Comparative Efficacy Research Articles

Comparison of short-term clinical efficacy between CO external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures

To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.

Efficacy comparison and outcome predictors of GPi- and STN-targeted deep brain stimulation for Meige syndrome: a systematic review of individual patient data.

The aim of this study was to evaluate outcomes of deep brain stimulation (DBS) for Meige syndrome, compare the efficacy of globus pallidus internus (GPi) and subthalamic nucleus (STN) as targets, and identify potential outcome predictors. The PubMed, Embase, and Web of Science databases were systematically searched to collect individual data from patients with Meige syndrome receiving DBS. Outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale motor (BFMDRS-M) and disability (BFMDRS-D) scores. Data were analyzed using pooled meta-analysis. The study is registered in the PROSPERO database. The analysis included 233 patients from 26 studies, with significant publication bias (p = 0.008, Egger's test), but showed significant improvements in BFMDRS-M (65.09% ± 26.65%) and BFMDRS-D (53.48% ± 42.44%) scores at the final follow-up (mean duration 27.10 ± 33.64 months). No significant differences were observed in BFMDRS-M score improvement (mean difference -2.58%, 95% CI -15.84% to 10.69%; p = 0.430) or risk difference for response (-0.97%, 95% CI -10.08% to 8.15%; p = 0.835) between the GPi and STN target groups at the final follow-up across all follow-up periods (0 to ≤ 6, > 6 to ≤ 12, > 12 to ≤ 24, > 24 to ≤ 36, and > 36 months). Multiple regression analysis revealed a negative correlation between disease duration and treatment efficacy and a positive correlation between preoperative BFMDRS score and treatment outcome. DBS significantly improves motor symptoms and disability in patients with Meige syndrome, with GPi and STN targets providing comparable efficacy. The efficacy of DBS diminishes with longer disease duration, underscoring the importance of early intervention.

Comparison of Woven EndoBridge and stent-assisted coiling for treatment of acutely ruptured wide-neck bifurcation aneurysms: Single-center experience.

Treating wide-necked bifurcation aneurysms (WNBA) is challenging. Nevertheless, recent progress in endovascular techniques is promising. Woven EndoBridge devices (WEB) have exhibited outcomes comparable to conventional treatments like stent-assisted coiling (SAC) in treating aneurysms. However, their safety and efficacy in managing acutely ruptured aneurysms remain a topic of interest. This study focuses on this issue. We searched our database from 2020 to 2023 and found 38 patients with acutely (< a week) ruptured WNBA. We extracted radiologic and clinical data from the available medical reports. Favorable functional and radiologic outcomes were assessed using the modified Rankin scale (mRS) and modified Raymond-Roy occlusion classification (MRRC). Our study population comprised 15 aneurysms treated with WEB and 25 treated with SAC. Operational time was significantly lower in the WEB compared to the SAC group (39.3 vs 66.2 minutes, p value: < 0.001). Immediate (p value=0.64) and the 18th-month (p value=0.42) occlusion rates were comparable between the two groups. Favorable mRS scores in the 3rd month were seen in 100% of SAC patients and 93.3% of WEB patients (p value=0.79). Retreatment (p value=1.0) and complication (p value=0.39) rates were comparable. Vasospasms after the procedure were the most common complication. WEB demonstrated comparable safety and efficacy to SAC in patients with acutely ruptured WNBA. Notably, WEB had a shorter procedure duration. Additional studies with extended follow-up periods are necessary for comprehensive evaluation.

Streamlining the Journey of Research Into Clinical Practice: Making Your Patients and Practice Flourish Evaluation and Treatment of Pyogenic Spondylodiscitis of the Spine: AO Spine Knowledge Forum Trauma and Infection.

