A novel dosing approach for rituximab in glomerular diseases based on a population pharmacokinetic analysis.

Objectives: Rituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug.

Methods: We compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023.

Increased Cardiovascular Risk in Young Patients with CKD and the Role of Lipid-Lowering Therapy.

Purpose Of Review: Chronic kidney disease (CKD) is associated with a significantly increased risk of cardiovascular disease (CVD). This review summarizes known risk factors, pathophysiological mechanisms, and current therapeutic possibilities, focusing on lipid-lowering therapy in CKD.

Recent Findings: Novel data on lipid-lowering therapy in CKD mainly stem from clinical trials and clinical studies.

Elimination and penetration of amikacin into urine in patients with decreased glomerular filtration rate.

Background: Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR).

Methods: A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted.

The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials.

Significance Statement: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.

The treatment with trandolapril and losartan attenuates pressure and volume overload alternations of cardiac connexin-43 and extracellular matrix in Ren-2 transgenic rats.

Heart failure (HF) is life-threatening disease due to electro-mechanical dysfunction associated with hemodynamic overload, while alterations of extracellular matrix (ECM) along with perturbed connexin-43 (Cx43) might be key factors involved. We aimed to explore a dual impact of pressure, and volume overload due to aorto-caval fistula (ACF) on Cx43 and ECM as well as effect of renin-angiotensin blockade. Hypertensive Ren-2 transgenic rats (TGR) and normotensive Hannover Sprague-Dawley rats (HSD) that underwent ACF were treated for 15-weeks with trandolapril or losartan.

Anti-Fibrotic Potential of Angiotensin (1-7) in Hemodynamically Overloaded Rat Heart.

The extracellular matrix (ECM) is a highly dynamic structure controlling the proper functioning of heart muscle. ECM remodeling with enhanced collagen deposition due to hemodynamic overload impairs cardiomyocyte adhesion and electrical coupling that contributes to cardiac mechanical dysfunction and arrhythmias. We aimed to explore ECM and connexin-43 (Cx43) signaling pathways in hemodynamically overloaded rat heart as well as the possible implication of angiotensin (1-7) (Ang (1-7)) to prevent/attenuate adverse myocardial remodeling.

Association of topical glaucoma medications with lacrimal drainage obstruction and eyelid malposition.

Background/objectives: Adverse effects of topical glaucoma medications (TGMs) may include development of ocular adnexal disorders. We undertook a study to determine the effect of TGMs on the risk of developing lacrimal drainage obstruction (LDO) and eyelid malposition.

Subjects/methods: All patients 66 years of age and older in Ontario, Canada initiating TGM and all patients diagnosed with glaucoma/suspected glaucoma but not receiving TGM from 2002 to 2018 were eligible for inclusion in this retrospective cohort study.

Implications of rituximab pharmacokinetic and pharmacodynamic alterations in various immune-mediated glomerulopathies and potential anti-CD20 therapy alternatives.

The specific B-cell depleting anti-CD20 monoclonal antibody rituximab (RTX) is effective in terms of the treatment of various immune-mediated glomerulopathies. The administration of RTX has been shown to be reliable and highly effective particularly in patients with ANCA-associated vasculitis, which is manifested predominantly with non-nephrotic proteinuria. Stable long-term B-cell depletion is usually readily attained in such patients using standard dosing regimens.

Dosing of Aminoglycosides in Chronic Kidney Disease and End-Stage Renal Disease Patients Treated with Intermittent Hemodialysis.

Background: The dosing of aminoglycosides (AGs) in patients with kidney disease is challenging due to their markedly prolonged half-life, which renders pulse dosing schedules unsuitable. We performed a review of the literature that describes the pharmacokinetics of, and dosing recommendations for, AG for patients with abnormal renal functions and various renal replacement therapy modalities, focusing on patients treated with intermittent hemodialysis (iHD).

Summary: During one iHD session, dialysis removes a remarkable amount of the drug regardless of the dialyzer type.

Myopic Correction with Iris-Fixated Phakic Intraocular Lenses: Twelve-Year Results.

Purpose: To evaluate a 12-year follow-up of myopic patients after iris-fixated phakic intraocular lenses (IF pIOLs) implantation. . Ophthalmology Department, Military University Hospital in Prague (Czech Republic).

