Cholesterol sulfate inhibits osteoclast differentiation and survival by regulating the AMPK-Sirt1-NF-κB pathway.

Cholesterol sulfate (CS) is an activator of retinoic acid-related orphan receptor α (RORα). CS treatment or RORα overexpression attenuates osteoclastogenesis in a collagen-induced arthritis mouse model. However, the mechanism by which CS and RORα regulate osteoclast differentiation remains largely unknown. Thus, we aimed to investigate the role of CS and RORα in osteoclastogenesis and their underlying mechanism. CS inhibited osteoclast differentiation, but RORα deficiency did not affect osteoclast differentiation and CS-mediated inhibition of osteoclastogenesis. CS enhanced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and sirtuin1 (Sirt1) activity, leading to nuclear factor-κB (NF-κB) inhibition by decreasing acetylation at Lys310 of p65. The NF-κB inhibition was restored by AMPK inhibitor, but the effects of CS on AMPK and NF-κB were not altered by RORα deficiency. CS also induced osteoclast apoptosis, which may be due to sustained AMPK activation and consequent NF-κB inhibition, and the effects of CS were significantly reversed by interleukin-1ß treatment. Collectively, these results indicate that CS inhibits osteoclast differentiation and survival by suppressing NF-κB via the AMPK-Sirt1 axis in a RORα-independent manner. Furthermore, CS protects against bone destruction in lipopolysaccharide- and ovariectomy-mediated bone loss mouse models, suggesting that CS is a useful therapeutic candidate for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Association between 20% Albumin Use and Acute Kidney Injury in Major Abdominal Surgery with Transfusion.

Red blood cell (RBC) transfusion and albumin administration can affect kidney function. We aimed to evaluate the association between intraoperative 20% albumin administration and acute kidney injury (AKI), along with the duration of hospitalization and 30-day mortality in patients undergoing major abdominal surgery with RBC transfusion. This retrospective study included 2408 patients who received transfusions during major abdominal surgery. Patients were categorized into albumin (n = 842) or no-albumin (n = 1566) groups. We applied inverse probability of treatment weighting (IPTW), propensity score (PS) matching (PSM), and PS covariate adjustment to assess the effect of albumin administration on the outcomes. In the unadjusted cohort, albumin administration was significantly associated with increased risk of AKI, prolonged hospitalization, and higher 30-day mortality. However, there was no significant association between albumin administration and AKI after adjustment (OR 1.26, 95% CI 0.90-1.76 for the IPTW; OR 1.03, 95% CI 0.72-1.48 for the PSM; and OR 1.04, 95% CI 0.76-1.43 for the PS covariate adjustment methods). While albumin exposure remained associated with prolonged hospitalization after adjustment, it did not affect 30-day mortality. Our findings suggest that hyper-oncotic albumin can be safely administered to patients who are at risk of developing AKI due to RBC transfusion.

Influence of age on gender-related differences in acute kidney injury after minimally invasive radical or partial nephrectomy.

BACKGROUND: Female gender is known to be protective against acute kidney injury (AKI) after radical or partial nephrectomy and estrogen is considered a protective factor. If estrogen is a major contributor to the protective effects of female gender against renal injury, these protective effects may be diminished in postmenopausal women. Therefore, this retrospective study investigated the influence of female age on gender-related differences in AKI after minimally invasive radical or partial nephrectomy. METHODS: Patients who underwent minimally invasive radical (n = 765) or partial (n = 1161) nephrectomy were selected. These patients were stratified by gender and divided into three age categories considered to be pre, peri, and postmenopausal periods in women: ≤ 40 years, 41-59 years, and ≥ 60 years, respectively. Adjusted logistic regression analyses were conducted to identify the risk of AKI according to gender and age. RESULTS: The incidence of AKI after radical or partial nephrectomy was significantly higher in men as compared to women in all age categories. Women aged ≥ 60 years had a significantly increased risk of AKI as compared to women aged < 60 years in radical nephrectomy, but not in partial nephrectomy. When compared with women aged ≥ 60 years, men aged > 40 years accompanied significantly higher risk of AKI following both radical and partial nephrectomy, even after adjusting confounders. However, men aged ≤ 40 years had a similar risk of AKI after radical nephrectomy, but a significantly higher risk after partial nephrectomy as compared to women aged ≥ 60 years. CONCLUSION: Male gender was associated with a higher risk of AKI after radical and partial nephrectomy as compared to postmenopausal women. This calls for more thorough preoperative counseling and renal protective strategies in male patients when undergoing radical and partial nephrectomy.

