Arch Endocrinol Metab
December 2024
Pharmacological treatment of obesity is passing through many changes in the last decades; different agents have been approved, and newer options are leaning towards higher efficacy and a more favourable safety profile; however, medications approved for a longer time are still available and useful for many patients. This document is an 2024 Update Position Statement of Specialists from the Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso) and the Brazilian Society of Endocrinology and Metabolism (SBEM), with the aim of reviewing all the approved medications for the management of obesity in Brazil (sibutramine, orlistat, liraglutide, semaglutide and bupropion/naltrexone fixed dose), with the addition of tirzepatide, that is approved in other countries and likely approved soon in Brazil. The review is focused on efficacy, safety profile and the impact of drugs (based on existing studies) on different comorbidities.
View Article and Find Full Text PDFPolyethyleneimine (PEI) is a widely used cationic polyelectrolyte. In organic electronics, it is a universal surface modifier for shifting the electrode work function (Φ) and improving charge injection into electronic devices. This effect may depend on the conformation and dipolar order of the PEI ultrathin film, but their detailed experimental evaluation has not yet been reported.
View Article and Find Full Text PDFObjective: In the absence of head-to-head clinical trials, matching-adjusted indirect comparison (MAIC) was used to compare two Bruton tyrosine kinase inhibitors (BTKis) approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL). This analysis compares the efficacy and safety of acalabrutinib versus ibrutinib using a more mature dataset than a previously published MAIC.
Methods: Individual patient data from 122 patients treated with acalabrutinib in a phase 2 study were weighted to match aggregate baseline characteristics of patients pooled from three separate trials of ibrutinib.
Background: Functional Movement Screen (FMS) is an important tool in the assessment of exercise practice. Assuming FMS lacks precise validity for assessing postural deficits, further research is needed to assess whether it is a sufficiently precise tool for analysing joint mobility. Research aims were to evaluate: convergent validity of Deep Squat (DS) - one of FMS tests - regarding joint mobility, using data from a three-dimensional motion analysis as a comparable method; DS's ability to discriminate between subjects with different joint mobility levels.
View Article and Find Full Text PDFBefore targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL), defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK), had poorer prognosis with chemoimmunotherapy. Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts.
View Article and Find Full Text PDFThis analysis investigated the incidence of sudden deaths (SDs) and non-fatal and fatal ventricular arrhythmias (VAs) in five acalabrutinib clinical trials. In total, 1299 patients received acalabrutinib (exposure, 4568.4 patient-years).
View Article and Find Full Text PDFArch Endocrinol Metab
November 2023
Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD.
Material And Methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD.
Follicular unit excision (FUE) graft dissection has become the dominant method of donor harvesting globally, however, only a percentage of donor hair can be excised inside the safe donor area before visible donor thinning occurs. Compared to linear strip excision (LSE) where all follicular units inside the harvested ellipse of hair are used, FUE poses substantial limitations for lifetime graft yield and, therefore, cosmetic coverage in patients with advanced pattern hair loss. This paper reviews how combining the donor harvesting methods of FUE and LSE has been shown to optimize graft yield while minimizing the risk of donor depletion from overharvesting.
View Article and Find Full Text PDFArch Endocrinol Metab
August 2023
Obesity is largely undertreated, in part because of the stigma surrounding the disease and its treatment. The use of the term "weight loss drugs" to refer to medications for the treatment of obesity may contribute to this stigma, leading to the idea that anyone who wants to lose weight could use them and that short-term use, only in the active weight loss phase would be enough. On the contrary, the use of terms such as "medications to treat obesity" or "anti-obesity medications" conveys the idea that the treatment is directed at the disease rather than the symptom.
View Article and Find Full Text PDFBackground: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020.
Methods: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications.
ELEVATE-RR demonstrated noninferior progression-free survival and lower incidence of key adverse events (AEs) with acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia. We further characterize AEs of acalabrutinib and ibrutinib via post hoc analysis. Overall and exposure-adjusted incidence rate was assessed for common Bruton tyrosine kinase inhibitor-associated AEs and for selected events of clinical interest (ECIs).
