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Both inhalational and intravenous anesthetics affect myocardial remodeling, but the precise effect of each anesthetic on molecular signaling in myocardial remodeling is unknown. Here, we performed in silico analysis to investigate signaling alterations in cardiomyocytes induced by inhalational [sevoflurane (Sevo)] and intravenous [propofol (Prop)] anesthetics. Bioinformatics analysis revealed that nuclear factor‐kappa B (NF‐kB) signaling was inhibited by Sevo and promoted by Prop. Moreover, nuclear accumulation of p65 and transcription of NF‐kB‐regulated genes were suppressed in Sevo‐administered mice, suggesting that Sevo inhibits the NF‐kB signaling pathway. Our data demonstrate that NF‐kB signaling is inhibited by Sevo and promoted by Prop. As NF‐kB signaling plays an important role in myocardial remodeling, our results suggest that anesthetics may affect myocardial remodeling through NF‐kB., The precise nature of the molecular alterations occurring after inhalation or intravenous anesthesia remains unclear. Here, in silico gene expression analysis of patient cardiomyocytes and a mouse animal model revealed that nuclear factor‐kappa B signaling is upregulated by sevoflurane and downregulated by propofol. Interestingly, this effect was observed only in the postanesthesia acute phase, not in the late phase.

It has been considered that activation of peripheral μ-opioid receptors (MORs) induces side effects of opioids. In this study, we investigated the possible improvement of the immune system in tumour-bearing mice by systemic administration of the peripheral MOR antagonist naldemedine.The inhibitory effect of naldemedine on MOR-mediated signalling was tested by cAMP inhibition and β-arrestin recruitment assays using cultured cells. We assessed possible changes in tumour progression and the number of splenic lymphocytes in tumour-bearing mice under the repeated oral administration of naldemedine.Treatment with naldemedine produced a dose-dependent inhibition of both the decrease in the cAMP level and the increase in β-arrestin recruitment induced by the MOR agonists. Repeated treatment with naldemedine at a dose that reversed the morphine-induced inhibition of gastrointestinal transport, but not antinociception, significantly decreased tumour volume and prolonged survival in tumour-transplanted mice. Naldemedine administration significantly decreased the increased expression of immune checkpoint-related genes and recovered the decreased level of toll-like receptor 4 in splenic lymphocytes in tumour-bearing mice.The blockade of peripheral MOR may induce an anti-tumour effect through the recovery of T-cell exhaustion and promotion of the tumour-killing system.

Chronic postsurgical pain (CPSP) is a serious problem. We developed a mouse model of CPSP induced by electrocautery and examined the mechanism of CPSP. In this mouse model, while both incision and electrocautery each produced acute allodynia, persistent allodynia was only observed after electrocautery. Under these conditions, we found that the mRNA levels of Small proline rich protein 1A (Sprr1a) and Annexin A10 (Anxa10), which are the key modulators of neuropathic pain, in the spinal cord were more potently and persistently increased by electrocautery than by incision. Furthermore, these genes were overexpressed almost exclusively in chronic postsurgical pain-activated neurons. This event was associated with decreased levels of tri-methylated histone H3 at Lys27 and increased levels of acetylated histone H3 at Lys27 at their promoter regions. On the other hand, persistent allodynia and overexpression of Sprr1a and Anxa10 after electrocautery were dramatically suppressed by systemic administration of GSK-J4, which is a selective H3K27 demethylase inhibitor. These results suggest that the effects of electrocautery contribute to CPSP along with synaptic plasticity and epigenetic modification. Supplementary Information The online version contains supplementary material available at 10.1186/s13041-021-00854-y.