Effects of intraoperative dexmedetomidine infusion on renal function in elective living donor kidney transplantation: a randomized controlled trial.

PURPOSE: Ischemia-reperfusion injury is inevitable during donor organ harvest and recipient allograft reperfusion in kidney transplantation, and affects graft outcomes. Dexmedetomidine, an α2-adrenoreceptor agonist, has renoprotective effects against ischemia-reperfusion injury. We investigated the effects of intraoperative dexmedetomidine infusion on renal function and the development of delayed graft function after elective living donor kidney transplantation in a randomized controlled trial. METHODS: A total of 104 patients were randomly assigned to receive either an intraoperative infusion of dexmedetomidine 0.4 µg·kg-1·hr-1 or 0.9% saline. The primary outcome was the serum creatinine level on postoperative day (POD) 7. Secondary outcomes were renal function and the degree of inflammation and included the following variables: serum creatinine level and estimated glomerular filtration rate up to six months; incidence of delayed graft function; and levels of serum cystatin C, plasma interleukin (IL)-1ß, and IL-18 during the perioperative period. RESULTS: The mean (standard deviation) serum creatinine level on POD 7 was comparable between the groups (dexmedetomidine vs control: 1.11 [0.87] mg·dL-1 vs 1.06 [0.73] mg·dL-1; mean difference, 0.05; 95% confidence interval, -0.27 to 0.36; P = 0.77). Delayed graft function occurred in one patient in each group (odds ratio, 1.020; P > 0.99). There were no significant differences in the secondary outcomes between the groups (all P > 0.05). CONCLUSIONS: Intraoperative dexmedetomidine infusion did not produce any beneficial effects on renal function or delayed graft function in patients undergoing elective living donor kidney transplantation. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03327389); registered 31 October 2017.

RéSUMé: OBJECTIF: Les lésions d'ischémie-reperfusion sont inévitables lors du prélèvement d'organes du donneur et de la reperfusion de l'allogreffe chez le receveur pour une transplantation rénale, et affectent le devenir du greffon. La dexmédétomidine, un agoniste des adrénorécepteurs de type α2, a des effets néphroprotecteurs sur les lésions d'ischémie-reperfusion. Nous avons réalisé une étude randomisée contrôlée afin d'examiner les effets d'une perfusion peropératoire de dexmédétomidine sur la fonction rénale et l'apparition d'un retard de fonctionnement du greffon après une transplantation rénale élective issue de donneurs vivants. MéTHODE: Au total, 104 patients ont été aléatoirement répartis pour recevoir une perfusion peropératoire de 0,4 µg·kg-1·r-1 de dexmédétomidine ou une solution saline à 0,9 %. Le critère d'évaluation principal était la créatininémie au jour postopératoire (JPO) 7. Les critères d'évaluation secondaires étaient la fonction rénale et le degré d'inflammation et comprenaient les variables suivantes : créatininémie et infiltration glomérulaire estimée jusqu'à six mois; incidence de retard de fonctionnement du greffon; et taux sériques de cystatine C, d'interleukine plasmatique (IL)-1ß et d'IL-18 pendant la période périopératoire. RéSULTATS: Le taux moyen (écart type) de créatinine sérique au JPO 7 était comparable entre les groupes (dexmédétomidine vs témoin : 1,11 [0,87] mg·dL-1 vs 1,06 [0,73] mg·dL-1; différence moyenne, 0,05; intervalle de confiance à 95 %, -0,27 à 0,36; P = 0,77). Un patient de chaque groupe a subi un retard de fonctionnement du greffon (rapport de cotes, 1,020; P > 0.99). Aucune différence intergroupe significative n'a été observée en ce qui concerne les critères d'évaluation secondaires. CONCLUSION: La perfusion peropératoire de dexmédétomidine n'a produit aucun effet bénéfique sur la fonction rénale ou le retard de fonctionnement du greffon chez les patients bénéficiant d'une transplantation rénale élective issue de donneur vivant. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03327389); enregistrée le 31 octobre 2017.

