a positive ultrasound-guided AIIS injection (injection group), with 57 patients per group. Matching variables were age, sex, body mass index, lateral center-edge angle, alpha angle, Tönnis grade, and Beighton score. All patients underwent arthroscopic subspine decompression. Patient-reported outcomes and rates of achieving the minimal clinically important difference, Patient Acceptable Symptom State (PASS), and substantial clinical benefit (SCB) were compared. RESULTS: Preoperative patient-reported outcome scores were similar between groups (all P > .05). At minimum 2-year follow-up, the injection group had significantly better scores on the modified Harris Hip Score (90.8 vs 84.2), Hip Outcome Score-Activities of Daily Living (88.4 vs 82.4), Hip Outcome Score-Sports Subscale (71.9 vs 64.1), 12-item International Hip Outcome Tool (83.9 vs 76.1), and visual analog scale for pain (1.2 vs 2.0) (all P < .001). Minimal clinically important difference rates were high in both groups, with higher rates in the injection group for modified Harris Hip Score (93% vs 77%; P = .033) and Hip Outcome Score-Activities of Daily Living (91% vs 75%; P = .042). PASS and SCB rates were significantly higher in the injection group across all patient-reported outcome measures (all P < .05). Revision and complication rates were low and did not differ significantly between groups. CONCLUSION: Both groups improved significantly after arthroscopic subspine decompression. However, patients with a positive ultrasound-guided diagnostic AIIS injection achieved higher PASS and SCB rates than those selected by CT morphology alone, suggesting that injection-confirmed SSI may improve patient selection for subspine decompression.

Humans↗

PubMed2026

Generation of germline-transmitting transgenic sheep by piggyBac-mediated transgenesis using pronuclear and cytoplasmic gene injection approaches.

Sheep represent an important large-animal model for biomedical research and biopharmaceutical production. Although the piggyBac transposon system offers efficient and stable genomic integration, the optimal gene delivery strategy for ovine embryos remains unclear. This study evaluated piggyBac-mediated transgenesis using pronuclear injection (PNI) in both in vivo- and in vitro-derived embryos and assessed cytoplasmic injection (CTI) as an alternative approach. In vivo-derived embryos were obtained from superovulated Kıvırcık ewes approximately 40 h after gonadotropin-releasing hormone administration, whereas in vitro-derived embryos were produced from slaughterhouse-derived oocytes. All embryos were injected with the hyperactive piggyBac transposase-based pmhyGENIE-3 construct (10 ng/µL). In vivo-derived embryos were transferred immediately after injection, whereas in vitro-derived embryos were cultured for 3 days and screened for EGFP expression prior to transfer. Among 65 in vitro-derived embryos injected by PNI, no transgenic offspring was obtained. In contrast, PNI of 19 in vivo-derived embryos resulted in one transgenic lamb (5.3%). CTI of 12 in vivo-derived embryos similarly produced one transgenic lamb (8.3%). Whole-genome sequencing of the healthy founder male produced by CTI identified a single detectable genomic integration locus on chromosome 10 within a non-coding RNA locus (LOC121820439). Germline transmission was confirmed by in vitro fertilization using sperm from the founder male, with EGFP expression detected in 10.1% (10/99) resulting embryos. These findings provide proof-of-concept evidence for piggyBac-mediated transgenesis in sheep and support the feasibility of cytoplasmic injection as an alternative gene-delivery approach under the conditions tested.

Animals↗

PubMed2026

Intratumoral Sotigalimab with Pembrolizumab Induces Rapid Activation of Antigen-Presenting Cells and Drives Antitumor Responses in Non-injected Tumors in Metastatic Melanoma: A Phase I/II Study.