Hintergrund: Die Entwöhnung von einer längerfristigen maschinellen Beatmung bei tracheotomierten Patienten mit restriktiver Lungenfunktionsstörung ist extrem schwierig. Eine Sauerstoffgabe mit hoher Flussrate über das Tracheostoma liefert erwärmtes und befeuchtetes Sauerstoffgas mit >10 l/min. Jedoch liegen erst wenige Berichte zur Anwendung von Sauerstoff mit hoher Flussrate über Tracheostoma im Rahmen der Entwöhnung vom Beatmungsgerät bei Patienten mit restriktiver Lungenfunktionsstörung vor. Wir berichten über erfolgreiches Weaning vom Beatmungsgerät bei Patienten mit restriktiver Lungenfunktionsstörung mittels Sauerstoffgabe mit hoher Flussrate über Tracheostoma. Vorstellung der Fälle: Der erste Patient ist ein 78-jähriger Japaner mit schwerer Pneumokokken-Pneumonie, der nach Ösophagektomie wegen eines Ösophaguskarzinoms mehr als einen Monat lang beatmet wurde. Nach einer Tracheotomie wegen der längerfristigen maschinellen Beatmung entwickelte sich eine restriktive Lungenfunktionsstörung mit einem Atemzugvolumen von 230-240 ml und einer statischen Compliance von 14-15 ml/cm H2O mit 10 cm H2O Druckunterstützung. Das Weaning erfolgte unter inspiratorischer Unterstützung mit Sauerstoff mit hoher Flussrate über Tracheostoma über einen Zeitraum von 16 Tagen (Flussrate von 40 l/min und inspiratorische Sauerstofffraktion von 0,25). Der zweite Patient ist ein 69-jähriger Japaner, bei dem nach Ösophagektomie eine Aspirationspneumonie auftrat und der längerfristig über Tracheostoma beatmet wurde. Er entwickelte eine restriktive Lungenfunktionsstörung. Die Sauerstoffgabe mit hoher Flussrate über das Tracheostoma (Flussrate 40 l/min und inspiratorische Sauerstofffraktion von 0,25) erfolgte unter Messung des Atemwegsdrucks am Eingang des Tracheotomietubus. Folgende Werte wurden gemessen: 0,21-0,3 cm H2O, 0,21-0,56 cm H2O, 0,54-0,91 cm H2O, 0,76-2,01 cm H2O, 1,17-2,01 cm H2O und 1,76-2,01 cm H2O bei 10 l/min, 20 l/min, 30 l/min, 40 l/min, 50 l/min bzw. 60 l/min. Der Atemwegsdruck war kontinuierlich positiv und wurde auch während der Inspiration nicht negativ, was darauf hindeutet, dass die Sauerstoffgabe mit hoher Flussrate über Tracheostoma die Inspirationsanstrengung verringert. Das Weaning erfolgte unter inspiratorischer Unterstützung mit Sauerstoff mit hoher Flussrate über Tracheostoma über einen Zeitraum von 12 Tagen. Schlussfolgerungen: Die Sauerstoffgabe mit hoher Flussrate über Tracheostoma kann mit der Sauerstoffzufuhr die Inspirationsanstrengung verringern und das Atemzugvolumen vergrößern und so das Weaning nach Langzeitbeatmung bei Patienten mit restriktiver Lungenfunktionsstörung erleichtern.

Postherpetic itch (PHI), or herpes zoster itch, is an intractable and poorly understood disease. We targeted 94 herpes zoster patients to investigate their pain and itch intensities at three separate stages of the condition (acute, subacute, and chronic). We used painDETECT questionnaire (PDQ) scores to investigate the correlation between PHI and neuropathic pain. Seventy-six patients were able to complete follow-up surveys. The prevalence of PHI was 47/76 (62%), 28/76 (37%), and 34/76 (45%) at the acute, subacute, and chronic stages, respectively. PHI manifestation times and patterns varied. We investigated the relationship of PHI with neuropathic pain using the visual analog scale (VAS), which is a measure of pain intensity, and the PDQ, which is a questionnaire used to evaluate the elements of neuropathic pain. The VAS and PDQ scores did not differ significantly between PHI-positive and PHI-negative patients. A large neuropathic component was not found for herpes zoster itch, suggesting that neuropathic pain treatments may not able to adequately control the itch. Accordingly, we suggest that a more PHI-focused therapy is required to address this condition.

