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Dermatology and Therapy Jul 2024Abrocitinib, an oral, once-daily, Janus kinase (JAK) 1-selective inhibitor, is approved for the treatment of adults and adolescents with moderate-to-severe atopic...
Abrocitinib, an oral, once-daily, Janus kinase (JAK) 1-selective inhibitor, is approved for the treatment of adults and adolescents with moderate-to-severe atopic dermatitis (AD). Abrocitinib has shown rapid and sustained efficacy in phase 3 trials and a consistent, manageable safety profile in long-term studies. Rapid itch relief and skin clearance are more likely to be achieved with a 200-mg daily dose of abrocitinib than with dupilumab. All oral JAK inhibitors are associated with adverse events of special interest and laboratory changes, and initial risk assessment and follow-up monitoring are important. Appropriate selection of patients and adequate monitoring are key for the safe use of JAK inhibitors. Here, we review the practical use of abrocitinib and discuss characteristics of patients who are candidates for abrocitinib therapy. In general, abrocitinib may be used in all appropriate patients with moderate-to-severe AD in need of systemic therapy, provided there are no contraindications, e.g., in patients with active serious systemic infections and those with severe hepatic impairment, as well as pregnant or breastfeeding women. For patients aged ≥ 65 years, current long-time or past long-time smokers, and those with risk factors for venous thromboembolism, major adverse cardiovascular events, or malignancies, a meticulous benefit-risk assessment is recommended, and it is advised to start with the 100-mg dose, when abrocitinib is the selected treatment option.
PubMed: 38954384
DOI: 10.1007/s13555-024-01200-5 -
Journal of Veterinary Pharmacology and... Jul 2024Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia... (Review)
Review
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual β-cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis.
PubMed: 38954371
DOI: 10.1111/jvp.13466 -
In Silico Drug Repurposing Against PSMB8 as a Potential Target for Acute Myeloid Leukemia Treatment.Molecular Biotechnology Jul 2024PSMB8 emerges as a prominent gene associated with cancer survival, yet its potential therapeutic role in acute myeloid leukemia (AML) remains unexplored within the...
PSMB8 emerges as a prominent gene associated with cancer survival, yet its potential therapeutic role in acute myeloid leukemia (AML) remains unexplored within the existing literature. The principal aim of this study is to systematically screen an expansive library of molecular entities, curated from various databases to identify the prospective inhibitory agents with an affinity for PSMB8. A comprehensive assortment of molecular compounds obtained from the ZINC15 database was subjected to molecular docking simulations with PSMB8 by using the AutoDock tool in PyRx (version 0.9.9) to elucidate binding affinities. Following the docking simulations, a select subset of molecules underwent further investigation through comprehensive ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis employing AdmetSar and SwissADME tools. Finally, RMSD, RMSF, Rg, and H bond analyses were conducted via GROMACS to determine the best conformationally dynamic molecule that represents the candidate agent for the study. Following rigorous evaluation, Adozelesin, Fiduxosin, and Rimegepant have been singled out based on considerations encompassing bioavailability scores, compliance with filter criteria, and acute oral toxicity levels. Additionally, ligand interaction analysis indicates that Adozelesin and Fiduxosin exhibit an augmented propensity for hydrogen bond formation, a factor recognized for its facilitative role in protein-ligand interactions. After final analyses, we report that Fiduxosin may offer a treatment possibility by reversing the low survival rates caused by PSMB8 high activation in AML. This study represents a strategic attempt to repurpose readily available pharmaceutical agents, potentially obviating the need for de novo drug development, and thereby offering promising avenues for therapeutic intervention in specific diseases.
PubMed: 38954355
DOI: 10.1007/s12033-024-01224-4 -
CNS Drugs Jul 2024TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone that is approved by the United States Food and Drug Administration for the...
BACKGROUND
TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone that is approved by the United States Food and Drug Administration for the treatment of schizophrenia in adults. In the phase 3, randomized, double-blind RIsperidone Subcutaneous Extended-release (RISE) study, TV-46000 once monthly (q1m) and once every 2 months (q2m) significantly prolonged time to impending relapse compared with placebo [5.0-fold (q1m) and 2.7-fold (q2m)]. This phase 3, randomized, double-blind Safety in Humans of TV-46000 subcutaneous INjection Evaluation (SHINE) study was designed to evaluate the long-term safety, tolerability, and exposure of TV-46000 in schizophrenia.