Literature Review with clinical recommendations. To highlight impactful studies on pyogenic spondylodiscitis (PS), identified by the AO Spine Knowledge Forum Trauma and Infection, with recommendations for their integration into clinical practice. Five influential studies on PS that have the potential to shape current practice in spinal infections were selected and reviewed. Each study was chosen for its contribution to a critical phase in PS management: diagnosis, imaging, surgical vs conservative treatment, and antibiotic duration. Recommendations were graded as strong or conditional following the GRADE methodology. Five studies were highlighted. Article 1: Pluemer et al introduced the Spinal Infection Treatment Evaluation (SITE) Score, a novel scoring tool for standardizing treatment decision-making. Conditional recommendation to incorporate the SITE Score or SISS Score for improved treatment outcomes. Article 2: Maamari et al conducted a meta-analysis comparing imaging modalities, with conditional recommendation to consider 18F-FDG PET/CT to diagnosis PS as an adjunct to MRI which remains the gold standard. Article 3: Thavarajasingam et al demonstrated the potential survival benefit of early surgery in specific PS cases, leading to a strong recommendation for early intervention in appropriate patients. Article 4: Neuhoff et al compared conservative and surgical treatments in well-resourced settings, concluding a strong recommendation for early surgery in appropriate patients. Article 5: Bernard et al evaluated antibiotic treatment duration, with a conditional recommendation for a 6-week course in confirmed cases, based on comparable efficacy to a 12-week regimen. Management of PS remains complex and varied. This perspective provides spine surgeons with evidence-based recommendations to enhance standardization and effectiveness in clinical practice.

Comparative efficacy and safety of the novel Picosecond Alexandrite Laser and the traditional combined Q-switched and long-pulse Nd: YAG lasers in melasma treatment: a randomized evaluator-blinded trial

Melasma significantly impacts life quality, and while various laser therapies show promise, rigorous comparative studies, especially between the novel Picosecond Alexandrite Laser (PSAL) and the traditional combined modality of Q-switched and Long-pulse Nd: YAG Lasers (QLNYL), are notably lacking. This study aims to fill this gap by evaluating the efficacy and safety of these modalities, providing insights into their comparative advantages for clinical practice. In a prospective, evaluator-blinded study, 40 participants with Fitzpatrick Skin Types (FST) III and IV underwent three treatment sessions at four-week intervals with either PSAL or QLNYL. Efficacy was primarily assessed by changes in Melasma Area and Severity Index (MASI) scores at baseline, 4, 8, 12, and 24 weeks, along with patient satisfaction evaluations at the 12- and 24-week marks, and safety assessments conducted throughout the study. Both groups experienced significant reductions in MASI scores post-treatment. Overall, the improvement in MASI scores in the QLNYL group significantly surpassed that in the PSAL group (P = 0.010). Patient satisfaction was comparably high between groups, and no significant differences were noted in safety profiles. The PSAL group showed a slightly higher incidence of adverse reactions (not significant) and significantly higher pain scores (P = 0.018). Recurrence rates at the 24-week follow-up were 10.5% for PSAL and 0% for QLNYL, with no significant difference. Both PSAL and QLNYL proved effective in treating melasma, with the traditional combined modality of QLNYL demonstrating superior efficacy in FST III-IV. Safety profiles were similar comparable.

Comparative efficacy and safety of 20 intravenous pharmaceutical intervention for prevention of etomidate-induced myoclonus: a systematic review and Bayesian network meta-analysis

Comparative efficacy and safety of 20 intravenous pharmaceutical intervention for prevention of etomidate-induced myoclonus: a systematic review and Bayesian network meta-analysis

Comparative efficacy of combined myo-inositol and D-chiro inositol versus metformin across PCOS Phenotypes: enhancing ovarian function, ovulation, and stress response in a prospective clinical trial.

