Effect of tranexamic acid administration on intraoperative blood loss during peritonectomy: a single-center retrospective observational study.

BACKGROUND: The efficacy of tranexamic acid in elective major invasive abdominal surgeries has not yet been established. We investigated the effect of tranexamic acid administration on intraoperative blood loss during peritoneal resection of pseudomucinoma and cancerous peritoneal dissemination. METHODS: Patients aged ≥ 20 years old who underwent peritoneal resection for pseudomucinoma or cancerous peritoneal dissemination at the Kishiwada Tokushukai Hospital were included in this single-center retrospective observational study. The tranexamic acid group received 1000 mg of tranexamic acid at the start of the operation, while the control group received the same intraoperative management as the tranexamic acid group, except for the tranexamic acid administration. The primary endpoint was intraoperative blood loss, and a multivariate analysis of the contributing factors was performed. RESULTS: The median volume of intraoperative blood loss was 1372 [interquartile range, 842 - 1877] mL and 907 [516 - 1537] mL in the control and tranexamic acid groups, respectively (p < 0.01). The total volume of blood transfusion during the operation was 2040 [1480 - 2380] mL and 1560 [1000 - 2120] mL in the control and tranexamic acid groups, respectively (p = 0.02). Postoperative blood test results revealed D-dimer values of 7.5 [4.1 - 10.7] µg/mL and 1.8 [1.0 - 3.3] µg/mL in the control and tranexamic acid groups, respectively (p < 0.01). Multivariate analysis showed that tranexamic acid administration was significantly associated with decreased intraoperative blood loss (p = 0.02). CONCLUSION: Tranexamic acid administration may be useful in reducing intraoperative blood loss and blood transfusion volume during highly-invasive surgeries such as peritoneal resection of pseudomucinoma and cancerous peritoneal dissemination.

DNA demethylation increases NETosis.

Neutrophil extracellular traps (NETs) occur during the development of autoimmune diseases, cancer and diabetes. A novel form of cell death that is induced by NETs is called NETosis. Although these diseases are known to have an epigenetic component, epigenetic regulation of NETosis has not previously been explored. In the present study, we investigated the effects of epigenetic change, especially DNA demethylation, on NETosis in neutrophil-like cells differentiated from HL-60 cells, which were incubated for 72 h in the presence of 1.25% DMSO. DMSO-differentiated neutrophil-like cells tended to have increased methylation of genomic DNA. NETosis in the neutrophil-like cells was induced by the treatment with A23187, calcium ionophore, and increased by the addition of the DNMT inhibitor 5-azacytidine (Aza) during differentiation. Interestingly, Aza-stimulated neutrophil-like cell induced NETosis without treatment with A23187. Although reactive oxygen species (ROS), especially superoxide and hypochlorous acid, are important in NETosis induction, treatment with Aza decreased production of ROS, while mitochondria ROS scavenger tended to decrease Aza-induced NETosis. Moreover, the genomic DNA in Aza-stimulated neutrophil-like cell was demethylated, and the expression of peptidylarginine deiminase4 (PAD4) and citrullinated histone H3 (R2+R8+R17) was increased, but myeloperoxidase expression was unaffected. Additionally, PAD4 inhibition tended to decrease Aza-induced NETosis. The DNA demethylation induced by the DNMT inhibitor in neutrophil-like cells enhanced spontaneous NETosis through increasing PAD4 expression and histone citrullination. This study establishes a relationship between NETosis and epigenetics for the first time, and indicates that various diseases implicated to have an epigenetic component might be exacerbated by excessive NETosis also under epigenetic control.

Formation of neutrophil extracellular traps in mitochondrial DNA-deficient cells.

Neutrophil extracellular trap (NET) formation plays an important role in inflammatory diseases. Although it is known that NET formation occurs via NADPH oxidase (NOX)-dependent and NOX-independent pathways, the detailed mechanism remains unknown. Therefore, in this study, we aimed to elucidate the role of mitochondria in NOX-dependent and NOX-independent NET formation. We generated mitochondrial DNA-deficient cells (ρ0 cells) by treating HL-60 cells with dideoxycytidine and differentiated them to neutrophil-like cells. These neutrophil-like ρ0 cells showed markedly reduced NOX-independent NET formation but not NOX-dependent NET formation. However, NET-associated intracellular histone citrullination was not inhibited in ρ0 cells. Furthermore, cells membrane disruption in NOX-dependent NET formation occurred in a Myeloperoxidase (MPO) and mixed lineage kinase domain like pseudokinase (MLKL)-dependent manner; however, cell membrane disruption in NOX-independent NET formation partially occurred in an MLKL-dependent manner. These results highlight the importance of mitochondria in NOX-independent NET formation.

