Discovery of a peripheral 5HT2A antagonist as a clinical candidate for metabolic dysfunction-associated steatohepatitis.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.

Sex-Specific B Cell and Anti-Myelin Autoantibody Response After Peripheral Nerve Injury.

Immunotherapy holds promise as a non-addictive treatment of refractory chronic pain states. Increasingly, sex is recognized to impact immune regulation of pain states, including mechanical allodynia (pain from non-painful stimulation) that follows peripheral nerve trauma. This study aims to assess the role of B cells in sex-specific responses to peripheral nerve trauma. Using a rat model of sciatic nerve chronic constriction injury (CCI), we analyzed sex differences in (i) the release of the immunodominant neural epitopes of myelin basic protein (MBP); (ii) the levels of serum immunoglobulin M (IgM)/immunoglobulin G (IgG) autoantibodies against the MBP epitopes; (iii) endoneurial B cell/CD20 levels; and (iv) mechanical sensitivity behavior after B cell/CD20 targeting with intravenous (IV) Rituximab (RTX) and control, IV immunoglobulin (IVIG), therapy. The persistent MBP epitope release in CCI nerves of both sexes was accompanied by the serum anti-MBP IgM autoantibody in female CCI rats alone. IV RTX therapy during CD20-reactive cell infiltration of nerves of both sexes reduced mechanical allodynia in females but not in males. IVIG and vehicle treatments had no effect in either sex. These findings provide strong evidence for sexual dimorphism in B-cell function after peripheral nervous system (PNS) trauma and autoimmune pathogenesis of neuropathic pain, potentially amenable to immunotherapeutic intervention, particularly in females. A myelin-targeted serum autoantibody may serve as a biomarker of such painful states. This insight into the biological basis of sex-specific response to neuraxial injury will help personalize regenerative and analgesic therapies.

Clinical outcomes of early gastric cancer with non-curative resection after pathological evaluation based on the expanded criteria.

Additional surgical resection should be considered for the patients with pathological findings beyond the expanded criteria with the risk for LN metastasis. However, close observation without additional surgery may be applied because of various reasons. We aimed to determine the clinical outcomes of early gastric cancer beyond the expanded criteria after endoscopic resection according to the pathological extent. A total of 288 patients with 289 lesions beyond the expanded criteria of endoscopic submucosal dissection for early gastric cancer were analyzed between 2005 and 2016, and classified into two groups according to additional treatment: observation (n = 175 patients, 175 lesions) and surgery (n = 113 patients, 114 lesions). The depth of tumor invasion was greater and the tumor-positive vertical margin and lymphatic and venous invasion were more common in the surgery group than in the observation group (P<0.001). Residual, synchronous, and metachronous tumors were more common in the observation group; however, the occurrence of regional lymph node and distant metastasis did not differ between the groups. Overall survival and 5-year disease-specific survival did not differ between the groups (observation vs surgery, 88.6 vs 93.8%; P = 0.259, 98.2 vs 100%; P = 0.484, respectively), but the 5-year disease-free survival was lower in the observation group (73.5 vs 97.9%; P<0.001). On multivariate analysis, tumor-positive lateral margin was a risk factor for residual tumor and lymphatic and venous invasion were risk factors for regional lymph node metastasis. In conclusion, the clinical course of beyond the expanded criteria of endoscopic submucosal dissection for early gastric cancer showed good prognosis over 98% in 5-year disease specific survival. If additional surgery cannot be performed, a close follow-up with endoscopy and abdominal computed tomography can be considered as an alternative for carefully selected patients without lymphatic and vascular invasion.

Clinical Implication and Risk Factors for Malignancy of Atypical Gastric Gland during Forceps Biopsy.

Background/Aims: Although forceps biopsy is performed for suspicious gastric tumors during endoscopy, it is difficult to determine treatment strategies for atypical gastric glands due to uncertainty of the diagnosis. The aim of this study was to investigate clinical implications and risk factors for predicting malignancy in atypical gastric glands during forceps biopsy. Methods: We retrospectively reviewed medical records of 252 patients with a diagnosis of atypical gastric gland during forceps biopsy. Predictors of malignancy were analyzed using initial endoscopic findings and clinical data. Results: The final diagnosis for 252 consecutive patients was gastric cancer in 189 (75%), adenoma in 26 (10.3%), and gastritis in 37 (14.7%). In the multivariate analysis, lesion sizes of more than 10 mm (odds ratio [OR], 3.021; 95% confidence interval [CI], 1.480 to 6.165; p=0.002), depressed morphology (OR, 3.181; 95% CI, 1.579 to 6.406, p=0.001), and surface nodularity (OR, 3.432; 95% CI, 1.667 to 7.064, p=0.001) were significant risk factors for malignancy. Conclusions: Further evaluation and treatment should be considered for atypical gastric gland during forceps biopsy if there is a large-sized (>10 mm) lesion, depressed morphology, or surface nodularity.