UNLABELLED: Immune checkpoint blockers (ICB) improve outcomes in metastatic melanoma (MM), but resistance limits benefit. This phase I/II (NCT02706353) study evaluated intratumoral sotigalimab (anti-CD40 agonist) with pembrolizumab in 32 patients with ICB-naïve MM. Primary endpoints were safety and objective response rate (ORR). Sotigalimab was well tolerated. At the recommended phase II dose, the ORR was 50%, and the disease control rate was 92%, with ORRs of 67% in injected and 50% in non-injected tumors. Multiomic analyses of tumor and blood showed that sotigalimab effectively engaged the CD40 pathway, boosting infiltration and activation of myeloid cells, including CD11c+DC-LAMP+ dendritic cells and macrophages. The combination therapy activated innate and adaptive immunity in injected tumors and cytotoxic responses in non-injected tumors. T-cell receptor sequencing showed increased T-cell clonality with expanded new clones shared across tumors. Clinical responses correlated with these immunologic changes but not with baseline features associated with response to anti-PD-1 monotherapy. SIGNIFICANCE: In this study, we provide compelling data that intratumoral sotigalimab combined with pembrolizumab is safe, activates antigen-presenting cells, and elicits broad innate and adaptive immune responses in both injected and non-injected tumors, supporting further randomized phase II trials to evaluate sotigalimab's potential to enhance anti-PD-1 therapy through "in situ" immunization.

Humans↗

PubMed2026

Analyzing the impact of subcutaneous injection needle, device, and administration characteristics on patient pain, anxiety, and safety: a systematic literature review.

The subcutaneous (SC) injection route is a commonly used and important method for therapeutic delivery of a wide range of compounds, and needle characteristics have a significant influence on patient pain, anxiety, safety, and other outcomes. This systematic review evaluates the evidence on how needle-specific characteristics (e.g. gauge, length, tip design, wall thickness, concealment) and administration- or device-related factors can affect patient-reported outcomes and clinical safety indicators during and following SC injections. A comprehensive search was conducted in MEDLINE, PubMed, Embase, and ClinicalTrials.gov in June 2024. Studies were included if they assessed the relationship between needle characteristics and pain, anxiety, safety, or related outcomes in individuals receiving SC injections. A dual-reviewer process was used for study selection, data extraction, and quality assessment. Sixty-two studies met inclusion criteria. Evidence consistently indicated that thinner and shorter needles reduced patient-reported pain and adverse events such as bruising and bleeding. Tapered and lubricated needles, hidden or retractable needle designs, and use of autoinjectors or prefilled syringes also contributed to reduced anxiety and improved user satisfaction. However, results were heterogeneous, and many studies lacked sufficient power or single-variable evaluation of individual needle parameters, limiting definitive conclusions. Needle characteristics significantly influence patient experience and safety with SC delivery. While both clinical evidence and practical experience clearly favor thinner, shorter, and concealed needles, further standardized, high-quality research is needed to isolate and quantify the specific contributions of individual needle characteristics to optimize injection practices and support patient-centered device design.

Humans↗

PubMed2026

Variations in the viral hepatitis C prevalence and treatment status by material hardship and cumulative risk among people who inject drugs.

People who inject drugs (PWID) are disproportionately impacted by viral hepatitis C (HCV). Among PWID, homelessness, poverty, and material insecurity elevate infectious disease risk. We hypothesized a positive association between material hardship (difficulty accessing basic needs) and lifetime diagnosis of HCV, and a negative association between cumulative risk (material hardship and years since first injection) and HCV treatment. From 2021-22, we conducted a survey among community-recruited PWID that included items on HCV outcomes, material hardship (a sum score of usually (4) to never (1) having difficulty finding food, clothing, shelter, restrooms, and showers in the past 3 months), and years since injection drug use initiation. We developed a latent variable, cumulative risk, by combining individual scores of material hardship indicators and years since first injection drug use. Among our sample of PWID (n = 471), 246 (53%) participants reported lifetime HCV diagnosis and 27% of those who tested positive for HCV reported ever or current treatment (n = 67). In modified-Poisson regression, a one-unit increase in material hardship score was associated with a 3% (OR: 1.03, 95% CI: 1.01%, 1.05%) increase in odds of HCV diagnosis. In latent modeling, among PWID testing positive for HCV, a one-unit increase in cumulative risk score was associated with a 0.28 (OR: -0.28, 95% CI: -0.50, -0.06), decrease in the Z-score odds of receiving HCV treatment. Findings emphasize structural interventions to strengthen material security and co-delivering basic needs with health services to improve HCV-related outcomes among PWID.