General Anesthesia Management for Adult Mucopolysaccharidosis Patients Undergoing Major Spine Surgery.

OBJECTIVE: Mucopolysaccharidosis (MPS) are a group of rare systemic lysosomal storage diseases associated with severe airway obstruction and cardiac disease, making anesthesia management difficult. Contemporary treatment extends the lifespan of affected individuals, increasing the need for major surgery in adulthood. CLINICAL PRESENTATION AND INTERVENTION: We provided general anesthesia for 6 adult MPS patients undergoing spine surgery. The airway was assessed as difficult in all, with 2 receiving awake fiberoptic intubation and 1 successfully undergoing video-laryngoscopy, while 3 video-laryngoscopy procedures failed and required conversion to fiberoptic intubation. One patient developed ventricular fibrillation. CONCLUSION: Adult MPS patients have substantial anesthesia risk.

17-ß-estradiol enhances neutrophil extracellular trap formation by interaction with estrogen membrane receptor.

Cell death-associated neutrophil extracellular trap formation (NETosis) occurs during various autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, as well as during gestation. Although increasing estrogen concentrations associated with pregnancy might induce NETosis via nuclear estrogen receptor (ERα/ERß), little is known about the mechanisms associated with estrogen-induced NETosis. Here, we investigated the effects of estrogen (17-ß-estradiol; E2) on NETosis, focusing on mechanisms associated with estrogen membrane receptor (GPR30) in neutrophil-like HL-60 cells. Our results show that E2 and the GPR30 agonist G-1 increases level of NETosis and NET formation. Moreover, NETosis-associated intracellular and extracellular histone citrullination and peptidyl arginine deiminase 4 (PAD4) expression were also increased by E2 or G-1 treatment. Furthermore, GPR30 antagonist pre-treatment inhibited increases in NETosis and PAD4 expression mediated by G-1 and partially inhibited these effects mediated by E2. These results demonstrate that E2 treatment induces NETosis via not only ERα/ERß but also GPR30 in neutrophil-like HL-60 cells.

Reduction of oxidative stress a key for enhanced postoperative recovery with fewer complications in esophageal surgery patients: Randomized control trial to investigate therapeutic impact of anesthesia management and usefulness of simple blood test for prediction of high-risk patients.

BACKGROUND: Oxidative stress may be an integral determinant of surgical stress severity. We examined whether the preoperative level of derivatives of reactive oxygen metabolites (d-ROMs), an oxidative stress biomarker based on total hydroperoxides in circulating blood, is predictive of increased risk of delayed recovery and complications after surgery, as well as the effects of anesthesia management on postoperative recovery in light of oxidative stress. METHODS: Patients (American Society of Anesthesiologists physical status I-II) scheduled for a radical esophagectomy (n = 186) were randomly selected to receive inhalational sevoflurane (n = 94) or intravenous propofol (n = 92) anesthesia. Preoperative blood d-ROMs level, as well as pre-and postoperative plasma ferric-reducing ability, were analyzed to assess oxidative stress, with white blood cell (WBC) count, C-reactive protein (CRP) level, incidence of severe postoperative complications, and postoperative recovery process within 30 days after surgery also examined in a double-blind fashion. RESULTS: Postoperative normalization of WBC and CRP was extended in patients with elevated preoperative d-ROMs [WBC versus d-ROMs: correlation coefficient (r) = 0.58 P < .001; CRP versus d-ROMs: r = 0.46 P < .001]. Receiver operating characteristics analysis of d-ROMs in relation to incidence of severe postoperative complications revealed an optimum d-ROMs threshold value of 410 UCarr and that patients with ≥410 UCarr had a greater risk of complications as compared to those with lower values (odds ratio = 4.7). Plasma ferric-reducing ability was decreased by 61 ±â€Š185 mmol·l (P < .001) after surgery, demonstrating development of surgery-related oxidative stress, the magnitude of which was positively correlated with preoperative d-ROMs level (r = 0.16, P = .043). A comparison of the 2 anesthesia management protocols showed that patients who received propofol, an antioxidant anesthetic, had no postoperative decrease in ferric-reducing ability, lower incidence of severe postoperative complications (7 of 92 versus 18 of 94, P = .030, odds ratio = 0.35), and faster uneventful recovery time (WBC normalization days 7.1 ±â€Š5.2 versus 13.6 ±â€Š10.2, P < .001) as compared to those who received sevoflurane. CONCLUSIONS: Elevated preoperative blood d-ROMs predicts greater intraoperative oxidative stress and increased postoperative complications with prolonged recovery, thus is useful for identifying high-risk patients for delayed and complicated surgical recovery. Reduction of oxidative stress is vital for enhanced recovery, with control by antioxidants such as propofol a possible solution.

