Efficacy of combined disinfection with a nitric oxide donor in controlling biofilm formation on the reverse osmosis water pathway for hemodialysis.

The water treatment system for hemodialysis (HD) is used to treat multiple patients requiring HD simultaneously. This system requires a large amount of purified reverse osmosis (RO) water. However, a major drawback of this method is the formation of biofilms in dialysate pathways. The purpose of this study was to investigate the efficacy of NOC 18, a nitric oxide (NO) donor that can be used at neutral pH, in disinfecting the RO water pathway. Silicone tubes were obtained from the terminal sites of two different HD units. The biofilm coverage and mean biofilm thickness on the tube lumen were evaluated by scanning electron microscopy. The results demonstrated that treatment with NOC 18 alone and in conjunction with sodium hypochlorite reduced biofilm coverage and mean biofilm thickness. Thus, NO donor is a potential disinfectant that enhances bacterial dispersion from biofilms formed on the silicone tube lumen and reduces biofilm coverage and thickness on the RO water pathway at neutral pH. Furthermore, combined disinfection with the NO donor and sodium hypochlorite might enhance biofilmremoval efficacy in clinical practice.

Renal replacement therapy removes a large number of nitric oxide donors responsible for the nitrate-nitrite-nitric oxide pathway.

BACKGROUNDS: Nitric oxide has a broad-spectrum antibacterial property promising as a new therapeutic agent for severe acute respiratory syndrome coronavirus-2 because nitric oxide donor (such as S-nitroso-N-acetylpenicillamine) reduces the replication of coronavirus-2. Patients with coronavirus disease 2019 undergoing dialysis generally have a higher mortality rate than the general population. Although the higher mortality rate in these patients may be related to their advanced age, it has been suggested that plasma nitrite and nitrate levels (products of nitric oxide metabolism) are significantly decreased after hemodialysis which may compromise the nitrate-nitrite-nitric oxide pathway and impair nitric oxide homeostasis. It results in increased cardiovascular mortality in patients undergoing dialysis. However, the profile of nitric oxide-producing substances is poorly understood during renal replacement therapy. METHODS: We simulated continuous hemodialysis and hemodiafiltration to measure the amount of nitric oxide (nitric oxide-producing substance) clearance in vitro. RESULTS: The results demonstrated increased nitric oxide clearance and higher clearance than creatinine (molecular weight: 113) and vitamin B12 (molecular weight: 1355) using highly efficient renal replacement therapy modes. CONCLUSION: The high nitric oxide clearance may have partly contributed to the high cardiovascular and coronavirus-2 mortality risk in patients on dialysis.

Predictive value of computed tomography for short-term mortality in patients with acute respiratory distress syndrome: a systematic review.

The best available evidence and the predictive value of computed tomography (CT) findings for prognosis in patients with acute respiratory distress syndrome (ARDS) are unknown. We systematically searched three electronic databases (MEDLINE, CENTRAL, and ClinicalTrials.gov). A total of 410 patients from six observational studies were included in this systematic review. Of these, 143 patients (34.9%) died due to ARDS in short-term. As for CT grade, the CTs used ranged from 4- to 320-row. The index test included diffuse attenuations in one study, affected lung in one study, well-aerated lung region/predicted total lung capacity in one study, CT score in one study and high-resolution CT score in two studies. Considering the CT findings, pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 62% (95% confidence interval [CI] 30-88%), 76% (95% CI 57-89%), 2.58 (95% CI 2.05-2.73), 0.50 (95% CI 0.21-0.79), and 5.16 (95% CI 2.59-3.46), respectively. This systematic review revealed that there were major differences in the definitions of CT findings, and that the integration of CT findings might not be adequate for predicting short-term mortality in ARDS. Standardisation of CT findings and accumulation of further studies by CT with unified standards are warranted.