LATERAL TARSAL STRIP TECHNIQUE IN CORRECTION OF EYELID ECTROPION AND ENTROPION.

Background: Ectropion and entropion are eyelid malpositions associated with a number of unpleasant symptoms. One of several surgical methods that can correct these problems is referred to as the lateral tarsal strip technique. In this paper, we evaluate the postoperative results and quality of this technique.

AT receptor blocker, but not an ACE inhibitor, prevents kidneys from hypoperfusion during congestive heart failure in normotensive and hypertensive rats.

To provide novel insights into the pathogenesis of heart failure-induced renal dysfunction, we compared the effects of ACE inhibitor (ACEi) and AT receptor blocker (ARB) on systemic and kidney hemodynamics during heart failure in normotensive HanSD and hypertensive transgenic (TGR) rats. High-output heart failure was induced by creating an aorto-caval fistula (ACF). After five weeks, rats were either left untreated or treatment with ACEi or ARB was started for 15 weeks.

Guidelines for vismodegib in the management of periocular basal cell carcinoma.

Objective: The management of advanced basal cell carcinoma (BCC) in the periocular region remains a clinical challenge. Vismodegib (Erivedge) has been approved in 2013 by Health Canada for adult patients with "histologically confirmed metastatic BCC or locally advanced BCC inappropriate for surgery or radiation." An expert consensus was sought to create a standardised approach in the use of this novel treatment.

Histiocytic sarcoma of the eyelid.

Histiocytic Sarcoma is a rare malignant hematopoietic neoplasm that can present in extranodal sites including lymph nodes, skin, gastrointestinal tract, and the central nervous system. Only 10% of cases manifest as skin lesions and very few are reported in the head and neck. The authors report a case of histiocytic sarcoma of the eyelid in a 72-year-old male that was clinically diagnosed as a chalazion.

Enhanced Renal Vascular Responsiveness to Angiotensin II and Norepinephrine: A Unique Feature of Female Rats with Congestive Heart Failure.

Background/aims: We found recently that the aortocaval fistula (ACF)-induced heart failure (HF) results in higher mortality in female than in male rats. Possibly, the development of renal dysfunction in the females, unlike in males, is associated with altered renal vascular responsiveness to angiotensin II (ANG II).

Methods: Five or 20 weeks after ACF creation (compensated and decompensated HF, respectively), we assessed renal blood flow (RBF) responses to intrarenal administration of ANG II, norepinephrine (NE), and acetylcholine (Ach) in female ACF and sham-operated rats.

Novel taste test for nasolacrimal duct obstruction using denatonium benzoate: a randomized controlled pilot study.

Objective: To evaluate a novel, simple, noninvasive method (known as the "bitter taste test") of establishing nasolacrimal duct patency in healthy asymptomatic eyes.

Design: Double-blind, randomized controlled pilot study.

Participants: Healthy asymptomatic medical students, residents, and allied health staff at our institution.

The Role of Renal Vascular Reactivity in the Development of Renal Dysfunction in Compensated and Decompensated Congestive Heart Failure.

Background/aims: Reduction of renal blood flow (RBF) is commonly thought to be a causative factor of renal dysfunction in congestive heart failure (CHF), but the exact mechanism of the renal hypoperfusion is not clear. Apart from the activation of neurohormonal systems controlling intrarenal vascular tone, the cause might be altered reactivity of the renal vasculature to endogenous vasoactive agents.

Methods: To evaluate the role of this mechanism, we assessed by an ultrasonic transient-time flow probe maximum RBF responses to renal artery infusion of angiotensin II (ANG II), norepinephrine (NE) and acetylcholine (Ach) in healthy male rats and animals with compensated and decompensated CHF.

20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic rats.

We hypothesized that vascular actions of 20-hydroxyeicosatetraenoic acid (20-HETE), the product of cytochrome P450 (CYP450)-dependent ω-hydroxylase, potentiate prohypertensive actions of angiotensin II (ANG II) in Cyp1a1-Ren-2 transgenic rats, a model of ANG II-dependent malignant hypertension. Therefore, we evaluated the antihypertensive effectiveness of 20-HETE receptor antagonist (AAA) in this model. Malignant hypertension was induced in Cyp1a1-Ren-2 transgenic rats by activation of the gene using indole-3-carbinol (I3C), a natural xenobiotic.