Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

BACKGROUND: Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). CONCLUSIONS: Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Utility of growth differentiation factor-15 as a predictor of cardiovascular surgery outcomes: Current research and future directions.

In a world increasingly confronted by cardiovascular diseases (CVDs) and an aging population, accurate risk assessment prior to cardiac surgery is critical. Although effective, traditional risk calculators such as the Japan SCORE, Society of Thoracic Surgeons score, and EuroSCORE II may not completely capture contemporary risks, particularly due to emerging factors such as frailty and sarcopenia. These calculators often focus on regional and ethnic specificity and rely heavily on evaluations based on age and underlying diseases. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that has been identified as a potential biomarker for sarcopenia and a tool for future cardiac risk assessment. Preoperative plasma GDF-15 levels have been associated with preoperative, intraoperative, and postoperative factors and short- and long-term mortality rates in patients undergoing cardiac surgery. Increased plasma GDF-15 levels have prognostic significance, having been correlated with the use of cardiopulmonary bypass during surgery, amount of bleeding, postoperative acute kidney injury, and intensive care unit stay duration. Notably, the inclusion of preoperative levels of GDF-15 in risk stratification models enhances their predictive value, especially when compared with those of the N-terminal prohormone of brain natriuretic peptide, which does not lead to reclassification. Thus, this review examines traditional risk assessments for cardiac surgery and the role of the novel biomarker GDF-15. This study acknowledges that the relationship between patient outcomes and elevated GDF-15 levels is not limited to CVDs or cardiac surgery but can be associated with variable diseases, including diabetes and cancer. Moreover, the normal range of GDF-15 is not well defined. Given its promise for improving patient care and outcomes in cardiovascular surgery, future research should explore the potential of GDF-15 as a biomarker for postoperative outcomes and target therapeutic intervention.

Impella - Current issues and future expectations for the percutaneous, microaxial flow left ventricular assist device.

The importance of temporary mechanical circulatory support for treating acute heart failure with cardiogenic shock is increasingly recognized, and Impella (Abiomed, Danvers, MA, USA) has received particular attention in this regard. Impella is an axial flow left ventricular assist device (LVAD) built into the tip of a catheter. It is inserted via a peripheral artery and implanted into the left ventricle. Although the morphology of Impella is different from a typical LVAD, it has similar actions and effects as an LVAD in terms of left ventricular drainage and aortic blood delivery. Impella increases mean arterial pressure (MAP) and systemic blood flow, thereby improving peripheral organ perfusion and promoting recovery from multiple organ failure. In addition, left ventricular unloading with increased MAP increases coronary perfusion and decreases myocardial oxygen demand, thereby promoting myocardial recovery. Impella is also useful as a mechanical vent of the left ventricle in patients supported with veno-arterial extracorporeal membrane oxygenation. Indications for Impella include emergency use for cardiogenic shock and non-emergent use during high-risk percutaneous coronary intervention and ventricular tachycardia ablation. Its intended uses for cardiogenic shock include bridge to recovery, durable device, heart transplantation, and heart surgery. Prophylactic use of Impella in high-risk patients undergoing open heart surgery to prevent postcardiotomy cardiogenic shock is also gaining attention. While there have been many case reports and retrospective studies on the benefits of Impella, there is little evidence based on sufficiently large randomized controlled trials (RCTs). Currently, several RCTs are now ongoing, which are critical to determine when, for whom, and how these devices should be used. In this review, we summarize the principles, physiology, indications, and complications of the Impella support and discuss current issues and future expectations for the device.

Minimally invasive cardiac surgery via bilateral thoracotomy in treatment of left ventricle aneurysm: a case report.

BACKGROUND: Left ventricle aneurysm (LVA) as a sequela to myocardial infarction or iatrogenic injury is required surgical treatment with full median sternotomy. Herein, we report a case of successful surgical treatment of left ventricle aneurysm performed by minimally invasive cardiac surgery (MICS). CASE PRESENTATION: We describe a case of a LVA treated by minimally invasive cardiac surgery in an 82-year-old woman who reported to the hospital with the complaint of chest pains at rest. Computed tomography (CT) coronary angiography revealed a left ventricle apical aneurysm. The aneurysm was suspected to be a pseudoaneurysm caused by a previous myocardial infarction. Surgery was performed under general anesthesia, with the patient in a supine position. A small incision was made in the 3rd intercostal space through which an aortic root vent cannula and aortic clamp were inserted, followed by exposing the aneurysm via incision of the left 6th intercostal space. The aneurysm was resected and pathologically examined, revealing it to be a "true" aneurysm. The left ventricle wall was closed using polypropene mattress sutures. Postoperative CT scan revealed successful resection of the aneurysm. Usually, a surgical treatment with full median sternotomy and left ventriculostomy is indicated for LVA. We decided to treat the LVA with bilateral thoracotomy MICS. We preferred to perform this procedure under cardiac arrest to ensure safe and secure closure of the aneurysm. The right small thoracotomy was necessary for aortic cross-clamping and aortic root venting. CONCLUSIONS: The procedure was safe and simple and yielded excellent postoperative outcomes. Therefore, we speculate that this method can be applied to the management of larger aneurysms.

