Isoniazid and rifampicin exposure during treatment in drug-susceptible TB.

Observational real-world studies on therapeutic drug monitoring (TDM) in relation to pharmacokinetic (PK) target values are lacking. This study aims to describe the PK of rifampicin (RIF) and isoniazid (INH) in a real-world setting of patients with drug-susceptible TB in relation to frequently used threshold values. A total of 116 patients with TB using standard doses of RIF and INH and who had TDM as part of clinical care were included.

Photoresponsive molecular tools for emerging applications of light in medicine.

Light-based therapeutic and imaging modalities, which emerge in clinical applications, rely on molecular tools, such as photocleavable protecting groups and photoswitches that respond to photonic stimulus and translate it into a biological effect. However, optimisation of their key parameters (activation wavelength, band separation, fatigue resistance and half-life) is necessary to enable application in the medical field. In this perspective, we describe the applications scenarios that can be envisioned in clinical practice and then we use those scenarios to explain the necessary properties that the photoresponsive tools used to control biological function should possess, highlighted by examples from medical imaging, drug delivery and photopharmacology.

Sodium-glucose cotransporter 2 inhibitors: extending the indication to non-diabetic kidney disease?

This year the medical community was pleasantly surprised by the results of the first large outcome trial that primarily examined the renal effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (CANA) in subjects with diabetes and impaired kidney function. The Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial showed that CANA, relative to placebo, reduces the risk for end-stage renal disease, doubling of creatinine or renal death by 34% [hazard ratio 0.66 (95% confidence interval 0.

Evaluating Glomerular Filtration Rate Slope as a Surrogate End Point for ESKD in Clinical Trials: An Individual Participant Meta-Analysis of Observational Data.

Background: Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR.

Methods: To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.

GFR Slope as a Surrogate End Point for Kidney Disease Progression in Clinical Trials: A Meta-Analysis of Treatment Effects of Randomized Controlled Trials.

Background: Surrogate end points are needed to assess whether treatments are effective in the early stages of CKD. GFR decline leads to kidney failure, but regulators have not approved using differences in the change in GFR from the beginning to the end of a randomized, controlled trial as an end point in CKD because it is not clear whether small changes in the GFR slope will translate to clinical benefits.

Methods: To assess the use of GFR slope as a surrogate end point for CKD progression, we performed a meta-analysis of 47 RCTs that tested 12 interventions in 60,620 subjects.

Ganciclovir Therapeutic Drug Monitoring: A Case Series.

This article presents 3 cases of immunocompromised patients for whom therapeutic drug monitoring of ganciclovir in combination with cytomegalovirus viral load measurement was used to guide treatment. The first patient is diagnosed with thymoma A, the second is a heart transplant recipient, and the third is an HIV-positive patient. These patients were all diagnosed with cytomegalovirus and treated with ganciclovir.

Early Proteinuria Lowering by Angiotensin-Converting Enzyme Inhibition Predicts Renal Survival in Children with CKD.

Although pharmacotherapeutic proteinuria lowering was found to be nephroprotective in adults, the predictive value of early drug-induced proteinuria reduction for long-term renal survival in pediatric CKD is unknown. We analyzed data from the ESCAPE Trial for a potential association between initial antiproteinuric effect of standardized angiotensin-converting enzyme (ACE) inhibition and renal disease progression in children with CKD. In total, 280 eligible children with CKD stages 2-4 (mean age 11.

Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment.

Treatment of human epidermal growth factor receptor 2 (HER2)-driven breast cancer with tyrosine kinase inhibitor lapatinib can induce a compensatory HER3 increase, which may attenuate antitumor efficacy. Therefore, we explored in vivo HER3 tumor status assessment after lapatinib treatment with zirconium-89 (Zr)-labeled anti-HER3 antibody mAb3481 positron emission tomography (PET). Lapatinib effects on HER3 cell surface expression and mAb3481 internalization were evaluated in human breast (BT474, SKBR3) and gastric (N87) cancer cell lines using flow cytometry.

Plasma Vitamin D Level and Change in Albuminuria and eGFR According to Sodium Intake.

Background And Objectives: Low circulating 25-hydroxyvitamin D [25(OH)D] and high sodium intake are both associated with progressive albuminuria and renal function loss in CKD. Both vitamin D and sodium intake interact with the renin-angiotensin-aldosterone system. We investigated whether plasma 25(OH)D or 1,25-dihydroxyvitamin D [1,25(OH)2D] is associated with developing increased albuminuria or reduced renal function and whether these associations depend on sodium intake.

Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets.

Purpose: In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.

Procedures: Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense™ 680 and imaged with IVIS® Spectrum.

Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD: The Pro View.

The presence of elevated levels of albuminuria is associated with an increased risk of progressive renal function loss over time. This association is found in various pathophysiological conditions, including diabetic nephropathy, hypertensive nephropathy, and various primary renal diseases, but also, the general, otherwise healthy population. Emerging data report that elevated albuminuria causes tubulointerstitial damage through activation of proinflammatory mediators, which ultimately leads to a progressive decline in renal function.