Route Of Administration Research Articles

Cubosomes in non-oral drug delivery: Advancing precision therapeutics from bench to bedside.

Cystic fibrosis (CF) leads to chronic airway obstruction, inflammation, and infection, resulting in pulmonary exacerbations (PEx) that negatively impact lung function, quality of life, and mortality. The introduction of highly effective CFTR modulator therapy (HEMT) has improved outcomes in people with CF (pwCF), reducing the frequency of PEx and antibiotics. Using data from a single-center retrospective review and the Pediatric Health Information System (PHIS) database, this study evaluates the impact of HEMT on antibiotic utilization in people with CF (pwCF). A single-center, retrospective analysis was conducted comparing antibiotic use in the pre-ETI (2017-2019) and post-ETI (2020-2022) periods. Inclusion criteria were pwCF receiving care at for at least one year in both periods. Data on antibiotic agent, duration, and route of administration were collected. Additionally, a multicenter, retrospective study using the PHIS database was performed between January 2015 through June 2023, analyzing antibiotic utilization in hospitalized pwCF across multiple pediatric hospitals. Metrics included days of therapy (DOT) per 1000 patient days and length of stay. In the single-center analysis, there was a 36.2 % decrease in IV and 19.5% decrease in PO antibiotic use in the post-ETI period, with no change in treatment duration. In the PHIS analysis, antibiotic utilization decreased from the pre-ETI to post-ETI period, with reductions in Anti-PsA and Anti-MRSA agents and a decrease in length of stay. The median DOT per 1000 patient days decreased from 2257 (IQR: 1950, 2417) to 1710 (IQRL 1371, 1909) (p<0.001). The introduction of HEMT has led to reduction in antibiotic utilization for PEx among pwCF, at a single center and across multiple institutions. This decrease in antibiotic use highlights the potential for antibiotic stewardship programs to reassess and optimize antibiotic management in pwCF. Additional research is needed to determine the optimal duration and choice of antibiotics in the context of HEMT, with the goal of minimizing antibiotic exposure and associated risks.

Characterization of Women's Health Benefit Claims Made on Cannabis e-commerce Platforms: A Retrospective Market Surveillance Study.

This review integrates the biology and clinical translation of hydrogen sulfide (H2S) in balneology. It frames H2S as a gasotransmitters with dual chemical and biological actions and summarizes the H2S/HS− equilibrium as a function of pH, temperature, and oxygenation, which governs bioaccessibility in sulfurous waters. Endogenous and exogenous sources, transport, and mitochondrial catabolism are outlined, together with core cellular mechanisms: protein persulfidation; activation of Nrf2/ARE; modulation of NF-κB; regulation of ion channels; and engagement of PI3K/Akt, MAPK/ERK, and Wnt pathways, plus epigenetic interactions with HDACs and sirtuins. Preclinical and clinical evidence in dermatology, musculoskeletal disease, and respiratory care is synthesized, alongside metabolic, cardiovascular, gastrointestinal, and renal effects. Technical aspects that preserve the bioactive fraction of H2S while meeting environmental safety limits are highlighted. Routes of administration (bathing, peloids, inhalation, and drinking cures) and key operational parameters are described. Overall, the review links physicochemical and molecular foundations with clinical indications for sulfurous waters and derivatives and identifies opportunities for research and development in H2S donors and thermal cosmetics without extrapolating beyond the available data.

Glioblastoma multiforme (GBM) is highly lethal brain tumor with limited benefit from standard treatment, such as surgery, radiotherapy, and chemotherapy. Its location within the central nervous system, together with the blood-brain barrier, and immunosuppressive niche restricts access and efficacy of therapies. This review examines the current progress of the chimeric antigen receptor (CAR) T cell therapy in GBM, emphasizing therapeutically significant target antigens, delivery strategy and innovations designed to improve safety and persistence. Evidence from preclinical research and early phase clinical trials was assessed to identify key antigen, evaluate routes of administration, and summarize next-generation engineering concepts. Clinical experiences demonstrate that locoregional delivery can enhance tumor penetration compared with systemic infusion. Moreover, CAR-T cells engineered to recognize epidermal growth factor receptor variant III, interleukin-13 receptor subunit alpha-2, human epidermal growth factor receptor 2, or disialoganglioside have shown biological activity in GBM. Emerging platforms, such as dual-target CARs, synNotch, and cytokine-releasing "armored" T cells, develop specificity and overcome barriers posed by tumor heterogeneity and immune suppression. CAR-T therapy in GBM has moved beyond proof-of-concept, with encouraging but preliminary signals of efficacy. Future success will require multi-target approaches, integration with modulators of tumor microenvironment, and optimized delivery systems to achieve durable clinical benefit.