METHODS
Patients who completed RISE without relapse (rollover) or who were newly recruited (de novo) were eligible for the SHINE study. Patients were initially stabilized on oral risperidone for 12 weeks (completed in RISE for rollover, or in SHINE for de novo). Patients in the de novo cohort and patients who received placebo in RISE were randomized 1:1 in SHINE to receive TV-46000 q1m or q2m for up to 56 weeks. Primary endpoint for SHINE was frequency of reported adverse events (AEs); event rates [ER; events per 100 patient-years (PYs)] were calculated for each AE by patients upon general questioning.
RESULTS
Overall, 336 patients were randomized in SHINE [TV-46000 q1m, n = 174; TV-46000 q2m, n = 162; of these, de novo, n = 109 and rollover, n = 227 (n = 172 patients were treated and n = 55 received placebo)]. A total of 334 patients were evaluated for safety [q1m, n = 172 (PY = 97.8); q2m, n = 162 (PY = 104.5)]. Proportions of patients (ER) with ≥ 1 AE and ≥ 1 treatment-related AE were 37% (180.0) and 21% (84.9) for TV-46000 q1m and 46% (157.9) and 20% (70.8) for TV-46000 q2m, respectively. Frequent treatment-related AEs [≥ 3% of patients in either group; proportion of patients (ER)] were injection site pain [q1m, 5% (24.5); q2m, 4% (22.0)] and injection site nodule [q1m, 2% (9.2); q2m, 6% (12.4)]. The proportions of patients with serious AEs was 5% for TV-46000 q1m and 7% for TV-46000 q2m; serious AEs reported for ≥ 2 patients overall were worsening schizophrenia [q1m, n = 1 (< 1%; ER, 1.02); q2m, n = 2 (1%; ER, 1.91)] and hyperglycemia [q1m, n = 1 (< 1%; ER, 1.02); q2m, n = 1 (< 1%; ER, 0.96)]. Of three reported deaths, none were related to treatment. Overall, eight patients discontinued treatment because of AEs. Similar or somewhat lower rates of AEs were reported for patients who rolled over from TV-46000 treatment compared with those who had no prior TV-46000 treatment (de novo and placebo rollover). Most AEs related to injection site reactions were mild; no patient had a severe reaction.
CONCLUSION
Results from this long-term safety study add to the favorable safety profiles of TV-46000 q1m and q2m, consistent with other formulations of risperidone and previous studies with TV-46000.
REGISTRATION
ClinicalTrials.gov, NCT03893825; 27 March 2019.
PubMed: 38954317
DOI: 10.1007/s40263-024-01102-2 -
Oral and Maxillofacial Surgery Jul 2024An extensive literature search among six eletronic databases and Grey Literature was used to identify systematic reviews (S) that could respond if: in individuals... (Review)
Review
MATERIALS AND METHODS
An extensive literature search among six eletronic databases and Grey Literature was used to identify systematic reviews (S) that could respond if: in individuals diagnosed with OKC (P), is there any influence of the treatment method (I/C) on the recurrence rate of the lesion (O)? After evaluating all titles and abstracts and then applying the eligibility criteria, the included studies were read in full, and data were extracted based on a standardized sheet ordered in the PICO sequence. The assessment of the quality of the systematic reviews included, was determined by AMSTAR2, and final synthesis were descriptively made based on the results and quality of the systematic reviews.
RESULTS
From a total of 19 included systematic reviews, it was observed that the most used treatment for OKC was enucleation, followed by enucleation with adjuvant techniques and marsupialization. The mean percentage of recurrence was 16,2%, and the highest OKC recurrence rate was 43.2% after simple enucleation. The use of adjuvant techniques promoted reductions in OKC recurrence rates. The overall methodological quality of systematic reviews was critically low, and this parameter demonstrate the need for more studies to facilitate the choose of the treatment.
CONCLUSION
Despite being the most used treatment, simple enucleation is related to the highest rate of recurrence, except when performed after marsupialization/decompression. In addition, the use of adjuvant techniques has a strong impact on reducing the likelihood of recurrence. However, these findings are not conclusive because of the critically low quality of the systematic reviews.