Clinical Utility of Surgical Lung Biopsy for Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Surgical lung biopsy (SLB) is performed in patients with acute respiratory distress syndrome (ARDS); however, its clinical utility remains unclear. OBJECTIVES: We categorized the pathological diagnoses and investigated the predictive value for short-term mortality. METHOD: Three electronic databases (MEDLINE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) were searched for the included studies. The QUADAS-2 was used to evaluate the risk of bias and its applicability. The types and populations of pathological diagnoses were investigated. The pooled sensitivity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were estimated at a fixed specificity. Hierarchical summary receiver operating characteristic curves were drawn. RESULTS: A total of 16 studies that enrolled 758 patients were included. The pathological diagnoses were as follows: diffuse alveolar damage (DAD) 29.9%; infection 24.7%; interstitial lung disease 17.2%; malignancy 3.6%; cardiovascular disease 3.6%; drug toxicity 2.3%; connective tissue disease 2.2%; allergic disease 1.1%; and nonspecific diagnosis 15.4%. To predict short-term mortality, 13 studies that enrolled 613 patients used DAD as an index test and recorded a mortality rate of 56.9% (349 of 613 patients). A total of 3 studies that used index tests other than DAD were excluded. The pooled sensitivity, fixed specificity, LR+, LR-, and DOR were 0.46 (95% confidence interval [CI]: 0.29-0.56), 0.69, 1.48 (95% CI: 0.92-1.81), 0.78 (95% CI: 0.63-1.03), and 1.90 (95% CI: 0.89-2.86), respectively. CONCLUSIONS: SLB is unlikely to provide a specific diagnosis and should not be recommended for confirming DAD or predicting ARDS prognosis.

Nitric oxide delivery using nitric oxide-containing fluid in continuous hemofiltration: an in vitro study.

Administering nitrite has therapeutic effects on ischemic conditions wherein the enzymatic production of nitric oxide depends on oxygen. We developed a supplemental fluid containing nitric oxide (NO) and determined the clearance and supply between the pre- and post-dilution modes of continuous hemofiltration in vitro. Nitric oxide gas, 1000 mL or 2000 mL, at a concentration of 1000 ppm, was injected into 2020 mL of conventional supplemental fluid (experimental solution). The same volume of nitrogen gas was injected into the supplemental fluid (control solution). NO concentrations were measured using commercially available NO assay kit. Pre- or post-dilution continuous hemofiltration was performed using a control solution as supplemental fluid to determine the NO clearance. We determined the NO concentration of the outlet blood circuit to confirm the NO supply using the experimental solution as supplemental fluid. Also, using the bovine blood, white blood cell and platelet change rates and the dialysis membrane water flux during continuous hemodiafiltration were evaluated ex vivo as index of the biocompatibilities of a nitric oxide-containing solution. NO was not detected in the control solutions. The experimental solutions significantly increased in nitric oxide concentrations. NO clearance increased as the increase in supplemental and ultrafiltration flow rates using the control solution as supplemental fluid. However, using the experimental solution as supplemental fluid, nitric oxide supply showed a similar trend of NO clearance. Without any changes in biocompatibility using the supplemental fluid containing NO, it could maintain intravascular nitric oxide during continuous renal replacement therapy.

Benefits of consulting a certified orthoptist in a pediatric vision screening program.

In Japan, all 3-year-old children undergo a three-step municipal vision screening that includes home-based screening, secondary screening at a health center, and comprehensive ophthalmologic examination, if warranted. We investigated whether screening by a certified orthoptist (CO) could improve the detection of visual dysfunctions, including amblyopia. Three-year-olds in Nobeoka City were invited to undergo primary and secondary screenings from April 2008 to March 2011. COs performed the secondary screening tests; children with a positive secondary screening received a comprehensive ophthalmologic examination. Of the 3,303 eligible children, 98 were positive on detailed examination. Of these, 25% were classified as false-negatives. Eight children with amblyopia in the false-negative group accounted for 24% of all 33 amblyopia cases detected on detailed examination.

