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New Trends in Pharmacological Treatments for Osteoarthritis
Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.
Journal Article
Latest insights in disease-modifying osteoarthritis drugs development
Osteoarthritis (OA) is a prevalent and severely debilitating disease with an unmet medical need. In order to alleviate OA symptoms or prevent structural progression of OA, new drugs, particularly disease-modifying osteoarthritis drugs (DMOADs), are required. Several drugs have been reported to attenuate cartilage loss or reduce subchondral bone lesions in OA and thus potentially be DMOADs. Most biologics (including interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibitors), sprifermin, and bisphosphonates failed to yield satisfactory results when treating OA. OA clinical heterogeneity is one of the primary reasons for the failure of these clinical trials, which can require different therapeutic approaches based on different phenotypes. This review describes the latest insights into the development of DMOADs. We summarize in this review the efficacy and safety profiles of various DMOADs targeting cartilage, synovitis, and subchondral bone endotypes in phase 2 and 3 clinical trials. To conclude, we summarize the reasons for clinical trial failures in OA and suggest possible solutions.
Journal Article
Evaluating the biodistribution for 68GaGa-PSMA-11 and 18FF-PSMA-1007 PET/CT with an inter- and intrapatient based analysis
Background
Liver uptake in [
68
Ga]Ga-PSMA-11 PET is used as an internal reference in addition to clinical parameters to select patients for [
177
Lu]Lu-PSMA-617 radioligand therapy (RLT). Due to increased demand, [
68
Ga]Ga-PSMA-11 was replaced by [
18
F]F-PSMA-1007, a more lipophilic tracer with different biodistribution and splenic uptake was suggested as a new internal reference. We compared the intra-patient tracer distribution between [
68
Ga]Ga-PSMA-11 and [
18
F]F-PSMA-1007.
Methods
Fifty patients who underwent PET examinations in two centers with both [
18
F]F-PSMA-1007 and [
68
Ga]Ga-PSMA-11 within one year were included. Mean standardized uptake values (SUV
mean
) were obtained for liver, spleen, salivary glands, blood pool, and bone. Primary tumor, local recurrence, lymph node, bone or visceral metastasis were also assessed for intra- and inter-individual comparison.
Results
Liver SUV
mean
was significantly higher with [
18
F]F-PSMA-1007 (11.7 ± 3.9) compared to [
68
Ga]Ga-PSMA-11 (5.4 ± 1.7,
p
< .05) as well as splenic SUV
mean
(11.2 ± 3.5 vs.8.1 ± 3.5,
p
< .05). The blood pool was comparable between the two scans. Malignant lesions did not show higher SUV
mean
on [
18
F]F-PSMA-1007. Intra-individual comparison of liver uptake between the two scans showed a linear association for liver uptake with SUV
mean
[
68
Ga]Ga-PSMA-11 = 0.33 x SUV
mean
[
18
F]F-PSMA-1007 + 1.52 (
r
= .78,
p
< .001).
Conclusion
Comparing biodistribution of [
68
Ga]Ga and [
18
F]F tracers, liver uptake on [
68
Ga]Ga-PSMA-11 PET is the most robust internal reference value. Liver uptake of [
18
F]F-PSMA-1007 was significantly higher, but so was the splenic uptake. The strong intra-individual association of hepatic accumulation between the two scans may allow using of a conversion factor for [
18
F]F-PSMA-1007 as a basis for RLT selection.
Journal Article
Physiology-Guided Selection of Hardware-Assisted Airway Clearance Techniques during Acute Exacerbations of Non-Cystic Fibrosis Bronchiectasis
Introduction: The aim of this study was to assess the short-term clinical effects of individualized, hardware-assisted airway clearance techniques (ACTs) during acute non-cystic fibrosis bronchiectasis (NCFB exacerbations). Methods: In this prospective, controlled cohort study, 46 adults hospitalized with computed tomography-confirmed bilateral (CT-confirmed bilateral) NCFB were assigned to an intervention group (ACT plus pharmacological therapy; n = 23) or a control group (pharmacological therapy alone; n = 23). ACT modality (intrapulmonary percussive ventilation [IPV], high-frequency chest wall oscillation, or mechanical insufflation-exsufflation) was selected based on IPV tolerability and respiratory muscle strength maximum inspiratory pressure Z-score. Outcomes included 24-hour sputum volume, dyspnea (modified medical research council dyspnea scale [mMRC], Borg), spirometry, inflammatory markers, and length of hospital stay. Results: Compared with controls, the intervention group showed greater reductions in sputum volume (−15 vs. −10 mL; p = 0.005) and dyspnea (mMRC −1.0 vs. 0.0; Borg −2.0 vs. −1.0; all p < 0.05), as well as a shorter hospital stay (median 7 vs. 9 days; p < 0.05). There were no differences between groups in spirometric or inflammatory outcomes, and no serious adverse events occurred. Conclusions: Individualized, physiology-guided device-based ACTs improved mucus clearance and dyspnea during acute NCFB exacerbations and were well tolerated, without short-term spirometric change. Larger studies with longer follow-up are needed to confirm efficacy before routine clinical implementation.