Clinical efficacy of endoscopic ultrasonography for decision of treatment strategy of gastric cancer.

BACKGROUND: Accurate preoperative tumor staging of gastric cancer is indispensable with expansion of indications for laparoscopic surgery and endoscopic resection. It is important to distinguish mucosal cancer (T1a) in smaller lesion and differentiate early gastric cancer (EGC) in larger lesion considering endoscopic resection indication and laparoscopic surgery indication. We evaluated the clinical outcomes of endoscopic ultrasonography (EUS) for the decision of treatment strategy of gastric cancer compared with pathological staging. METHODS: The patients who underwent EUS and surgical or endoscopic resection for gastric cancer were retrospectively reviewed between September 2005 and February 2016. The depth of tumor invasion (T staging) by EUS was compared with the pathological staging after endoscopic or surgical resection. RESULTS: A total of 6084 patients were finally analyzed. The accuracy rates for T1a and EGC were 75.0 and 89.4%, respectively. The overall accuracy of T staging by EUS was 66.3% when divided by T1a, T1b, and over T2. The accuracy of EUS prior to endoscopic resection was 75.1% in absolute indication and 73.1% in expanded criteria, respectively. The accuracy rates for T1a with lesion ≤ 2 cm in miniprobe EUS and EGC with lesion > 2 cm in conventional EUS were 84.6 and 83.2%, respectively. In multivariate analysis, presence of ulcer, large tumor size, and radial EUS were associated with overestimation, and small tumor size and miniprobe were associated with underestimation in T staging. CONCLUSIONS: EUS showed the high accuracy of 84.6% for T1a in lesion ≤ 2 cm in miniprobe EUS and 83.2% for EGC in lesion > 2 cm in conventional EUS, respectively. EUS can be a complementary diagnostic method to determine endoscopic or surgical treatment modality.

Co-Expression of a Chimeric Protease Inhibitor Secreted by a Tumor-Targeted Salmonella Protects Therapeutic Proteins from Proteolytic Degradation.

Sunflower trypsin inhibitor (SFTI) is a 14-amino-acid bicyclic peptide that contains a single internal disulfide bond. We initially constructed chimeras of SFTI with N-terminal secretion signals from the Escherichia coli OmpA and Pseudomonas aeruginosa ToxA, but only detected small amounts of protease inhibition resulting from these constructs. A substantially higher degree of protease inhibition was detected from a C-terminal SFTI fusion with E. coli YebF, which radiated more than a centimeter from an individual colony of E. coli using a culture-based inhibitor assay. Inhibitory activity was further improved in YebF-SFTI fusions by the addition of a trypsin cleavage signal immediately upstream of SFTI, and resulted in production of a 14-amino-acid, disulfide-bonded SFTI free in the culture supernatant. To assess the potential of the secreted SFTI to protect the ability of a cytotoxic protein to kill tumor cells, we utilized a tumor-selective form of the Pseudomonas ToxA (OTG-PE38K) alone and expressed as a polycistronic construct with YebF-SFTI in the tumor-targeted Salmonella VNP20009. When we assessed the ability of toxin-containing culture supernatants to kill MDA-MB-468 breast cancer cells, the untreated OTG-PE38K was able to eliminate all detectable tumor cells, while pretreatment with trypsin resulted in the complete loss of anticancer cytotoxicity. However, when OTG-PE38K was co-expressed with YebF-SFTI, cytotoxicity was completely retained in the presence of trypsin. These data demonstrate SFTI chimeras are secreted in a functional form and that co-expression of protease inhibitors with therapeutic proteins by tumor-targeted bacteria has the potential to enhance the activity of therapeutic proteins by suppressing their degradation within a proteolytic environment.

Combined use of dexmedetomidine and propofol in monitored anesthesia care: a randomized controlled study.