HCV↗

PubMed2026

Differential gene transcription following intravenous injection of air bubbles in rats with varying resistance to decompression sickness.

Decompression sickness (DCS) is a pathology caused by the appearance of gas emboli in the bloodstream and tissues. However, the weak correlation between the amount of venous gas emboli (VGE) and the development of DCS, as well as the considerable interindividual variability in DCS susceptibility, suggests that a higher DCS resistance could be associated with a better management of VGE-induced stress. To study the effects of VGE independently of the hyperbaric stress induced by diving, Wistar and DCS-resistant male and female rats received 5 mL/kg of a 0.9% NaCl solution containing air microbubbles through the tail vein. After 120 min, the liver and lungs were harvested. Wet-to-dry weight ratio was determined in the lungs. Gene expression was quantified by reverse transcription-polymerase chain reaction in the liver. Compared with standard Wistar, DCS-resistant rats exhibited a lower lung wet-to-dry weight ratio after air microbubble injection, suggesting lower pulmonary fluid accumulation. In the liver, DCS-resistant rats showed higher tissue factor transcription at the basal state and post-air microbubble injection. Tissue factor pathway inhibitor was lower in DCS-resistant rats at the basal state but higher following air microbubble injection. Levels of heat shock protein 70 (HSP70), heat shock protein 27 (HSP27), and early growth response 1 (Egr-1) were higher in DCS-resistant rats after air microbubble injection. At the basal state, only HSP27 was higher in DCS-resistant rats, with HSP70 lower and Egr-1 not different. These results help clarify the pathways involved in the response to VGE and highlight potential mechanisms underlying resistance to DCS, including enhanced anticoagulant pathways and improved cellular stress responses.NEW & NOTEWORTHY This study suggests for the first time that DCS resistance may be associated with a better tolerance to VGE. This greater DCS resistance could be achieved through improved control of the procoagulant effects of bubbles via TFPI-dependent inhibitory mechanisms and an enhanced cellular stress response to VGE by HSP70, HSP27, and EGR-1. It also suggests that it may be possible to stratify the individual DCS risk based on the thromboinflammatory response to bubbles.

Animals↗

PubMed2026

Changes in heroin-related ambulance attendances following the introduction of a medically supervised injecting room in Victoria, Australia.

BACKGROUND: Injecting drug use contributes significantly to morbidity, mortality and broader social harms globally. Supervised Injecting Facilities (SIFs) are harm reduction interventions that reduce overdose risk and facilitate access to health services for marginalised individuals. While international evidence supports the effectiveness of SIFs, Australian population-level surveillance data quantifying their impact on emergency medical service utilisation remain limited. METHODS: Using data from the National Ambulance Surveillance System, we conducted a retrospective, interrupted time series analysis of heroin-related ambulance attendances within the local catchment of the Medically Supervised Injecting Room (MSIR) between January 2015 and December 2023. Supplementary analysis included comparisons with central Melbourne suburbs and the broader state of Victoria. Key intervention timepoints, including the opening of the MSIR on 30 June 2018, expansion of its operating hours in July 2019, and the COVID-19 pandemic from April 2020 to October 2021, were examined to assess changes in heroin-related attendances over time. Segmented regression models were used to assess changes in heroin-related ambulance attendance trends over time. RESULTS: At the time the MSIR opened, the model-predicted heroin-related ambulance attendance rate within the MSIR catchment was 123 per 100,000 population per month, equivalent to approximately 48 heroin-related ambulance attendances per month. Prior to implementation, the attendance rate was increasing by an estimated 0.74 per 100,000 population per month. Following the opening of the MSIR, the previously increasing trajectory reversed, with ambulance attendance rates declining by approximately 2.3 per 100,000 population per month relative to the pre-intervention trend. By the end of the study period (December 2023), the predicted monthly heroin-related ambulance attendance rate had declined to 36 per 100,000 population (approximately 14 attendances per month), representing an overall reduction of 70.7% from the time of MSIR implementation. These reductions persisted throughout the COVID-19 lockdown period and were sustained after restrictions lifted. Supplementary analysis showed no comparable reductions in the central Melbourne region or the remainder of Victoria. CONCLUSIONS: The introduction of the MSIR in Richmond was associated with a sustained reduction in heroin-related ambulance attendances within its catchment area. These findings provide strong population-level evidence that SIFs reduce acute heroin-related harms requiring emergency ambulance response, reinforcing their role as an effective harm reduction strategy within the Australian context.