PubMed: 38954313
DOI: 10.1007/s10006-024-01277-4 -
Hemifacial microsomia: a scoping review on progressive facial asymmetry due to mandibular deformity.Oral and Maxillofacial Surgery Jul 2024This scoping review explores various parameters of the mandible in progressive facial asymmetry (FA) in hemifacial microsomia (HFM) patients, highlighting its... (Review)
Review
PURPOSE
This scoping review explores various parameters of the mandible in progressive facial asymmetry (FA) in hemifacial microsomia (HFM) patients, highlighting its relationship with sex, population, and age group.
METHODS
The review was based on a comprehensive search of PubMed, EBSCOhost, and Web of Science. Eligible studies that met the inclusion criteria form part of the selection study. The included studies were appraised using screening and quantitative criteria of mixed-method appraisal tools. The authors utilised a pre-set data extraction form to obtain information from the included studies.
RESULTS
Eleven studies met the inclusion criteria. The mandible parameters used were angular measurements, chin point, ramal height, body length, and total length. There was no relationship between FA and sex in HFM patients in the included studies. Most of the studies were comprised of European participants (55%), followed by Americans (36%) and Chinese (9%). The age groups included in the selected studies were categorised as dentition age (18%), early-to-middle childhood (18%), and varied ages (64%). The data presented in this review only pertains to the anomalous characteristics recorded on the affected side in HFM patients. No concomitant control data was recorded in this review.
CONCLUSION
An assessment of the included studies revealed that FA does not increase with age in HFM. Hence, FA is non-progressive in HFM patients. This information is relevant to diagnosing and managing HFM patients. More reports are needed on the progression of FA in HFM patients.
PubMed: 38954312
DOI: 10.1007/s10006-024-01276-5 -
Probiotics and Antimicrobial Proteins Jul 2024Metabolic syndrome (MetS) is a global epidemic complex and will cause serious metabolic comorbidities without treatment. A prevention strategy for MetS development has...
Effect of Lacticaseibacillus casei LC2W Supplementation on Glucose Metabolism and Gut Microbiota in Subjects at High Risk of Metabolic Syndrome: A Randomized, Double-blinded, Placebo-controlled Clinical Trial.
Metabolic syndrome (MetS) is a global epidemic complex and will cause serious metabolic comorbidities without treatment. A prevention strategy for MetS development has been proposed to modulate gut microbiota by probiotic administration to improve intestinal dysbiosis and benefit the host. Lacticaseibacillus casei LC2W has exhibited positive effects in preventing colitis and anti-hypertension in vivo. However, the effect of L. casei LC2W on subjects at high risk of MetS is unknown. Here, a randomized, double-blinded, placebo-controlled study was conducted on 60 subjects with high risk of MetS, and the hypoglycemic and hypolipidemic activity and possible pathways of L. casei LC2W were inferred from the correlation analysis with gut microbiome composition, function, and clinical phenotypic indicators. The results showed that oral administration of L. casei LC2W could exert significant benefits on weight control, glucose and lipid metabolism, inflammatory and oxidative stress parameters, and SCFA production, as well as modulate the composition of gut microbiota. The relative abundance of Lacticaseibacillus, Bifidobacterium, Dorea, and Blautia was enriched, and their interaction with other gut microbes was strengthened by oral administration of L. casei LC2W, which was beneficial in ameliorating gut inflammation, promoting glucose and lipids degradation pathways, thus alleviated MetS. The present study confirmed the prevention effects of L. casei LC2W towards MetS from aspects of clinical outcomes and microflora modulation, providing an alternative strategy for people at high risk of MetS.Trial registration: The study was proactively registered in ClinicalTrial.gov with the registration number of ChiCTR2000031833 on April 09, 2020.
PubMed: 38954305
DOI: 10.1007/s12602-024-10312-5 -
Pituitary Jun 2024We previously showed the clinical characteristics of acromegaly with a paradoxical growth hormone (GH) response to oral glucose or thyrotropin-releasing hormone....
PURPOSE
We previously showed the clinical characteristics of acromegaly with a paradoxical growth hormone (GH) response to oral glucose or thyrotropin-releasing hormone. However, the clinical characteristics of acromegaly with an increased GH response to luteinizing hormone-releasing hormone (LHRH responders) remain unclear. The aim of the present study was to evaluate the clinical characteristics, especially gonadotroph-related characteristics of LHRH responders in acromegaly.
METHODS
The clinical characteristics of 33 LHRH responders and 81 LHRH nonresponders were compared.