BACKGROUD: Although propofol and dexmedetomidine have been widely used for monitored anesthesia care, their adverse effects necessitate the search for better methods. Therefore, we performed this randomized controlled trial to evaluate the combined use of propofol and dexmedetomidine. METHODS: Eighty-seven adult patients undergoing hand surgery under brachial plexus block were randomly allocated to receive 1.6 µg/ml of the target effect site concentration of propofol (P group) and infusion of 0.4 µg/kg/h dexmedetomidine following a loading dose of 1.0 µg/kg for 10 min (D group). The M group received a half-dose of both drugs simultaneously. The maintenance dose was adjusted to maintain an Observer Assessment of Alertness/Sedation score of 3. Cardiorespiratory variables, adverse effects, and drug efficacy were observed. RESULTS: The significantly higher mean arterial pressure (mmHg) in the D group [P group 86.9 (12.6), D group 96.0 (12.2), M group 85.6 (10.6), p = 0.004)] and a significantly higher heart rate (beat/min) in the P group were observed [P group 67.3 (9.0), D group 57.8 (6.9), M group 59.2 (7.4), p < 0.001)]. The M group had a significant lower incidence of airway obstruction (p < 0.001) and the D group had a higher incidence of bradycardia requiring atropine (p = 0.001). The P group had higher incidences of hypoxia (p = 0.001), spontaneous movement (p < 0.001) and agitation (p = 0.001). The satisfaction scores of the patients (p = 0.007) and surgeon (p < 0.001) were higher in the M group. Onset time was significantly longer in the D group (p < 0.001). CONCLUSIONS: The combined use of propofol and dexmedetomidine provided cardiovascular stability with decreased adverse effects. Additionally, it led to a similar onset time of propofol and achieved higher satisfaction scores. TRIAL REGISTRATION: KCT0001284 . Retrospectively registered 25 November 2014.

Successful transfusion-free pancreatectomy in Jehovah's Witness patients.

BACKGROUNDS/AIMS: Although perioperative therapies have improved greatly, pancreatectomies still often need blood transfusions. However, the morbidity from blood transfusions, the poor prognosis of blood transfused patients, high cost, and decreasing supply of blood products is accelerating transfusion-free (TF) surgery in the patients who have pacreatectomies. The aim of this study was to assess the feasibility of TF pancreatectomies for patients who are Jehovah's Witness. METHODS: We investigated the possibility of TF pancreatectomies for the Jehovah's Witness patients undergoing pancreatectomies between January 2007 and Februay 2014. There were 4 cases of Whipple's operation, 4 of pylorus-preserving pancreaticoduodenectomy, 2 of radical antegrade modular pancreatosplenectomy and 1 of laparoscopic distal pancreatectomy. All were performed by one surgeon. RESULTS: Most of the TF pancreatecomies patients received perioperative blood augmentation and intraoperative acute normovolemic hemodilution (ANH). They received no blood transfusions at any time during their hospitalization, and pre- and intra-operative data and outcomes were acceptably favorable. CONCLUSIONS: To the best of our knowledge, this report is the first successful consecutive pancreatectomy program for Jehovah's Witness not involving blood transfusion. TF pancreatectomy can be performed successfully in selected Jehovah's Witness. Postoperative prognosis and outcomes should be confirmed in follow up studies.

An apolipoprotein B100 mimotope prevents obesity in mice.

Although apolipoprotein B100 (ApoB100) plays a key role in peripheral fat deposition, it is not considered a suitable therapeutic target in obesity. In the present study we describe a novel ApoB100 mimotope, peptide pB1, and the use of pB1-based vaccine-like formulations (BVFs) against high-fat diet (HFD)-induced obesity. In HFD- compared with chow-fed adolescent mice, BVFs reduced the 3-month body-weight gains attributable to increased dietary fat by 44-65%, and prevented mesenteric fat accumulation and liver steatosis. The body-weight reductions paralleled the titres of pB1-reactive immunoglobulin G (IgG) antibodies, and pB1-reactive antibodies specifically recognized native ApoB100 and a synthetic peptide from the C-terminal half of ApoB100. In cultured 3T3L1 adipocytes, anti-pB1 antibodies increased lipolysis and inhibited low-density lipoprotein (LDL) uptake. In cultured RAW 264.7 macrophages, the same antibodies enhanced LDL uptake (without causing foam cell formation). These findings make ApoB100 a promising target for an immunization strategy against HFD-induced obesity.