The number older patients with cancer who are terminally ill is expected to increase with global population aging. However, reports on the actual use of opioids for pain relief in patients aged ≥ 90years with cancer at the end of life are limited. To investigate opioid use in older patients with cancer aged ≥ 90years who died in a palliative care unit. Patients with cancer who died in the palliative care unit between August 2020 to August 2024 and were aged ≥ 90years were included. We analyzed their data on opioid use, including opioid type and route of administration, and morphine equivalent daily dose (MEDD), at the time of death. Ninety-one patients with cancer were included in the study. Their median age was 92.0years (interquartile range [IQR] 91.0-93.0). Seventy-six patients (83.5%) were administered opioids at the time of death, and hydromorphone delivered via continuous subcutaneous injection was the most common (41 patients). The median MEDD at the time of death for the 76 patients was 19.6mg/day (IQR 12-42). Four patients were administered high doses of opioids (MEDD of > 120mg/day) at the time of death. Of the patients aged ≥ 90years with cancer who were terminally ill, more than 80% had used opioids. Their median MEDD tended to be low at 19.6mg/day. Future studies are required to help appropriately use opioids for patients aged ≥ 90years with cancer.

Stroke, stemming from either hemorrhagic or ischemic cerebrovascular events, remains a leading cause of mortality and morbidity worldwide. While there is currently no effective medical therapy for hemorrhagic strokes, ischemic strokes, constituting the majority of cases, benefit from limited curative interventions, namely thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy. However, these options are constrained by narrow post-stroke therapeutic windows. Cerebral edema, characterized by blood-brain barrier disruption and endothelial dysfunction, is a major contributor to stroke-related mortality. Endothelial progenitor cells, released by bone marrow in response to ischemic injury, have in recent years emerged as key players in vascular repair, blood- brain barrier restoration, angiogenesis and vasculogenesis. Despite accumulating evidence, the definition and characterization of endothelial progenitor cells remain inconsistent which complicates their development as so-called efficacious novel therapeutics. Concomitant targeting of markers for stemness, immaturity, and endothelial cell maturity, including CD34, CD133, and KDR, helps delineate true endothelial progenitor cells from hematopoietic cells. The synthesis, recruitment, and functionality of endothelial progenitor cells are regulated by a variety of signaling pathways, notably stromal cell-derived factor-1α/chemokine receptor 4, vascular endothelial growth factor, endothelial nitric oxide synthase/nitric oxide, and Notch1/Jagged1. These processes are influenced by several physiopathological factors such as aging, inflammation, and ischemic injury. In translational studies, endothelial progenitor cells demonstrate robust potential in attenuating infarct size, inflammation, and apoptosis while inducing angiogenesis and improving motor and cognitive functions. Although autologous and allogeneic endothelial progenitor cell-based therapies have shown safety and some efficacy in early-phase clinical trials, results remain inconclusive, and large-scale studies are required to confirm or dismiss the current findings. Issues regarding the number, route, and frequency of endothelial progenitor cell administration also need addressing. For instance, routes of endothelial progenitor cell administration present varying degrees of invasiveness, efficacy, and feasibility. Emerging research highlights the endothelial progenitor cell secretome, composed of several growth factors, cytokines, and extracellular vesicles, as a cell-free therapeutic option. Secretome-based therapeutic interventions avoid many safety and logistical challenges of cell therapies while offering comparable regenerative benefits in preclinical stroke models. Temporal dynamics in secretome composition, especially those in post-stroke pro-angiogenic and anti-angiogenic factor bioavailability, indicate the requirement for precise therapeutic timing. Clinical studies also suggest ischemic injury itself, rather than comorbid risk factors, as the principal driver of secretome alterations such as tumor necrosis factor-α upregulation. In conclusion, endothelial progenitor cells and their secretome hold significant promise as novel therapeutics for stroke. However, unresolved issues surrounding cell characterization, delivery methods, optimal time of administration, and safety must be addressed through rigorous translational and clinical studies before their use in clinical settings.