Humans↗

PubMed2026

Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB↗

PubMed2026

Distribution of transgene in the rodent choroid plexus after intracerebroventricular injection of adeno-associated virus.

Using adeno-associated virus to transfer genetic information to the choroid plexus has emerged as a promising route for long-term gene therapy in the brain for a variety of conditions. Overexpression of proteins has proved effective in small animal models but few attempts have been made to translate this technology to clinic, suppress the activity of a protein of interest, or further expand the limited capsid serotypes known to have choroid plexus tropism. We utilise transfer of green fluorescent protein to show choroid plexus epithelium tropism for novel AAV6 derived capsid ShH10Y445F in mouse, rat and porcine tissue explant cultures. In vivo tropism is shown in the mouse following stereotactic intracerebroventricular injection. We examined the distribution of viral transduction across the choroid plexus in all four ventricles following a single unilateral intracerebroventricular injection using both green fluorescent protein as a transgene, but also the CRISPR/Cas9 system to deliver permanent knockdown of apical water channel aquaporin-1. Quantitative immunofluorescence and SURVEYOR assay were used to statistically assess the magnitude and extent of choroid plexus knockdown across the ventricular system. We conclude that serotype ShH10Y445F targets choroid plexus epithelium in mouse, rat and pig; and when carrying the CRISPR/Cas9 system can reduce target protein expression in these cells. Transduced choroid plexus epithelial cells distribute unevenly with a bias toward the lateral ventricle on the injected side and a preferential infection of choroid plexus in the lateral over the third and fourth ventricles. Overcoming irregular distribution represents a challenge for clinical translation of this technology where clinical efficacy may require manipulation of the entire choroid plexus.

Animals↗

PubMed2026

Rates, Timing, and Predictors of Retreatment Across Risk-Cohorts in Retinopathy of Prematurity: Intravitreal Bevacizumab Injection Versus Laser.

OBJECTIVE: To characterize rates, timing, and predictors of retinopathy of prematurity (ROP) retreatment among infants treated with primary laser or intravitreal bevacizumab injection. DESIGN: Retrospective consecutive, comparative clinical study. PARTICIPANTS: Infants who underwent initial treatment for treatment-warranted ROP (TW-ROP) with either intravitreal bevacizumab or laser photocoagulation between 2017 and 2023. METHODS: Patients were stratified into two treatment groups: primary laser group vs primary bevacizumab group. MAIN OUTCOME MEASURES: Retreatment within the first 3 months (0-90 days) was assessed and classified as early (≤30 days) or late (31-90 days). RESULTS: Two hundred and thirty eight eyes of 122 infants were treated for ROP; of those, 181 (76.1%) eyes of 93 (76.2%) patients were included. There were 116 (64.1%) eyes in the bevacizumab group, and 65 (35.9%) eyes in the laser group. Thirty-three (18.2%) eyes-all micro- or nano-premature (<27 weeks GA and/or <800 grams)-required retreatment for TW-ROP. Sixteen (8.8%) required early retreatment at a median postmenstrual age (PMA) of 40.4 weeks (IQR, 38.44-43.3). There were differences in the proportion of early retreated infants (21.5% for laser vs 1.7% for injection, P < .001). Seventeen (9.4%) eyes required late retreatment. The median PMA at late retreatment was 45.6 weeks (IQR, 43.7-47.4). Infants in the bevacizumab group had lower odds of retreatment within three months than those with laser (OR, 0.23; 95% CI, 0.06-0.82). Similarly, patients in the bevacizumab group had lower odds of requiring early retreatment compared to those with laser (OR, 0.08; 95% CI, 0.04-0.18). Within eyes with retreatment, infants in the bevacizumab group had a later PMA at retreatment than those in the laser group (B = 6.81; 95% CI: 4.68-8.93). AROP was associated with earlier PMA at retreatment (B = -7.72; 95% CI, -9.36 to -6.10). CONCLUSION: In this study, early retreatment was low (8.8%), with most eyes initially treated with laser (21.5%) rather than bevacizumab (1.7%). Aggressive ROP was associated with earlier retreatment, highlighting its role as a marker of more severe disease. Compared to laser, bevacizumab was associated with lower overall and early retreatment, and delayed need for additional intervention when necessary. All retreatments occurred in micro- or nano-premature infants, suggesting that medium-to-low risk infants may require less strict post-treatment monitoring.