Airway management in patient with continuous bleeding lesion of the trachea: a case report.

Hemoptysis requires proper treatment to prevent blood aspiration and asphyxiation. If the patient loses consciousness or is anesthetized, the bleeding inside the trachea may continuously flow into the distal part, which may be fatal. Fatal damage resulting from hemoptysis is mainly caused by asphyxiation, and it is important to find the exact location of the bleeding in order to prevent it from spreading to both lungs. However, endotracheal intubation may increase the bleeding by stimulating the bleeding lesion in the respiratory track, and can make airway management more difficult. We report a successful case of airway management using the cuff and Murphy eye of the endotracheal tube in a patient with tracheal bleeding.

The influence of mild hypothermia on reversal of rocuronium-induced deep neuromuscular block with sugammadex.

BACKGROUND: Mild hypothermia may be frequently induced due to cool environments in the operating room. The study analyzed patient recovery time and response to sugammadex after a prolonged rocuronium-induced deep neuromuscular block (NMB) during mild hypothermia. METHODS: Sixty patients were randomly (1:1) allocated to the mild hypothermia and normothermia groups, defined as having core temperatures between 34.5-35°C and 36.5-37°C, respectively. Patients received 0.6 mg/kg of rocuronium, followed by 7-10 µg/kg/min to maintain a deep NMB [post-tetanic count (PTC) 1-2]. After surgery, the deep NMB was reversed with sugammadex 4.0 mg/kg. The primary end-point was the time until the train-of-four (TOF) ratio was 0.9. RESULTS: The appropriate neuromuscular function (TOF ratio ≥ 0.9) was restored after sugammadex was administered, even after hypothermia. The length of recovery in the hypothermia patients [mean (SD), 171.1 (62.1) seconds (s)] was significantly slower compared with the normothermia patients [124.9 (59.2) s] (p = 0.005). There were no adverse effects from sugammadex. CONCLUSIONS: Sugammadex safely and securely reversed deep rocuronium-induced NMB during mild hypothermia. An additional 46 s was required for recovery from a deep NMB in hypothermia patients. Based on the results, we think this prolonged recovery time is clinically acceptable. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01965067.

The use of 3 sugammadex out of 5 reversal of during recovery of rocuronium-induced neuromuscular blockade in a patient with post-tonsillectomy hemorrhage: a case report.

Post-tonsillectomy hemorrhage (PTH) is the most frequent complication of tonsillectomy, and occasionally results in a lethal outcome. A 21-year-old man (height 180 cm, weight 95 kg) was scheduled for a bilateral tonsillectomy and uvulopalatopharyngoplasty for treatment of obstructive sleep apnea. He required 5 rounds of general anesthesia due to recurrent PTH. The anesthesiologist used sugammadex a total of 3 times to achieve the successful reversal of the deep neuromuscular blockade (NMB) induced by rocuronium. After sugammadex 2 mg/kg was administered, the NMB was reversed in 2 minutes each time. Re-administration of rocuronium within a short time interval after sugammadex may result in unpredictable effects of neuromuscular blocking agents. Sugammadex made it possible to perform a rapid, complete reverse when the residual block was maintained by an incomplete reversal of anticholinesterase.

Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.

BACKGROUND: Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. METHODS: This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. RESULTS: The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). CONCLUSIONS: Precurarization with 0.04 mg/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.

Secondary skull reconstruction with autogenous split calvarial bone grafts versus nonautogenous materials.

BACKGROUND: Skull reconstructions, which can be required for various reasons, including decompressive craniectomy, trauma, and tumors, are challenging issues in plastic surgery. Moreover, obtaining a low complication ratio in secondary skull reconstructions is more difficult than in primary skull reconstructions. Because standardized protocols have not been established, we here compare cranioplasty performance using fresh autogenous split calvarial bone grafts and allogenic or alloplastic materials in secondary revisional cases. METHODS: Surgical correction of skull defects was performed in 25 patients in our center between 2005 and 2012. Only secondary cranioplasty cases were reviewed retrospectively. There were 17 men and 8 women, with ages ranging from 8 to 62 years at the time of surgery. The mean follow-up was 55.6 months. The surgical procedure in each case was a routine cranioplasty. In most of the cases, a 1-piece split calvarial bone graft was used while minimizing the separation of the bone flap into multiple pieces. RESULTS: In comparison with the skull reconstructional approach using nonautogenous materials, the functional and esthetic results of skull reconstruction using autogenous calvarial bone grafts were better and more consistent in secondary revisional cases. The group that received autogenous calvarial bone grafts showed a reconstruction success rate of 80% without esthetic and functional complications. In contrast, the group that received nonautogenous materials had a 30% success rate. CONCLUSIONS: Secondary cranial defect reconstructions with autogenous calvarial bone grafts showed better functional and esthetic results than skull reconstructions with nonautogenous materials.