This study aimed to evaluate the comparative efficacy of Myo-inositol (MI) and D-chiro-inositol (DCI) with metformin in enhancing ovarian function, promoting ovulation, and reducing perceived stress in patients with polycystic ovary syndrome (PCOS). Women with PCOS were identified using the Androgen Excess Society's criteria, and 60 participants were enrolled and divided equally into two groups. One group received a 40:1 ratio of MI plus DCI, while the other received metformin for a 12-week period. Endocrine and metabolic parameters, insulin-resistance, stress levels, and quality of life were assessed pre- and post-treatment. Both MI plus DCI and metformin significantly improved insulin sensitivity (HOMA-IR, p < 0.001), SHBG levels (p = 0.021), ovarian volume (p < 0.001), and menstrual regularity (p = 0.002), along with BMI, quality of life, and PSS scores (p < 0.001). Metformin showed slightly better outcomes in certain parameters, such as insulin sensitivity and endocrine markers, probably due to a higher representation of Phenotype A. In contrast, we hypothesize that MI plus DCI may be more effective for Phenotypes C and D. Our findings support both MI plus DCI and metformin as effective treatments for PCOS, with each treatment offering specific benefits. These results highlight the potential for a phenotype-specific tailored therapeutic approach to better manage the complex metabolic, endocrine, and stress-related challenges of PCOS. Trial Registration: clinicalTrial.gov NCT05767515. Registered 3 February, 2023.

NEDD4-Mediated GSNOR Degradation Aggravates Cardiac Hypertrophy and Dysfunction.

The decrease in S-nitrosoglutathione reductase (GSNOR) leads to an elevation of S-nitrosylation, thereby exacerbating the progression of cardiomyopathy in response to hemodynamic stress. However, the mechanisms under GSNOR decrease remain unclear. Here, we identify NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) as a novel molecule that plays a crucial role in the pathogenesis of pressure overload-induced cardiac hypertrophy, by modulating GSNOR levels, thereby demonstrating significant therapeutic potential. Protein synthesis and degradation inhibitors were used to verify the reasons for the decrease in GSNOR. Mass spectrometry and database filtering were used to uncover NEDD4, the E3 Ub (ubiquitin) ligase, involved in GSNOR decrease. NEDD4 cardiomyocyte-specific deficiency mice were used to evaluate the role of NEDD4 and NEDD4-induced ubiquitination of GSNOR in cardiac hypertrophy in vivo. Both IBM, a highly specific NEDD4 inhibitor, and indole-3-carbinol, a NEDD4 inhibitor currently undergoing phase 2 clinical trial, were used to effectively suppress the NEDD4/GSNOR axis. GSNOR protein levels were reduced, while mRNA levels remained unchanged in myocardium samples from hypertrophic patients and transverse aortic constriction-induced mice, indicating GSNOR is regulated by ubiquitination. NEDD4, an E3 Ub ligase, was associated with GSNOR ubiquitination, which exhibited significantly higher expression levels in hypertrophic myocardial samples. Moreover, either the NEDD4 enzyme-dead mutant or GSNOR nonubiquitylated mutant decreased GSNOR ubiquitination and inhibited cardiac hypertrophic growth. Cardiomyocyte-specific NEDD4 deficiency inhibited cardiac hypertrophy in vitro and in vivo. NEDD4 inhibitor IBM effectively suppressed GSNOR ubiquitination and cardiac hypertrophy. Clinically, indole-3-carbinol, a NEDD4 inhibitor in phase II clinical trials used as an antitumor drug, demonstrated comparable efficacy. Our findings showed that upregulated NEDD4 leads to GSNOR ubiquitination and subsequent degradation, thereby facilitating the progression of cardiac hypertrophy. NEDD4 inhibitors may serve as a potential therapeutic strategy for the treatment of cardiac hypertrophy and heart failure.

Clinical effectiveness of progestogens compared to combined oral contraceptive pills in the treatment of endometriosis: A systematic review and meta-analysis.