Flunarizine inhibits osteoclastogenesis by regulating calcium signaling and promotes osteogenesis.

Many bone diseases such as osteoporosis and periodontitis are caused by hyperactivation of osteoclasts. Calcium (Ca2+ ) signals are crucial for osteoclast differentiation and function. Thus, the blockade of Ca2+ signaling may be a strategy for regulating osteoclast activity and has clinical implications. Flunarizine (FN) is a Ca2+ channel antagonist that has been used for reducing migraines. However, the role of FN in osteoclast differentiation and function remains unknown. Here, we investigated whether FN regulates osteoclastogenesis and elucidated the molecular mechanism. FN inhibited osteoclast differentiation along with decreased expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and attenuated osteoclast maturation and bone resorption. FN inhibition of osteoclast differentiation was restored by ectopic expression of constitutively active NFATc1. FN reduced calcium oscillations and its inhibition of osteoclast differentiation and resorption function was reversed by ionomycin, an ionophore that binds Ca2+ . FN also inhibited Ca2+ /calmodulin-dependent protein kinase IV (CaMKIV) and calcineurin leading to a decrease in the cAMP-responsive element-binding protein-dependent cFos and peroxisome proliferator-activated receptor-γ coactivator 1ß expression, and NFATc1 nuclear translocation. These results indicate that FN inhibits osteoclastogenesis via regulating CaMKIV and calcineurin as a Ca2+ channel blocker. In addition, FN-induced apoptosis in osteoclasts and promoted osteogenesis. Furthermore, FN protected lipopolysaccharide- and ovariectomy-induced bone destruction in mouse models, suggesting that it has therapeutic potential for treating inflammatory bone diseases and postmenopausal osteoporosis.

Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis.

Cinchonine (CN) has been known to exert antimalarial, antiplatelet, and antiobesity effects. It was also recently reported to inhibit transforming growth factor ß-activated kinase 1 (TAK1) and protein kinase B (AKT) through binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). However, its role in bone metabolism remains largely unknown. Here, we showed that CN inhibits osteoclast differentiation with decreased expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. Immunoblot and quantitative real-time polymerase chain reaction analysis as well as the reporter assay revealed that CN inhibits nuclear factor-κB and activator protein-1 by regulating TAK1. CN also attenuated the activation of AKT, cyclic AMP response element-binding protein, and peroxisome proliferator-activated receptor-γ coactivator 1ß (PGC1ß), an essential regulator of mitochondrial biogenesis. Collectively, these results suggested that CN may inhibit TRAF6-mediated TAK1 and AKT activation, which leads to downregulation of NFATc1 and PGC1ß resulting in the suppression of osteoclast differentiation. Interestingly, CN not only inhibited the maturation and resorption function of differentiated osteoclasts but also promoted osteoblast differentiation. Furthermore, CN protected lipopolysaccharide- and ovariectomy-induced bone destruction in mouse models, suggesting its therapeutic potential for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Comparison of Sufentanil- and Fentanyl-based Intravenous Patient-controlled Analgesia on Postoperative Nausea and Vomiting after Laparoscopic Nephrectomy: A Prospective, Double-blind, Randomized-controlled Trial.

Background: The incidence of postoperative nausea and vomiting (PONV) remains high. The effects of sufentanil for PONV is not firmly confirmed. The aim of this study was to compare the effect of sufentanil- and fentanyl-based intravenous patient-controlled analgesia (IV-PCA) on the incidence of PONV after laparoscopic nephrectomy. Methods: Eighty-six patients were randomly allocated to receive either the sufentanil (n =43) or fentanyl (n =43). IV-PCA was prepared using either sufentanil 3 µg/kg or fentanyl 20 µg/kg, ramosetron 0.3 mg, and ketorolac 120 mg. The primary outcome of was the incidence of PONV during 24 h after post anesthesia care unit (PACU) discharge. The secondary outcomes were the modified Rhodes index and patient satisfaction scores at 24 h after PACU discharge, need for rescue antiemetics, pain score, need for additional analgesics, and cumulative consumption of IV-PCA Results: The incidence of PONV was comparable between the sufentanil and fentanyl groups (64.3% vs. 65%, p = 0.946; respectively). The number of patients who required antiemetics (p = 0.946) and the modified Rhodes index at 24 h after post-anesthesia care unit discharge (p = 0.668) were also comparable in both groups. No significant differences were found in the secondary outcomes, including the analgesic profiles and adverse events between the groups. Conclusions: In conclusion, sufentanil- and fentanyl-based IV-PCA showed similar incidence of PONV with comparable analgesic effects after laparoscopic nephrectomy. Based on these results, we suggest that sufentanil and fentanyl may provide comparable effects for IV-PCA after laparoscopic nephrectomy.

