Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC

IntroductionWe retrospectively analyzed the effects of crizotinib on serum creatinine and creatinine-based estimated glomerular filtration rate (eGFR) in patients with anaplastic lymphoma kinase–positive advanced NSCLC across four trials (NCT00585195, NCT00932451, NCT00932893, and NCT01154140).MethodsChanges from baseline data in serum creatinine and eGFR, calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based equation, were assessed over time. eGFR was graded using standard chronic kidney disease criteria.ResultsMedian serum creatinine increased from 0.79 mg/dL at baseline to 0.93 mg/dL after 2 weeks of treatment (median percentage increase from baseline, 21.2%), was stable from week 12 (0.96 mg/dL) to week 104 (1.00 mg/dL), and decreased to 0.90 mg/dL at 28 days after last dose (median percentage increase from baseline, 13.1%). Median eGFR decreased over time (96.42, 80.23, 78.06 and 75.45 mL/min/1.73 m² at baseline, week 2, week 12, and week 104, respectively) and increased to 83.02 mL/min/1.73 m² at 28 days after the last dose. Median percentage decrease from baseline was 14.9%, 17.0%, and 10.4% at week 2, week 12, and 28 days after last dose of crizotinib, respectively. Overall, 12.6% of patients had a shift from eGFR grade less than or equal to 3a (≥45 mL/min/1.73 m²) at baseline to greater than or equal to 3b (<45 mL/min/1.73 m²) post-baseline.ConclusionsCrizotinib resulted in a decline in creatinine-based estimates of renal function mostly over the first 2 weeks of treatment. However, there was minimal evidence of cumulative effects with prolonged treatment and these changes were largely reversible following treatment discontinuation, consistent with previous reports suggesting this may be predominantly an effect on creatinine secretion as opposed to true nephrotoxicity.     

Temperature Measurement by Sublimation Rate as a Process Analytical Technology Tool in Lyophilization

Product temperature (T_b) and drying time constitute critical material attributes and process parameters in the lyophilization process and especially during the primary drying stage. In the study, we performed a temperature measurement by the sublimation rate (TMbySR) to monitor the T_b value and determine the end point of primary drying. First, the water vapor transfer resistance coefficient through the main pipe from the chamber to the condenser (C_r) was estimated via the water sublimation test. The use of C_r value made it possible to obtain the time course of T_b from the measurement of pressure at the drying chamber and at the condenser. Second, a Flomoxef sodium bulk solution was lyophilized by using the TMbySR system. The outcome was satisfactory when compared with that obtained via conventional sensors. The same was applicable for the determination of the end point of primary drying. A laboratory-scale application of the TMbySR system was evidenced via the experiment using 220-, 440-, and 660-vial scales of lyophilization. The outcome was not dependent on the loading amount. Thus, the results confirmed that the TMbySR system is a promising tool in laboratory scale.     

Implantation failures in women with infertility associated endometriosis

Abstract

Endometriosis is currently considered as one of the most common diseases associated with infertility. A controversial issue is whether endometriosis per se exerts a detrimental effect on IVF outcomes. Failure of implantation due to endometriosis-associated infertility is a contradictory and widely discussed burden nowadays. The purpose of the study is to assess the quality of embryos and implantation rate in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 26 and 40 years who underwent IVF and ICSI procedures. The patients were divided into two groups: group I (n?=?70) involved 70 patients with recurrent unilateral endometriomas, II control group (n?=?50) with tubal factor infertility. The quality of the retrieved embryos was assessed according to the generally accepted classification of Gardner, indicating the rate of implantation in each group. Embryo transfer was performed in case of high quality embryos. Assessing the ovarian reserve indicators, in the group I patients with recurrent unilateral endometriomas the serum level of AMH was significantly lower (2.1?±?1.75 vs. 3.2?±?1.4, p?<?.005), as well as the number of retrieved oocytes (8.1?±?3.9 and 10.1?±?6.8, p?<?.005). The analysis of the results demonstrated that the duration of stimulation in the group patients with recurrent unilateral endometriomas was significantly higher in comparison with the group II (12.2?±?1.8 and 10.2?±?1.6 days, p?<?.001). Nevertheless, the number of good quality embryos retrieved was comparable in both groups (2.2?±?1.5 and 2.8?±?1.8). In the group I patients with recurrent unilateral endometriomas, there was a statistically significant decrease of implantation rate (17.1% vs. 24% p?<?.005). The results of the study revealed no statistical difference in embryo quality in the study cohort. However, it is important to note that a statistically significant difference in implantation rate in the group of endometriosis-associated infertility compared was obtained 1.5 times lower than in the control group (15.8% vs. 24.0% p?<?.005). The achieved results demonstrated an adverse IVF outcome in infertile women with recurrent endometrioma compared to the control group.     

Postural Orthostatic Tachycardia Syndrome: JACC Focus Seminar

Postural orthostatic tachycardia syndrome (POTS), the most common form of orthostatic intolerance in young people, affects approximately 500,000 people in the United States alone, typically young women at the peak of their education and the beginning of their working lives. This is a heterogeneous disorder, the pathophysiology and mechanisms of which are not well understood. There are multiple contributing factors and numerous potential mimics. This review details the most current views on the potential causes, comorbid conditions, proposed subtypes, differential diagnoses, evaluations, and treatment of POTS from cardiological and neurological perspectives.     

Decreased Basal Metabolic Rate Can Be an Objective Marker for Sarcopenia and Frailty in Older Males

Objectives

The aim of this study is to demonstrate the ability of the basal metabolic rate (BMR) to detect frailty and sarcopenia in older males.