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Journal of Infection and Public Health Jul 2024Neutralizing monoclonal antibodies (NMabs) are recognized for their efficacy against non-severe COVID-19. However, spike protein mutations may confer resistance. This... (Comparative Study)
Comparative Study
Unveiling therapeutic dynamics: An in-depth comparative analysis of neutralizing monoclonal antibodies and favipiravir in alleviating COVID-19 outpatients impacts among middle-aged and special populations (MA-FAST).
BACKGROUND
Neutralizing monoclonal antibodies (NMabs) are recognized for their efficacy against non-severe COVID-19. However, spike protein mutations may confer resistance. This study evaluates the effectiveness of favipiravir (FPV) versus NMabs in preventing severe COVID-19 in special populations.
METHODS
A retrospective cohort was conducted on middle-aged, elderly, diabetic, or obese patients with COVID-19 treated with either FPV or NMabs. Propensity score matching (PSM) was used for analysis.
RESULTS
The study included 1410 patients, resulting in four cohorts: middle-aged (36), elderly (48), diabetic (46), and obese (28) post-PSM. No significant differences were noted in 28-day emergency department (ED) visits across all groups between NMabs and FPV treatments, despite lower immunity in the FPV group. However, the diabetic group treated with FPV had higher 28-day hospitalization and oxygen supplemental, with no differences in the other groups. Intensive care unit (ICU) admissions, invasive mechanical ventilation, and mortality rates were similar between the two treatments.
CONCLUSIONS
Early dose-adjusted FPV showed no difference from NMabs in preventing ED visits, ICU admissions, ventilator needs, or mortality among patients with major comorbidities. Diabetic patients on FPV experienced higher hospitalizations and oxygen needs, with no observed differences in other groups. FPV may be a viable alternative, especially in settings with limited resources.
Topics: Humans; Amides; Pyrazines; Middle Aged; Male; Female; Retrospective Studies; Aged; Antibodies, Neutralizing; COVID-19 Drug Treatment; SARS-CoV-2; Antiviral Agents; Antibodies, Monoclonal; COVID-19; Hospitalization; Obesity; Outpatients; Diabetes Mellitus; Adult
PubMed: 38865775
DOI: 10.1016/j.jiph.2024.102471 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Jun 2024To assess the safety of sitagliptin added to metformin on cardiovascular adverse events in real world patients with type 2 diabetes mellitus (T2DM).
OBJECTIVE
To assess the safety of sitagliptin added to metformin on cardiovascular adverse events in real world patients with type 2 diabetes mellitus (T2DM).
METHODS
Real world data from Yinzhou Regional Health Care Database were used to select T2DM patients with diagnosis and treatment records in the platform from January 1, 2017 to December 31, 2022. According to drug prescription records, the patients were divided into metformin plus sitagliptin group (combination group) and metformin monotherapy group(monotherapy group). A series of retrospective cohorts were constructed according to the index date.Finally, full retrospective cohorts were constructed according to propensity score model, including baseline covariates that might be related to outcomes, to match the subjects in the combination group and monotherapy group for the purpose of increasing the comparability of baseline characteristics. The participants were followed up from the index date until the first occurrence of the following events: Diagnosis of outcomes, death, or the end of the study period (December 31, 2022). Cox proportional risk model was used to estimate the hazard ratio()and 95% confidence interval () of sitagliptin added to metformin on 3-point major adverse cardiovascular events (3P-MACE) combination outcome and secondary cardiovascular outcomes.
RESULTS
Before propensity score matching, the proportion of the patients in combination group using insulin, α glucosidase inhibitors, sodium-glucose transporter 2 inhibitors (SGLT-2I) and glienides at baseline was higher than that in monotherapy group, and the baseline fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels in combination group were higher than those in monotherapy group. After propensity score matching, 5 416 subjects were included in the combination group and the monotherapy group, and baseline characteristics were effectively balanced between the groups. The incidence densities of 3P-MACE were 6.41/100 person years and 6.35/100 person years, respectively. Sitagliptin added to metformin did not increase or decrease the risk of 3P-MACE compared with the metformin monotherapy (=1.00, 95% : 0.91-1.10). In secondary outcomes analysis, the incidence of cardiovascular death was lower in the combination group than in the monotherapy group (=0.59, 95% : 0.41-0.85), and no association was found between sitagliptin and the risk of myocardial infarction and stroke (=1.12, 95% : 0.89-1.41; =0.99, 95% : 0.91-1.12).