A case report of seizure during emergence from general anesthesia after lumbar spinal surgery-common cases can develop potentially life-threatening adverse intracranial events.

BACKGROUND: Adverse intracranial events after spinal surgery were related with intracranial hypotension due to surgical injury of dura mater. CASE PRESENTATION: A 72-year-old woman received posterior lumbar interbody fusion under general anesthesia. Immediately after the patient was transitioned to the supine position and muscular relaxants were reversed, she developed generalized seizure. The seizure was immediately suppressed with propofol. Brain computed tomography was unremarkable. Although she returned to the surgical suite, an evident point of dural laceration was not found. The dura was covered with fibrin glue. Magnetic resonance imaging revealed subarachnoid hemorrhage (SAH) on postoperative day 1. By postoperative day 2, the seizure had resolved. The cause of her seizure was suspected to be SAH due to intracranial hypotension. Seizure was masked by ongoing anesthesia and muscle relaxation. CONCLUSIONS: Although spinal surgeries are common procedure, we must carefully consider its related potentially life-threatening adverse events.

Challenges to prevent secondary fractures in patients with hip fractures in Joetsu Myoko, Japan through the increased use of osteoporosis treatment and collaboration with family doctors.

The Niigata Prefectural Central Hospital (NPCH) is one of the main hospitals for the cities of Joetsu and Myoko, Niigata Prefecture, Japan, an area with a population of 240,141, of whom 26.7 % were aged ≥65 years in 2009. In the NPCH, patients with hip fractures are admitted to an orthopedic ward within 4 h, 89.2 % of patients are operated on within 48 h during working hours, and the prevalence of pressure ulcers is 1.5 %. To reduce the incidence of hip fractures, two major challenges emphasizing secondary fracture prevention were initiated in 2012. The first challenge used a team approach-hospital pharmacists asked patients about their drug use histories, orthopedic surgeons began drug therapy for osteoporosis after explaining to patients its importance for the prevention of secondary hip fractures, nurses assessed the risk of falling, and physiotherapists conducted rehabilitation with the aim of preventing falls. The second challenge focused on maintaining treatment for osteoporosis after discharge, when patients were under the oversight of family doctors. The percentages of patients with primary hip fractures who were taking anti-osteoporosis medications at the time of discharge in 2009, 2012, 2013 and 2014 were 21, 33, 41, and 43 %, respectively. The 12-month incidences of hip fractures on the unaffected side in 2009, 2012, 2013 and 2014 were 7.4, 2.2, 0, and 2.4 %, respectively, and the 24-month incidences of such fractures in 2009, 2012 and 2013 were 12, 7.6, and 5.2 %, respectively. Our challenges were effective at decreasing the incidence of secondary fractures.

In-line positioning of ultrasound images using wireless remote display system with tablet computer facilitates ultrasound-guided radial artery catheterization.

Ultrasound-guided procedures may be easier to perform when the operator's eye axis, needle puncture site, and ultrasound image display form a straight line in the puncture direction. However, such methods have not been well tested in clinical settings because that arrangement is often impossible due to limited space in the operating room. We developed a wireless remote display system for ultrasound devices using a tablet computer (iPad Mini), which allows easy display of images at nearly any location chosen by the operator. We hypothesized that the in-line layout of ultrasound images provided by this system would allow for secure and quick catheterization of the radial artery. We enrolled first-year medical interns (n = 20) who had no prior experience with ultrasound-guided radial artery catheterization to perform that using a short-axis out-of-plane approach with two different methods. With the conventional method, only the ultrasound machine placed at the side of the head of the patient across the targeted forearm was utilized. With the tablet method, the ultrasound images were displayed on an iPad Mini positioned on the arm in alignment with the operator's eye axis and needle puncture direction. The success rate and time required for catheterization were compared between the two methods. Success rate was significantly higher (100 vs. 70 %, P = 0.02) and catheterization time significantly shorter (28.5 ± 7.5 vs. 68.2 ± 14.3 s, P < 0.001) with the tablet method as compared to the conventional method. An ergonomic straight arrangement of the image display is crucial for successful and quick completion of ultrasound-guided arterial catheterization. The present remote display system is a practical method for providing such an arrangement.