Endometriosis involves the growth of endometrium-like cells outside the uterus, affecting reproductive-aged women. Symptoms such as dysmenorrhea, pelvic pain, and infertility significantly impair quality of life. Among therapeutic options, progestogens have demonstrated efficacy in managing pain and reducing recurrence rates. This study aimed to compare the clinical effectiveness of progestogens versus combined oral contraceptive pills in alleviating pelvic pain, dyspareunia, dysmenorrhea, and associated side effects. A systematic review and meta-analysis were conducted by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials, with the last search conducted in October 2024. The review was registered under PROSPERO registration number CRD42024609658. Studies were included regardless of language, publication year, or country. Articles not comparing progestogens and combined oral contraceptives or lacking relevant outcomes were excluded, as were abstracts, theses, case reports, opinion pieces, and correspondence. Risk of bias was assessed using the modified Cochrane Risk of Bias tool 2.0 for randomized studies. Seven studies, including 948 patients (476 receiving progestogens), met inclusion criteria. The meta-analysis found no significant differences between progestogens and COCPs for pelvic pain (SMD = 0.02; 95% CI: -0.37 to 0.40; P = 0.04; I2=66.7%), dysmenorrhea (SMD = 0.00; 95% CI: -0.19 to 0.19), dyspareunia (SMD = 0.21; 95% CI: -0.42 to 0.85; P = 0.02; I2=81.4%), or psychological health (SMD = 0.01; 95% CI: -0.21 to 0.23; P = 0.19; I2=39.1%). Similarly, no significant differences were observed in side effects, including breast tenderness, weight gain, amenorrhea, and bleeding. Progestogens and COCPs demonstrate comparable efficacy in managing pelvic pain, dysmenorrhea, dyspareunia, and psychological health, with similar side effect profiles. These findings suggest both treatments are equally effective options for symptom management in endometriosis.

Not All Planes Have Propellers: Using Context Variability to Treat Word Learning in Late Talkers With the Vocabulary Acquisition and Usage for Late Talkers Protocol.

The purpose of this study was to determine if the Vocabulary Acquisition and Usage for Late Talkers (VAULT) intervention could be efficaciously applied to a new treatment target: words a child neither understood nor said. We also assessed whether the type of context variability used to encourage semantic learning (i.e., action or object) would affect learning outcomes. Nineteen primarily English-speaking late-talking toddlers received 8 weeks of VAULT intervention. They were quasirandomly assigned to a condition that highlighted either object or action variability. Individual effect sizes were calculated for target (treated) and control (not treated) words for each child. These were combined to assess group-level comparisons of treatment efficacy and treatment conditions. Generalization of the word-learning ability was assessed by comparing rates of learning on a vocabulary checklist prior to and during intervention. Bayesian statistics (e.g., t tests, analysis of variance) were used for the analyses. There was strong evidence for a treatment effect showing that children produced more target than control words and moderate evidence that they understood more target than control words. There was strong evidence for generalization. Children learned an average of 6.8 words per week during treatment. There was anecdotal evidence for no difference between treatment conditions. VAULT, with a focus on context variability, can be used efficaciously to teach children to say words they do not understand at the start of treatment. The effects were most pronounced in the generalization data. Additionally, children were able to learn later-acquired words. https://doi.org/10.23641/asha.28200074.

Comparative Efficacy of Antithrombotic Strategies in Bioprosthetic Aortic Valve Replacement: A Network Meta-Analysis.

This meta-analysis evaluates outcomes in patients undergoing bioprosthetic aortic valve replacement (bAVR), comparing different antithrombotic strategies. We conducted a systematic search through May 2024. A standard meta-analysis compared outcomes between patients who received anticoagulation therapy (AC) and those who did not. Therapeutic categories were subdivided into four groups: AC alone, AC with antiplatelet therapy (AP), AP alone, and no antithrombotic therapy. A network meta-analysis was performed for these categories. The review included 16 studies, comprising a total of 59,054 patients. There was no significant difference in all-cause mortality rates (HR: hazard ratio [95% CI: confidence interval] = 0.98 [0.77-1.25], P = .88) or thromboembolic events (HR [95% CI] = 0.91 [0.65-1.28], P = .60) between patients with and without AC. However, bleeding events were significantly higher in patients receiving AC (HR [95% CI] = 1.55 [1.20-2.00], P < .01). Network meta-analysis showed that AP alone was associated with lower mortality rates compared with other therapeutic categories. Additionally, AP alone was associated with fewer bleeding events compared with AC alone and AC with AP. This meta-analysis suggests that AP alone in patients undergoing bAVR is associated with superior outcomes compared with other antithrombotic strategies.