Data on producing an infusion fluid that contains nitric oxide.

Nitric oxide (NO) is a vasodilator and platelet aggregation inhibitor. In patients with pulmonary hypertension, inhalation of NO is used as a therapeutic option. It has been proposed that nitrite (NO2 -) is a constitute intravascular storage and delivery source of NO, a potent cardioprotective-signaling molecule. The administration of NO2 - could have therapeutic effects in conditions where the oxygen-dependent enzymatic production of NO is compromised (i.e., ischemia). Thus, if NO could be supplied by an intravenous infusion fluid, it would be an easier method than by inhalation or delivery to the blood vessels by the blood stream. We produced 2 types of solutions, i.e., a nitrogen gas injected solution (control solution) and NO gas injected solution (experimental solution). NO was measured by the Microplate Photometer (MultiSkan FC, Thermo Fisher Scientific K.K., Tokyo, Japan) with a 540-nm wavelength and NO assay kit (Quantichrom™ Nitric Oxide Assay Kit, BioAssay Systems, Hayward, CA, USA). Gas profiles were measured by the EG6+ (Abbott Japan Co., Ltd., Osaka, Japan) with an i-STAT system (300F, Abbott Japan Co., Ltd.). Comparisons of gas profiles and measured NO concentrations in vitro and ex vivo are shown between the control and experimental solutions. Since NO is oxidized to NO2 - and nitrate (NO3 -), it is common practice to quantitate total NO2 -/NO3 - as a measure of the NO level. We used the assay that was designed to accurately measure NO production following reduction of NO3 - to NO2 - using the Griess method. The data in this document describe production of an infusion fluid that contains NO without any special devices.

Oxygen delivery to the blood stream by the dialysis fluid during continuous renal replacement therapy ex vivo.

Continuous renal replacement therapy (CRRT) maintains a balance in body water and electrolytes. CRRT supplies a higher quantity of fluid than intravenous fluid therapy along with simultaneous fluid withdrawal. We hypothesized that use of a high-oxygen-containing solution for high-volume fluid exchange would improve oxygenation in the blood during CRRT. To start with, we prepared a solution containing high oxygen. The objective of this study was to determine if this solution would increase the partial pressure of oxygen (pO2) in the blood more than that using a conventional solution during CRRT. We compared the gas profile of the experimental fluid ex vivo in a simulated CRRT for 24 h, using 2-L batches of bovine blood. A significant increase in the pO2, pH, and total oxygen delivery, and a significant decrease in the partial pressure of carbon dioxide (pCO2) were estimated in the bovine blood using the experimental solution during the simulated CRRT. This method is simpler to apply for oxygenation than the conventional method, and will be beneficial to hypoxic patients in terms of improving their blood oxygenation during CRRT.

Data on a simple method for producing a solution that contains a high partial pressure of oxygen and a low partial pressure of carbon dioxide.

The data presented here shows a simple method for producing a solution that contains a high partial pressure of oxygen (pO2) and a low partial pressure of carbon dioxide (pCO2). This novel solution was created by simply injecting oxygen gas into conventional supplemental bicarbonate fluid for renal replacement therapy. We compared the gas profiles of the novel solution and the conventional fluid in vitro. There was a significant increase in pO2 and pH, and a significant decrease in pCO2 in the experimental solution, in each of which an additional volume of oxygen was injected. The method shown here is capable of facilitating an increase of pO2 and decrease of pCO2 by using a closed fluid bag without any special devices.

Simple method to make a supersaturated oxygen fluid.