Prosthetic Valve Function after Aortic Valve Replacement for Severe Aortic Stenosis by Transcatheter Procedure versus Surgery.

Background This study compared the clinical outcomes of transcatheter (TAVR) and surgical (SAVR) aortic valve replacements, focusing on postoperative valvular performance assessed by echocardiography. Method and Results A total of 425 patients who underwent TAVR (230 patients) or SAVR (195 patients) were included. Postoperative effective orifice area index (EOAI) was higher in the TAVR group (1.27 ± 0.35 cm2/m2) than in the SAVR group (1.06 ± 0.27 cm2/m2, p < 0.001), and patient−prosthesis mismatch (PPM) was more frequent in the SAVR group (22.6%) than in the TAVR group (8.7%, p < 0.001). Mild or greater paravalvular leakage (PVL) was more frequent in the TAVR group (21.3%) than in the SAVR group (0%, p < 0.001). Moreover, there was no difference in freedom from all-cause death, stroke, or rehospitalization between the groups. Patients with moderate or greater PPM (EOAI < 0.85 cm2/m2) had lower freedom from composite events than those without this PPM criterion (p = 0.008). Patients with mild or greater PVL also had lower freedom from composite events than those without this PVL criterion (p = 0.017). Conclusions Postoperative valvular performance of TAVR was superior to that of SAVR in terms of EOAI. This merit was counterbalanced by the significantly lower rates of PVL in patients who underwent SAVR. The overall clinical outcomes were similar between the study groups.

Impella support as a bridge to heart surgery in patients with cardiogenic shock.

OBJECTIVES: In patients with cardiogenic shock, delayed surgery after stabilization of haemodynamics and improvement in end-organ function by mechanical circulatory support is known to yield better outcomes than emergency surgery. We aimed to investigate the effectiveness of Impella (Abiomed, Danvers, MA, USA) as a bridge to cardiac surgery in patients with cardiogenic shock. METHODS: We reviewed 7 patients with cardiogenic shock who underwent Impella support as a bridge to cardiac surgery using cardiopulmonary bypass at our institution between April 2018 and August 2021. RESULTS: Cardiogenic shock was caused by ventricular septal rupture in 3 patients, papillary muscle rupture in 1 and acute myocardial infarction in 3. Cardiac surgery was delayed by 1-7 (3.9 ± 2.5) days with Impella support after the diagnosis of cardiogenic shock, during which the hepatic and renal function of the patients improved significantly. Device-related or operation-related adverse events included re-exploration for bleeding in 3 patients, acute limb ischaemia due to thromboembolism in 1 and intraoperative aortic dissection in 1. Thirty-day mortality was 14.3%, and the cumulative survival was 71.4% at 1 year. The survival tended to be better than that in historical control group in which extracorporeal membrane oxygenation was used as a bridge to surgery (P = 0.0992). CONCLUSIONS: Impella is an effective tool for bridging patients with cardiogenic shock to surgery. This strategy may improve surgical outcomes in patients with cardiogenic shock. However, prolonged Impella support may increase significant adverse events, and further investigation is required to determine the optimal duration of support before surgery.

Contemporary short-term outcomes of surgery for aortic stenosis: transcatheter vs. surgical aortic valve replacement.