Journal Article
Liquid Biopsy for Monitoring EC Patients: Towards Personalized Treatment
Endometrial cancer (EC) is the most frequent gynecological cancer in developed countries and its incidence shows an increasing trend. Fortunately, the prognosis of the disease is good when the tumour is diagnosed in an early phase, but some patients recur after surgery and develop distant metastasis. The therapy options for EC for advanced disease are more limited than for other tumours. Therefore, the application of non-invasive strategies to anticipate the recurrence of localized tumours and guide the treatment in advanced stages represents a clear requirement to improve the survival and quality of life of patients with EC. To achieve this desired precision oncology, it is necessary to invest in the identification and validation of circulating markers that allow a more effective stratification and monitoring of patients. We here review the main advances made for the evaluation of circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), circulating extracellular vesicles (cEVs), and other non-invasive biomarkers as a monitoring tool in the context of localized and advanced endometrial tumours, with the aim of providing a global perspective of the achievements and the key areas in which the use of these markers can be developed into a real clinical tool.
Journal Article
Prioritizing the glucose-lowering medicines for type 2 diabetes by an extended fuzzy decision-making approach with target-based attributes
Different therapeutic classes have been authorized for the treatment of hyperglycemia in type 2 diabetic patients, and even more drug classes are under development. This variety of alternative treatments and the general treatment algorithms of the clinical guidelines lead to a nonuniform prescription of drugs by endocrinologists and diabetic specialists. Diabetes medication choice is a multi-objective problem with many difficulties in making rational decisions because of the wide range of hyperglycemia-lowering agents with multiple benefits and multiple risk elements. This paper proposes a group Entropy–CRiteria Importance Through Inter-criteria Correlation (CRITIC)–Weighted Aggregated Sum Product ASsessment (WASPAS) multi-criteria decision-making (MCDM) model with target-based criteria to prioritize and rank the glucose-lowering medicines for type 2 diabetes using the American Diabetes Association and International Diabetes Federation Clinical Guidelines. The proposed model consists of a weighting method comprising both objective and subjective approaches; the two most common objective approaches (i.e., Entropy and CRITIC methods) are used to find the objective weights. Then, these weights are aggregated with the subjective weights that endocrinologists assign to the criteria. Afterward, a WASPAS target-based method is developed to provide the final ranking of the medications. Finally, the close correlation between the final ranking of the proposed methodology and the average priority order of the medications obtained by different MCDM methods implies the strength and validity of the model performance.
