Tag: nevin manimala

JAMA Neurol. 2023 Jun 20. doi: 10.1001/jamaneurol.2023.1660. Online ahead of print.

ABSTRACT

IMPORTANCE: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers.

OBJECTIVE: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke.

DESIGN, SETTING, AND PARTICIPANTS: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT.

INTERVENTIONS: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated.

MAIN OUTCOMES AND MEASURES: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score).

RESULTS: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00).

CONCLUSIONS AND RELEVANCE: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734548.

PMID:37338893 | DOI:10.1001/jamaneurol.2023.1660

JAMA. 2023 Jun 20;329(23):2023-2025. doi: 10.1001/jama.2023.8972.

NO ABSTRACT

PMID:37338887 | DOI:10.1001/jama.2023.8972

JAMA. 2023 Jun 20;329(23):2050-2056. doi: 10.1001/jama.2023.8549.

ABSTRACT

IMPORTANCE: Many randomized clinical trials yield statistically nonsignificant results. Such results are difficult to interpret within the dominant statistical framework.

OBJECTIVE: To estimate the strength of evidence in favor of the null hypothesis of no effect vs the prespecified effectiveness hypothesis among nonsignificant primary outcome results of randomized clinical trials by application of the likelihood ratio.

DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of statistically nonsignificant results for primary outcomes of randomized clinical trials published in 6 leading general medical journals in 2021.

OUTCOME MEASURES: The likelihood ratio for the null hypothesis of no effect vs the effectiveness hypothesis stated in the trial protocol (alternate hypothesis). The likelihood ratio quantifies the support that the data provide to one hypothesis vs the other.

RESULTS: In 130 articles that reported 169 statistically nonsignificant results for primary outcomes, 15 results (8.9%) favored the alternate hypothesis (likelihood ratio, <1), and 154 (91.1%) favored the null hypothesis of no effect (likelihood ratio, >1). For 117 (69.2%), the likelihood ratio exceeded 10; for 88 (52.1%), it exceeded 100; and for 50 (29.6%), it exceeded 1000. Likelihood ratios were only weakly correlated with P values (Spearman r, 0.16; P = .045).

CONCLUSIONS: A large proportion of statistically nonsignificant primary outcome results of randomized clinical trials provided strong support for the hypothesis of no effect vs the alternate hypothesis of clinical efficacy stated a priori. Reporting the likelihood ratio may improve the interpretation of clinical trials, particularly when observed differences in the primary outcome are statistically nonsignificant.

PMID:37338877 | DOI:10.1001/jama.2023.8549

Medeni Med J. 2023 Jun 20;38(2):111-119. doi: 10.4274/MMJ.galenos.2023.42383.

ABSTRACT

OBJECTIVE: Currently, multiple classification systems exist for the assessment of facial nerve paralysis. This study was designed to choose the most practical system for use in a clinical setting depending on the clinician need. We compared the responsiveness of the 3 facial nerve grading systems, i.e., House-Brackmann, Sydney, and Sunnybrook, as the subjective method and compared the outcomes with the objective method, i.e., the nerve conduction study. The correlation between the subjective and objective assessments was determined.

METHODS: A total of 22 consented participants with facial palsy was assessed with photos and videography recordings where they performed 10 standard facial expressions. The severity of facial paralysis was evaluated with the House-Brackmann, Sydney, and Sunnybrook grading scales subjectively and with the facial nerve conduction study objectively. The assessments were repeated after 3 months.

RESULTS: A Wilcoxon signed-rank test showed that there were statistically significant change in all three gradings after 3-month of assessment. The responsiveness of the nerve conduction study was significant for the nasalis and orbicularis oris muscles. It was not significant for the orbicularis oculi muscle. The nasalis and orbicularis oculi showed statistically significant correlation with the three classification systems except for the orbicularis oculi muscle.

CONCLUSIONS: All three grading systems, House-Brackmann, Sydney, and Sunnybrook, showed statistically significant responsiveness after 3 months of evaluation. The nasalis and orbicularis oculi muscle can be used to predict facial palsy recovery because they showed strong positive and negative correlations with the extent of facial nerve degeneration from the nerve conduction study.

PMID:37338861 | DOI:10.4274/MMJ.galenos.2023.42383

Medeni Med J. 2023 Jun 20;38(2):102-110. doi: 10.4274/MMJ.galenos.2023.48768.