Cluster composition distributions of pure ethanol: influence of water and ion-molecule reactions revealed by liquid-ionization tandem mass spectrometry.

Studies of clusters in condensed phase at atmospheric pressure are very important for understanding the properties and structures of liquids. Liquid-ionization (LPI) mass spectrometry is useful to study hydrogen-bonded clusters at the liquid surface and in a gas phase. An improved ion source connected to a tandem mass spectrometer provides detailed information about clusters. Mass spectra of pure ethanol (99.5%) observed by the first mass analyzer (Q1) showed neat ethanol cluster ions (C2H5OH) m H(+) with m up to 10 and hydrate ions (C2H5OH) m (H2O) n H(+) with m larger than 7 and n=1, such as those with m-n=8-1 and 9-1. When the flow rate of ethanol (liquid) was increased, large ethanol cluster ions with m larger than 25 were observed by the second mass analyzer (Q3). It is interesting to note that neat ethanol cluster ions are more abundant than corresponding (with the same m) hydrate ions (n=1), and major hydrate ions contain only one molecule of water. Results indicate that ion-molecule reactions occur between Q1 and Q3, because such mass spectra have never been observed by Q1. Various results indicate that neat ethanol clusters exist at the liquid surface and are ionized to give cluster ions.

Open abdominal surgery increases intraoperative oxidative stress: can it be prevented?

BACKGROUND: The involvement of reactive oxygen species early in the development of surgical stress and injury is highly suspected but has not been confirmed. Medical approaches to manage this type of oxidative stress are unknown. METHODS: We measured levels of blood hydroperoxides as an index of oxidative injury of cellular components, as well as plasma ferric-reducing ability as an index of total antioxidant potential, during sigmoidectomy under four conditions: open sigmoidectomy with sevoflurane anesthesia, laparoscopic sigmoidectomy with sevoflurane anesthesia, open sigmoidectomy with propofol anesthesia, and laparoscopic sigmoidectomy with propofol anesthesia. RESULTS: Ferric-reducing ability decreased significantly during surgery for the open sigmoidectomy with sevoflurane anesthesia, by 387 +/- 153 mmol/L, though the hydroperoxides level did not change, showing that oxidative stress increases in surgical patients. However, its toxicity may not be high enough to injure cellular components, since hydroperoxides, which are typical oxidized products of cellular components, did not increase. There were no changes in the hydroperoxides level or the ferric-reducing ability for the laparoscopic sigmoidectomy with sevoflurane anesthesia, indicating that this procedure does not increase surgical oxidative stress. Only hydroperoxides decreased significantly at the end of surgery for the open sigmoidectomy with propofol anesthesia and laparoscopic sigmoidectomy with propofol anesthesia, by 120 +/- 73 and 144 +/- 107 UCarr (1 UCarr corresponds to 0.8 mg/L H(2)O(2)), respectively. CONCLUSIONS: It seems certain that open abdominal surgery of the intestinal tract increases intraoperative oxidative stress. A laparoscopic procedure was not associated with oxidative stress, and propofol anesthesia reduced it by apparently functioning as an antioxidant.

Ossifying fibromyxoid tumor of soft parts with clonal chromosomal aberrations.

Ossifying fibromyxoid tumor (OFMT) is a rare but morphologically distinctive soft-tissue tumor. The histologic origin of this tumor is not clearly known, but its various features suggest a schwannian, neuronal, or chondroid origin. We herein report a case of a typical OFMT that occurred in the shoulder of a 65-year-old man. The karyotype exhibited the following complex numeric and structural aberrations: 42 approximately 46,XY,-Y,add(1)(q42),add(6)(p21),t(10;18)(q26;q11),der(11)t(11;15)(q23;q15),add(12)(q13),ins(14;?)(q13;?),-15,+mar. Combined with several previously reported studies, these aberrations could not identify a common cytogenetic abnormality in OFMT.