Production of 1,3-propanediol from glycerol using the newly isolated Klebsiella pneumoniae J2B.

Recently, novel Klebsiella pneumoniae J2B, which grows rapidly on glycerol as the carbon source without forming pathogenic and sticky lipopolysaccharides, was isolated. Current study examined the ability of K. pneumoniae J2B to produce 1,3-propanediol (PDO) from glycerol. To this end, a deletion mutant for lactate formation was constructed. The ldhA mutant strain produced negligible lactate but more 2,3-butanediol (BDO). When K. pneumoniae ΔldhA was cultivated in glycerol fed-batch mode, the PDO titer of 58.0 g/L with a yield of 0.35 g/g and an overall volumetric productivity of 1.3g/L/h were obtained. BDO was the main byproduct (26.6g/L). Less than 10 g/L of the other metabolites was produced. As PDO and other metabolites accumulated, the rate of PDO production decreased significantly due mainly to the toxic effects of these metabolites. This study highlights the potential of newly isolated K. pneumoniae J2B for the production of PDO from glycerol.

Identification of acetoin reductases involved in 2,3-butanediol pathway in Klebsiella oxytoca.

The acetoin reductase (AR) of Klebsiella oxytoca is responsible for converting acetoin into 2,3-butanediol (2,3-BDO) during sugar fermentation. Deleting the AR encoding gene (budC) in the 2,3-BDO operon does not block production of 2,3-BDO, as another similar gene exists in addition to budC called diacetyl/acetoin reductase (dar) which shares 53% identity with budC. In the present study, both budC and dar of K. oxytoca were independently cloned and expressed in Escherichia coli along with budA (acetolactate decarboxylase) and budB (acetolactate synthase), which are responsible for converting pyruvate into acetoin. The recombinant E. coli expressing budABC and budAB-dar produced 2,3-BDO from glucose but E. coli expressing only budAB did not and produced acetoin alone. This demonstrates that Dar functions similar to BudC. Mutants of budC, dar, and both genes together were developed in K. oxytoca ΔldhA (lactate dehydrogenase). K. oxytoca ΔldhA ΔbudC Δdar, deficient in both AR genes, showed reduced 2,3-BDO concentration when compared to K. oxytoca ΔldhA and K. oxytoca ΔldhA ΔbudC by 84% and 69%, respectively. Interestingly, K. oxytoca ΔldhA Δdar resulted in a significant reduction in the reversible conversion of 2,3-BDO into acetoin than that of K. oxytoca ΔldhA, which was observed in a glucose depleted fermentation culture. In addition, we observed that Dar played a key role in dissimilation of 2,3-BDO in media containing 2,3-BDO alone.

2,3-Butanediol recovery from fermentation broth by alcohol precipitation and vacuum distillation.

This study presents a new and effective downstream process to recover 2,3-butanediol (2,3-BD) from fermentation broth which is produced by a recombinant Klebsiella pneumoniae strain. The ldhA-deficient K. pneumoniae strain yielded about 90 g/L of 2,3-BD, along with a number of by-products, such as organic acids and alcohols, in a 65 h fed-batch fermentation. The pH-adjusted cell-free fermentation broth was firstly concentrated until 2,3-BD reached around 500 g/L by vacuum evaporation at 50°C and 50 mbar vacuum pressure. The concentrated solution was further treated using light alcohols, including methanol, ethanol, and isopropanol, for the precipitation of organic acids and inorganic salts. Isopropanol showed the highest removal efficiency, in which 92.5% and 99.8% of organic acids and inorganic salts were precipitated, respectively. At a final step, a vacuum distillation process enabled the recovery of 76.2% of the treated 2,3-BD, with 96.1% purity, indicating that fermentatively produced 2,3-BD is effectively recovered by a simple alcohol precipitation and vacuum distillation.

