Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Modeling of Serum M-Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma.

Modakafusp alfa (TAK-573) is a novel, first-in-class fusion protein of a humanized anti-CD38 IgG4 kappa antibody fused to attenuated human interferon alfa-2b. It acts as an agonistic innate immunity enhancer through targeted interferon (IFN) signaling and has been investigated as an immune-oncology therapeutic agent in patients with relapsed/refractory multiple myeloma (RRMM). Population PK analysis and sequential PK-PD analysis of serum M-protein (MP) as a primary marker of tumor burden in RRMM were conducted using dose escalation (Part 1) and dose expansion (Part 2) data from 96 RRMM patients enrolled in the Phase 1/2 iinnovate-1 trial.

Interleukin-18 cytokine gene polymorphism 137G/C (rs187238) and susceptibility to tuberculosis in north India.

Tuberculosis (TB) regained its position globally as the leading cause of mortality from a single infectious agent after being surpassed by COVID-19 for 3 years consecutively. Host genetic factors, particularly cytokine gene polymorphisms, play a significant role in influencing susceptibility to TB. Interleukin-18 (IL-18) is a proinflammatory cytokine involved in immune regulation against Mycobacterium tuberculosis.

Assessment of the Effects of Fruquintinib on Cardiac Safety in Patients with Metastatic Colorectal Cancer.

Fruquintinib is a highly selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved by the US Food and Drug Administration and the European Commission for the treatment of previously treated metastatic colorectal cancer (mCRC), regardless of biomarker status. This study used concentration QT interval (C-QTc) modeling, utilizing data from the phase 3 FRESCO-2 study (NCT04322539) in which patients with mCRC received fruquintinib 5 mg, once daily, or matching placebo in a 28-day cycle, to evaluate the potential of fruquintinib to delay cardiac repolarization. The primary objectives were to assess the relationship between change from baseline in the QTc and plasma concentrations of fruquintinib and its metabolite M11, and to predict placebo-corrected change from baseline in the corrected QT interval (ΔΔQTc) associated with clinically relevant fruquintinib or M11 concentrations.

Quasar radiation transforms the gas in a merging companion galaxy.

Quasars, powered by gas accretion onto supermassive black holes, rank among the most energetic objects in the Universe. Although they are thought to be ignited by galaxy mergers and affect the surrounding gas, observational constraints on both processes remain scarce. Here we describe a major merging system at redshift z ≈ 2.

Evaluation of Potential Effects of CYP3A Inhibition and CYP3A Induction on the Pharmacokinetics of Fruquintinib in Healthy Subjects.

Cytochrome P450 (CYP) 3A plays a significant role in fruquintinib metabolism in vitro. This 2-part, 2-period fixed-sequence study investigated the impact of CYP3A inhibition (itraconazole) and CYP3A induction (rifampin) on the pharmacokinetics (PK) of fruquintinib and M11, its main metabolite. Fourteen healthy subjects in each part received a single dose of fruquintinib 5 mg alone in Period 1 and with itraconazole (Part A) or rifampin (Part B) in Period 2 under fasted conditions.

Effects of Hepatic or Renal Impairment on Pharmacokinetics of Fruquintinib.

Fruquintinib (FRUZAQLA) is a highly selective tyrosine kinase inhibitor of all three vascular endothelial growth factor receptors (-1, -2, and -3). Two Phase 1, open-label, single-dose studies investigated the impact of hepatic or renal impairment on the pharmacokinetics and tolerability of fruquintinib. Participants with moderate renal impairment (creatinine clearance [CrCl] 30-59 mL/min; eight participants) and matched healthy controls (eight participants for each study) received fruquintinib 5 mg.

Nuclear Nanomedicines: Utilization of Radiolabelling Strategies, Drug Formulation, Delivery, and Regulatory Aspects for Disease Management.

By integrating the sensitivity of nuclear medicine and the precision of nanotechnology, mankind can explore the very promising nuclear nanomedicine technology. Such integration enabled the imaging of biological processes at the molecular level which is a blessing to modern disease management. The present work is an effort to highlight the multifaceted applications of radiolabelled nanomaterials across various imaging modalities, formulation assessment, drug development, regulatory considerations, and therapeutic interventions.