Exploiting novel placental homing peptides for targeted drug delivery in breast Cancer.

More effective drug formulations are needed to increase the selectivity and efficacy of available chemotherapeutics. We have previously shown that nanoparticles decorated with the tumour homing peptide CGKRK can selectively deliver payloads to the placenta. In this study, we investigated whether two novel placental homing peptides NKGLRNK (NKG) and RSGVAKS (RSG) can be utilized to selectively deliver doxorubicin (DOX) to breast cancer cells. Fluorescence microscopy and flow cytometry showed that NKG and RSG bind to and accumulate in MDA-MB-231 and MCF-7 cells in a time-dependent manner, to a similar extent as CGKRK, but accumulate in healthy MCF-10 A cells to a much lesser degree. NKG- and RSG-decorated liposomes facilitated equivalent delivery of DOX to MDA-MB-231 and MCF-7 cells, with a comparable efficacy to CGKRK-decorated liposomes. These findings suggest that NKG and RSG represent novel breast tumour-binding sequences that could be utilized to develop more efficacious targeted breast cancer therapies.

Comparative Efficacy and Safety of Endovascular vs. Surgical Treatment in Spinal Dural Arteriovenous Fistulas: A Systematic Review and Meta-Analysis.

Systematic Review and Meta-analysis. This study aims to compare the efficacy and safety of surgical and endovascular treatments for SDAVFs. Spinal dural arteriovenous fistulas (SDAVFs) result from an abnormal connection between the radiculomeningeal artery and the radicular vein, leading to venous hypertension and potential neurological damage. The two primary treatment strategies are surgical closure and endovascular obliteration of the fistula. PubMed, Scopus, and Web of Science databases were searched from inception to July 2024. We defined the successful treatment as fistula occlusion with sufficient embolic material penetration or obliteration during surgery. A total of 1192 articles were identified, with 40 studies meeting the inclusion criteria, comprising 1818 patients (surgical: 804, endovascular: 1014). The surgical group demonstrated higher rates of complete occlusion at last follow-up (96.8%, 363/375) compared to the endovascular group (72.5%, 470/648) (OR: 0.16; CI: 0.09 to 0.28, P<0.01). Surgical treatment also had higher successful treatment rates (97.5%, 392/402) compared to endovascular treatment (66.7%, 529/793) (OR: 0.11; CI: 0.06 to 0.19, P<0.01). Recurrence rates were lower in the surgical group (OR: 6.04; CI: 3.45 to 10.57, P<0.01) and retreatment rates were also lower (OR: 7.16; CI: 4.11 to 12.48, P<0.01). Initial treatment failure was significantly higher in the endovascular group (32.2%, 329/1023) compared to the surgical group (2.3%, 19/804) (OR: 8.97; CI: 5.56 to 14.45, P<0.01). Surgical treatment for SDAVFs achieves higher rates of complete occlusion and successful treatment compared to endovascular treatment, with lower rates of recurrence, retreatment, and initial treatment failure. Although both treatments show similar improvements in neurological status and periprocedural complications, surgery remains the preferred approach for definitive results. Treatment decisions should be individualized based on patient-specific factors and anatomical characteristics. Further research is needed to confirm these results.

Robotic versus manual disinfection of global priority pathogens at COVID-19 dedicated hospitals.

