Current Issue : October-December Volume : 2025 Issue Number : 4 Articles : 5 Articles
Adrenomedullin (AM) is a bioactive peptide that is strongly induced during severe inflammation, including pneumonia and sepsis, and serves as an organ-protective factor. The plasma concentration ofAMis markedly increased in the novel coronavirus disease COVID- 19 and is closely related to the severity of the disease and prognosis of patients. We performed two investigator-initiated trials to evaluate the efficacy and safety of AM in patients with moderate-to-severe COVID-19. This multicenter, double-blind, placebo-controlled phase-2a trial evaluated COVID-19 patients with severe (n = 33) and moderate (n = 31) pneumonia in Japan. Patients were randomly assigned to receive either 15 ng/kg/min AM or placebo. The primary endpoint was the duration of mechanical ventilation (MV) for severe pneumonia and oxygen support for moderate pneumonia. The main secondary endpoint was clinical status up to 30 days after the intervention. No differences in primary or secondary endpoints were observed between the AM and placebo groups in patients with severe or moderate pneumonia. In the severe pneumonia group, three patients in the placebo group died due to respiratory failure, and one patient in the AM group died due to respiratory failure. The respiratory function test at 30 days in the moderate pneumonia group tended to be better than that in the AM group and approached significance (p = 0.073). Although mild adverse events caused by the vasodilatory effects of AM were noted, the safety of AM for treating pneumonia was confirmed. In these trials, we did not observe a definitive efficacy of AM in moderate to severe pneumonia. Alternative strategies for the treatment of AM in pneumonia require further research....
Background/Objectives: Hypertension affects over 1.3 billion people globally, and inadequate therapy is reported in 80% of cases. Patients increasingly turn to complementary therapies, including hawthorn (Crataegus spp.), a traditional remedy for cardiovascular diseases. Hawthorn has long been used in folk medicine to lower blood pressure; however, its efficacy has not been fully established. This meta-analysis aimed to evaluate the antihypertensive effects and safety of hawthorn in randomized, placebo-controlled trials. Methods: A systematic review and meta-analysis were conducted, including six studies with a total of 428 participants. The trials focused on systolic (SBP) and diastolic blood pressure (DBP) changes over treatment periods of 10 weeks to 6 months. Literature searches were conducted in the Embase, PubMed, Cochrane, and Web of Science databases. Studies that met the predefined PICO criteria were included. Data analysis was performed using a random-effects model, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Results: Hawthorn statistically significantly decreased SBP (MD: −6.65 mmHg; 95% CI [−11.72; 1.59]) and non-significantly reduced DBP (MD: −7.19 mmHg; 95% CI [−15.17; 0.79]) after 2–6 months of treatment. Variations in dosage (250– 1200 mg/day) and study protocols contributed to this heterogeneity. Conclusions: The effect of hawthorn on blood pressure is clinically significant. However, larger, well-designed trials are needed to establish optimal dosing, duration, and efficacy with greater reliability....
Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown benefits in promoting tear secretion and corneal healing. This study evaluated the safety and efficacy of insulin nanoemulsion eye drops (20 IU/mL, three times daily for 30 days) in patients with SjD. Thirty-two patients were randomized in a double-masked design to receive either insulin or placebo drops. Symptoms (assessed by OSDI questionnaire) and objective measures (tear film breakup time, corneal and conjunctival staining, and Schirmer Test) were recorded at baseline, after 4 weeks of treatment, and at a 4-week follow-up. Twenty-three participants completed the study. Both groups showed significant improvement in symptoms and objective signs after treatment (p < 0.05), but no significant differences were found between the insulin and placebo groups. No clinically relevant adverse effects were reported. Insulin nanoemulsion eye drops are safe for SjD patients, but their therapeutic advantage remains unclear. Further studies with larger samples, extended follow-up, and dose adjustments are needed to better understand their potential....