Background Neutrophil gelatinase-associated lipocalin (NGAL) is a diagnostic marker for acute kidney injury (AKI). NGAL expression is highly induced not only in kidney injury but also in bacterial infection, inflammation, and cancer. The factors regulating NGAL expression are proinflammatory cytokines, and plasma NGAL levels have been increased in septic shock. However, there are no reports of urine neutrophil gelatinase-associated lipocalin (uNGAL) levels after open esophagectomy. Methods We prospectively enrolled critically ill patients, including patients with sepsis (n = 45) and patients who underwent open esophagectomy (n = 40). We compared vital signs, PaO2/FIO2, serum C-reactive protein (CRP) levels, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and uNGAL levels between the sepsis group and the esophagectomy group. Then, we investigated whether uNGAL is associated with the severity of illness and organ failure, and whether uNGAL is a reliable screening test for AKI. Results The median uNGAL levels, APACHE II score, SOFA score, and serum CRP levels were significantly (p p p Conclusions uNGAL levels were correlated with the severity of illness and organ failure in critically ill patients. The value of uNGAL increases under the surgical and inflammatory responses, thereby losing a significance of a screening test of AKI in critically ill patients.

Background Weaning from prolonged mechanical ventilation is extremely difficult in tracheostomized patients with restrictive pulmonary dysfunction. High-flow oxygen via tracheostomy supplies heated and humidified oxygen gas at > 10 L/minute. However, little has been reported on the use of high-flow oxygen via tracheostomy during weaning from ventilators in patients with restrictive pulmonary dysfunction. We report successful weaning from ventilators in patients with restrictive pulmonary dysfunction using high-flow oxygen via tracheostomy. Case presentation The first patient is a 78-year-old Japanese man with severe pneumococcal pneumonia who was mechanically ventilated for more than 1 month after esophagectomy for esophageal cancer. After he underwent tracheostomy because of prolonged mechanical ventilation, restrictive pulmonary dysfunction appeared: tidal volume 230–240 mL and static compliance 14–15 mL/cmH2O with 10 cmH2O pressure support ventilation. He was weaned from the ventilator under inspiratory support with high-flow oxygen via tracheostomy over a period of 16 days (flow at 40 L/minute and fraction of inspired oxygen of 0.25). The second patient is a 69-year-old Japanese man who developed aspiration pneumonia after esophagectomy and received prolonged mechanical ventilation via tracheostomy. He developed restrictive pulmonary dysfunction. High-flow oxygen via tracheostomy (flow at 40 L/minute with fraction of inspired oxygen of 0.25) was administered with measurement of the airway pressure and at the entrance of the tracheostomy tube. The measured values were as follows: 0.21–0.3 cmH2O, 0.21–0.56 cmH2O, 0.54–0.91 cmH2O, 0.76–2.01 cmH2O, 1.17–2.01 cmH2O, and 1.76–2.01 cmH2O at 10 L/minute, 20 L/minute, 30 L/minute, 40 L/minute, 50 L/minute, and 60 L/minute, respectively. The airway pressures were continuously positive and did not become negative even during inspiration, suggesting that high-flow oxygen via tracheostomy reduces inspiratory effort. He was weaned from the ventilator under inspiratory support with high-flow oxygen via tracheostomy over a period of 12 days. Conclusions High-flow oxygen via tracheostomy may reduce the inspiratory effort and enhance tidal volume by delivering high-flow oxygen and facilitate weaning from prolonged mechanical ventilation in patients with restrictive pulmonary dysfunction.

Background Cardiac herniation is a serious postoperative complication of extrapleural pneumonectomy (EPP) and is reportedly preventable by reducing the suction pressure of the chest drain. Case presentation We describe a patient in whom respiratory failure, which was caused by impending tension pneumothorax after EPP, was successfully treated via normal suction pressure of the chest drain. A lower suction pressure (− 7 cmH2O) was chosen as an alternative to the setting typically used for postoperative drainage (− 15 cmH2O). As a result, the wound in the chest wall functioned as an antireflux check valve, leading to the development of impending tension pneumothorax. Conclusions Impending tension pneumothorax presents with an abnormal elevation of intrapleural pressure on the affected side. This phenomenon can be effectively treated by increasing the suction pressure in the chest drain.