Recent Scenario of Diagnostic and Prognostic Biomarkers of Sepsis in Clinical Practice and the Role of Multi-marker Approach: An Update.

Despite extensive work done in the field of sepsis biomarkers; still, there is no consensus on which parameter could be considered as an ideal biomarker for sepsis diagnosis. This review aims to look into the existing biomarkers of clinical utility which are currently being used for sepsis diagnostics along with their advantages and disadvantages. We also provide an insight into the usefulness of a multi-marker approach to diagnosing sepsis and what could be the future direction.

Does the Lumbar Paraspinal Muscle Status Have a Role in Predicting Mechanical Complications After Adult Spinal Deformity Surgery?

Study designRetrospective analysis.ObjectivesTo assess the role of paraspinal muscle morphology in predicting complications after adult spinal deformity (ASD) surgery.Materials and MethodsA total of 93 patients who underwent surgery for ASD from 2017 to 2022 were enrolled.

Attitudes of Australian patients receiving inpatient mental health care towards deprescribing: a cross-sectional survey.

Background: Psychotropic polypharmacy is common, increasing, and associated with higher risks of adverse effects, hospitalisations and mortality. This study aimed to explore the attitudes and beliefs of people receiving inpatient mental health care toward deprescribing (discontinuing a medication when the current or potential risk outweighs the current or potential benefit) and determine any patient characteristics associated with these attitudes and beliefs.

Methods: A cross-sectional survey of patients admitted to two open acute psychiatric inpatient units was conducted over a 6-month period in the Australian metropolitan city of Adelaide.

Comparative study between ultrasound-guided closed pleural biopsy and thoracoscopic pleural biopsy in undiagnosed exudative pleural effusions.

Pleural biopsies are often required to establish a diagnosis in exudative pleural effusions, which remain undiagnosed after initial pleural fluid analysis. Medical thoracoscopy offers a high diagnostic yield but has limited availability in resource-constrained settings. This prospective comparative study evaluated the diagnostic yield between ultrasound-guided closed pleural biopsy and medical thoracoscopy among patients with undiagnosed exudative pleural effusions with pleural-based lesions at least 10 mm in size.

Optimizing Brentuximab Vedotin Dosing in Pediatric Patients with Advanced Hodgkin Lymphoma: A Population Pharmacokinetic and Exposure-Response Analysis.

Pediatric patients with advanced-stage newly diagnosed Hodgkin lymphoma (HL) were treated with brentuximab vedotin (BV) combined with adriamycin, vinblastine, and dacarbazine (A + AVD). Weight-based BV dosing is employed in adult patients, while both body weight- and body surface area (BSA)-based dosing are used in pediatric patients. Data from two pediatric studies were used for a population pharmacokinetics (PK) analysis.

Assessment of Food Effect and pH-Dependent Drug-Drug Interactions of Fruquintinib in Healthy Subjects.

This two-sequence, three-period study (NCT04645940) was designed to evaluate the effect of food and concomitant rabeprazole, a proton pump inhibitor, on the pharmacokinetics (PK) and safety of fruquintinib and its metabolite M11 after a single oral dose of fruquintinib 5 mg in healthy subjects. In the food effect treatment periods, 14 subjects were randomized in a 1:1 ratio utilizing a two-sequence (fed/fasted vs. fasted/fed), two-period, cross-over design.

Population Pharmacokinetic and Exposure-Response Analyses for Ponatinib in the Phase 3 PhALLCON Study.

In March 2024, ponatinib received accelerated FDA approval for the treatment of newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) in combination with chemotherapy based on the Phase 3 PhALLCON study (NCT03589326), which demonstrated a higher rate of minimal residual disease (MRD)-negative complete remission (CR) at the end of induction (EOI) with ponatinib (34.4%) versus imatinib (16.7%; p = 0.

Multidrug-resistant sepsis in special newborn care units in five district hospitals in India: a prospective cohort study.

