Decreased GFR estimated by MDRD or Cockcroft-Gault equation predicts incident CVD: the Strong Heart Study

Background—Kidney function, expressed as glomerular filtration rate (GFR), is commonly estimated from serum creatinine (Scr) and, when decreased, may serve as a nonclassical risk factor for incident cardiovascular disease (CVD). The ability of estimated GFR (eGFR) to predict CVD events during 5–10 years of follow-up is assessed using data from the Strong Heart Study (SHS), a large cohort with a high prevalence of diabetes. Methods—eGFRs were calculated with the abbreviated Modification of Diet in Renal Disease study (MDRD) and the Cockcroft-Gault (CG) equations. These estimates were compared in participants with normal and abnormal Scr. The association between eGFR and incident CVD was assessed. Results—More subjects were labeled as having low eGFR (<60 ml/min per 1.73 m2) by the MDRD or CG equation, than by Scr alone. When Scr was in the normal range, both equations labeled similar numbers of participants as having low eGFRs, although concordance between the equations was poor. However, when Scr was elevated, the MDRD equation labeled more subjects as having low eGFR. Persons with low eGFR had increased risk of CVD. Conclusions—The MDRD and CG equations labeled more participants as having decreased GFR than did Scr alone. Decreased eGFR was predictive of CVD in this American Indian population with a high prevalence of obesity and type 2 diabetes mellitus

Cancer stem cells, not bulk tumor cells, determine mechanisms of resistance to SMO inhibitors.

The emergence of treatment resistance significantly reduces the clinical utility of many effective targeted therapies. Although both genetic and epigenetic mechanisms of drug resistance have been reported, whether these mechanisms are stochastically selected in individual tumors or governed by a predictable underlying principle is unknown. Here, we report that the dependence of cancer stem cells (CSCs), not bulk tumor cells, on the targeted pathway determines the molecular mechanism of resistance in individual tumors. Using both spontaneous and transplantable mouse models of sonic hedgehog (SHH) medulloblastoma (MB) treated with an SHH/Smoothened inhibitor, sonidegib/LDE225, we show that genetic-based resistance occurs only in tumors that contain SHH-dependent CSCs (SD-CSCs). In contrast, SHH MBs containing SHH-dependent bulk tumor cells but SHH-independent CSCs (SI-CSCs) acquire resistance through epigenetic reprogramming. Mechanistically, elevated proteasome activity in SMOi-resistant SI-CSC MBs alters the tumor cell maturation trajectory through enhanced degradation of specific epigenetic regulators, including histone acetylation machinery components, resulting in global reductions in H3K9Ac, H3K14Ac, H3K56Ac, H4K5Ac, and H4K8Ac marks and gene expression changes. These results provide new insights into how selective pressure on distinct tumor cell populations contributes to different mechanisms of resistance to targeted therapies. This insight provides a new conceptual framework to understand responses and resistance to SMOis and other targeted therapies

Postoperative Discharge Destination Impacts 30-Day Outcomes: A National Surgical Quality Improvement Program Multi-Specialty Surgical Cohort Analysis

Surgical patients can be discharged to a variety of facilities which vary widely in intensity of care. Postoperative readmissions have been found to be more strongly associated with post-discharge events than pre-discharge complications, indicating the importance of discharge destination. We sought to evaluate the association between discharge destination and 30-day outcomes. A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were dichotomized based on discharge destination: home versus non-home. The main outcome of interest was 30-day unplanned readmission. The secondary outcomes included post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. In this cohort study of over 1.5 million patients undergoing common surgical procedures across eight surgical specialties, we found non-home discharge to be associated with adverse 30-day post-operative outcomes, namely, unplanned readmissions, post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. Non-home discharge is associated with worse 30-day outcomes among patients undergoing common surgical procedures. Patients and caregivers should be counseled regarding discharge destination, as non-home discharge is associated with adverse post-operative outcomes

Internal Flow Field and Loss Analysis of a Magnetic Drive Pump’s Cooling Circuit

The cooling circuit is an important component of the magnetic drive pump because it prevents demagnetization of the permanent magnet and damage to the containment shell owing to a high temperature increase. In this paper, the flow field and losses of the cooling circuit of the magnetic pump are discussed and experimentally verified based on numerical simulation methods. Five different lengths of magnetic couplings were designed, and the flow field distribution, cooling flow rate, and loss variation laws of the cooling circuit were analyzed. The results show that the pump flow rate and magnetic coupling length have a minimal effect on the velocity distribution in the cooling circuit. When the magnet length increases from 30 mm to 55 mm, the temperature rise of the cooling circuit and the pressure drop at the gap increase by 23.1% and 25.3%, respectively. When the length of the magnetic coupling remains constant, the cooling flow rate of the cooling circuit falls with an increasing pump flow rate, and it reduces by 8.4% when the pump flow rate increases from 0.7 Q to 1.3 Q. The water friction loss and eddy current loss of the cooling circuit increase with an increase in the magnetic coupling length, while the cooling flow rate decreases. When the magnet length increases from 30 mm to 55 mm, the eddy current losses in the coupling circuit and the water friction losses in the cooling circuit increase by 45% and 35%, respectively, while the cooling flow rate decreases by 13%

Effect of Blade Thickness on Internal Flow and Performance of a Plastic Centrifugal Pump

Blade thickness is an essential parameter of the impeller, which has significant effects on the pump performance. The plastic pump generally adopts thick blade due to low strength of plastic. The effects of blade thickness on the internal flow and performance of a plastic centrifugal pump were discussed based on the numerical methods. Two kinds of blade profile, the constant thickness blade (CTB) and the variable thickness blade (VTB), were investigated. The results indicated that, for the CTB, when the blade thickness was less than 6 mm, the pump performance did not change significantly. When the blade thickness exceeded 6 mm, the pump head and efficiency decreased rapidly. The pump head and efficiency of CTB 10 decreased by 42.2% and 30% compared with CTB 4, respectively. For the VTB, with blade thickness in a certain range (6 mm–14 mm), the pump performance changed slightly with the increased of trailing edge thickness. The minimum blade thickness of the plastic centrifugal pump should be 4 mm based on the finite element analysis. A variable thickness blade (VTB 4-8-4) with the maximum thickness located at 60% chord length was proposed to improve the pump performance, and its efficiency was 1.67% higher than that of the CTB 4 impeller

Effect of Blade Thickness on Internal Flow and Performance of a Plastic Centrifugal Pump

Blade thickness is an essential parameter of the impeller, which has significant effects on the pump performance. The plastic pump generally adopts thick blade due to low strength of plastic. The effects of blade thickness on the internal flow and performance of a plastic centrifugal pump were discussed based on the numerical methods. Two kinds of blade profile, the constant thickness blade (CTB) and the variable thickness blade (VTB), were investigated. The results indicated that, for the CTB, when the blade thickness was less than 6 mm, the pump performance did not change significantly. When the blade thickness exceeded 6 mm, the pump head and efficiency decreased rapidly. The pump head and efficiency of CTB 10 decreased by 42.2% and 30% compared with CTB 4, respectively. For the VTB, with blade thickness in a certain range (6 mm&ndash;14 mm), the pump performance changed slightly with the increased of trailing edge thickness. The minimum blade thickness of the plastic centrifugal pump should be 4 mm based on the finite element analysis. A variable thickness blade (VTB 4-8-4) with the maximum thickness located at 60% chord length was proposed to improve the pump performance, and its efficiency was 1.67% higher than that of the CTB 4 impeller