Incidence and Risk Factors of Acute Kidney Injury after Kasai Operation for Biliary Atresia: A Retrospective Study.

Background: Biliary atresia is a progressive, inflammatory, and destructive pathology of the bile ducts. Patients who undergo surgery for correction of biliary atresia (Kasai operation) are at risk of acute kidney injury (AKI) because of their young age at the time of surgery, long operation time, and liver fibrosis or failure as complication of biliary atresia. Conversely, AKI is associated with poor outcomes after surgery. This study therefore aimed to evaluate the incidence, risk factors, and outcomes of AKI after Kasai operation. Methods: All consecutive patients who underwent Kasai operation between March 2006 and December 2015 in a single tertiary-care university hospital were enrolled. AKI was defined based on the Acute Kidney Injury Network criteria. Multivariate logistic regression models were used to assess risk factors for AKI. Results: One hundred sixty-six patients received Kasai operation during study period. Of these, AKI occurred in 37 of 166 patients (22.3%). In multivariate logistic regression analysis, age older than 30 days, higher preoperative estimated glomerular filtration rate, and preoperative contrast use within 7 days were associated with the development of AKI. Perioperative packed red blood cells transfusion was related to reduced occurrence of AKI. AKI was associated with longer ICU stay (OR = 1.015, p = 0.016). More patients with AKI were also found to receive additional surgery except liver transplantation within 1 year compared to those without AKI (10.8 % vs. 2.3 %, p = 0.045). Conclusions: Increased age is strongly associated with the development of AKI after Kasai operation. These findings indicate a rational basis for early corrective surgery for biliary atresia, early screening for AKI, and intervention to improve the results of Kasai operation.

Effect of different general anaesthetics on ventricular repolarisation in robot-assisted laparoscopic prostatectomy.

BACKGROUND: Ventricular repolarisation is affected differently by the types of anaesthetics used. This study aimed to compare the effect of different types of anaesthetics on ventricular repolarisation during robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: Sixty-nine patients were randomly assigned in a 1:1:1 ratio to the Sevoflurane (sevoflurane/remifentanil), Desflurane (desflurane/remifentanil) or total intravenous anaesthesia (TIVA [propofol/remifentanil]) groups; however, only 67 patients completed the study. The primary outcome was heart rate-corrected QT (QTc) interval collected at nine time points during RALP. Bazett's (QTcB) and Fridericia's (QTcF) formulae were used for QT interval correction. The secondary outcomes were Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio that were collected at the same time points. RESULTS: The QTcB and QTcF intervals were significantly prolonged during surgery in all groups; however, these values showed significant intergroup differences with time. After assuming the Trendelenburg position, the QTcB and QTcF intervals were significantly longer in the Desflurane group than in the other two groups, and this prolongation continued until the end of surgery. Intra-operatively, the QTcB and QTcF intervals exceeded 450 ms in six and five patients, respectively, in the Desflurane group, but in none in the TIVA group. Moreover, the incidence of intra-operative QTc interval prolongation >20 ms and >60 ms was significantly higher in the Desflurane group than in the TIVA group. There were no significant differences in Tp-e intervals and Tp-e/QT ratio among the three groups during surgery. CONCLUSIONS: To minimise QTc interval prolongation during RALP, TIVA with propofol/remifentanil is recommended for general anaesthesia.

Comparisons of Pressure-controlled Ventilation with Volume Guarantee and Volume-controlled 1:1 Equal Ratio Ventilation on Oxygenation and Respiratory Mechanics during Robot-assisted Laparoscopic Radical Prostatectomy: a Randomized-controlled Trial.