ABSTRACT

OBJECTIVE: Neuroblastoma is one of the common tumors of childhood. The demonstration of new factors such as isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations will be important in the diagnosis and treatment. IDH1 and IDH2 mutations have been found in many types of cancer, such as malignant gliomas, acute myeloid leukemias, chondrosarcoma, and thyroid carcinoma. This study aimed to investigate the presence of IDH1 or IDH2 mutations in patients with neuroblastoma and to determine whether these mutations were different in terms of age, clinical findings, and response to treatment.

METHODS: Biopsy specimens of 25 patients with pediatric neuroblastoma patients were evaluated for IDH mutations. The clinical and laboratory features of the patients with/without mutation were retrospectively analyzed from a hospital database.

RESULTS: A total of 25 patients for whom genetic analysis could be performed were included in the study (60% male, n=15). The mean age was 32.2±25.9 months (3 days-96 months). IDH1 mutation was detected in 8 (32%) and IDH2 mutations in 5 (20%) patients. These mutations showed no statistically significant relationship with age, tumor localization, laboratory results, stage, and prognosis. However, in the case of IDH mutation, patients were diagnosed at the advanced stage.

CONCLUSIONS: This study demonstrated the relationship between neuroblastoma and IDH mutation for the first time. Because to the fact that the mutation is very heterogeneous, it would be appropriate to conduct a larger series of patients in terms of the impact of the clinical significance of each mutation on the diagnosis and prognosis.

PMID:37338860 | DOI:10.4274/MMJ.galenos.2023.48768

J Dtsch Dermatol Ges. 2023 Jun;21(6):645-647. doi: 10.1111/ddg.15003_g.

NO ABSTRACT

PMID:37338840 | DOI:10.1111/ddg.15003_g

Int Braz J Urol. 2023 Jun 20;49. doi: 10.1590/S1677-5538.IBJU.2023.9909. Online ahead of print.

ABSTRACT

PURPOSE: To analyze the histology and distribution of abdominal testicular vessels in human fetuses Patients and Methods: We studied 19 fetuses (34 testes) ranging in age from 12 to 19 weeks post-conception. The fetuses were evaluated regarding crown-rump length (CRL), total length (TL) and body weight immediately before dissection. Each testis was dissected and embedded in paraffin, from which 5 μm thick sections were obtained and stained with Masson’s trichrome and Anti-CD31 antibody to quantify the vessels. The stereological analysis was carried out with the Image Pro and Image J programs, using a grid to determine volumetric densities (Vv). Means were statistically compared using the unpaired T-test (p<0.05).

RESULTS: The fetuses presented mean weight of 222.5g, mean CRL of 15.3 cm and mean TL of 23.2 cm. All testes were in the abdominal position. The mean percentage of vessels (Vv) in the upper portion of the testis was 7.6% (4.6 to 15%) and in the lower portion the mean was 5.11% (2.3 to 9.8%), with a significant difference (p=0.0001). In the analysis between the upper portion of the right and left testes (p=0.99) and in the analysis of the lower portion of the right and left testes (p=0.83), we did not observe significant differences.

CONCLUSION: The upper portion of the abdominal testis in human fetuses had a higher concentration of vessels than the lower portion. These results suggest that manipulation of the lower end of the testis during Fowler-Stephens surgery should be avoided in order to preserve the collateral circulation.

PMID:37338817 | DOI:10.1590/S1677-5538.IBJU.2023.9909

Biol Trace Elem Res. 2023 Jun 20. doi: 10.1007/s12011-023-03726-9. Online ahead of print.

ABSTRACT

A cross-sectional study was carried out with 210 women divided into a case group (obese, n = 84) and a control group (eutrophic, n = 126). Body weight, height, waist circumference (WC), and hip and neck circumference were measured and the waist-hip ratio and conicity index were calculated. Selenium in plasma, erythrocytes and urine, erythrocyte GPx activity, lipid profile, Castelli I and II indices, and systolic and diastolic blood (DBP) pressure were evaluated. Mean dietary selenium intake (µg/kg/day) and plasma and erythrocyte concentrations were lower in the obese group compared to the healthy group (p < 0.001). while urinary selenium concentrations were higher (p < 0.001). There was a statistical difference between groups regarding cardiovascular risk parameters: waist circumference, neck circumference, waist-hip ratio, conicity index, triacylglycerols (TGC), and lipoproteins rich in triacylglycerols (VLDL-c) (p > 0.05). There was a negative correlation between plasma selenium concentrations and total cholesterol (TC), non-high-density lipoprotein (non-HDL), low-density lipoprotein (LDL-c), and systolic blood pressure (SBP). Urinary selenium correlated negatively with waist circumference and hip circumference and positively with neck circumference, TC, TGC, high-density lipoprotein (HDL-c), non-HDL, and VLDL-c. There was a negative correlation between dietary selenium and waist circumference, waist-hip ratio, neck circumference, conicity index, non-HDL cholesterol, LDL-c, and Castelli indices I and II, as well as a positive correlation with HDL-c and diastolic blood pressure. Women with obesity present changes in their nutritional status related to selenium, as well as increased cardiovascular risk parameters. Thus, the positive role of selenium in protecting the risk of cardiovascular disease is likely.