Products containing semi-synthetic 7-hydroxymitragynine (7-OH), a potent mu-opioid receptor (MOR) agonist, have proliferated in the United States. In kratom leaf, trace amounts of 7-OH are formed by spontaneous oxidization of kratom's primary alkaloid, mitragynine. Hepatic and intestinal microsomes also convert mitragynine to 7-OH. Some products have sublingual and nasal administration routes that circumvent hepatic first-pass metabolism, increasing bioavailability and accelerating effect onset, features that increase risk. We report a patient who developed substance use disorder (SUD) related to a 7-OH sublingual film. A 35-year-old man with supraventricular tachycardia and profound urinary retention described using "Hydroxie," a novel, semi-synthetic 7-OH product. He currently vaped cannabis and nicotine, and reported injection heroin addiction a decade prior. He used kratom 6 months before trying Hydroxie, which began 10 weeks before hospitalization. Within days of initiating use, he noticed tolerance; within 2 weeks, he was using one film every 1-2 hours. The patient met criteria for severe SUD related to Hydroxie and was inducted onto buprenorphine. Analysis confirmed 7-OH in the product and blood. The MOR selectivity and brief duration of action of some 7-OH formulations support our observation that repeated use may lead to physical dependence. Standard laboratory testing can detect mitragynine but not 7-OH due to its relatively shorter half-life, an issue that may confuse semi-synthetic 7-OH use with kratom. Novel 7-OH products are not kratom. The potency of 7-OH places unwitting consumers who may believe they are using kratom, not a partial MOR agonist, at risk.

Background: Cardiac surgery can often be associated with significant postoperative bleeding. This complication results from a combination of surgical trauma, cardiopulmonary bypass (CPB)-induced coagulopathy, and enhanced fibrinolytic activity, all of which contribute to increased morbidity and mortality. Tranexamic acid (TXA) can be administered as an antifibrinolytic agent to control bleeding. While intravenous TXA is effective, there are concerns about its neurotoxicity by ability to cross the blood-brain barrier. Objective: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of topical versus intravenous TXA in patients undergoing cardiac surgery. Methods: PubMed, Embase, and Cochrane were searched from inception to March 2025 for randomized controlled trials (RCTs) comparing topical versus intravenous TXA in cardiac surgery patients. Primary outcomes included postoperative blood loss and seizure incidence. Secondary outcomes included blood product transfusion requirements, thromboembolic events, reoperation, all-cause mortality, and intensive care unit (ICU) stay. Data were pooled using a random effects model with 95% confidence intervals (CI). Risk ratios (RR) were calculated for dichotomous outcomes, and standardized mean differences (SMD) and incidence rate ratios (IRR) were calculated for continuous outcomes. Results: Of 1430 potential articles, seven RCTs comprising 3617 patients met the inclusion criteria. No significant difference in postoperative blood loss was observed between the intravenous and topical administration routes (SMD -0.00 ml; 95% CI -0.24, 0.23; p=0.98; I2=0%). Topical TXA significantly reduced seizure (RR 0.34; 95% CI 0.12, 0.92; p=0.03; I2=0%), with an absolute risk reduction of 0.57% and a number needed to treat 175. No significant differences were found in blood product transfusion requirements (IRR 1.10; 95% CI 0.73, 1.65), thromboembolic events (RR 1.00; 95% CI 0.38, 2.69), reoperation (RR 0.94; 95% CI 0.21, 4.22), mortality (RR 1.18; 95% CI 0.53, 2.62), or ICU stay (SMD -0.02 days; 95% CI -0.27, 0.23). GRADE assessments rated evidence as moderate for seizures and very low for blood loss. Conclusions: Topical TXA provides similar hemostatic efficacy to intravenous TXA in cardiac surgery while slightly reducing the risk of postoperative seizures. Future research should focus on investigating specific patient subgroups who might derive maximal benefit from this administration route.