OBJECTIVES: This study aimed to compare the short-term outcomes of transcatheter and surgical aortic valve replacements (TAVR and SAVR) in high-, intermediate-, and low-preoperative risk patients. METHODS: A total of 454 patients who underwent TAVR or SAVR were included. Patients were categorized into high-, intermediate-, and low-risk according to the Society of Thoracic Surgery-Predicted Risk of Mortality score and clinical outcomes were compared between TAVR and SAVR groups. RESULTS: TAVR was less invasive, with less bleeding and transfusion (p < 0.001), less frequent new-onset atrial fibrillation (p < 0.001), and shorter intensive care unit stay (p < 0.001). Furthermore, transcatheter valves performed better than surgical valves, with lower peak velocity (p = 0.003) and pressure gradient (p < 0.001) and higher effective orifice area index (p < 0.001). The clinical outcomes of TAVR were comparable to or even superior to those of SAVR in high- and intermediate-risk patients. In low-risk patients, the 1- and 2-year mortality rates were 6.3% and 12.1%, respectively, in the TAVR group and 0% and 0.9%, respectively, in the SAVR group (p < 0.001). Mild or greater paravalvular leakage was a risk factor for mortality (hazard ratio 35.78; p < 0.001). CONCLUSIONS: TAVR was superior to SAVR in the sense of less invasiveness and valvular function. However, the indication of TAVR in low-risk patients should be carefully discussed, because paravalvular leakage was a risk factor for short-term mortality.

Preoperative Serum GDF-15, Endothelin-1 Levels, and Intraoperative Factors as Short-Term Operative Risks for Patients Undergoing Cardiovascular Surgery.

OBJECTIVES: The Society of Thoracic Surgeons (STS) risk score is widely used for the risk assessment of cardiac surgery. Serum biomarkers such as growth differentiation factor-15 (GDF-15) and endothelin-1 (ET-1) are also used to evaluate risk. We investigated the relationships between preoperative serum GDF-15, ET-1 levels, and intraoperative factors and short-term operative risks including acute kidney injury (AKI) for patients undergoing cardiovascular surgery. METHODS: In total, 145 patients were included in this study (92 males and 53 females, age 68.4 ± 13.2 years). The preoperative STS score was determined, and the serum GDF-15 and ET-1 levels were measured by ELISA. These were related to postoperative risks, including AKI, defined according to the Acute Kidney Injury Network (AKIN) classification criteria. RESULTS: AKI developed in 23% of patients. The GDF-15 and ET-1 levels correlated with the STS score. The STS score and GDF-15 and ET-1 levels all correlated with preoperative eGFR, Alb, Hb, and BNP levels; perioperative data (urine output); ICU stay period; and postoperative admission days. Patients with AKI had longer circulatory pulmonary bypass (CPB) time, and male patients with AKI had higher ET-1 levels than those without AKI. In multivariable logistic regression analysis, the preoperative ET-1 level and CPB time were the independent determinants of AKI, even adjusted by age, sex, and BMI. The preoperative GDF-15 level, CPB time, and RCC transfusion were independent determinants of 30-day mortality plus morbidity. CONCLUSION: Preoperative GDF-15 and ET-1 levels as well as intraoperative factors such as CPB time may be helpful to identify short-term operative risks for patients undergoing cardiovascular surgery.

Giant coronary sinus aneurysm misdiagnosed as an extracardiac mediastinal tumor.

Coronary sinus aneurysm is a rare heart anomaly. Herein, we report a rare case with giant coronary sinus aneurysm misdiagnosed as an extracardiac mediastinal tumor. The preoperative diagnostic imaging failed to diagnose the correct location of the tumor and a simple resection was planned. It turned out to be coronary sinus aneurysm intraoperatively and required cardiopulmonary bypass support for the resection.

Investigation of Cooperative Modes for Collective Molecules Using Grid-Based Principal Component Analysis.

A grid-based principal component analysis method (GBPCA) has been developed and implemented to investigate the modes of collective molecules present in the cube in the grid system from their trajectories using molecular dynamics (MD) simulation. This method is applied to the simulations of water, methane, and hydrated proteins. In the cases of single molecules, GBPCA demonstrates that while individual molecules interact with other molecules and move randomly, the collective molecules nevertheless produce cooperative principal component (PC) modes. Notably, these PC modes of the collective molecules formed vorticial or symmetrical structures, with some resembling torus-like structures. Such structures were observed not only in simulations with models that reproduced real molecules, such as water or methane, but also in simulations with artificial molecules that were modified to interact weakly or only repulsively. On the contrary, molecules without any interactions did not exhibit the cooperative PC modes that lead to the formation of specific structures. These results imply that when molecules subject to intermolecular forces are located in a space in which they can interact with one another, the PC modes of the collective molecules will form vorticial and torus-like structures. In the cases of hydrated proteins, the results reveal that the collective molecules in the protein and water molecules showed cooperative PC modes, forming vorticial or torus-like structures, as in the cases of the water or methane molecules. The PC modes of the water molecules close to the protein were influenced by the protein motion and indicated cooperative modes with the protein. Moreover, proteins with the same folds had similar PC mode structures. Besides, the PC modes of the proteins composed of multiple domains appeared independently in the protein domain. Hence, it can be understood that the cooperative motions of the collective molecules of the protein and surrounding water molecules contribute strongly to the protein's structure and function. These results are expected to help our understanding of the dynamics of molecules in the liquid state.