PMID:37338800 | DOI:10.1007/s12011-023-03726-9

Braz J Microbiol. 2023 Jun 20. doi: 10.1007/s42770-023-01039-6. Online ahead of print.

ABSTRACT

OBJECTIVES: The prevalence of infection by Neisseria gonorrhoeae is the second highest among bacterial sexually transmitted infections worldwide. It can lead to severe complications, especially in the female reproductive system. So, the objective of the present study was to assess the prevalence of Neisseria gonorrhoeae infection in a large population of female patients from a private health service in São Paulo (Brazil), thereby identifying the main age groups affected by the agent and how prevalence progressed over time.

METHODS: A cross-sectional study was conducted based on the results of all molecular biology tests performed for detecting Neisseria gonorrhoeae. The tests were conducted between January 2005 and December 2015. Positive test results were grouped by year and age group.

RESULTS: Of those tests, 35,886 were considered eligible for the statistical data. The overall prevalence of Neisseria gonorrhoeae infection in the study population was 0.4%. A higher prevalence of infection was observed in the group whose participants’ age was ≤ 25 years, at a rate of 0.6%. There was no significant increase or decrease in the number of positive test results over time. The prevalence of the infection in those aged between 10 and 19 years, 20-29 years, 30-39 years, 40-49 years, 50-59 years, and 60 years or above was respectively 0.87%, 0.50%, 0.36%, 0.22%, 0.17%, and 0.26%.

CONCLUSION: The screening of asymptomatic young women would have the potential to reduce infection, transmission, and sequelae of infection by this agent.

PMID:37338789 | DOI:10.1007/s42770-023-01039-6

Braz J Microbiol. 2023 Jun 20. doi: 10.1007/s42770-023-01027-w. Online ahead of print.

ABSTRACT

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as blisters/ulcers. However, severe conditions such as keratitis, encephalitis, and systemic infections may occur, generally associated with the patient’s immunological condition. Although Acyclovir® (ACV) and its analogs are the reference drugs for herpetic infections, the number of ACV-resistant HSV infections is growing exponentially. Therefore, new natural products’ bioactive compounds have been studied to develop novel effective anti-herpetics. Trichilia catigua is a plant widely used in traditional medicine, including the treatment of skin diseases and sexual infections. In our study, 16 extracts from the bark of T. catigua, obtained with different solvents and their combinations, were evaluated against HSV-1 AR and HSV-2, respectively, ACV resistance and genital strains in vitro. The extracts with the highest selectivity index were used to prepare new topical anti-herpetic formulations and confirmed in vivo. Two new topical formulations were suggested to treat cutaneous and genital herpetic recurrent lesions. The cytotoxicity and antiviral activity were tested using the MTT method. The cytotoxic (CC₅₀) and inhibitory (IC₅₀) concentrations of 50% and the selectivity index (SI: CC₅₀/IC₅₀) were determined. Tc12, Tc13, and Tc16 were added to the formulations. Infected BALB/c mice were treated for 8 days, and the severity of the herpetic lesions was analyzed daily. All CEs showed a CC₅₀ value ranging from 143 to 400 µg/mL, except for Tc3 and Tc10. Tc12, Tc13, and Tc16 showed the best SI in the 0 h, virucidal, and adsorption inhibition assays. In the in vivo test against HSV-1 AR, the infected animals treated with creams were statistically different from the infected non-treated animals and similar to ACV-treated mice. In HSV-2-infected genitalia, similar effects were found for Tc13 and Tc16 gels. The present study demonstrated that extracts from the bark of T. catigua, traditionally used in folk medicine, are a valuable source of active compounds with anti-herpetic activity. The extracts showed a virucidal mechanism of action and prevented the initial stages of viral replication. The cutaneous and genital infections were strongly inhibited by the Tc12, Tc13, and Tc16 extracts. New topical therapeutic alternatives using Trichilia catigua extracts are suggested for patients infected with ACV-resistant strains of HSV.

PMID:37338788 | DOI:10.1007/s42770-023-01027-w