Access to evidence-based treatment for opioid use disorder remains limited, particularly for individuals who have not responded to oral opioid agonist treatment (OAT). A community pharmacy-based model of injectable OAT (iOAT) was piloted in Vancouver, Canada from March 2017 to December 2018. This brief report describes the program structure, participant sociodemographics, reported outcomes, and strengths and areas for improvement of the program. A retrospective review of cross-sectional, interviewer-led questionnaire data from participants who accessed iOAT at the pharmacy site (n = 176) and provided informed consent was conducted. Outcomes include participant-reported changes in symptomatology, function and satisfaction, analysed through descriptive statistics. Open-ended responses were analysed using content analysis to identify strengths and areas for improvement of the program. Fifty-one participants (29%) completed the questionnaire, and most had multiple previous overdoses and trials of oral OAT. The most commonly reported outcomes were reduction in illicit opioid use (76%), opioid cravings (45%) and illicit substance use (45%). Participants identified key strengths of the program as positive experiences with staff and efficiency of the pharmacy model including flexible dosing time and the ability to pick up other medications at the same time. Suggested improvements focused on medication options (e.g., access to diacetylmorphine, alternate routes of administration), expanded hours and flexibility, additional support services, and increased capacity and space. Community pharmacy-based iOAT represents a novel strategy to expand access to evidence-based opioid use disorder treatment among individuals who inject opioids and have not responded to or do not prefer oral OAT.

Introduction: Friedreich’s ataxia (FA) is an autosomal recessive neurodegenerative disorder caused by variants in the frataxin ( FXN) gene, leading to mitochondrial dysfunction and impaired energy metabolism. Cardiomyopathy is the leading cause of death in FA and represents a critical therapeutic target alongside progressive neurological decline. Hypothesis: AAV-mediated gene replacement therapy can safely restore FXN expression in disease-relevant tissues and modify the course of FA. Approach: A gene therapy candidate (SGT-212) utilizing an AAVhu68 capsid and a ubiquitous promoter to express human FXN was developed. SGT-212 was administered using a dual route of administration via intravenous (IV) and intraparenchymal dentate nucleus (IDN) infusions. Cardiac and neurologic efficacy was evaluated in conditional Fxn knockout mouse models (cKO and nKO, respectively). Long-term safety and biodistribution were assessed in non-human primates (NHPs). Results: In Fxn cKO mice, a single IV dose led to dose-dependent improvements in cardiac function (assessed by echocardiography), histopathology, and survival. FXN protein levels and the number of FXN+ cardiomyocytes increased in a dose-dependent manner. In Fxn nKO mice, a single IV administration improved sensorimotor function (Neuroscore, RotaRod), extended lifespan, and restored FXN expression in dorsal root ganglia. In NHPs, the gene therapy was administered via dual IV/IDN routes and monitored for 12 months. SGT-212 treatment was well tolerated across dose levels with no adverse findings. Robust expression of FXN was observed in key target tissues, including myocardium, DRG, and dentate nuclei. Conclusions: These nonclinical studies demonstrate that a one-time administration of SGT-212 can restore FXN expression in disease-relevant tissues, improve cardiac and neurologic phenotypes in mouse models, and is well tolerated in NHPs. These findings support advancement to a Phase 1b clinical trial using combined IV/IDN administration.