Twelve bacterial families were identified as global priority pathogens by the World Health Organization in 2017, recognizing the greatest threat they pose to human health and the declining antibiotic efficacy. Robotics has emerged as a swift and contactless tool for disinfecting bacterial surface contamination in healthcare facilities, however, head-to-head comparison of disinfection efficacy of robotic versus manual disinfections is limited. This study aimed at comparing how robotic disinfection performs over manual disinfection against the global priority pathogens in the healthcare setting. A spraying disinfection robot was developed, and its disinfection efficacy was compared against manual disinfection during July 2020-December 2020. Disinfections were performed on the clinical surfaces and inanimate objects at two hospitals in Nepal using robotic or manual application of a disinfectant (NaOCl). Swab samples from floor, bed, doorknob, and medical devices at both hospitals were collected before and after disinfection and examined for total heterotrophic plate count and bacterial pathogens were identified based on Gram's staining and biochemical characteristics. Disinfection outcomes were reported as log reduction (log10 CFU/inch2) of heterotrophic count and presence or absence of target bacteria. A total of 76 samples were collected from two study sites including major pathogens: Staphylococcus aureus, Escherichia coli, Acinetobacter spp., and Klebsiella pneumoniae, among others. Both robotic and manual disinfection significantly reduced microbial load (log 2.3 to log 5.8) in the hospitals. No pathogens were detected post-disinfection using the robot. The use of robotic disinfection was more effective, significantly reducing more bacterial load (log 5.8) compared to manual disinfection (log 3.95). Our results showed better efficacy of robotic disinfection compared to manual disinfection of hospital surfaces, and thus contactless robotic disinfection is recommended for disinfecting bacterial contamination of surfaces in the hospital and clinical settings as it favors patient safety against global priority pathogens.

Indirect treatment comparison of lanadelumab and a C1-esterase inhibitor in pediatric patients with hereditary angioedema.

Aim: To compare the efficacy and safety of lanadelumab versus other approved long-term prophylaxis (LTP) treatments in patients with pediatric hereditary angioedema (HAE) aged <12years. Materials & methods: A systematic literature review was conducted to identify studies of LTP in patients with HAE aged <12years. Two studies met the inclusion criteria in an indirect treatment comparison of efficacy and safety data in pediatric HAE patients. These were for lanadelumab (SPRING, NCT04070326) and intravenous-C1-esterase inhibitor (C1-INH[IV], NCT02052141). A propensity score analysis used individual patient-level data from both studies in a logistic regression model to estimate inverse probability weights. To avoid convergence issues and an underpowered analysis due to the small sample size (n=29), the base case was defined as Poisson regression analyses on monthly attack rate adjusting for one covariate (baseline attack rate). Model selection among unadjusted, adjusted and weighted regression models was conducted through the Akaike and Bayesian Information Criteria. Results: Lanadelumab 150mg every 2weeks (Q2W) reduced the monthly HAE attack rate by 82.1% versus C1-INH(IV) 1000 IU twice weekly (every 3-4days [BIW]; rate ratio [RR], 0.1792 [95% CI: 0.0296-1.0853]) and by 88.9% versus C1-INH(IV) 500 IU BIW (RR: 0.1107 [95% CI: 0.0234-0.5239]). Treatment with lanadelumab Q2W reduced the risk of total adverse events by 56.2% versus C1-INH(IV) 1000 IU BIW (RR:0.4377 [95% CI: 0.1536-1.2469]) and by 66.0% versus C1-INH(IV) 500 IU BIW (RR: 0.3401 [95% CI: 0.1234-0.9371]). Conclusion: This exploratory analysis suggested a trend toward greater efficacy and fewer adverse events with lanadelumab 150mg Q2W compared with C1-INH(IV) BIW 1000 IU and 500 IU in pediatric patients with HAE. Future studies could potentially assess larger samples over longer periods of time for the long-term preventative efficacy, safety and tolerability of lanadelumab and C1-INH(IV).

Synthesis and Evaluation of Coumarin Clubbed Sulfanilamide and 2-Aminobenzothiazole Hybrids for Antibacterial Applications.

