Safety of prolonged aortic clamping with blood cardioplegia. II. Glutamate enrichment in energy-depleted hearts

Cold blood cardioplegic techniques are limited in their ability to protect energy-depleted hearts during aortic clamping. This study extends our previous observations on the benefits of amino acid (L-glutamate) enrichment of blood cardioplegic solutions as well as the added metabolic benefits of normothermic induction of cardioplegic arrest to increase the rate of repair of energy-depleted hearts. The results demonstrate that L-glutamate enrichment of blood cardioplegic solutions significantly improves metabolic recovery (greater oxygen consumption, better anaerobic metabolism) and ventricular performance. Normothermic induction of glutamate-enriched cardioplegia allowed complete recovery of myocardial metabolism and function compared to cold blood cardioplegic technique and may be used as a form of "active resuscitation" of energy-depleted hearts.     

Feasibility of a self‐assembling peptide hydrogel scaffold for meniscal defect: An in vivo study in a rabbit model

The inner avascular zone of the meniscus has limited healing capacity as the area is poorly vascularized. Although peptide hydrogels have been reported to regenerate bone and cartilage, their effect on meniscus regeneration remains unknown. We tested whether the self‐assembling peptide hydrogel scaffold KI24RGDS stays in the meniscal lesion and facilitates meniscal repair and regeneration in an induced rabbit meniscal defect model. Full‐thickness (2.0 mm diameter) cylindrical defects were introduced into the inner avascular zones of the anterior portions of the medial menisci of rabbit knees (n = 40). Right knee defects were left empty (control group) while the left knee defects were transplanted with peptide hydrogel (KI24RGDS group). Macroscopic meniscus scores were significantly higher in the KI24RGDS group than in the control group at 2, 4, and 8 weeks after surgery. Histological examinations including quantitative and qualitative scores indicated that compared with the control group, the reparative tissue in the meniscus was significantly enhanced in the KI24RGDS group at 2, 4, 8, and 12 weeks after surgery. Immunohistochemical staining showed that the reparative tissue induced by KI24RGDS at 12 weeks postimplantation was positive for Type I and II collagen. KI24RGDS is highly biocompatible and biodegradable, with strong stiffness, and a three dimensional structure mimicking native extracellular matrix and RGDS sequences that enhance cell adhesion and proliferation. This in vivo study demonstrated that KI24RGDS remained in the meniscal lesion and facilitated the repair and regeneration in a rabbit meniscal defect model.     

Podocyte EGFR Inhibits Autophagy Through Upregulation of Rubicon in Type 2 Diabetic Nephropathy

Renal epidermal growth factor receptor (EGFR) signaling is activated in models of diabetic nephropathy (DN), and inhibition of the EGFR signaling pathway protects against the development of DN. We have now determined that in cultured podocytes, high glucose led to increases in activation of EGFR signaling but decreases in autophagy activity as indicated by decreased beclin-1 and inhibition of LC3B autophagosome formation as well as increased rubicon (an autophagy inhibitor) and SQSTM1 (autophagy substrate). Either genetic (small interfering [si]EGFR) or pharmacologic (AG1478) inhibition of EGFR signaling attenuated the decreased autophagy activity. In addition, rubicon siRNA knockdown prevented high glucose–induced inhibition of autophagy in podocytes. We further examined whether selective EGFR deletion in podocytes affected the progression of DN in type 2 diabetes. Selective podocyte EGFR deletion had no effect on body weight or fasting blood sugars in either db/db mice or nos3^−/−; db/db mice, a model of accelerated type 2 DN. However selective podocyte EGFR deletion led to relative podocyte preservation and marked reduction in albuminuria and glomerulosclerosis, renal proinflammatory cytokine/chemokine expression, and decreased profibrotic and fibrotic components in nos3^−/−; db/db mice. Podocyte EGFR deletion led to decreased podocyte expression of rubicon, in association with increased podocyte autophagy activity. Therefore, activation of EGFR signaling in podocytes contributes to progression of DN at least in part by increasing rubicon expression, leading to subsequent autophagy inhibition and podocyte injury.     

The effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy: A longitudinal analysis (FRARP-QL Study)

ObjectivesWe aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP).Materials and MethodsWe longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP.ResultsThe median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening.ConclusionsFrailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.     

Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.     

Fibrinogen osaka IV: A congenital dysfibrinogenemia found in a patient originally reported in relation to surgery,now defined to have an Aα arginine-16 to histidine substitution

We discovered a congenital heterozygous dysfibrinogen in a patient and reported this case in relation to surgery some time ago (Jpn J Surg (1988) 18:43–46).³ Further studies on the isolated abnormal population of fibrinogen derived from this patient have revealed that fibrinopeptide A was not cleaved by ancrod, a snake venom-derived thrombin-like enzyme, but by thrombin, slowly but completely. The released fibrinopeptide A components, being the A, AY, and AP peptides, were all found to be abnormal, as evidenced by slightly earlier elution positions on high-performance liquid chromatography, compared with the normal counterparts. By analyzing their amino acid sequence, we have identified an arginine to histidine substitution at position 16 of the A chain, the thrombin cleavage site. Utilizing insolubilized abnormal fibrinogen, we confirmed that the polymerization site assigned to the central E domain, the A site, was exposed by thrombin, but not by ancrod. This dysfibrinogen, designated as fibrinogen Osaka IV, is the second abnormal molecule with an A arginine-16 to histidine substitution identified among Japanese families.     

Airway occlusion pressure (P0.1) — A useful predictor for the weaning outcome in patients with acute respiratory failure —

Twenty-five patients who required mechanical ventilatory support (MVS) after major surgery or severe burns were studied to determine whether airway occlusion pressure (P_0.1) is a clinically useful indicator to predict the success or failure of the weaning trial. A total of 33 weaning trials were attempted on these patients. Of the 33 trials, 24 were followed by successful weaning and 9 by failure. Although the success group, when compared with the failure group, had a lower respiratory rate (P 0.001), a lower minute ventilation (P 0.001), a higher maximal voluntary ventilation to minute ventilation ratio (P 0.01) and a higher forced vital capacity (P 0.05), no threshold values separated the success from the failure group. The alveolar-arterial P_{O 2} gradient, with an Fi _{O 2} of 1.0, in weaning success and failure showed no statistical difference. In contrast, all patients in the success group had a P_0.1 of less than 3.5cmH₂O and those in the failure group had a P_0.1 of greater than 3.5cmH₂O (P 0.001). We conclude that P_0.1 is a clinically superior indicator for discontinuing MVS in patients with acute respiratory failure.(Okamoto K, Sato T, Morioka T: Airway occlusion pressure (P_0.1)—A useful predictor for the weaning outcome in patients with acute respiratory failure—. J Anesth 4: 95–101, 1990)     

Evaluation of conventional weaning criteria in patients with acute respiratory failure

We evaluated the reliability of conventional weaning criteria from a ventilator during 33 weaning trials on 25 patients with acute respiratory failure (ARF). Of 13 criteria, a ratio of maximal voluntary ventilation to minute ventilation (MV) 2, a vital capacity 12ml·kg^–1, a spontaneous respiratory rate 25 breaths·min^–1, and a MV 10l·min^–1 appeared to be useful for predicting successful weaning outcome. However, even using those criteria, there were many falsely-negative cases. The alveolar-arterial P_{O 2} gradient 350mmHg at an Fi _{O 2} 1.0 was not useful as a predictor of weaning outcome. The present study demonstrates that conventional criteria are frequently inaccurate for predicting weaning outcomes and suggests that the use of some of these criteria may unnecessarily prolong the length of ventilator support. Since ventilation of most patients with poor oxygenation can be successfully discontinued by placing them on a continuous positive airway pressure system, these results suggest that the improvement of oxygenation is not an indispensable prerequisite for weaning from mechanical ventilators.(Okamoto K, Iwamasa H, Dogomori H, et al.: Evaluation of conventional weaning criteria in patients with acute respiratory failure. J Anesth 4: 213–218, 1990)