Intravenous oxygenation has demonstrated significant increase in partial pressure of oxygen (PO2) in animal models. A highly dissolved oxygen solution might be able to provide a sufficient level of oxygen delivery to the tissues and organs in patients with hypoxia. However, conventional fluid oxygenation methods have required the use of original devices. If simpler oxygenation of a solution is possible, it will be a useful strategy for application in clinical practice. We simply developed its administration by injection of either air or oxygen gas into conventional saline. We determined the PO2 values in the solutions in comparison with conventional saline in vitro. To examine the effects of the administration of the new solutions on the blood gas profile, we diluted bovine blood with either conventional or the new solutions and analyzed PO2, oxygen saturation (SO2) and total oxygen content. PO2 levels in the blood and new solution mixture significantly increased with each additional injected gas volume. Significant increases in the PO2 and SO2 of the bovine blood were found in those blood samples with the new solution, as compared with those with the control solution. These results suggest that this solution promotes oxygen delivery to the hypoxic tissue and recovery from hypoxia. This method is simpler and easier than previous methods.

Asymmetric triacetate membrane keeps high water flux during ultrafiltration: in vitro study.

Membrane fouling is a primary challenge encountered during the administration of hemodialysis (HD) and hemodiafiltration (HDF). A high-flux membrane is suitable for dialyzer reuse, since it is used repeatedly. Water flux is a benchmark used to assess the effectiveness of the dialysis membrane during treatment and it is usually evaluated to determine whether membrane fouling has occurred. Polysulfone (PS) membrane has good biocompatibility and solute permeability; however, polyethersulfone (PES) is often used as a hemodiafilter membrane because of better hydrophilicity compared to PS. We evaluated water flux across hemodiafilters using newly developed asymmetric triacetate (ATA) and PES as conventional membranes in vitro. Water flux of across ATA and PES membranes significantly decreased 30 min after the start of the experiments and thereafter showed stabilization. Water flux across the ATA membrane consistently showed significantly higher values of greater than 100 mL/m2/h/mmHg, compared to lower values observed across the PES membrane. These results suggest that the ATA membrane has a potential use not only for HDF, but also for long-time therapies of HD and HDF.

Hyperbaric Oxygen Therapy Suppresses Apoptosis and Promotes Renal Tubular Regeneration After Renal Ischemia/Reperfusion Injury in Rats.

BACKGROUND: Renal ischemia/reperfusion (I/R) injury remains a major cause of acute kidney injury (AKI), in addition to I/R injury-induced tissue inflammation, necrosis and apoptosis. Hyperbaric oxygen therapy (HBO) is defined as a treatment in which a patient is intermittently exposed to 100% oxygen pressurized to a pressure above sea level (> 2.0 atmospheres absolute (ATA), 1.0 ATA = 760 mmHg). It has been used in a number of medical conditions with a proven efficacy in a limited number of disorders. However, the effects of HBO therapy on apoptosis and proliferative activity after I/R injury have not been fully understood. OBJECTIVES: We studied the possible beneficial effects of HBO therapy on apoptosis and tubular cell regeneration after renal I/R injury in rats. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomized into three groups: Sham (Sham-operated rats); I/R (animals submitted to I/R); and I/R + HBO (I/R rats exposed to HBO). Tubular cell apoptosis was confirmed by DNA laddering and the terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay. Cellular proliferation activity was determined using the anti-Ki-67 antibody. RESULTS: A significant decrease in apoptotic cells and increase in proliferative reaction were observed in the I/R + HBO group compared to the I/R group. CONCLUSIONS: We demonstrated that HBO suppressed apoptosis, which caused inflammation after renal I/R, and promoted tubular cell regeneration. HBO has protective effects against AKI caused by renal I/R through the inhibition of apoptosis.

Dialysate with high dissolved hydrogen facilitates dissociation of indoxyl sulfate from albumin.

BACKGROUND: Protein-bound toxins such as indoxyl sulfate (IS) are not efficiently removed by conventional hemodialysis (HD). OBJECTIVES: To improve the removal of IS, we performed an in vitro study to evaluate the effects of high dissolved hydrogen on the dissociation of IS from albumin using simulated HD. MATERIALS AND METHODS: Wasted dialysate from peritoneal dialysis was concentrated a hundred times using extracorporeal ultrafiltration method. Dialysate with high dissolved hydrogen was made by mixing concentrated dialysis solution and electrolyzed-reduced water. The amounts of free fractions of IS were determined by high performance liquid chromatography. RESULTS: IS was significantly dissociated from albumin using dialysate with high dissolved hydrogen compared with conventional dialysate (P < 0.05). CONCLUSIONS: Effective removal of IS is expected using a dialysate with high dissolved hydrogen.