The increasing prevalence of drug-resistant bacterial infections poses a significant challenge to global healthcare, necessitating the development of novel antibacterial agents. Coumarin-based derivatives are well-recognized for their diverse biological activities, and hybridization with other pharmacophores offers a promising strategy for enhancing therapeutic efficacy and overcoming resistance. This study aimed to synthesize and evaluate a novel series of coumarin hybrids by integrating the coumarin scaffold with sulfanilamide (9a-e) and 2-aminobenzothiazole (10a-e), targeting bacterial pathogens through a dual pharmacophoric approach. The synthesized hybrids were characterized using mass spectrometry, FTIR, and NMR (1H and 13C) to confirm their structural integrity. Antibacterial activity was assessed in vitro against Escherichia coli and Staphylococcus aureus at concentrations of 100, 250, and 500 μg/ml, with ciprofloxacin as the standard. The molecular binding mechanism was explored using molecular docking and pharmacophore-based analysis. Among the synthesized derivatives, compounds 9e and 10e exhibited the highest antibacterial activity, with inhibition zones of 22 mm and 21 mm against E. coli and 25 mm and 22 mm against S. aureus at 500 μg/ml, demonstrating comparable efficacy to ciprofloxacin. Molecular docking studies revealed strong interactions of these compounds with bacterial enzymes, supporting the in vitro results and highlighting their potential as protein-inhibitor candidates. The novel hybrid derivatives demonstrated significant antibacterial activities, suggesting their potential as promising therapeutic agents. Their effectiveness against various bacterial strains indicated that these compounds could serve as a foundation for the development of new antibacterial drugs. Further research and optimization are needed to enhance their potency and ensure their safety, paving the way for future clinical applications.

Spinal Cord Stimulation for Refractory Angina Pectoris: Current Status and Future Perspectives, a Narrative Review.

Refractory angina pectoris (RAP) is a clinical syndrome characterized by persistent chest pain caused by myocardial ischemia that is unresponsive to optimal pharmacological therapy and revascularization procedures. Spinal cord stimulation (SCS) has emerged as a promising therapeutic option for managing RAP, offering significant symptom relief and improved quality of life. A systematic literature review was conducted to evaluate the clinical effectiveness, mechanisms of action, and safety profile of SCS in treating RAP. Comprehensive searches were performed in PubMed, Scopus, and Web of Science for studies published between 1990 and 2023. Of 328 articles identified, 6 met the inclusion and exclusion criteria for final analysis. The included studies consistently demonstrated that SCS significantly reduces the frequency of anginal episodes and nitroglycerin use while improving exercise capacity and quality of life. Proposed mechanisms include modulation of pain signals via the gate control theory, enhancement of autonomic balance, and redistribution of myocardial perfusion. Novel stimulation modalities, including high-frequency, Burst, and Differential Target Multiplexed (DTM), show potential advantages in enhancing patient comfort and clinical outcomes. Nevertheless, long-term studies are necessary to validate these findings and establish the comparative efficacy of these advanced technologies. SCS is a safe and effective therapy for patients with RAP who are unsuitable for surgical interventions. Innovations in neurostimulation, including closed-loop systems and personalized treatment strategies have the potential to further optimize outcomes. Rigorous clinical trials are needed to consolidate the role of SCS as a cornerstone therapy for the management of RAP.

Revolutionizing Diabetes Management: A Comparative Analysis of Novel Vaccine Therapies with Conventional Treatments

This comprehensive review compares novel vaccine therapies to conventional treatments for diabetes management, examining efficacy, safety, cost-effectiveness, and patient compliance. Conventional treatments (insulin, oral medications, lifestyle modifications) have limitations, such as hypoglycemic and decreased adherence. Vaccine therapies (T-cell targeted, peptide-based, DNA vaccines) demonstrate potential benefits, including improved glycemic control, reduced hypoglycemia, and enhanced patient compliance. Comparative analysis reveals vaccine therapies exhibit comparable or superior efficacy to conventional treatments, with reduced adverse effects and improved quality of life. Cost-effectiveness analysis suggests long-term economic benefits. Patient compliance and satisfaction are higher with vaccine therapies. Future directions include personalized medicine, combination therapies, and potential prevention and reversal of diabetes. Emerging trends focus on novel antigens, adjuvants, and delivery systems.

Utility of 18F-FDG PET/CT metabolic parameters on post-transplant lymphoproliferative disorder diagnosis.