Background: During robot-assisted laparoscopic radical prostatectomy (RALP), steep Trendelenburg position and carbon dioxide pneumoperitoneum are inevitable for surgical exposure, both of which can impair cardiopulmonary function. This study was aimed to compare the effects of pressure-controlled ventilation with volume guarantee (PCV with VG) and 1:1 equal ratio ventilation (ERV) on oxygenation, respiratory mechanics and hemodynamics during RALP. Methods: Eighty patients scheduled for RALP were randomly allocated to either the PCV with VG or ERV group. After anesthesia induction, volume-controlled ventilation (VCV) was applied with an inspiratory to expiratory (I/E) ratio of 1:2. Immediately after pneumoperitoneum and Trendelenburg positioning, VCV with I/E ratio of 1:1 (ERV group) or PCV with VG using Autoflow mode (PCV with VG group) was initiated. At the end of Trendelenburg position, VCV with I/E ratio of 1:2 was resumed. Analysis of arterial blood gases, respiratory mechanics, and hemodynamics were compared between groups at four times: 10 min after anesthesia induction (T1), 30 and 60 min after pneumoperitoneum and Trendelenburg positioning (T2 and T3), and 10 min after desufflation and resuming the supine position (T4). Results: There were no significant differences in arterial blood gas analyses including arterial oxygen tension (PaO2) between groups throughout the study period. Mean airway pressure (Pmean) were significantly higher in the ERV group than in the PCV with VG group T2 (p<0.001) and T3 (p=0.002). Peak airway pressure and hemodynamic data were comparable in both groups. Conclusion: PCV with VG was an acceptable alternative to ERV during RALP producing similar PaO2 values. The lower Pmean with PCV with VG suggests that it may be preferable in patients with reduced cardiovascular function.

Simulated internal jugular vein cannulation using a needle-guiding device.

BACKGROUND: Using a two-dimensional ultrasound-guided approach does not guarantee success during the first attempt at internal jugular vein cannulation. Our randomized, parallel simulation study examined whether a new disposable device could improve the success rate of the first attempt at ultrasound-guided internal jugular vein cannulation of a simulated internal jugular vein. METHODS: Eighty-eight participants were randomized to perform needle insertion for internal jugular vein cannulation of a phantom using the ultrasound-guided approach with (case group) or without (control group) this new device. The primary outcome was the success rate of the first attempt. The secondary outcome was the frequency of mechanical complications such as arterial puncture and posterior wall puncture, procedure time, and level of difficulty. RESULTS: Among 44 participants using the device, 33 (75.0%) achieved successful cannulation on the first attempt. However, only 12 (27.3%) of the 44 participants not using the device recorded success during the first attempt (risk difference, 0.477; 95% confidence interval [CI] 0.294-0.661; P<0.001). The number of attempts was significantly lower (risk difference, -3.955; 95% CI, -5.014 to -3.712; P<0.001) when participants performed cannulation with the device (1.63±1.71) than without the device (5.59±5.78). Our study also showed that participants were comfortable when performing the ultrasound-guided approach with the new device (risk difference, -1.955; 95% CI, -2.016 to -1.493; P<0.0001). CONCLUSIONS: The new disposable device was effective for successful first attempts at needle insertion during ultrasound-guided internal jugular vein cannulation. Future clinical trials are needed to assess the effectiveness of this device.

Relationship between the photoinduced electron transfer and binding modes of a pyrene-porphyrin dyad to DNA.