Graphical abstract
Journal Article
Baseline DISE Anatomy Predicts Jaw-Thrust Responsiveness in Obstructive Sleep Apnea
Background: Drug-induced sleep endoscopy (DISE) with a jaw-thrust maneuver is used to simulate mandibular advancement in obstructive sleep apnea (OSA), yet determinants of functional airway improvement remain incompletely defined. Objective: To identify clinical, polysomnographic, and baseline DISE anatomic factors associated with jaw-thrust responsiveness. Methods: We conducted a single-center retrospective observational study of adults with polysomnography-confirmed OSA who underwent DISE with paired baseline and jaw-thrust VOTE assessments between 1 January 2015 and 31 December 2025 (n = 355). Jaw-thrust responsiveness was defined a priori as a within-subject reduction in the number of obstructed VOTE sites (grade ≥ 1). Multivariable logistic regression was used to identify independent correlates within a prespecified explanatory modeling framework. The study was approved by the Institutional Review Board of Taipei Tzu Chi Hospital (protocol 14-IRB079), with the need for informed consent being waived. Results: Jaw thrust reduced overall obstruction burden from two (two to three) to one (one to two) sites (Wilcoxon p < 0.001). Hypopharyngeal levels demonstrated the greatest improvement, particularly at the tongue base (39.2% to 7.6%) and epiglottis (23.9% to 5.4%) (both p < 0.001). Overall, 62.8% met responder criteria and 18.9% achieved complete normalization. In multivariable analysis (n = 272), baseline tongue-base collapse (adjusted odds ratio [aOR] 2.46, 95% CI 1.20–5.04) and greater baseline multilevel obstruction burden (aOR 1.85 per SD, 95% CI 1.19–2.85) were independently associated with responsiveness, whereas conventional PSG severity metrics were not. Conclusions: In adults with OSA, jaw-thrust responsiveness during DISE is more strongly associated with baseline anatomic phenotype than with global PSG severity. Standardized DISE functional assessment may provide complementary information to support phenotype-informed selection of non-CPAP therapies, pending prospective validation.
Journal Article
Prognostic Factors and Life Expectancy in Canine Leishmaniosis
Canine leishmaniosis (CanL) is a chronic and potentially fatal disease. The prognosis of CanL depends on the severity of the clinical signs and clinicopathological abnormalities presented by the dog at the time of diagnosis. This study aims to estimate the survival time of dogs with CanL, determining the prognostic value of different clinical and clinicopathological parameters. Medical records of 99 dogs diagnosed with CanL in five veterinary centers of the Alentejo region (Portugal) were examined retrospectively. The majority of dogs presented hyperproteinemia, moderate normocytic normochromic anemia, normal blood urea and creatinine levels and were classified as stage 1 according to the International Interest Society (IRIS) guidelines at the time of diagnosis. The severity of anemia, presence of concomitant infectious diseases at the time of diagnosis and the anti-Leishmania therapy were correlated with the survival time. The influence of renal dysfunction was evaluated by Receiver Operating Characteristic (ROC) curve and survival analysis. Survival analysis demonstrated that patients classified as IRIS 1 at the time of diagnosis survived more than four years, in contrast with dogs classified as IRIS 2 that survived around two and half years and dogs classified as IRIS 3–4 that survived around one month. IRIS stage deteriorated during the course of CanL in one third of the dogs and was the principal cause of death or euthanasia in a high proportion of animals. In some cases, dogs did not receive anti-Leishmania treatment or abandoned the veterinary follow-ups, which may have considerable repercussions for animal wellbeing and public health. This study reinforces the value of blood urea and creatinine levels as prognostic factors in CanL.
Journal Article
Prognostic Factors and Life Expectancy in Canine Leishmaniosis
Canine leishmaniosis (CanL) is a chronic and potentially fatal disease. The prognosis of CanL depends on the severity of the clinical signs and clinicopathological abnormalities presented by the dog at the time of diagnosis. This study aims to estimate the survival time of dogs with CanL, determining the prognostic value of different clinical and clinicopathological parameters. Medical records of 99 dogs diagnosed with CanL in five veterinary centers of the Alentejo region (Portugal) were examined retrospectively. The majority of dogs presented hyperproteinemia, moderate normocytic normochromic anemia, normal blood urea and creatinine levels and were classified as stage 1 according to the International Interest Society (IRIS) guidelines at the time of diagnosis. The severity of anemia, presence of concomitant infectious diseases at the time of diagnosis and the anti-Leishmania therapy were correlated with the survival time. The influence of renal dysfunction was evaluated by Receiver Operating Characteristic (ROC) curve and survival analysis. Survival analysis demonstrated that patients classified as IRIS 1 at the time of diagnosis survived more than four years, in contrast with dogs classified as IRIS 2 that survived around two and half years and dogs classified as IRIS 3–4 that survived around one month. IRIS stage deteriorated during the course of CanL in one third of the dogs and was the principal cause of death or euthanasia in a high proportion of animals. In some cases, dogs did not receive anti-Leishmania treatment or abandoned the veterinary follow-ups, which may have considerable repercussions for animal wellbeing and public health. This study reinforces the value of blood urea and creatinine levels as prognostic factors in CanL.
Journal Article