Effect of additional preoperative administration of the neutrophil elastase inhibitor sivelestat on perioperative inflammatory response after pediatric heart surgery with cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response. Our previous reports revealed that prophylactic sivelestat administration at CPB initiation suppresses the postoperative acute inflammatory response due to CPB in pediatric cardiac surgery. The purpose of this study was to compare the effects of sivelestat administration before CPB and at CPB initiation in patients undergoing pediatric open-heart surgery. Twenty consecutive patients weighing 5-10 kg and undergoing ventricular septal defect closure with CPB were divided into pre-CPB (n = 10) and control (n = 10) groups. Patients in the pre-CPB group received a 24 h continuous intravenous infusion of 0.2 mg/kg/h sivelestat starting at the induction of anesthesia and an additional 0.1 mg/100 mL during CPB priming. Patients in the control group received a 24-h continuous intravenous infusion of 0.2 mg/kg/h sivelestat starting at the commencement of CPB. Blood samples were tested. Clinical variables including blood loss, water balance, systemic vascular resistance index, and the ratio between partial pressure of oxygen and fraction of inspired oxygen (P/F ratio) were assessed. White blood cell count and neutrophil count as well as C-reactive protein levels were significantly lower in the pre-CPB group according to repeated two-way analysis of variance, whereas platelet count was significantly higher. During CPB, mixed venous oxygen saturation remained significantly higher and lactate levels lower in the pre-CPB group. Postoperative alanine aminotransferase and blood urea nitrogen levels were significantly lower in the pre-CPB group than in the control group. The P/F ratio was significantly higher in the pre-CPB group than in the control group. Fluid load requirement was significantly lower in the pre-CPB group.Administration of sivelestat before CPB initiation is more effective than administration at initiation for the suppression of inflammatory responses due to CPB in pediatric open-heart surgery, with this effect being confirmed by clinical evidence.

Effect of the neutrophil elastase inhibitor sivelestat on perioperative inflammatory response after pediatric heart surgery with cardiopulmonary bypass: a prospective randomized study.

Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response. The neutrophil elastase inhibitor sivelestat is known to suppress this systemic inflammatory response, which can eventually result in acute organ failure. The prophylactic effect of sivelestat on acute lung injury, especially in pediatric cardiac surgery, remains unclear. This prospective double-blind, randomized study evaluated the perioperative prophylactic effect of sivelestat in patients undergoing elective pediatric open heart surgery with CPB. Thirty consecutive patients, weighing 5-10 kg and undergoing open heart surgery with CPB, were assigned to sivelestat (n = 15) or control (n = 15) groups. From CPB initiation to 24 h after surgery, patients in the sivelestat group received a continuous intravenous infusion of 0.2 mg/kg/h sivelestat, whereas patients in the control group received the same volume of 0.9% saline. Blood samples were collected, and levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, polymorphonuclear elastase (PMN-E), C-reactive protein (CRP), as well as the white blood cell (WBC) count, platelet count, and neutrophil count (NC) were measured. PMN-E levels, IL-8 levels, WBC count, NC, and CRP levels were significantly lower, and platelet count was significantly higher in the sivelestat group, according to repeated two-way analysis of variance. The activated coagulation time was significantly shorter in the sivelestat group, similarly, blood loss was significantly less in the sivelestat group. In conclusion, Sivelestat attenuates perioperative inflammatory response and clinical outcomes in patients undergoing pediatric heart surgery with CPB.

Virus associated hemophagocytic syndrome accompanied by acute respiratory failure caused by influenza A (H3N2).