Feasibility test of utilizing Saccharophagus degradans 2-40(T) as the source of crude enzyme for the saccharification of lignocellulose.

In the conversion of lignocellulose into high-value products, including fuels and chemicals, the production of cellulase and the enzymatic hydrolysis for producing fermentable sugar are the largest contributors to the cost of production of the final products. The marine bacterium Saccharophagus degradans 2-40(T) can degrade more than ten different complex polysaccharides found in the ocean, including cellulose and xylan. Accordingly, S. degradans has been actively considered as a practical source of crude enzymes needed for the saccharification of lignocellulose to produce ethanol by others including a leading commercial company. However, the overall enzyme system of S. degradans for hydrolyzing cellulose and hemicellulose has not been quantitatively evaluated yet in comparison with commercial enzymes. In this study, the inductions and activities of cellulase and xylanase of cell-free lysate of S. degradans were investigated. The growth of S. degradans cells and the activities of cellulase and xylanase were promoted by adding 2 % of cellulose and xylan mixture (cellulose:xylan = 4:3 in mass ratio) to the aquarium salt medium supplemented with 0.2 % glucose. The specific cellulase activity of the cell-free lysate of S. degradans, as determined by the filter paper activity assay, was approximately 70 times lower than those of commercial cellulases, including Celluclast 1.5 L and Accellerase 1000. These results imply that significant improvement in the cellulase activity of S. degradans is needed for the industrial uses of S. degradans as the enzyme source.

Optimal positive end-expiratory pressure during robot-assisted laparoscopic radical prostatectomy.

BACKGROUND: Increased intra-abdominal pressure during laparoscopic surgery causes cephalad displacement of the diaphragm, resulting in the formation of atelectasis, which can be overcome by positive end-expiratory pressure (PEEP). The aim of this prospective study was to investigate the level of optimal PEEP to maintain adequate arterial oxygenation and hemodynamics during robot-assisted laparoscopic radical prostatectomy (RLRP). METHODS: One hundred patients undergoing RLRP were randomly allocated to one of five groups (n = 20) (0, 3, 5, 7 and 10 cmH2O of PEEP). Hemodynamic variables and respiratory parameters were measured at baseline with the patient in the supine position; at 30 min, 1, 2, 3 and 4 h during CO2 insufflation with the patient in the post-Trendelenburg position; and after deflation in the supine position with increasing PEEP. RESULTS: The PaO2 levels and alveolar-arterial difference in oxygen tension (AaDO2) were improved in patients with PEEPs compared with patients in whom PEEP was not used. The application of PEEP (10 cmH2O) resulted in higher PaO2 levels compared to those with lower PEEP levels, but excessive peak airway pressure (PAP) was sometimes observed. The application of a PEEP of 7 cmH2O resulted in similar PaO2 levels without causing excessive PAP. There was a significant difference in central venous pressure between the groups, but there were no significant differences in heart rate, mean arterial pressure or minute ventilation between the groups. CONCLUSIONS: A PEEP of 7 cmH2O is associated with the greater improvement of PaO2 and AaDO2 without causing excessive PAP during RLRP.

The effect of hand dominance on neuromuscular monitoring at the adductor pollicis muscle.

BACKGROUND: Neuromuscular blockade of the adductor pollicis muscle may be influenced by hand dominance resulting in conflicting results of several studies. The current study examined whether hand dominance could influence the measurements of neuromuscular blockade with acceleromyography at the adductor pollicis. METHODS: The acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in both hands in 31 patients after induction of anesthesia. Onset, maximum effect, and offset of rocuronium were measured and compared in both hands. The train-of-four (TOF) ratios to 0.9 were recorded in all patients. RESULTS: In total, 27 patients were right-handed and 4 patients were left-handed. The mean supramaximal threshold or initial TOF ratio was not different between dominant and nondominant hands. No statistically significant differences were found between 716 paired TOF ratios in both hands. A correlation was seen between the dominant and nondominant hand (Nondominant = 0.931·Dominant + 1.714, R = 0.929). The analysis by the Bland-Altman plot showed an excellent agreement with a bias of 1.6% and limits of agreement of -21.2 to 24.5%. CONCLUSIONS: Dominant and nondominant hands can be used interchangeably for neuromuscular monitoring at the adductor pollicis.