Objective: A combination of midazolam and opioid is usually used to achieve conscious sedation and analgesia during colonoscopy, but many patients may tolerate the procedure well without any sedation. This randomized trial aimed to compare the efficacy and recovery time of 3 different regimens consisting of (a) midazolam plus meperidine (b) midazolam plus fentanyl and (c) placebo. The endoscopists’ and patients’ satisfaction was assessed by an appropriate questionnaire. Methods: A total 248 consecutive, unselected patients attending outpatient colonoscopy at a University Hospital were enrolled with informed consent and were randomized to receive (a) midazolam with meperidine [group A] (b) midazolam with fentanyl [group B] or (c) placebo [group C]. Data for procedure times, perceived patient’s discomfort (using a relative patient questionnaire) and physician’s satisfaction from the procedure were collected. Patients and all endoscopy staff directly involved with the procedure except the research nurse were blinded to the regimens used. Results: The mean age of the patients was 58 ± 15 years (range 19–85 years) and 130 were males. The completion rate and time to reach cecum did not differ among the three groups. The recovery time was significantly shorter in group C (placebo, 10.4 ± 2.9 min) compared to the other groups (p < 0.000), but it was also shorter in group B (midazolam plus fentanyl, 43.0 ± 9.3 min) compared to group A (midazolam plus pethidine, 50.1 ± 9.0 min) (p = 0.001). Patients of group B (midazolam plus fentanyl) experienced less pain and discomfort than patients of group A (midazolam plus meperidine) (p = 0.02) and patients of group A experienced less pain than patients of group C (placebo). Many more patients in group B were extremely or very satisfied by the procedure(86.7%) compared to group A (59.7%) and group C (44.5%) (p = 0.001). Adverse events were mild in all groups and slightly less in group B. Conclusions: Sedation with midazolam and fentanyl was more effective, better tolerated and led to slightly faster recovery time than sedation with midazolam and meperidine. According to our findings and the literature, the most appropriate regimen for conscious sedation during colonoscopy is the combination of midazolam and fentanyl. However, both sedation regimens were proven to be effective and safe and even a significant proportion of unsedated patients could tolerate the procedure fairly well....
Background: pGX9501 is a prophylactic DNA vaccine encoding the spike protein of SARS-CoV-2 and can induce immune response in the human body so as to prevent COVID-19. With respect to non-clinical studies, pGX9501 has been demonstrated to induce both cellular and humoral immune responses in various animal models. It was found that the level of antibody titers following a two-dose regimen was higher than that following a single-dose regimen in nonhuman primate challenge model. Methods: In China, a phase I, randomized, double-blind, placebo-controlled clinical trial has been conducted in Huashan Hospital, Shanghai, China to evaluate the safety, tolerability, and immunogenicity of DNA vaccine pGX9501 administered intradermally (ID) followed by electroporation (EP) in 45 Chinese healthy volunteers aged 18 to 59 years old. Results: No adverse events of special interest (AESIs), death, or treatment-related SAEs occurred in this study. All the treatment-related (vaccine or EP) adverse events (TRAEs) were of grade 1 and 2 in severity. The solicited AEs were reported in thirty-two (32/36, 88.9%) and nine (9/9, 100.0%) subjects, respectively, in the DNA vaccine and placebo group. The frequency of solicited AEs did not increase with vaccine dose level and frequency. The DNA vaccine pGX9501 effectively enhanced both humoral and cellular immune responses in a dose-dependent manner, with increased antibody GMTs and peak seroconversion rates observed on day 42. The significant rise in IFN-γ levels confirmed the vaccine’s ability to induce cellular immune responses. Variations in the microbiome structure suggested a tangible impact of the gut microbiota on vaccine immunogenicity. Conclusions: The findings from this study confirm the immunogenicity and safety of the DNA vaccine pGX9501 and point to the potential role of the gut microbiota in vaccine immune responses. These insights provide practical references for the future design and development of DNA vaccines....
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