RESULTS
No differences in age, sex or basal serum levels of GH, insulin-like growth factor-1 (IGF-1), and gonadotropin were observed between the two groups. Steroidogenic factor 1 (SF-1), gonadotropin-releasing hormone receptor (GnRHR), and LH expression was more frequently observed in LHRH responders (P < 0.05). In addition, a greater increased rate of GH after LHRH loading, and the proportion of GnRHR and gonadotropin expression was observed in pituitary tumor with SF-1 expression than that without the expression (P < 0.01). LHRH responders showed a greater GH decrease in the octreotide test and a greater IGF-1 decrease after first-generation somatostatin ligand than LHRH nonresponders (P < 0.05). Furthermore, the proportion of hypointense pituitary tumors on T2-weighted magnetic resonance imaging and tumors with densely granulated type was higher in LHRH responders than in LHRH nonresponders, respectively (P < 0.05). No difference between the two groups was observed in either somatostatin receptor 2 or 5 expression.
CONCLUSIONS
The increased GH response to LHRH is associated with the gonadotroph-related characteristics. This response may reflect the biological characteristics of somatotroph tumors.
PubMed: 38954291
DOI: 10.1007/s11102-024-01410-2 -
Veterinary Research Communications Jul 2024Due to events related to the urbanization process, specimens of Saimiri collinsi are often referred to veterinarians specializing in the treatment of wild animals. With...
Due to events related to the urbanization process, specimens of Saimiri collinsi are often referred to veterinarians specializing in the treatment of wild animals. With these professionals and the oral health of this species in mind, we evaluated the skull and the exact location of the infraorbital, mentual and mandibular foramens, with the aim of supporting the anesthetic block for dental procedures in Saimiri collinsi. The infraorbital foramen was located in the maxillary bone and was arranged with one on each side, except in one individual, with a pair in each antimer. The mentual foramen was located in the diastema between the canine tooth and the lateral incisor. The mandibular foramen was located medially on the ramus of the mandible, close to the mandibular incisure. The distances between the foramina and the main reference points, were greater in females than in males (p < 0.05). For access purposes, in the foramens investigated we suggest using a Gingival Needle 30G 21 mm Short, positioned externally at 15º to the maxillary bone to access the infraorbital foramen. Externally, perpendicular to the chin, in the diastema between the lower lateral incisor tooth and the canine tooth, to approach the mentual foramen, and ventral to the edge of the mandibular body, at a 90º angle, to access the mandibular foramen.
PubMed: 38954255
DOI: 10.1007/s11259-024-10447-4 -
Folia Microbiologica Jul 2024Oral microorganisms are closely related to oral health, the occurrence of some oral diseases is associated with changes in the oral microbiota, and many studies have...
Oral microorganisms are closely related to oral health, the occurrence of some oral diseases is associated with changes in the oral microbiota, and many studies have demonstrated that traditional smoking can affect the oral microbial community. However, due to the short time since the emergence of e-cigarettes, fewer studies are comparing oral microorganisms for users of e-cigarettes versus cigarettes. We collected saliva from 40 non-smokers (NS), 46 traditional cigarette smokers (TS), and 27 e-cigarette consumers (EC), aged between 18 and 35 years. We performed 16S rRNA gene sequencing on the saliva samples collected to study the effects of e-cigarettes versus traditional cigarettes on the oral microbiome. The results showed that compared with the NS group, the alpha diversity of oral flora in saliva was altered in the TS group, with no significant change in the e-cigarette group. Compared with the NS and EC groups, the relative abundance of Actinomyces and Prevotella was increased in the TS group. However, compared with the NS and TS groups, the relative abundance of Veillonella was increased, and the relative abundance of Porphyromonas and Peptostreptococcus was decreased in the EC group. These results showed that both e-cigarettes and traditional cigarettes could alter the structure and composition of oral microbiota. The use of traditional cigarettes promotes the growth of some anaerobic bacteria, which may contribute to dental decay and bad breath over time. E-cigarettes have a different effect on the structure and composition of the oral microbial community compared to conventional cigarettes. In order to better understand the effects of e-cigarettes and traditional cigarettes on users' mouths, future studies will investigate the relationship between diseases such as dental caries and periodontitis and changes in oral microbial species levels.
PubMed: 38954243
DOI: 10.1007/s12223-024-01185-w