Sarcopenia assessed by the quantity and quality of skeletal muscle is a prognostic factor for patients undergoing cardiac surgery.

PURPOSE: Sarcopenia was assessed as a prognostic factor for patients undergoing cardiac surgery by evaluating the quantity and quality of skeletal muscle. METHODS: Sarcopenia was assessed by perioperative abdominal computed tomography using the total psoas muscle index (TPI) and intra-muscular adipose tissue content (IMAC). Patients were classified into high- (HT, n = 143) and low- (LT, n = 63) TPI groups and low- (LI, n = 122) and high- (HI, n = 84) IMAC groups. RESULTS: There were significantly more complications in the LT and HI groups than in the HT and LI groups. (HT 15.4% vs. LT 30.2%, P = 0.014) (LI 11.5% vs. HI 31.1%, P < 0.001). There were more respiratory complications in the LT group (HT 0% vs. LT 6.3%, P = 0.002) and more surgical site infections in the HI group than in the LI group (LI 0.8% vs. HI 7.1%, P = 0.014). A multivariable analysis showed that low TPI and high IMAC significantly predicted more major complications than other combinations (odds ratio [OR] 2.375; 95% confidence interval [CI] 1.152-5.783; P = 0.036, OR 3.973; 95% CI 1.737-9.088; P = 0.001). CONCLUSIONS: Sarcopenia is a risk factor for complications. The quantity and quality of muscle must be assessed to predict operative outcomes. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000027077.

Identification of novel bacterial urease inhibitors through molecular shape and structure based virtual screening approaches.

The enzyme urease is an essential colonizing factor of the notorious carcinogenic pathogen Helicobacter pylori (H. pylori), conferring acid resistance to the bacterium. Recently, antibiotic resistant strains have emerged globally with little to no alternative treatment available. In this study we propose novel urease inhibitors capable of controlling infection by H. pylori and other pathogenic bacteria. We employed hierarchal computational approaches to screen new urease inhibitors from commercial chemical databases followed by in vitro anti-urease assays. Initially ROCS shape-based screening was performed using o-chloro-hippurohydroxamic acid followed by molecular docking studies. Out of 1.83 million compounds, 1700 compounds were retrieved based on having a ROCS Tanimoto combo score in the range of values from 1.216 to 1.679. These compounds were further screened using molecular docking simulations and the 100 top ranked compounds were selected based on their Glide score. After structural classification of the top ranked compounds, eight compounds were selected and purchased for biological assays. The plausible binding modes of the most active compounds were also confirmed using molecular dynamics (MD) simulations. Compounds 1, 2 and 3 demonstrated good urease inhibitory properties (IC50 = 0.32, 0.68 and 0.42 µM) compared to the other compounds. Enzyme kinetic studies revealed that compounds 1 and 3 are competitive inhibitors while 2 is a mixed type inhibitor of the urease enzyme. Cell based urease inhibition and MTT assay showed that these compounds blocked H. pylori urease activity, affecting bacterial growth and acid tolerance.

Effect of coffee on the compositional shift of oral indigenous microbiota cultured in vitro.

Coffee is a widely consumed beverage containing organic compounds with antibacterial activity. To investigate its possible effect on the growth of oral indigenous microbiota, saliva samples collected from nine young adults were inoculated into brain heart infusion (BHI) medium with or without addition of coffee compounds and cultured at 37°C in 5% CO2 for 12 h. The total bacterial density and composition after cultivation for 0, 6, and 12 h were determined by quantitative PCR analysis and 16S rRNA gene sequencing, respectively. The increase in total bacterial load was significantly inhibited by addition of the coffee compounds. The microbiota was mostly composed of Streptococcus species after culture in BHI medium regardless of the addition of coffee compounds. The proportion of Streptococcus salivarius was significantly reduced after addition of coffee relative to that in untreated medium alone, whereas the proportions of Streptococcus mitis and Streptococcus infantis were increased. These results suggest that exposure to coffee affects the composition of the oral Streptococcus population, in addition to inhibiting the overall growth of salivary bacteria. Considered in the light of data from earlier epidemiological studies, it is possible to conclude that coffee consumption contributes to better health.