Menopause is characterized by significant physiological changes, including cardiovascular and hormonal alterations. Estrogen therapy is a critical intervention for managing menopausal symptoms and preventing long-term complications. Understanding the differences between the estrogen therapy administration routes is essential for optimizing treatment strategies. This study aimed to compare oral and transdermal routes of estrogen therapy among postmenopausal women and assess changes from baseline in key cardiovascular and lipid parameters, including systolic and diastolic blood pressure, heart rate, total cholesterol, low and high-density lipoprotein, and triglyceride levels. PubMed, Scopus, Web of Science, and ClinicalTrials. gov were searched for randomized clinical trials comparing oral and transdermal estrogen therapy in postmenopausal women. Pooled mean differences (MDs) with 95% CIs were estimated using a random effects model. Statistical analyses were performed using R version 4.3.2. Eight randomized clinical trials, with a total of 885 participants, were included. Of these participants, 453 (51.2%) received oral estrogen therapy. Participants receiving oral estrogen therapy had a higher mean change in high-density lipoprotein levels (MD=3.48mg/dL; 95% CI: 1.54-5.43; P<0.01) coupled with a significant rise in mean triglyceride levels (MD=19.82; 95% CI: 6.85-32.78; P<0.01), compared with participants receiving transdermal estrogen therapy. There were no significant differences in the mean changes from baseline in the systolic and diastolic blood pressure, heart rate, total cholesterol, and low-density lipoprotein levels. Compared with transdermal estrogen therapy, oral estrogen therapy was associated with a greater increase in high-density lipoprotein levels in postmenopausal women. However, this was associated with a greater increase in the triglyceride levels. This suggests that the choice of estrogen therapy route should be individualized, considering the patients' baseline hormonal and metabolic parameters, particularly lipid profiles.

People receiving treatment for advanced cancer invest substantial portions of their survival time receiving healthcare, labelled the 'time toxicity' of treatment. Although qualitative research has examined the impact of time burden on patients and their caregivers, its influence on treatment decision-making is unclear. Our objective was to explore treatment decision-making with patients with advanced gastrointestinal cancer, their caregivers, and oncologists, and unmask the role of time burden in those decisions. The objective was to inform the design of a subsequent discrete-choice experiment (DCE) investigating the importance of time burden in treatment decision-making. A two-step process was used. Factors relevant to treatment decision-making were discussed as part of semi-structured interviews. Responses were analysed using thematic analysis with a focus on measurable themes relevant to the development of candidate attributes for a DCE. Second, we reviewed stated-preferences studies in the field of treatment decision-making in cancer and compared the results with the candidate attributes identified from interviews. Interviews with 45 participants (20 patients, 10 caregivers,15 gastrointestinal oncologists; 53% metropolitan) revealed 4 themes and 6 candidate attributes: expected survival benefit of treatment, impact of physical side effects, effect on day-to-day functioning, route of administration, healthcare contact days, and planned length of the treatment course. Review of 45 published studies yielded no additional attributes. This study identified six candidate attributes for a forthcoming DCE on time burden in advanced cancer care. These findings support growing efforts to quantify and address time toxicity in cancer treatment decision-making.

Introduction: Dexamethasone is widely used to minimize postoperative pain, swelling, and trismus following third molar surgery; however, the optimal route of administration remains debated. Objective: To compare the clinical effectiveness of submucosal, intramuscular, and intravenous administration of dexamethasone in reducing postoperative complications after mandibular third molar extraction. Methods: This randomized controlled study was conducted at a private hospital in Multan from January to June 2024 after obtaining IRB approval. Thirty patients indicated for surgical removal of impacted mandibular third molars were randomly assigned to two groups (n = 15). Group A received 8 mg dexamethasone via the submucosal route at the surgical site, while Group B received the same dose through the systemic route (intramuscular or intravenous). Postoperative pain (VAS), facial swelling (linear measurement), and mouth opening (interincisal distance) were evaluated at 24 hours, 48 hours, and 7 days postoperatively. Data were analyzed using SPSS 26 with significance set at p &lt; 0.05. Results: The mean age of participants was 26.8 ± 5.7 years, with an equal gender distribution. Both groups showed statistically significant reductions in postoperative pain, swelling, and trismus (p &lt; 0.05). The submucosal group exhibited superior outcomes in pain and facial swelling reduction, particularly within the first 48 hours, though differences were not statistically significant. Conclusion: All routes of dexamethasone administration effectively reduced postoperative discomfort following third molar surgery. The submucosal route provided a slight clinical advantage, likely due to its localized anti-inflammatory effect, making it a practical and minimally invasive alternative for routine use.