The binding modes of a pyrene-porphyrin dyad, (1-pyrenyl)-tris(N-methyl-p-pyridino)porphyrin (PyTMpyP), to DNA and its photophysical properties have been investigated using various spectroscopic techniques. The circular dichroism (CD) spectrum of PyTMpyP bound to DNA (PyTMpyP-DNA) showed one negative and two positive bands in the Soret region. The CD signal in the pyrene absorption region was positive. The shape of the CD spectrum does not support an intercalative binding mode of TMpyP, which would typically afford a negative CD band in the absence of the pyrene moiety. Linear dichroism (LD) experiments revealed a very small signal in the Soret region, which also challenges the intercalation of TMpyP into DNA. Upon excitation of the pyrene moiety, the emission intensity of porphyrin in aqueous solution was quenched due to a photoinduced electron transfer (PET) process between the pyrenyl and porphyrin moieties. On the other hand, the emission of porphyrin was markedly enhanced upon binding to DNA, as the PET process from the excited pyrene moiety to TMpyP was suppressed when bound to DNA. The PET process occurs in the timescale of 65 ps, and could be detected by femtosecond transient absorption spectroscopic methods. Two fluorescence decay times were observed for PyTMpyP in aqueous solution (0.78 and 4.8 ns). Both decay times increased upon binding to DNA owing to environment and/or conformational changes in PyTMpyP. The driving force (ΔG) of the PET process was evaluated under conditions of minor and major groove binding. The PET process and photophysical properties of the PyTMpyP dyad were concluded to be influenced by the binding mode.

Effects of intravenous fentanyl around the end of surgery on emergence agitation in children: Systematic review and meta-analysis.

BACKGROUND: Emergence agitation is a serious postoperative problem in children undergoing general anesthesia. The use of fentanyl around the end of surgery has been proposed to prevent emergence agitation. However, the efficacy and disadvantages of this method remain uncertain because previous results have not been consistent, depending on the variable assessed. METHODS: In July 2016, the PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, and KoreaMed were searched for randomized controlled trials that compared fentanyl (1 µg/kg) and placebo administered around the end of surgery to prevent emergence agitation after general anesthesia in children between birth and 14 years of age. The collected outcomes included the incidence or score of emergence agitation, variables regarding anesthesia recovery, and adverse events (eg, postoperative nausea or vomiting). RESULTS: A total of 10 randomized controlled trials (718 patients, 357 receiving fentanyl) were included. Fentanyl around the end of surgery significantly decreased emergence agitation incidence (emergence agitation: relative risk 0.43, 95% confidence interval 0.35 to 0.53, I2 =0.0%; severe emergence agitation: relative risk 0.50, 95% confidence interval 0.31 to 0.81, I2 =0.0%). From subgroup analyses, fentanyl at the end of surgery was associated with a prolonged postanesthesia care unit stay and increased postoperative nausea or vomiting incidence (weighted mean difference 6.09, 95% confidence interval 2.77 to 9.41, I2 =58.6%; relative risk 2.61, 95% confidence interval 1.58 to 4.33, I2 =32.4%), whereas fentanyl at 10-20 minutes before the end of surgery did not increase postanesthesia care unit stay or postoperative nausea or vomiting risk (weighted mean difference -1.15, 95% confidence interval -5.15 to 2.85, I2 =89.0%; relative risk 1.32, 95% confidence interval 0.66 to 2.66, I2 =0.0%). CONCLUSIONS: The current analyses indicate that fentanyl around the end of surgery reduces the incidence of emergence agitation in children undergoing general anesthesia.

A Randomized, Double-blind, Non-inferiority Trial of Magnesium Sulphate versus Dexamethasone for Prevention of Postoperative Sore Throat after Lumbar Spinal Surgery in the Prone Position.

BACKGROUND: Postoperative sore throat (POST) is a frequent complication of tracheal intubation, particularly after surgery in the prone position. We designed this study to validate the non-inferiority of magnesium sulphate against dexamethasone for prevention of POST after lumbar spinal surgery. METHODS: One hundred and forty-six patients were randomly allocated to receive either magnesium or dexamethasone. Before anesthetic induction, the magnesium group (n = 73) received magnesium sulphate 30 mg/kg followed by 10 mg/kg/h by continuous infusion until the end of surgery. The dexamethasone group (n = 73) received dexamethasone 8 mg. The primary endpoint was the overall incidence of POST, which was assessed serially over 48 hr postoperatively. The predefined margin of non-inferiority for magnesium against dexamethasone was 15%. RESULTS: Overall incidences of POST at rest (50.7% versus 49.3% in the magnesium and dexamethasone group, respectively, p = 0.869) and swallowing (65.8% versus 61.6% in the magnesium and dexamethasone group, respectively, p = 0.606) were not different between the groups. The upper limit of the 90% confidence interval, which must be lower than the predefined margin of non-inferiority to prove the non-inferiority of magnesium sulphate against dexamethasone, for at rest and swallowing were 14.97% (p = 0.0496) and 17.19% (p = 0.0854), respectively. The incidences and severities of POST and hoarseness were also not different between the groups throughout the study period. CONCLUSIONS: Prophylactic magnesium sulphate appears to be non-inferior to dexamethasone for the prevention of POST at rest in patients undergoing lumbar spinal surgery in the prone position.