Background Maternal critical illness occurs in 1.2 to 4.7 of every 1000 live births in the United States and approximately 1 in 100 women who become critically ill will die. Patient characteristics and comorbid conditions are commonly summarized as an index or score for the purpose of predicting the likelihood of dying; however, most such indices have arisen from non-pregnant patient populations. We sought to systematically review comorbidity indices used in health administrative datasets of pregnant women, in order to critically appraise their measurement properties and recommend optimal tools for clinicians and maternal health researchers. Methods We conducted a systematic search of MEDLINE and EMBASE to identify studies published from 1946 and 1947, respectively, to May 2017 that describe predictive validity of comorbidity indices using health administrative datasets in the field of maternal health research. We applied a methodological PubMed search filter to identify all studies of measurement properties for each index. Results Our initial search retrieved 8944 citations. The full text of 61 articles were identified and assessed for final eligibility. Finally, two eligible articles, describing three comorbidity indices appropriate for health administrative data remained: The Maternal comorbidity index, the Charlson comorbidity index and the Elixhauser Comorbidity Index. These studies of identified indices had a low risk of bias. The lack of an established consensus-building methodology in generating each index resulted in marginal sensibility for all indices. Only the Maternal Comorbidity Index was derived and validated specifically from a cohort of pregnant and postpartum women, using an administrative dataset, and had an associated c-statistic of 0.675 (95% Confidence Interval 0.647–0.666) in predicting mortality. Conclusions Only the Maternal Comorbidity Index directly evaluated measurement properties relevant to pregnant women in health administrative datasets; however, it has only modest predictive ability for mortality among development and validation studies. Further research to investigate the feasibility of applying this index in clinical research, and its reliability across a variety of health administrative datasets would be incrementally helpful. Evolution of this and other tools for risk prediction and risk adjustment in pregnant and post-partum patients is an important area for ongoing study. Electronic supplementary material The online version of this article (10.1186/s12884-017-1558-3) contains supplementary material, which is available to authorized users.

Gabapentin (GBP) and pregabalin (PGB) exert antinociceptive effects on chronic nociceptive responses with neuropathic or inflammatory conditions. Furthermore, it is considered that GBP and PGB exhibit anti‑inflammatory effects by modulating the substance P (SP)‑mediated neurokinin‑1 receptor (NK1R; a SP receptor) response. Thus, in the present study, the effects of GBP and PGB on SP‑induced activation were investigated in the human glioblastoma astrocytoma U373 MG cell line, which expresses high levels of functional high‑affinity NK1R, and produces interleukin (IL)‑6 and IL‑8 in response to SP. The results indicated that GBP and PGB suppressed the SP‑induced production of IL‑6, and IL‑8 in U373 MG cells. Furthermore, GBP and PGB inhibited the SP‑induced phosphorylation of p38 mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB, and the nuclear translocation of NF‑κB in U373 MG cells. Together, these observations suggest that GBP and PGB likely prevent SP‑induced IL‑6 and IL‑8 production in U373 MG cells via the inhibition of signaling molecules, including p38 MAPK and NF‑κB, thereby exhibiting antineuroinflammatory effects.

Anesthesia for patient with large anterior mediastinal mass might induce life‐threatening complication. Maintaining the spontaneous breathing throughout the procedure and finding rescue position are the cornerstones of anesthetic management.

Thoracoscopic pulmonary lobectomy (TPL) is extremely challenging in cases where severe incomplete fissure causes densely fused pulmonary lobes (DFPL) since pulmonary arteries (PAs) are buried and completely concealed by DFPL. We describe TPL for DFPL including a technical tip to prevent pitfalls.Four congenital pulmonary airway malformation (CPAM) and DFPL (left-upper: 2, left-lower: 1, right-middle: 1) were treated. During TPL, DFPL prevent interlobar PAs from being identified and searching for them only promotes bleeding and air leakage, serious pitfalls that affect the safety and success of TPL. Our tip is to ligate and divide the pulmonary veins (PVs) at the pulmonary hilum and the hilar PA supplying the CPAM lobe to expose the bronchus of the lobe, which is then ligated and divided. The main PA supplying the lobe running underneath the DFPL is exposed and visible from the pulmonary hilum allowing the PA supplying the lobe to be ligated and divided safely. A line demarcating the fused fissure becomes apparent, and an endoscopic stapler or EnSealThere were no intra-/postoperative complications in any case. All patients performed well without respiratory tract-related symptoms after a mean follow-up of 4.6 years.TPL for DFPL in children with CPAM can be performed safely and successfully as a virtually bloodless procedure and without incidence of air leakage by ligating and dividing the PA after dividing the PVs and bronchus to the lobe.

