Feasibility of Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients With Diminished Renal Function

Background

Cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy is the standard of care in muscle-invasive bladder cancer. There are limited data regarding chemotherapy tolerability and outcomes for patients with low glomerular filtration rate (GFR) who receive cisplatin-based NAC.

Aortic valve and left ventricular outflow tract calcium volume and distribution in transcatheter aortic valve replacement: Influence on the risk of significant paravalvular regurgitation

ObjectivesWe sought to determine the impact of aortic root calcium on the risk of significant paravalvular regurgitation (sPAR) in transcatheter aortic valve replacement (TAVR).MethodsIn 302 consecutive patients from 3 centers, aortic root calcium was quantified volumetrically on pre-TAVR multidetector computed tomography (MDCT) in three regions: 1) the aortic valve region, 2) the overall left ventricular outflow tract (LVOT) and 3) the upper LVOT. Transcathether heart valve (THV) oversizing was calculated as (THV nominal area/MDCT annular area−1) × 100. The study endpoint sPAR was a composite of post-dilatation (PD) and PAR > mild.ResultssPAR occurred in 15% (46/302) of patients. Upper LVOT calcium volume was more predictive of sPAR than overall LVOT calcium volume, with an area under the receiver operating curve (AUC) (95% confidence interval [CI]) of 0.80 (0.67–0.89) vs. 0.60 (0.51–0.70); p = 0.0001. The optimal cut-off calcium volume thresholds determined from receiver operating curves were 21 mm³ and 30 mm³ for upper LVOT and overall LVOT calcium, respectively. Upper LVOT calcium ≥ 21 mm³, but not overall LVOT calcium ≥ 30 mm³, independently predicted sPAR, odds ratio (95%CI): 9.5 (4.1–22.3) vs 1.6 (0.6–2.7). Upper LVOT calcium was more predictive of sPAR in patients with THV oversizing ≥ 13% compared to patients with THV oversizing <13%, AUC (95% CI): 0.83 (0.72–0.93) vs. 0.67 (0.51–0.74); p < 0.0001.ConclusionsUpper LVOT calcium predicts more-than-mild paravalvular regurgitation following TAVR or the need for postdilatation. Upper LVOT calcium is most predictive of paravalvular regurgitation in the event of THV oversizing ≥ 13%.     

Prenatal diagnosis of glycerol-kinase deficiency associated with a DNA deletion on the short arm of the X-chromosome

Amniocentesis was performed in a woman who previously had given birth to a boy who died at 12 months of age with a diagnosis of glyceroluria and adrenal insufficiency. A high amount of glycerol (9.0 standard deviations above mean for controls) was found in the amniotic fluid. Enzyme activity of glycerol-kinase (ATP:glycerol-3-phosphotransferase, EC 2.7.1.30) in the cultured amniotic fluid cells was very low. The pregnancy was terminated and a male fetus was aborted. Examinations of DNA isolated from the fetus did demonstrate deletions of two out of 16 DNA probes mapping to the short arm of the X-chromosome. The probes failing to hybridize to DNA from the fetus were C7 (DXS28) and L1.4 (DXS68), both mapping to Xp21.3 and located terminal to the Duchenne locus.     

Die obliterative Intimafibrose der Nierenarterien unter Einflu\ der Hämodialyse bei Patienten mit chronischer Niereninsuffizienz

Zusammenfassung Die Arterienstrecken in geschrumpften Nieren von Patienten mit und ohne Hämodialysebehandlung wurden histologisch und morphometrisch untersucht, um die Wirkung der chronischen Hämodialyse auf die Nierengefäße bei chronischer Niereninsuffizienz zu erfassen. Die Dialysegruppe besteht aus 33 Patienten, von denen 28 Präparate aus beidseitigen Nephrektomien und 5 aus autopisch entnommenen Nieren untersucht wurden. Die Kontrollgruppe sind 21 Fälle von chronischer Niereninsuffizienz, die ohne Dialysebehandlung urämisch verstorben sind.Statistisch wurden zum einen die Meßwerte entsprechender Gefäßstrecken zwischen Dialyse- und Kontrollgruppe verglichen, zum andern eine Korrelationsmatrix nach dem sogenannten BMD- 03D-Programm aufgestellt, um die Einflüsse klinischer Befunde, wie bekannte Dauer der Nierenerkrankung und Niereninsuffizienz sowie Dauer und Höhe der Hypertonie auf die Nierengefäße für jede Patientengruppe getrennt zu berücksichtigen.Nach diesen Ergebnissen wird die Entwicklung einer Intimafibrose in den Arterien geschrumpfter Nieren durch die Hämodialysebehandlung entscheidend gefördert.Die Befunde werden durch eine zusätzliche Minderdurchblutung der geschrumpften Nieren während der Dialysezeit erklärt, weil es vergleichbare Beispiele in anderen Gefäßregionen gibt.