A 40-year-old Japanese woman was admitted to Oita University Hospital with progressive dyspnea, consciousness disturbance and severe cytopenias. Her chest roentgenogram showed diffuse bilateral infiltrates. She was therefore forced to receive mechanical ventilation. Bone marrow aspiration disclosed numerous hemophagocytic histiocytes, thus suggesting her condition to be hemophagocytic syndrome. In addition, she also developed myocarditis and renal failure. Pulsed methylprednisolone, gamma-globulin, granulocyte colony-stimulating factor and sivelestat sodium hydrate were administrated, and thereafter the patient recovered from cytopenia and organ failure. Afterwards, influenza A H3N2 was detected from bronchial extracts. We should recognize that an influenza A virus infection can induce hemophagocytic syndrome and acute respiratory failure as the initial manifestations of multiple organ failure.

Recto-peritoneal fistula following transperineal prostate biopsy.

A recto-peritoneal fistula is an extremely rare complication after prostate biopsy. We report herein on a peritonitis arising from a recto-peritoneal fistula 5 days after undergoing prostate biopsy. To our knowledge, this is the first case of recto-peritoneal fistula following transperineal needle biopsy of the prostate in the published literature.

[Effects of olprinone hydrochloride on intraocular pressure and ocular blood flow in patients after cardiac surgery under cardiopulmonary bypass].

BACKGROUND: We evaluated the effect of olprinone hydrochloride on intraocular pressure (IOP) and ocular blood flow in patients after cardiac surgery under cardiopulmonary bypass (CPB). METHODS: Nine patients after cardiac surgery under CPB were investigated. We measured IOP of the left eye using tonometer (Tonopen XL, BIO RAD, Osaka), and mean blood flow velocity in the left ophthalmic artery (Vm) and calculated the pulsatility index in the left ophthalmic artery (PI) using 2 MHz Doppler ultrasound system (Multidop P, DWL, Germany). After baseline measurement, the olprinone hydrochloride loading dosage was increased from 0.15 to 0.3 microgram.kg-1.min-1 every 60 minutes. The intraocular pressure and ocular blood flow were measured at each point. RESULTS: IOP and PI decreased significantly, and Vm increased significantly at the infusion rate of 0.3 microgram.kg-1.min-1 from baseline. There was a significant linear correlations between IOP and Vm. CONCLUSION: We demonstrated that olprinone hydrochloride led to a decrease in IOP and an increase in ocular blood flow in patients after cardiac surgery under CPB.

Measurement of whole blood factor Xa-activated clotting time during hemodialysis with low-molecular-weight heparin.

PURPOSE: To determine whole blood factor Xa-activated clotting time (XaACT), a test for monitoring low-molecular-weight heparins (LMWHs). METHODS: Blood was obtained from six healthy volunteers. Dalteparin, a LMWH, was mixed with the blood to concentrations of 0,05 and 1.0IU·ml-1. XaACT, activated clotting time (ACT), and activated partial thromboplastin time (APTT) were measured at each dalteparin concentration. XaACT of blood from the outflow and inflow sides of the blood circuit in seven hemodialysis patients was measured before and after bolus administration of 1000 IU of dalteparin, followed by continuous infusion at a rate of 500IU·h-1. RESULTS: XaACT, ACT, and APTT in dalteparin-containing blood from volunteers were correlated with dalteparin concentration (y=312.8x+86.4;r 2=0.88;P<0.001,y=41.8x +113.5;r 2=0.83;P<0.001, andy=59.5x+38.8;r 2=0.80;P<0.001, respectively). The regression slope of XaACT was steeper than those of ACT and APTT (P<0.001). In hemodialysis patients, dalteparin increased XaACT on the outflow and inflow sides of the circuit (P<0.001,P<0.05, respectively). CONCLUSION: The measurement of XaACT can be employed to monitor LMWHs in clinical settings.