Chronic kidney disease stage stratifies short- and long-term outcomes after aortic root replacement

OBJECTIVESChronic kidney disease (CKD) is prevalent in patients undergoing cardiovascular surgery, and it negatively impacts procedural outcomes; however, its influence on the outcomes of aortic surgery has not been well studied. This study aims to elucidate the importance of CKD on the outcomes of aortic root replacement (ARR).Open in a separate windowMETHODSPatients who underwent ARR between 2005 and 2019 were retrospectively reviewed (n = 882). Patients were divided into 3 groups based on the Kidney Disease: Improving Global Outcomes criteria: Group 1 [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m², n = 421); Group 2 (eGFR = 30–59 ml/min/1.73 m², n = 424); and Group 3 (eGFR < 30 ml/min/1.73 m², n = 37). To reduce potential confounding, a propensity score matching was also performed between Group 1 and the combined group of Group 2 and Group 3. The primary end point was 10-year survival. Secondary end points were in-hospital mortality and perioperative morbidity.RESULTSSevere CKD patients presented with more advanced overall chronic and acute illnesses. Kaplan–Meier analysis showed a significant correlation between CKD stage and 10-year survival (log-rank P < 0.001). The number of events for Group 1 was 15, Group 2 was 49 and Group 3 was 11 in 10 years. Group 3 had significantly higher in-hospital mortality (13.5% vs 3.5% in Group 2 vs 0.7% in Group 1, P < 0.001) and stroke (8.1% vs 7.1% vs 1.2%, P < 0.001) as well as introduction to new dialysis (27.0% vs 5.4% vs 1.7%, P < 0.001). eGFR was shown to be an independent predictor of mortality (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99). Comparison between propensity matched groups showed similar postoperative outcomes, and eGFR was still identified as a predictor of mortality (hazard ratio, 0.97; 95% confidence interval, 0.95–0.99).CONCLUSIONSHigher stage in CKD negatively impacts the long-term survival in patients who are undergoing ARR.     

Re-dosing of del Nido cardioplegia in adult cardiac surgery requiring prolonged aortic cross-clamp

Open in a separate window OBJECTIVESFew data exist on the use of del Nido cardioplegia in adults, specifically during operations requiring prolonged aortic cross-clamp. In this pilot study, we evaluate outcomes of patients undergoing surgery with cross-clamp time >3 h based on re-dosing strategy, using either full dose (FD; 1:4 blood to crystalloid ratio) or dilute (4:1 blood to crystalloid ratio) solution.METHODSConsecutive adult patients (>18 years) undergoing cardiac surgery from 2012 to 2018 with cross-clamp time >3 h were reviewed. Patients were excluded if del Nido cardioplegia was not used. Patients were categorized into FD or dilute groups based on re-dosing solution. Propensity score matching was used to control for baseline differences between groups. The primary endpoint was in-hospital mortality. Other outcomes examined included: postoperative mechanical support, arrhythmia, stroke, dialysis and cardiac function.RESULTSIncluded for analysis were 173 patients (115 male) with median age of 63.8 (interquartile range 53.9–73.1). Major comorbidities included diabetes (45), cerebrovascular disease (34), hypertension (131), atrial fibrillation (52) and previous cardiac surgery (83). There were 108 patients (62%) who received FD re-dosing, while 65 (38%) received dilute. A greater proportion of patients in the dilute group received retrograde delivery, for both induction (32/108 vs 39/65, P < 0.001) and re-dose (50/108 vs 53/65, P < 0.001). After propensity score matching, in-hospital mortality was not different between groups (6/48 vs 1/48, P = 0.131). There were no differences in rates of postoperative mechanical circulatory support, stroke, left ventricular ejection fraction or right ventricle dysfunction.CONCLUSIONSDel Nido cardioplegia has been used in complex cardiac surgery requiring prolonged cross-clamp. Re-dosing can be performed with either FD or dilute del Nido solution with no statistical difference in outcomes.     

Relationship between reduced b cell susceptibility to igm antibodies and reduced igd-bearing b cells in patients with systemic lupus erythematosus

Peripheral blood lymphocytes from 14 patients with systemic lupus erythematosus, 5 patients with rheumatoid arthritis, and 10 normal subjects were cultured for 7 days with or without anti-IgM or anti-IgD antibodies, and IgG- and IgM-secreting cells were assayed by reverse hemolytic plaque assay. Surface immunoglobulin (Ig) isotypes on peripheral blood B cells were also examined by a direct anti-Ig resetting reaction. In normal subjects and rheumatoid arthritis patients, the spontaneous development of IgG- and IgM-secreting cells was markedly suppressed by anti-IgM or anti-IgD antibodies. Over 50% of peripheral blood B cells were IgD- and/or IgM-bearing cells in normal subjects and in most patients with rheumatoid arthritis. In lupus patients, however, the suppression of IgG and IgM production by anti-IgM or anti-IgD antibodies was remarkably reduced, especially in the active stage. Furthermore, the percentage of IgD-bearing cells in peripheral blood B cells was remarkably reduced, especially in patients with active disease. There was a good correlation between reduced susceptibility of B cells to anti-IgM antibody-mediated suppression and reduced percentage of IgD-bearing cells in lupus patients.     

Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways,accumulation of α-synuclein,and apoptotic cell death in aged mice

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson''s disease. LRRK2 is a large protein containing a small GTPase domain and a kinase domain, but its physiological role is unknown. To identify the normal function of LRRK2 in vivo, we generated two independent lines of germ-line deletion mice. The dopaminergic system of LRRK2^−/− mice appears normal, and numbers of dopaminergic neurons and levels of striatal dopamine are unchanged. However, LRRK2^−/− kidneys, which suffer the greatest loss of LRRK compared with other organs, develop striking accumulation and aggregation of α-synuclein and ubiquitinated proteins at 20 months of age. The autophagy–lysosomal pathway is also impaired in the absence of LRRK2, as indicated by accumulation of lipofuscin granules as well as altered levels of LC3-II and p62. Furthermore, loss of LRRK2 dramatically increases apoptotic cell death, inflammatory responses, and oxidative damage. Collectively, our findings show that LRRK2 plays an essential and unexpected role in the regulation of protein homeostasis during aging, and suggest that LRRK2 mutations may cause Parkinson''s disease and cell death via impairment of protein degradation pathways, leading to α-synuclein accumulation and aggregation over time.     

Revised guideline for the diagnosis and treatment of acquired idiopathic generalized anhidrosis in Japan

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by an acquired impairment in total body sweating despite exposure to heat or exercise. Severe cases may result in heatstroke. Most cases of AIGA have been reported in Asia, especially in Japan. However, there is limited information on the epidemiology of this condition, and no diagnostic criteria or appropriate treatment options have been established. This guideline was developed to fill this gap. It contains information on the etiology, diagnosis, evaluation of disease severity and evidence‐based recommendations for the treatment of AIGA. Appropriate treatment according to disease severity may relieve the clinical manifestations and emotional distress experienced by patients with AIGA.