Investigation of a Pathway for Water Delivery in Photosystem II Protein by Molecular Dynamics Simulation.

To understand the mechanism of the water-splitting reaction in photosynthesis, the dynamics of water molecules surrounding the oxygen evolution center (OEC) involving the Mn4O5Ca cluster in photosystem II (PSII) is investigated using molecular dynamics (MD) simulation. During the simulation, the surrounding interspace around the Mn4O5Ca cluster was filled with numerous water molecules. The traffic of water molecules in the bidirectional pathway between the Mn4O5Ca cluster and outside of PSII is investigated by analyzing MD trajectories. The result of this simulation suggests that water delivery to the Mn4O5Ca cluster in PSII is driven by self-diffusion of water molecules coupled with the synchronized motion of the residues surrounding the Mn4O5Ca cluster. By tracing these water molecules, we find that the water molecules predominantly take five water pathways to enter into and leave from PSII. In these pathways, the water molecules move being strongly affected by the structure and dynamics of PSII. Nevertheless, the directions of each water molecule in these pathways are nearly random. In contrast, the principal component analysis for Cα atoms in the PSII complex revealed that the residues surrounding the OEC showed the collective and continuing motion. In an attempt to assess the validity, the MD simulation of the D1-D61A mutant is performed, comparing the distribution of water molecules near the Mn4O5Ca cluster. The results show that the change in the water distribution by the D1-D61A mutant is responsible for the experimentally observed decrease in the activLity of PSII. The details of the pathways for water delivery provide important information about the water-splitting reaction.

Lung-diffusing capacity for carbon monoxide predicts early complications after cardiac surgery.

PURPOSE: Preoperative pulmonary dysfunction has been associated with increased operative mortality and morbidity after cardiac surgery. This study aimed to determine whether values for the diffusing capacity of the lung for carbon monoxide (DLCO) could predict postoperative complications after cardiac surgery. METHODS: This study included 408 consecutive patients who underwent cardiac surgery between June 2008 and December 2015. DLCO was routinely determined in all patients. A reduced DLCO was clinically defined as %DLCO < 70%. %DLCO was calculated as DLCO divided by the predicted DLCO. The association between %DLCO and in-hospital mortality was assessed, and independent predictors of complications were identified by a logistic regression analysis. RESULTS: Among the 408 patients, 338 and 70 had %DLCO values of ≥ 70% and < 70%, respectively. Complications were associated with in-hospital mortality (P < 0.001), but not %DLCO (P = 0.275). A multivariate logistic regression analysis with propensity score matching identified reduced DLCO as an independent predictor of complications (OR, 3.270; 95%CI, 1.356-7.882; P = 0.008). CONCLUSIONS: %DLCO is a powerful predictor of postoperative complications. The preoperative DLCO values might provide information that can be used to accurately predict the prognosis after cardiac surgery. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000029985.

Effect of Atomic Charges on Octanol-Water Partition Coefficient Using Alchemical Free Energy Calculation.

The octanol-water partition coefficient (logPow) is an important index for measuring solubility, membrane permeability, and bioavailability in the drug discovery field. In this paper, the logPow values of 58 compounds were predicted by alchemical free energy calculation using molecular dynamics simulation. In free energy calculations, the atomic charges of the compounds are always fixed. However, they must be recalculated for each solvent. Therefore, three different sets of atomic charges were tested using quantum chemical calculations, taking into account vacuum, octanol, and water environments. The calculated atomic charges in the different environments do not necessarily influence the correlation between calculated and experimentally measured ∆Gwater values. The largest correlation coefficient values of the solvation free energy in water and octanol were 0.93 and 0.90, respectively. On the other hand, the correlation coefficient of logPow values calculated from free energies, the largest of which was 0.92, was sensitive to the combination of the solvation free energies calculated from the calculated atomic charges. These results reveal that the solvent assumed in the atomic charge calculation is an important factor determining the accuracy of predicted logPow values.

A study on an unusual SN2 mechanism in the methylation of benzyne through nickel-complexation.