Background: Neonatal sepsis epidemiology has been adequately reported in tertiary-care hospitals. However, such data are scarce from district hospitals in low-income and middle-income countries. This study aimed to evaluate the incidence of sepsis, pathogen profile, and antimicrobial resistance among neonates admitted to the special newborn care units in district hospitals in India.

Population Pharmacokinetics of Fruquintinib, a Selective Oral Inhibitor of VEGFR -1, -2, and -3, in Patients with Refractory Metastatic Colorectal Cancer.

Fruquintinib is a selective, oral tyrosine kinase inhibitor of all three vascular endothelial growth factor receptors 1, 2, and 3, which is approved for patients with previously treated metastatic colorectal cancer regardless of biomarker status. This population pharmacokinetic (PK) analysis characterized sources of interpatient variability on the PK of fruquintinib and its major metabolite M11 using data from 557 subjects who received fruquintinib in five phase I/Ib studies and the FRESCO-2 phase III study. The integrated model was a one-compartment model with first-order absorption, lag time in absorption, and linear elimination for fruquintinib and a one-compartment model with linear elimination for M11.

Effect of high flow nasal cannula conventional nasal cannula oxygen therapy in patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration.

Patients undergoing endobronchial ultrasound-guided fine needle aspiration may have multiple comorbidities, contributing to higher risks of hypoxia and adverse events, such as arrhythmias. The current study compared the efficacy of two oxygenation modalities: the high-flow nasal cannula (HFNC) vs. conventional oxygen therapy (CNC).

Cutoff levels of serum 25-OH-D for defining vitamin D deficiency in early infancy.

Background: Various organizations use different thresholds to define vitamin D deficiency (VDD), which complicates its diagnosis, particularly in infants, as these thresholds are often extrapolated from adult data. Routine vitamin D3 supplementation in infants based on these criteria may impose unnecessary economic costs without clear benefits. Recent evidence suggests that the Institute of Medicine's (IOM) current threshold of <12 ng/ml might overestimate VDD in infants.

Inhaled corticosteroids in asthma and chronic obstructive pulmonary disease combined phenotype: when to use and what to expect?

The term "asthma-chronic obstructive pulmonary disease (COPD) combined phenotype" describes patients with persistent airflow limitation and features of both asthma and COPD. There is a lack of data on effective treatments for this group, often excluded from asthma or COPD trials. Inhaled corticosteroids (ICS) are standard for asthma, while bronchodilators are key for COPD.

A Drug-Drug Interaction Study of Mobocertinib and Midazolam, a Cytochrome P450 3A Substrate, in Patients With Advanced Non-Small Cell Lung Cancer.

Mobocertinib is a kinase inhibitor designed to selectively target epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in non-small cell lung cancer. This drug-drug interaction study assessed the effect of multiple-dose administration of mobocertinib on the pharmacokinetics (PK) of midazolam, a sensitive cytochrome P450 3A substrate. Patients with locally advanced or metastatic non-small cell lung cancer refractory/intolerant to standard available therapy were enrolled.

Does early heart rate detection and continuous monitoring have an impact on neonatal resuscitation in newborns with intact cord? - An observational study.

Context: Heart rate (HR) is the most vital parameter to assess hemodynamic transition at birth. ECG is considered a gold standard for HR assessment. New devices with dry electrodes are easy to apply on a wet newborn.

Synthesis, Spectral Characterization, Antimicrobial Activity, DFT Calculations, Molecular Docking and ADME Studies of Novel Schiff Base Co(II), Ni(II), Cu(II) and Zn(II) Complexes Derived from 4-nitro-ortho-phenylenediamine.

A condensation reaction was carried out between 4-nitro-ortho-phenylenediamine and 5-bromosalicyaldehyde to synthesize a novel Schiff base ligand 2,2'-[(1E,1'E)-(4-nitro-1,2-phenylene) bis (azaneylylidene) bis (methaneylylidene)] bis (4-bromophenol) [NB] in the current investigation. This was followed by the synthesis of metallic complexes comprising the Co(II), Ni(II), Cu(II) and Zn(II) transition metal ions. A hexadentate environment encircling metal complexes was corroborated by the results of varied spectroscopic methods that were employed to unravel the structure of the ligand and metal complexes.