Humans↗

PubMed2013

Delivery of recombinant adeno-associated virus vectors to rat diaphragm muscle via direct intramuscular injection.

The diaphragm is the most important inspiratory muscle in all mammals, and ventilatory insufficiency caused by diaphragm dysfunction is the leading cause of morbidity and mortality in many genetic and acquired diseases affecting skeletal muscle. Currently, pharmacological inhibitors, genetically modified animals, and invasive procedures are used to study disorders affecting the diaphragm. However, these methodologies can be problematic because of off-target drug effects and the possible nonphysiological consequences of lifelong genetic alterations. Therefore, alternative methods to study this important respiratory muscle are needed. To resolve this, we have developed a methodology to deliver recombinant adeno-associated virus (rAAV) vectors to the rat diaphragm via direct intramuscular injection. We hypothesized that by direct injection of rAAV into the muscle we can selectively target the diaphragm and establish a novel experimental method for studying signaling pathways and also provide a strategy for effectively using rAAV to protect the diaphragm against disease. This report describes the methods and evidence to support the use of rAAV as a therapeutic intervention to study rat diaphragm biology during conditions that promote diaphragm dysfunction.

Animals↗

PubMed2026

Effects of single-injection vs. continuous brachial plexus blocks for shoulder surgeries on patient-reported outcomes: a systematic review and meta-analysis with trial sequential analysis of randomised controlled trials.

INTRODUCTION: Single-injection and continuous brachial plexus block techniques are used widely for postoperative analgesia in patients undergoing shoulder surgery. Although patient-reported outcomes are described in individual studies, their effects have not been synthesised comprehensively using a patient-centred framework. We sought to compare the effects of single-injection vs. continuous brachial plexus block techniques on patient-reported outcomes in adult patients following elective shoulder surgery. METHODS: Databases were searched from inception to October 2025 and randomised controlled trials reporting patient-reported outcomes were included. Co-primary outcomes were postoperative patient-reported pain intensity at rest and during movement at 12 h, 24 h and 48 h post-surgery. Secondary outcomes included nausea and vomiting; sleep quality; patient satisfaction; opioid requests; and functional scores. Random-effects meta-analysis and trial sequential analysis were performed, with risk of bias and quality of patient-reported outcome reporting assessed. RESULTS: Twenty randomised controlled trials that included 1198 patients were analysed. Continuous brachial plexus blocks were associated with lower pain at rest at 12 h, 24 h and 48 h, with mean differences (MD) of -1.96 (95%CI -2.81 to -1.11, p < 0.001), -1.66 (95%CI -2.27 to -1.05, p < 0.001) and - 1.18 (95%CI -1.84 to -0.53, p < 0.001), respectively. Pain on movement could only be pooled at 24 h and 48 h and showed MD -2.04 (95%CI -4.26-0.19, p = 0.07) and - 1.30 (95%CI -3.67-1.07, p = 0.28) respectively. The co-primary outcomes approached or exceeded the predefined minimal clinically important difference for pain scores after shoulder surgery, in favour of continuous techniques. DISCUSSION: Continuous brachial plexus blocks are associated with better pain at rest and other patient-centred outcomes following shoulder surgery, while effects on dynamic pain and long-term functional recovery remain uncertain.

Humans↗

PubMed2026

Pharmacokinetics of injectable favipiravir: phase I, randomized, double-blind, placebo-controlled study in healthy East Asian subjects.