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Obliterated intimofibrosis of the renal arteries under the influence of hemodyalysis in patients with chronic renal insufficiency

Summary Histologic and morphologic methods were employed to study the influence of chronic hemodialysis on kidney vessels in chronic renal insufficiency. Arteries of contracted kidneys from patients with and without hemodialysis treatment were investigated. The dialysis group was made up of 33 patients, 28 having undergone bilateral nephrectomy and 5 having died. The control group consisted of 21 patients with chronic renal insufficiency, who died in uremic coma without prior hemodialysis.A statistical evaluation was done by comparing measurements from corresponding arteries in the dialysis- and control groups. The correlation pattern from a BMD 03D-program, in which each group was separately assessed for the possible influence of various clinical findings, was determined. Clinical influences taken into account included the course of the kidney disease, grade of renal insufficiency, duration and degree of hypertension as affecting the renal arteries.The statistical results showed that hemodialysis treatment, even taking clinical data into consideration, influenced the development of intimal fibrosis in the arteries of contracted kidneys in an increasing positive manner. Decreased perfusion of the kidneys during hemodialysis suggested as a possible cause. The examination of early lesions in renal arteries following short-term dialysis treatment lends support to this possibility. Here edema and proliferation of the intimal cells in the arteries, similar to that in vessels having a reduced blood flow, is observed.

     

内毒素对实验性急性肝功能不全的作用

本文对大肠杆菌内毒素在半乳糖胺引起急性肝功能不全中的作用进行了研究。实验结果表明,内毒素加重半乳糖胺所致的肝细胞坏死,使大鼠血浆尿素氮、胆红素水平升高,凝血酶原时间延长,嗜睡时间提前与昏迷加重。经血浆、脑匀浆游离氨基酸分析提示,内毒素可使脑组织牛磺酸水平增高。上述结果表明,内毒素血症是诱发急性肝功能不全发生发展的重要因素。     

Effect of changes in Na,K, and Ca ion concentrations in the medium on frequency-strength of contraction relations in the pathologically changed myocardium

The following criteria of myocardial insufficiency were studied in fragments of human atrial myocardium (auricle) removed during operative correction of diseased heart valves: 1) the decrease in amplitude of contractions in a rhythmic series despite a frequency of stimulation of 1–3 Hz (the normal myocardium is characterized by an increase in the amplitude of contraction-Bowditch's positive treppe); 2) the monophasic character of the frequency-strength curve (in the normal myocardium the curve has three phases); 3) the absence of positive or appearance of a negative inotropic effect in response to a decrease in the external Na concentration or removal of K ions from the solution. The results suggest that myocardial failure of the cardiac cells of the affected heart is based on a disturbance of Ca ion transport through the surface membrane and the reduced ability of the sarcoplasmic reticulum to retain Ca ions.Department of Clinical and Experimental Physiology, A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 7, pp. 8–13, July, 1978.     

La prise en charge des troubles du métabolisme minéral et osseux avant le stade de la dialyse reste encore perfectible. À partir des données de l’Observatoire national du métabolisme minéral et osseux Photo-Graphe

Only limited data is available on the management of the chronic kidney disease-associated bone and mineral metabolism disorder (CKD-MBD) in the pre-dialysis stages of CKD in France. A better knowledge of current management habits could lead to an improvement in the implementation of international recommendations (KDIGO). The 3rd version of the French Phosphorus and Calcium Survey Photo-Graphe (Sanofi) included a cohort of CKD stages 4 and 5 patients, whose aim was to examine the prevalence of CKD-MBD and the quality of its management in patients under the care of 62 nephrologists from over 20 geographical regions in France. The study started in October 2011, i.e. one year after patient enrollment. We examined in particular the percentage of patients presenting with laboratory parameter abnormalities indicative of CKD-MBD who were not receiving adequate treatment. A total of 456 patients with CKD stage 4 and 154 with CKD stage 5 were studied. Their mean age was 72.9 ± 14.2 years, and male/female ratio was 58/42. KDIGO targets of serum PTH for CKD stages 4 and 5 were not achieved in respectively 80 and 84% of the patients, for serum calcium in 8 and 22% and for serum phosphate in 12 and 46%. As a potential explanation, insufficient therapy was estimated to account for respectively 45 and 60% of insufficiently controlled secondary hyperparathyroidism, and for 36% of persistent hyperphosphatemia in stage 5. It should be noted that 55.5 and 57.5% of patients were receiving native vitamin D. In this national observatory, the management of CKD-MBD stages 4 and 5 appears suboptimal, especially as regards the control of secondary hyperparathyroidism, which remained untreated in nearly 50% of the patients. Hyperphosphatemia was also common and inadequately controlled in CKD stage 5. To improve the management of CKD-MBD, nephrologists need to be more aware of the importance of aiming for recommended laboratory targets and how this can be achieved.