Using 18F-FDG PET/CT metabolic parameters to differentiate post-transplant lymphoproliferative disorder (PTLD) and reactive lymphoid hyperplasia (RLH), and PTLD subtypes. 18F-FDG PET/CT and clinical data from 63 PTLD cases and 19 RLH cases were retrospectively collected. According to the 2017 WHO classification, PTLD was categorized into four subtypes: nondestructive (ND-PTLD), polymorphic (P-PTLD), monomorphic (M-PTLD), and classic Hodgkin. Metabolic parameters included maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and at different thresholds of SUVmax (2.5 and 41%), as well as gross tumor volume (GTV) was also collected. Nonparametric test and receiver operating characteristic (ROC) curves were used for statistics. There were 42 ND-PTLD patients, 7 P-PTLD patients, and 14M-PTLD patients. Ki-67 was significantly correlated with all metabolic parameters (P all < 0.01). SUVmean, SUVmax, MTV, TLG and GTV were all highest in M-PTLD, followed by P-PTLD, ND-PTLD, and RLH. ROC curves showed 18F-FDG PET/CT metabolic parameters all had moderate diagnostic efficacy in differentiating between PTLD and RLH, the area under the curves (AUC) range from 0.682 to 0.747. Diagnostic efficacy for P-PTLD + M-PTLD showed excellent performance (AUC for RLH + ND-PTLD vs P-PTLD + M-PTLD was 0.848 for SUVmax, 0.846 for SUVmean41%, 0.834 for SUVmean2.5, and 0.819 for GTV). For MTV41%, TLG 41%, MTV2.5, TLG2.5, the AUC was 0.676, 0.761, 0.761, 0.787, respectively. 18F-FDG PET/CT metabolic parameters at different thresholds of SUVmax (2.5 and 41%) exhibited comparable diagnostic efficacy for PTLD and its subtypes. All metabolic parameters demonstrated moderate diagnostic efficacy in distinguishing PTLD and RLH. SUVmax, SUVmean41%, SUVmean2.5 and GTV showed excellent performance in diagnosing P-PTLD + M-PTLD.

PEGylation Improves the Therapeutic Index of Dexamethasone To Treat Acute Respiratory Distress Syndrome with Obesity Background in Mouse.

With increasing prevalence globally, obesity presents unique challenges to the clinical management of other diseases. In the case of acute respiratory distress syndrome (ARDS), glucocorticoid therapy (e.g., dexamethasone (DEX)) represents one of the few pharmacological treatment options, but it comes with severe adverse effects, especially when long-term usage (>1 week) is required. One important reason for the adverse effects of DEX is its nonspecific accumulation in healthy tissues upon systemic administration. Therefore, we hypothesize that refining its pharmacokinetics (PK) and in vivo biodistribution may improve its therapeutic index (higher efficacy, lower toxicity) and thus make it safer for obese populations. To achieve this goal, DEX was conjugated with polyethylene glycol (PEG) with three different molecular weights (Mw, 2K, 5K, and 10K) via a reactive oxygen species (ROS)-cleavable linker. Their anti-inflammatory efficacy and long-term adverse effects were evaluated in a murine obesity-ARDS model. Strikingly, DEX-PEG-2K (conjugates with 2K PEG Mw) provided the optimal therapeutic index compared to free DEX and to the other two conjugates with longer PEGs (Mw of 5K and 10K): While retaining the comparable therapeutic efficacy to DEX, DEX-PEG-2K significantly reduced the accumulation of free DEX in the liver and spleen, which led to a 51% reduction of fatty area in liver and a 32% reduction of blood triglycerides concentration. DEX-induced apoptosis of the thymus was also rescued by DEX-PEG-2K under normal conditions. The PK and biodistribution were also investigated to elicit the underlying mechanism. In summary, we provided here a chemical modification strategy to improve the therapeutic index of dexamethasone and possibly other glucocorticoid drugs for ARDS treatment with an obesity background.