Effect of Surgeon-Performed Thoracic Paravertebral Block on Postoperative Pain in Adolescent Idiopathic Scoliosis Surgery: A Prospective Randomized Controlled Trial.

Posterior spinal fusion for adolescent idiopathic scoliosis (AIS) causes severe postoperative pain. Thoracic paravertebral block (PVB) provides excellent analgesia during various surgeries. We examined the effects of PVB on postoperative analgesia in children undergoing AIS surgery. In this study, 32 children scheduled for AIS surgery were randomly assigned to receive either PVB (PVB group) or no block (control group). The PVB group underwent surgeon-performed PVB with 0.5 mL/kg of adrenalized 0.2% ropivacaine on each side. The primary outcome was the pain score at rest at 6 h postoperatively. Secondary outcomes included pain scores both at rest and during movement and analgesic use for 48 h postoperatively. The postoperative resting pain scores at 6 h were comparable between the control and PVB groups (5.2 ± 2.0 and 5.1 ± 1.8, respectively), with no significant differences. However, at 1 h postoperatively, the control group showed significantly higher resting and mean moving pain scores than the PVB group (p < 0.05). The pain scores at other time points and analgesic use were comparable between the groups. Initial benefits of surgeon-performed bilateral PVB were observed but diminished at 6 h postoperatively. Future research using various anesthetics is needed to extend the effects of PVB.

Influence of acute kidney injury and its recovery subtypes on patient-centered outcomes after lung transplantation.

This study aimed to investigate the association between acute kidney injury (AKI) recovery subtypes and days alive out of hospital within the first 3 months (DAOH-90) in patients undergoing lung transplantation. Patients who underwent lung transplantation from January 2012 to December 2021 were retrospectively analyzed and stratified into three groups: no-AKI, early recovery AKI (within 7 days), and non-early recovery AKI group. AKI occurred in 86 (35%) of patients, of which 40 (16%) achieved early recovery, and the remaining 46 (19%) did not. The median DAOH-90 was 21 days shorter in the AKI than in the no-AKI (P = 0.002), and 29 days shorter in the non-early recovery AKI group than in the no-AKI group (P < 0.001). Non-early recovery AKI and preoperative tracheostomy status were independently associated with shorter DAOH-90. The prevalence of CKD (76%), and 1-year mortality (48%) were highest in the non-early recovery AKI group. Postoperative AKI was associated with an adverse patient-centered quality measure for perioperative care, and shorter DAOH-90. The non-early recovery AKI group exhibited the worst prognosis in terms of DAOH-90, CKD progression, and 1-year mortality, highlighting the important role of AKI and early-recovery AKI on both the quality of life and clinical outcomes after lung transplantation.

Association of Pre- and Post-Donation Renal Function with Midterm Estimated Glomerular Filtration Rate in Living Kidney Donors: A Retrospective Study.

PURPOSE: The estimated glomerular filtration rate (eGFR) at 6 months after donation (eGFR6m) is strongly associated with the risk of end-stage renal disease in living kidney donors. This study aimed to investigate the incidence of eGFR6m <60 mL/min/1.73 m² (eGFR6m <60) and identify the risk factors that can predict the occurrence of eGFR6m <60 in living kidney donors. MATERIALS AND METHODS: Living kidney donors who underwent nephrectomy at Severance Hospital between January 2009 and December 2019 were identified. We excluded 94 of 1233 donors whose creatinine values at 6 months after donation were missing. The risk factors for eGFR6m <60 were assessed using multivariate regression analysis. The optimal cutoff points for candidate risk factors for predicting eGFR6m <60 occurrence were determined using the Youden index. RESULTS: The eGFR6m <60 occurred in 17.3% of the participants. Older age (≥44 years), history of hypertension, lower preoperative eGFR (<101 mL/min/1.73 m²), and degree of increase in creatinine levels on postoperative day 2 compared to those before surgery (ΔCr2_pre) (≥0.39 mg/dL) increased the risk of eGFR6m <60. The addition of ΔCr2_pre to preoperative eGFR yielded a higher predictive accuracy for predicting eGFR6m <60 than that with preoperative eGFR alone {area under the receiver operating characteristic curve=0.886 [95% confidence interval (CI), 0.863-0.908] vs. 0.862 (95% CI, 0.838-0.887), p<0.001}. CONCLUSION: The incidence of eGFR6m <60 was 17.3%. Older age, lower preoperative eGFR, history of hypertension, and greater ΔCr2_pre were associated with the occurrence of eGFR6m <60 after living donor nephrectomy. The combination of preoperative eGFR and ΔCr2_pre showed the highest predictive power for eGFR6m <60.