CONCLUSION
In T2DM patients in Yinzhou district of Ningbo, compared with metformin alone, sitagliptin added to metformin may reduce the risk of cardiovascular death, and do not increase the incidence of overall cardiovascular events. The results of this study can provide real-world evidence for post-marketing cardiovascular safety evaluation of sitagliptin.
Topics: Humans; Diabetes Mellitus, Type 2; Sitagliptin Phosphate; Metformin; Retrospective Studies; Hypoglycemic Agents; Male; Female; Drug Therapy, Combination; Cardiovascular Diseases; Middle Aged; Propensity Score; Proportional Hazards Models; Aged
PubMed: 38864127
DOI: 10.19723/j.issn.1671-167X.2024.03.008 -
BMC Endocrine Disorders Jun 2024Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph...
OBJECTIVE
Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs.
METHODS
Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases.
RESULTS
In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas.
CONCLUSION
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Topics: Humans; Ubiquitin Thiolesterase; Iran; Endosomal Sorting Complexes Required for Transport; Pituitary ACTH Hypersecretion; Adult; Female; Male; Endopeptidases; Mutation; Middle Aged; ACTH-Secreting Pituitary Adenoma; Middle Eastern People
PubMed: 38862897
DOI: 10.1186/s12902-024-01619-z -
Scientific Reports Jun 2024The European brittle star Amphiura filiformis emits blue light, via a Renilla-like luciferase, which depends on the dietary acquisition of coelenterazine. Questions...
The European brittle star Amphiura filiformis emits blue light, via a Renilla-like luciferase, which depends on the dietary acquisition of coelenterazine. Questions remain regarding luciferin availability across seasons and the persistence of luminous capabilities after a single boost of coelenterazine. To date, no study has explored the seasonal, long-term monitoring of these luminous capabilities or the tracking of luciferase expression in photogenic tissues. Through multidisciplinary analysis, we demonstrate that luminous capabilities evolve according to the exogenous acquisition of coelenterazine throughout adult life. Moreover, no coelenterazine storage forms are detected within the arms tissues. Luciferase expression persists throughout the seasons, and coelenterazine's presence in the brittle star diet is the only limiting factor for the bioluminescent reaction. No seasonal variation is observed, involving a continuous presence of prey containing coelenterazine. The ultrastructure description provides a morphological context to investigate the green autofluorescence signal attributed to coelenterazine during luciferin acquisition. Finally, histological analyses support the hypothesis of a pigmented sheath leading light to the tip of the spine. These insights improve our understanding of the bioluminescence phenomenon in this burrowing brittle star.
Topics: Animals; Seasons; Pyrazines; Imidazoles; Echinodermata; Luminescence; Luciferases; Luminescent Measurements; Light
PubMed: 38853171
DOI: 10.1038/s41598-024-64010-x -
International Journal of Food... Jun 2024The impact of paprika and dextrose addition on the surface of dry cured loins was analysed attending to differences in microbiota composition and aroma profile. Three...
The impact of paprika and dextrose addition on the surface of dry cured loins was analysed attending to differences in microbiota composition and aroma profile. Three different types of loins containing either dextrose (D), paprika (P) or a mixture of dextrose and paprika (DP) were manufactured. The loins were characterized using physic-chemical parameters, free amino acids, volatile compounds and aroma sensorial analysis, as well as applying microbiological counts and metagenomics of the 16S rRNA gene and its rDNA region. The analysis of volatile compounds clearly distinguished all loins, whereas the total content of free amino acids only separated P from D and DP loins. The main sensory differences were linked to paprika addition, which increased the perception of paprika and smoky odors as well as cured, savoury and cheesy notes. Microbial counts analysis could not differentiate between the three loin types; however, metagenomics analysis revealed clear differences in key bacterial and fungal genera among the three loins. Paprika addition favoured dominance of Latilactobacillus in the microbiota of P loins. On the contrary, dextrose addition caused the dominance of Staphylococcus in the microbiota of D loins. In DP loins, both genera were similarly represented in the bacterial community. Regarding fungi, large differences could be observed within the P and D loins, whereas the proportion of Debaryomyces in DP loins increased. The microbiota composition of DP loins controlled the lipid oxidation phenomenon, reducing the generation of derived volatiles producing rancid notes and increase the volatile compounds derived from amino acids such as branched aldehydes, pyrazines and pyrroles, providing particular aroma notes to the loins.