Feline infectious peritonitis (FIP) is a severe systemic viral disease affecting domestic and wild felines, characterized by a high mortality rate and varied clinical manifestations. The exacerbated immune response to feline coronavirus infection results in a complex clinical presentation that is difficult to treat. This literature review explores the therapeutic potential of antivirals such as GC376, GS-441524, and Mutian Xraphconn in the treatment of FIP, considering different administration routes and dosages. It also discusses the challenges associated with the illegal commercialization of these drugs and their use without veterinary guidance, which may compromise animal health and therapeutic efficacy. The promising results found open new perspectives for the treatment of FIP, increasing the life expectancy of affected felines.

Effective postoperative pain management after knee and hip arthroplasties offers substantial clinical benefits; however, clinicians are faced with numerous analgesic options, and therapeutic decision-making is hindered by limited comparative evidence on the relative efficacy and safety of these treatments. Previous studies were limited to pairwise comparisons and could not integrate the full spectrum of available treatments or were focused on specific routes of administration that overlooked variability among individual analgesics within and across these routes. Therefore, an analysis comparing all analgesics that have been evaluated in randomized trials for use after knee and hip arthroplasty is warranted. The purpose of this study was to perform a network meta-analysis that evaluates the relative efficacy and safety of currently available analgesics administered across different routes to determine which provide the greatest benefit in terms of (1) reducing postoperative pain, (2) improving function, and (3) minimizing adverse events. Given the distinct anatomic and biomechanical features of hips and knees and their differing postoperative pain trajectories, we conducted separate analyses for each procedure. For this network meta-analysis, we systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and reference lists from inception to July 6, 2023, with an update to July 13, 2025. We included RCTs that compared specific analgesics with placebo or other analgesics administered after knee or hip arthroplasty. Studies were eligible if they enrolled at least 10 participants per arm, administered analgesics postoperatively, and reported outcomes related to pain, function, or adverse events. We excluded secondary analyses, abstracts only, and trials focused on chronic pain starting 2 months or more postoperatively. Of the 49,400 studies retrieved, a total of 47,465 were excluded after duplication and title and abstract screening, leaving 1935 articles for full-text review. From these, 211 eligible RCTs were included, comprising 22,972 patients (median [range] age 67 years [43 to 80 years]; female proportion 24% to 98%) and encompassing 155 distinct analgesic regimens across five administration routes (intravenous, nerve-block, local infiltration analgesia, oral, and topical) and their combinations. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0 (79% were rated as having "some concerns" and 21% as "high risk"), and the confidence of the evidence was evaluated using The Confidence in Network Meta-Analysis framework, with ratings from moderate to very low. Pain was the primary outcome, with the focus on pain at 24 hours postoperatively; pain at 48 hours was included as a secondary outcome. We prioritized pain during movement over pain at rest, as it better reflects functional recovery. When studies reported multiple pain scales, data were extracted based on a predefined hierarchy: (1) VAS, (2) verbal rating scale, and (3) numeric rating scale. We prespecified a minimum clinically important difference (MCID) of -1.8 cm on a 10-cm VAS for pain, based on a previously published study. Function and adverse events were secondary outcomes. For data synthesis, we employed a Bayesian network meta-analysis model and used a random walk model to account for the temporal structure of pain outcomes. Heterogeneity was quantified using the between-trial variance (τ2) and a random-effects model was applied, given the observed small to moderate heterogeneity. For pain management after knee arthroplasty, compared with placebo, local levobupivacaine was the most effective analgesic (mean difference -4.9 cm [95% credible interval (CrI) -7.5 to -2.2]; surface under the cumulative ranking [SUCRA] 99%), exceeding the prespecified MCID of -1.8 cm with an 85% probability. After hip arthroplasty, compared with placebo, local ropivacaine combined with ketorolac and adrenaline was most effective (mean difference -3.5 cm [95% CrI -4.9 to -2.0]; SUCRA 73%), with a 99% probability of achieving the MCID. For postoperative functional improvement after knee arthroplasty, compared with placebo, nerve-block levobupivacaine combined with dexmedetomidine (used under monitored conditions) showed the greatest benefit (mean difference 63° [95% CrI 35° to 91°]; SUCRA 88%), with a higher degree value meaning a greater ROM. Regarding safety, compared with placebo, intravenous tramadol combined with metoclopramide reduced the risk of nausea (OR 0.1 [95% CrI 0.0 to 0.7]), whereas nerve-block bupivacaine combined with sufentanil increased the risk (OR 6 [95% CrI 1 to 31]). No other differences were observed across interventions for the remaining adverse events. For knee arthroplasty, local levobupivacaine appeared to be the most effective option. For hip arthroplasty, local ropivacaine combined with ketorolac and adrenaline appeared the best. In terms of functional improvement, nerve-block levobupivacaine combined with dexmedetomidine (used under monitored conditions) appeared the most effective after knee arthroplasty. Although most interventions had similar safety profiles, intravenous tramadol combined with metoclopramide decreased the risk of nausea. Clinicians should integrate these results with known safety profiles and patient-specific factors to guide individualized postoperative pain management after knee and hip arthroplasties. Level I, therapeutic study.