In this study, three reaction mechanisms of a benzyne-nickel (Ni) complex ([Ni(C6H4)(dcpe)]) with iodomethane during the methylation process were investigated, namely (a) SN2 reaction of the benzyne-Ni complex with iodomethane, (b) concerted σ-bond metathesis during the bond breaking/forming processes, and (c) oxidative addition of iodomethane to the Ni-center and the subsequent reductive elimination process. DFT calculations revealed that the reaction barrier of the SN2 reaction is slightly lower than those of the other mechanisms. The results of orbital analyses suggest that [Ni(C6H4)(dcpe)] forms a metallacycle structure between benzyne and the NiII (3d8) center instead of the η2-structure with the Ni0 (3d10) center. The metallacycle structures became inappropriate as the intermediates of oxidative addition in the formation of the NiII-Me bond, avoiding further oxidation to the high-valent NiIV. The high free energy along σ-bond metathesis was generated from the steric hindrance, thus invoking methylation and Ni-I bond formation concertedly.

Incidence of acute kidney injury among patients with chronic kidney disease: a single-center retrospective database analysis.

BACKGROUND: Acute kidney injury (AKI) is a serious complication among hospitalized individuals and is closely associated with chronic kidney disease (CKD). METHODS: This retrospective cohort study evaluated the incidences of AKI according to CKD stage at Kochi Medical School hospital during 1981-2011. AKI was defined and staged according to the kidney disease improving global outcomes criteria, using serum creatinine levels. RESULTS: We analyzed data from 122,653 Japanese patients (57,105 men, 46.6 %). The incidence of AKI was 7.8 % (95 % confidence interval 7.7-8.0 %). Compared to non-AKI patients, patients with stage 1-2 AKI were more likely to be men. Patients with stage 1-2 AKI were significantly older than non-AKI or stage 3 AKI patients. The incidences of AKI were 6.7, 5.9, 10.4, 18.4, 30.0, and 48.8 % among individuals with estimated glomerular filtration rates of ≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2, respectively; these were significantly different from the incidence for the baseline eGFR. The proportions of inpatients with AKI exhibited step-wise increases with more severe pre-existing reduced kidney function, and the proportions among outpatients exhibited step-wise increases with milder pre-existing reduced kidney function. CONCLUSIONS: CKD was a risk factor for AKI, and the incidence of AKI was positively associated with pre-existing reduced kidney function (CKD stage). We also found that the prevalence of AKI at early-stage CKD among outpatients was higher than expected. We suggest that outpatients should be monitored for AKI, given its unexpected incidence in that population.

Diastereomeric resolution directed towards chirality determination focussing on gas-phase energetics of coordinated sodium dissociation.

Defining chiral centres is addressed by introducing a pair of chiral auxiliary groups. Ions of diastereomeric pairs of molecules could be distinguished utilising energy-resolved mass spectrometry, and the applicability of the method to a series of compounds carrying amine, carboxylic acid, alcohol, and all the amino acids was verified. The method was further strengthened by distinguishing diastereomeric ions that did not undergo fragmentation. Mass spectrometric evaluation of the dissociation process of adducted sodium cations from the diastereomeric precursors agreed with the theoretical calculations, indicating the potential usefulness of the method for the determination of absolute configurations.

Serum uric acid level as a risk factor for acute kidney injury in hospitalized patients: a retrospective database analysis using the integrated medical information system at Kochi Medical School hospital.

BACKGROUND AND OBJECTIVES: Recent studies have shown that both low and high levels of serum uric acid (SUA) before cardiovascular surgery are independent risk factors for postoperative acute kidney injury (AKI). However, these studies were limited by their small sample sizes. Here, we investigated the association between SUA levels and AKI by performing a retrospective database analysis of almost 30 years of data from 81,770 hospitalized patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENT: Hospitalized patients aged ≥18 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline (KDIGO) criteria. Multivariate logistic regression analyses were performed to investigate the independent association between SUA levels and the incidence of AKI. SUA levels were treated as categorical variables because the relationship between SUA and the incidence of AKI has been suggested to be J-shaped or U-shaped. In addition to stratified SUA levels, we considered kidney function and related comorbidities, medications, and procedures performed prior to AKI onset as possible confounding risk factors. RESULTS: The final study cohort included 59,219 adult patients. Adjusted odds ratios of AKI incidence were higher in both the high- and low-SUA strata. Odds ratios tended to become larger in the higher range of SUA levels in women than in men. Additionally, this study showed that AKI risk was elevated in patients with SUA levels ≤7 mg/dL. An SUA level >7 mg/dL is considered the point of initiation of uric acid crystallization. CONCLUSIONS: SUA level could be an independent risk factor for AKI development in hospitalized patients. Additionally, our results might suggest that intervention to lower SUA levels is necessary, even in cases of moderate elevation that does not warrant hyperuricemia treatment. Results also showed that SUA levels that require attention are lower for women than for men.