PubMed: 38851175
DOI: 10.1016/j.ijfoodmicro.2024.110782 -
Food Chemistry: X Jun 2024The aim of this study deals with characterize the volatile profiles of gluten free flours and bakery products. An appropriate HS-SPME/GC-MS methods for the...
The aim of this study deals with characterize the volatile profiles of gluten free flours and bakery products. An appropriate HS-SPME/GC-MS methods for the quantification analyses was performed and corn starch solid as standards was used. 34 different samples were analysed, and 127 compounds distributed in 4 classes (alcohols, aldehydes and ketones, heterocyclic compounds, and terpenes), that make up the aroma of these gluten free, were identified. The developed method is characterized by detection limits of 0.0004 and 0.0047 mg/kg for camphor and pyrazine, respectively, and linearity of quantification standards were between 0.990 and 0.998 for a range of 3-50 mg/kg.
PubMed: 38840722
DOI: 10.1016/j.fochx.2024.101399 -
Oncoimmunology 2024Recently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and...
Recently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and surface exposure of calreticulin (CALR) in multiple myeloma (MM) cells responding to bortezomib. Hence, GABARAP-defective MM cells fail to undergo immunogenic cell death.
Topics: Multiple Myeloma; Humans; Bortezomib; Adaptor Proteins, Signal Transducing; Antineoplastic Agents; Microtubule-Associated Proteins; Apoptosis Regulatory Proteins; Immunogenic Cell Death; Cell Line, Tumor; Autophagy; Calreticulin
PubMed: 38812570
DOI: 10.1080/2162402X.2024.2360275 -
PloS One 2024To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency...
To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency testing performed DST, and the sensitivity, specificity, reproducibility, and accordance rate were calculated from data of 13 rounds proficiency testing results for DST from 2008 to 2021. A total of 30 and 20 strains of Mycobacterium tuberculosis with known susceptibility results were sent to each laboratory in 2008 to 2019, 2020 and 2021, respectively. The number of participating laboratories ranged from 30 in 2009 to 546 in 2021. L-J DST was the predominant method. The specificity presented relatively higher than sensitivity. Improvement of specificity were observed for all drugs through the years, while sensitivity did not show improvement for amikacin and capreomycin. Accordance rate of pyrazinamide and kanamycin and reproducibility of capreomycin and pyrazinamide were not significantly improved through the years. Most of the participating laboratories significantly improved the quality of their DST through the consecutive rounds of proficiency testing except for second-line injectable drugs and pyrazinamide. The results highlight the importance of developing novel and/or improving existing methods for phenotypic DST for certain drugs.
Topics: Mycobacterium tuberculosis; Microbial Sensitivity Tests; China; Antitubercular Agents; Humans; Laboratory Proficiency Testing; Reproducibility of Results; Phenotype; Amikacin; Pyrazinamide
PubMed: 38809914
DOI: 10.1371/journal.pone.0304265 -
Renal Failure Dec 2024As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a...
Chemotherapy plus therapeutic plasmapheresis with 4% human albumin solution in multiple myeloma patients with acute kidney injury: a prospective, open-label, proof-of-concept study.
As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median -12.12%, interquartile ranges (IQRs) -18.62 to -5.626) and creatine (median -46.91 μmol/L, IQR -64.70 to -29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m), IQR 16.03-25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.
Topics: Humans; Multiple Myeloma; Acute Kidney Injury; Plasmapheresis; Male; Female; Middle Aged; Prospective Studies; Glomerular Filtration Rate; Aged; Bortezomib; Proof of Concept Study; Serum Albumin, Human; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Adult; Combined Modality Therapy; Myeloma Proteins
PubMed: 38803220
DOI: 10.1080/0886022X.2024.2356708