PurposeTo analyze the clinical and volumetric responses to different corticosteroid administration methods for IgG4-related ophthalmic disease (IgG4-ROD).MethodsThe medical records of patients with bilateral lacrimal gland (LG) enlargement diagnosed with IgG4-ROD through unilateral LG biopsy between January 2011 and January 2022 were retrospectively reviewed. Clinical signs and the non-biopsied LG volume across three administration routes were compared: oral prednisolone (Pd), intravenous (IV) methylprednisolone (methylPd), and local triamcinolone (TA) injection. Radiological relapse was defined as the first instance of failure to satisfy the radiological response criteria, i.e., a post-treatment volume of <1.0 cm3 or a post-treatment to pre-treatment volume ratio of <35%.ResultsAmong the 28 patients, eight, ten, and ten received oral Pd, IV methylPd, and local TA injection, respectively. No significant differences were observed between the groups in terms of the baseline characteristics. Ophthalmic adverse effects were not observed in any patient. Kaplan–Meier survival analysis revealed that the 2-year radiological relapse-free survival in the IV methylPd group (80.0%) was higher than that in the oral Pd group (37.5%, p = 0.036) but comparable with that in the local TA group (100.0%, p = 0.886). The median post-treatment to pre-treatment volume ratio in the IV methylPd group (35.4%) was significantly lower than that in the oral Pd group (75.0%, p = 0.042) but comparable with that in the local TA injection group (38.5%, p = 0.321) one year after treatment.ConclusionCompared with oral Pd, IV methylPd yielded better and more sustained radiological responses in patients with LG-involving IgG4-ROD. Local TA injection was also an effective alternative treatment option.

Objective: To assess the clinical effectiveness of postauricular injection of methylprednisolone in the treatment of individuals with sudden deafness (SD) and to identify influencing factors. Methodology: In this retrospective study, we included clinical data of 106 eligible patients with SD who were hospitalized in the Department of Otorhinolaryngology of Nanjing Integrated Traditional Chinese and Western Medicine Hospital from October 2023 to October 2024. According to the different routes of administration of methylprednisolone, patients were divided into an observation (OBP) (n=54) and a control (CGP) (n=52) group. The CGP group received routine treatment of intravenous methylprednisolone combined with conventional medication and the OBP group received retroauricular injection of methylprednisolone in addition to the routine treatment. Results: Patients in the OBP group reported a considerably better overall efficacy (87.0% vs. 67.3%) and tinnitus (74.1% vs. 60.7%) than the CGP group. The vertigo disappearance time (5.19±1.29 d vs 5.35±1.06 d) and ear fullness sensation halo disappearance time (5.73±1.21 d vs 6.16±1.27 d) in the OBP group were considerably shorter than in the CGP group (P&lt;0.05). Levels of Homocysteine (HCY), High Shear Blood Viscosity (HBV), Low Shear Blood Viscosity (LBV), Plasma Viscosity (PV) and Hematocrit (HCT) in both groups decreased significantly after therapy and were substantially lower in the OBP group compared to the CGP group (p &lt; 0.05). Conclusion: Compared to conventional treatment, postauricular injection of methylprednisolone can enhance the treatment efficacy of SD and is associated with improvement in accompanying symptoms. Postauricular injection of methylprednisolone can more effectively reduce HCY, HBV, LBV, PV and HCT levels in SD patients.