Favipiravir, an oral antiviral medication, has been approved in Japan for the treatment of patients with novel or re-emerging influenza and severe fever with thrombocytopenia syndrome (SFTS). Randomized, double-blind, placebo-controlled trials were conducted in an East Asian population to characterize the pharmacokinetics and tolerability of an injectable favipiravir formulation. In the single-ascending dose trial, subjects received a single intravenous (IV) dose of 300-2,400 mg of favipiravir. In the multiple dose trial, 1,800 mg was administered twice daily on the first day, followed by 800 mg twice daily for the subsequent 10 days, which is the approved tablet dose for SFTS in Japan. This multiple-dose trial was divided into a cohort receiving intravenous administration throughout the treatment period (IV cohort) and a cohort switching to oral administration from Day 6 (Switching cohort). After a single administration of ≤2,400 mg, the pharmacokinetic parameters increased in a dose-dependent manner but showed slight deviation from linearity. The geometric mean maximum plasma concentration following a single 2,400 mg dose was 126 (range: 110 to 138) μg/mL. In the IV cohort, the trough (at 12 h post-dose) plasma concentrations were maintained at approximately 85 μg/mL after Day 2. These concentrations were approximately 20% higher than those achieved with the same oral doses. In the Switching cohort, these concentrations were maintained throughout the treatment. No serious adverse events were observed. These findings support advancing injectable favipiravir into clinical evaluation.CLINICAL TRIALSThis study is registered with the Japan Registry of Clinical Trials as jRCT2071210042 and jRCT2071210126.

Humans↗

PubMed2025

The early injected genomic region determines sensitivity to Type I restriction-modification defence against Autographiviridae phages.

Bacteriophages must evade bacterial defences to establish successful infections. Type I restriction-modification (RM) systems recognize specific DNA motifs and degrade unmethylated foreign DNA, restricting phage replication. In this study, we detected that Marinomonas mediterranea MMB-2 uses a Type I RM system (Mme2I) to protect against several new phages in the Murciavirus genus within the Autographiviridae family. Whole-genome sequencing and methylation analysis revealed a DNA sequence motif methylated in M. mediterranea MMB-2, which is also present in the phages. Phages lacking the motif within the leading, first injected, region of their genomes, either natural isolates or escape mutants of sensitive phages, successfully infect M. mediterranea MMB-2, despite the presence of the recognition motif elsewhere in their genomes. These results highlight the importance of considering RM motif locations when predicting avoidance of restriction sites as escape mechanisms from RM systems. Additionally, our findings indicate an important role for RM systems in specifically influencing the organization of the leading injected regions of phage genomes, which are highly variable and often encode diverse anti-defence systems.

Genome, Viral↗

PubMed2026

Invasive Wickerhamomyces anomalus Infections among Injecting Drug Users, France, 2012-20241.

Wickerhamomyces anomalus is a yeast rarely involved in human invasive fungal diseases (IFD). We retrospectively analyzed 44 episodes of W. anomalus IFD in France during 2012-2024. Injecting drug use (IDU) was the main risk factor among 26/35 (74.3%) incident cases. Most infections were community acquired; overall 3-month mortality rate was 1/30 (3.3%). Short tandem repeat (STR) genotyping and whole-genome sequencing analyses revealed substantial genetic diversity among isolates. However, 1 STR genotype was shared by 2 IDU patients, suggesting common exposure. In addition, 1 isolate obtained from a cotton filter used for drug preparation was identical by STR genotyping to the bloodstream isolate from the same patient, indicating direct inoculation via contaminated material or poor injection practices. Our findings highlight the increased risk for W. anomalus IFD among IDU patients and emphasize the importance of targeted preventive measures within that population.

Humans↗

PubMed2014

A needleless liquid jet injection delivery method for cardiac gene therapy: a comparative evaluation versus standard routes of delivery reveals enhanced therapeutic retention and cardiac specific gene expression.

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n = 24 rats), retention of dye was evaluated 10 min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52 ± 4] % and LVIC-OCCL [58 ± 3] % groups p < 0.05 compared with IM [31 ± 8] % and LVIC [35 ± 4] %. In the second (n = 16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6 weeks post-delivery, a similar trend was found with liquid jet [54 ± 5] % and LVIC-OCCL [60 ± 8] % featuring more LV expression as compared with IM [30 ± 9] % and LVIC [23 ± 9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.

Animals↗