Microsurgical Free Tissue Options for Fingertip Reconstruction.

Fingertip injuries occur commonly owing to trauma in everyday life. Performing amputation or stump revision for a fingertip injury can make it possible to quickly return to daily life, but causes functional and cosmetic problems. We believe that free flaps are the ideal way to minimize donor site morbidity and provide satisfactory reconstruction. Fingertips have different anatomic characteristics on the dorsum, volar aspect, and pulp, so it is necessary to select the appropriate free flap. Sometimes for larger defects, composite tissue transfer can be considered for reconstruction. This article discusses various free flap options for different fingertip defects.

Usefulness of non-invasive cardiac output monitoring in elderly patients undergoing monopolar transurethral resection of the prostate: a pilot study.

OBJECTIVE: To assess the impact of irrigating fluid on hemodynamic profiles using real-time non-invasive cardiac output monitoring (NICOM) in elderly patients undergoing monopolar transurethral resection of the prostate (TURP). METHODS: Twenty patients between 65 and 80 years of age who were scheduled for monopolar TURP and received spinal anesthesia up to T10 were enrolled. Irrigating fluid (2.7% sorbitol with 0.5% mannitol solution) was used. Hemodynamic profiles including cardiac index, and stroke volume variation (SVV) using NICOM were obtained. Estimated irrigating fluid absorption was indirectly calculated. RESULTS: The median amount of irrigating fluid used was 6000 mL. The median SVV was 11%, which increased to 12% at 10 minutes after initiating surgery. No significant changes in the cardiac index were observed. The estimated absorption of irrigating fluid was almost zero. CONCLUSIONS: Although the estimated amount of irrigating fluid that was absorbed was negligible, the increase in SVV may indicate intravascular volume depletion with diuresis resulting from mannitol in the irrigating fluid early during irrigation. Therefore, even during short irrigating times, intensive hemodynamic monitoring should be performed to monitor the possibility of intravascular volume depletion as well as volume overload, especially immediately after large amounts of irrigating fluid are used.

Dehydrocostus lactone inhibits NFATc1 via regulation of IKK, JNK, and Nrf2, thereby attenuating osteoclastogenesis.

Excessive and hyperactive osteoclast activity causes bone diseases such as osteoporosis and periodontitis. Thus, the regulation of osteoclast differentiation has clinical implications. We recently reported that dehydrocostus lactone (DL) inhibits osteoclast differentiation by regulating a nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), but the underlying mechanism remains to be elucidated. Here we demonstrated that DL inhibits NFATc1 by regulating nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and nuclear factor-erythroid 2- related factor 2 (Nrf2). DL attenuated IκBα phosphorylation and p65 nuclear translocation as well as decreased the expression of NF-κB target genes and c-Fos. It also inhibited c-Jun N-terminal kinase (JNK) but not p38 or extracellular signalregulated kinase. The reporter assay revealed that DL inhibits NF-κB and AP-1 activation. In addition, DL reduced reactive oxygen species either by scavenging them or by activating Nrf2. The DL inhibition of NFATc1 expression and osteoclast differentiation was less effective in Nrf2-deficient cells. Collectively, these results suggest that DL regulates NFATc1 by inhibiting NF-κB and AP-1 via down-regulation of IκB kinase and JNK as well as by activating Nrf2, and thereby attenuates osteoclast differentiation. [BMB Reports 2020; 53(4): 218-222].