Acupuncture enhances generation of nitric oxide and increases local circulation.

Although it is widely used, the mechanisms and effects of acupuncture on pain are not completely understood. Recently, increased nitric oxide (NO) synthase activity has been found in meridians and acupoints. Because NO is a key regulator of local circulation, and because change in circulation can affect the development and persistence of pain, we propose that acupuncture might regulate NO levels. We studied the effects of acupuncture on local NO levels and circulation in a randomized, double-blind, crossover study with 20 volunteers, each of whom underwent one session each of real and noninvasive sham acupuncture in a single hand and forearm with a 1-wk interval between treatments. NO concentration in the plasma from the acupunctured arm was significantly increased by 2.8 +/- 1.5 micromol/L at 5 min and 2.5 +/- 1.4 micromol/L at 60 min after acupuncture. Blood flow in palmar subcutaneous tissue of the acupunctured arm also increased, and this correlated with the NO increase. These changes were not observed in noninvasive sham-acupunctured hands and forearms. In conclusion, acupuncture increases the NO level in treated regions and thereby increases local circulation. These regulatory effects might contribute to pain relief provided by acupuncture.

[A comparison of propranolol with esmolol for the treatment of tachycardia during emergence from anesthesia].

BACKGROUND: Treating tachycardia occurring during emergence from general anesthesia is of the highest priority, because it frequently induces myocardial ischemia. Therefore we retrospectively compared the efficacy of esmolol with that of propranolol against such tachycardia. METHODS: Propranolol (n=22) or esmolol (n= 29) was given intravenously when the heart rate was above 100 beats x min(-1) during emergence from anesthesia. The drugs were titrated to decrease the heart rate the level before the induction of anesthesia. RESULTS: The total dose of propranolol was 0.52+/-0.21 mg (mean+/-SD), which decreased the heart rate significantly from 109.2 +/- 19.0 to 89.2 +/-11.8 beats x min(-1). The total dose of esmolol was 32.8 +/- 16.2 mg, which decreased the heart rate significantly from 110.0+/-13.9 to 84.9+/-10.7 beats x min(-1). The time required for the maximum effect of esmolol (3.2 1.8 min) was significantly shorter than that of propranolol (8.2 +/- 4.9 min). There were no episodes of adverse effects in either group. CONCLUSIONS: Both propranolol and esmolol are equally effective and safe for the treatment of tachycardia during emergence from anesthesia. The time required for the maximum effect of esmolol was shorter than that of propranolol, indicating an advantage of esmolol.

[Propofol suppresses the responses in hypoglossal nerve activity to hypercapnic-hypoxic stimulation].

BACKGROUND: Upper airway obstruction and inadequate ventilation often arise during sedation and anesthesia by propofol. To estimate the influence of propofol (PP) on respiratory control, we studied its effect on the neural activity and the respiratory response caused by a brief (60 sec) respiratory arrest (RA) manifesting in the hypoglossal nerve (HG) and the phrenic nerve (PN) in rabbits. METHODS: Experiments were performed on adult rabbits vagotomized, paralyzed and ventilated artificially with 50% N2O, 50% oxygen and 0.5% sevoflurane. We evaluated and compared the effects of PP on the peak amplitude (AMP) and the root mean square (RMS) of HG and PH, and respiratory cycle (Tc). RESULTS: PP depressed HG activity more than PH activity, and increased Tc in a dose related manner, with 0.25 mg x kg(-1) x min(-1) continuous infusion, propofol soon began to reduce both AMPs without any remarkable changing in Tc. AMP&RMS-HG were reduced to about 35% and AMP&RMS-PN to 80% of control. Administration of propofol 1.5 mg x kg(-1) x min(-1) vanished the activity of HG in all animals. RA made a mixed hypercapnic and hypoxic condition and induced RA response which was characterized by raised AMPs, augmented RMSs (deltaAMPs, deltaRMSs) in activity of both nerves activity and lengthened Tc (deltaTc). PP depressed RA response in HG dose-dependently, but did not do so in PN. Significant depressions in cardiovascular effects with tested dosage of PP occurred, but the values were kept in physiological ranges. CONCLUSIONS: These results suggest that propofol induces respiratory depression by its inhibitory effect on the neural regulation of respiration, especially on the maintenance system of upper airway patency and the reflex related to the chemosensitive upper airway patency control.