View Article and Find Full Text PDFPhysical membrane models permit to study and quantify the interactions of many external molecules with monitored and simplified systems. In this work, we have constructed artificial Langmuir single-lipid monolayers with dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), dipalmitoylphosphatidylserine (DPPS), or sphingomyelin to resemble the main lipid components of the mammalian cell membranes. We determined the collapse pressure, minimum area per molecule, and maximum compression modulus () from surface pressure measurements in a Langmuir trough.
View Article and Find Full Text PDFAcalabrutinib monotherapy (A) and acalabrutinib plus obinutuzumab (A + O) demonstrated improved efficacy and safety versus chlorambucil plus obinutuzumab (C + O) among treatment-naive patients with chronic lymphocytic leukaemia (CLL) in the ELEVATE-TN trial. The relative risk-benefit at a median follow-up of 47 months was assessed using Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST) methodology. Patient data were partitioned into 3 states: time with toxicity (TOX); time without symptoms or toxicity (TWiST); and time after relapse (REL).
View Article and Find Full Text PDFSixteen geosterane derivatives were synthesized in up to 57 % overall yields in four steps harnessing the olefin cross-metathesis (OCM) and Metal hydride H atom transfer (MHAT) or homogeneous hydrogenation reactions as key steps. Drawing on this strategy, the diastereomeric ratio (d. r.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
November 2022
Chitosan is a versatile and biocompatible cationic antimicrobial polymer obtained from sustainable sources that is effective against a wide range of microorganisms. Although it is soluble only at low pH, chitosan oligomers (ChitO) are soluble in pure water and thus more appropriate for antibacterial applications. Although there is a vast literature on chitosan's antimicrobial activity, the molecular details of its interaction with biomembranes remain unclear.
View Article and Find Full Text PDFThe gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains largely unexplored. Here we show that formate, a metabolite produced by the CRC-associated bacterium Fusobacterium nucleatum, promotes CRC development.
View Article and Find Full Text PDFEllipticine was synthesized in six steps and 20% global yield starting from the readily available 2,5-dimethoxy isoquinoline. Unprecedented regioselective control of the nucleophilic attack on the isoquinoline-5,8-dione is first described. Investigation of the possible pathways of this transformation through density functional theory calculations reveals unexpected -oxide assistance in cascade tautomerizations, which was crucial for directing the nucleophilic attack and hastening the overall process.
View Article and Find Full Text PDFBackground: Prior durvalumab (anti-PD-L1 agent) studies in platinum-refractory metastatic urothelial carcinoma evaluated a dose of 10 mg/kg administered every two weeks. The nonrandomised phase 3b STRONG study (NCT03084471) evaluated the safety and efficacy of fixed-dose durvalumab at a more convenient dosing schedule in a previously treated patient population, more similar to a real-world clinical setting.
Patients And Methods: 867 patients with urothelial or nonurothelial urinary tract carcinoma (UTC) who progressed on or after platinum or nonplatinum chemotherapy were treated with durvalumab 1500 mg every four weeks; 87% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and 13% had an ECOG PS of 2.
Growth Horm IGF Res
February 2022
Objective: Cardiovascular (CV) disease is still a major cause of excessive morbidity and mortality in patients with active acromegaly, which may be attributed to a high prevalence of associated pro-atherosclerotic risk factors. However, a direct effect of GH/IGF-1 excess on the vasculature has been previously suggested, warranting further investigation. The present study was designed to investigate whether chronic GH/IGF-1 excess is associated with an increased prevalence of subclinical atherosclerosis in patients with acromegaly.
View Article and Find Full Text PDFInt J Mol Sci
September 2021
,-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with - and -cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties.
View Article and Find Full Text PDFHypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition.
View Article and Find Full Text PDFCervical carcinoma is the fourth leading cause of death among women worldwide. Epidemiological studies claim that human papillomavirus (HPV) infection is a necessary condition for cervical cancer development. Knowledge of the geographic distribution of HPV is important in guiding the introduction of prophylactic vaccines.
View Article and Find Full Text PDFBackground: Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of <5% for those with metastatic, stage IV disease. We have reviewed current treatment paradigms and emerging treatment options for these patients.
Methods: The websites of seven national or international organizations were searched for metastatic UC treatment guidelines.