Local anesthetics are widely utilized by anesthesiologists and physicians to manage pain effectively. Local anesthetic systemic toxicity (LAST) is an infrequent occurrence that can lead to fatal outcomes. Although local anesthetics are commonly employed by non-anesthesiologists, a comprehensive analysis of case reports detailing LAST incidents caused by physicians other than anesthesiologists remains unknown. This review was performed to analyze case reports of LAST induced by non-anesthesiologists. Case reports regarding LAST induced by non-anesthesiologists were retrieved from PubMed using the following keywords: "bupivacaine toxicity," "levobupivacaine toxicity," "lidocaine toxicity," "ropivacaine toxicity," "tetracaine toxicity," and "prilocaine toxicity" until December 31, 2023. A total of 53 case reports involving 59 patients were identified. The distribution of local anesthetic use linked to LAST was as follows: lidocaine alone (59.33%), lidocaine plus prilocaine (11.86%), and bupivacaine or ropivacaine alone (10.17%). The predominant presumed cause of LAST was an overdose of local anesthetics (67.80% of all patients; lidocaine: 75% of local anesthetic overdoses), with or without accompanying patient's risk factors. The primary routes of administration resulting in LAST were subcutaneous infiltration (38.98%) and topical application (35.59%). Common symptoms associated with LAST included central nervous system symptoms alone (50.85%) such as seizures, and combined central nervous and cardiovascular system symptoms (27.12%). Local anesthetics implicated in LAST were predominantly used for pain management during various procedures (71.19%) and for post-operative analgesia (11.86%). Of the patients experiencing LAST, 28.81% received lipid emulsion treatment in addition to supportive measures, achieving a full recovery rate of 100%. Conversely, 71.19% of the patients with LAST received only supportive treatment, leading to a full recovery rate of 73.81%. These findings suggest that subcutaneous infiltration or topical administration of lidocaine overdoses by non-anesthesiologists, particularly in patients with or without risk factors for LAST, significantly contributes to LAST. Preventive strategies, including education on maximum recommended doses of local anesthetics, identification of patient risk factors for LAST, utilization of ultrasound-guided nerve blocks, and ensuring the availability of lipid emulsion treatment, should be emphasized. Lipid emulsions ought to be readily accessible for the management of LAST in all locations where local anesthetics are used.

Heart failure (HF) modeling requires standardized protocols to ensure translational relevance. Despite the widespread use of isoproterenol (ISO)—a β-adrenergic agonist—in HF modeling, methodological inconsistencies in dosing and administration routes limit reproducibility. This study evaluated the effects of subcutaneous (SC) and intraperitoneal (IP) administration of ISO at two literature-established doses (5 and 60 mg/kg/day for 14 days) on cardiac remodeling in C57BL/6J mice, aiming to identify the optimal protocol for HF modeling. Using a factorial design, male C57BL/6J mice aged 6–8 weeks were divided into six cohorts: (1) SC saline control, (2) IP saline control, (3) SC 5 mg/kg ISO, (4) IP 5 mg/kg ISO, (5) SC 60 mg/kg ISO, and (6) IP 60 mg/kg ISO, with daily administration for 14 days. High-dose ISO (60 mg/kg/day) induced a 25% mortality rate in both SC and IP cohorts, yet IP administration exhibited marked inter-individual variability, undermining model reliability. Echocardiography revealed SC 5 mg/kg group induced stable systolic dysfunction accompanied by left ventricular dilation, while maintaining 100% survival. This cohort also displayed significantly elevated hypertrophy indices. Histopathological quantification suggested that SC 60 mg/kg induced extensive fibrosis. All ISO-treated groups showed upregulated myocardial hypertrophy markers and approximately 2-fold elevation in serum NT-proBNP levels. In summary, SC 5 mg/kg/day regimen not only ensures reliable phenotype induction but also reduces animal attrition, offering a robust platform for investigating CHF mechanisms and accelerating therapeutic development.