Macrophages are key immune system cells involved in inflammatory processes. Classically activated (M1) macrophages are characterized by strong antimicrobicidal properties, whereas alternatively activated (M2) macrophages are involved in wound healing. Severe inflammation can induce postoperative complications during the perioperative period. Invasive surgical procedures induce polarization to M1 macrophages and associated complications. As perioperative management, it is an important strategy to regulate polarization and functions of macrophages during inflammatory processes. Although propofol has been found to exhibit anti-inflammatory activities in monocytes and macrophages, it is unclear whether propofol regulates the functions of M1 and M2 macrophages during inflammatory processes. This study therefore investigated the effects of propofol on human macrophage polarization. During M1 polarization, propofol suppressed the production of IL-6 and IL-1β but did not affect TNF-α production. In contrast, propofol did not affect the gene expression of M2 markers, such as IL-10, TGF-β, and CD206, during M2 polarization. Propofol was similar to the GABAA agonist muscimol in inducing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and inhibiting IL-6 and IL-1β, but not TNF-α, production. Knockdown of Nrf2 using siRNA significantly reduced the effect of propofol on IL-6 and IL-1β production. These results suggest that propofol prevents inflammatory responses during polarization of human M1 macrophages by suppressing the expression of IL-6 and IL-1β through the GABAA receptor and the Nrf2-mediated signal transduction pathway.

Ca v 2.3 (R-type) voltage-activated Ca 2+ channels (VACCs), encoded by the calcium channel, voltage-dependent, R-type, α1E subunit ( CACNA1E ) gene, are responsible for transmission of somatic inflammatory pain, and activation of antinociception elicited by visceral inflammatory pain stimuli. Carriers of the minor G allele of the rs3845446 single-nucleotide polymorphism (SNP) of the CACNA1E gene reportedly exhibit a decrease in opioid requirements to control typical somatic inflammatory pain after orthognathic surgery (ie, a painful cosmetic surgery), suggesting the downregulation of Ca v 2.3 VACC function that is responsible for transmission of somatic inflammatory pain in these carriers. Gastrointestinal surgery involves somatic and visceral inflammatory pain, in which visceral inflammatory pain stimuli activate Ca v 2.3 VACC-mediated antinociception. Unknown is whether pain-related phenotypes after gastrointestinal surgery are affected in these carriers. The present study used a correlational design to examine the effect of the rs3845446 SNP on postoperative pain-related phenotypes in 2 groups of patients who underwent gastrointestinal surgery. Carriers of the minor G allele had greater opioid requirements after laparoscopic colectomy when intravenous patient-controlled analgesia was used, and reported higher pain scores after open gastrointestinal surgery when postoperative analgesia was managed with continuous epidural analgesia and rescue analgesics. These results suggest that pain-related phenotypes after gastrointestinal surgery are enhanced in carriers of the minor G allele of the rs3845446 SNP, possibly through impairment of Ca v 2.3 VACC function that is responsible for the activation of visceral inflammatory pain stimulus-elicited antinociception. Perspective Carriers of the minor allele of the rs3845446 SNP of the CACNA1E gene required more opioid or reported higher pain scores after gastrointestinal surgery, and required less opioid after orthognathic surgery. The difference may result from the presence of visceral inflammatory pain stimulus that activates Ca v 2.3 VACCs-mediated antinociception.

The Joint Commission International (JCI) is responsible for upholding standards in healthcare and organizations in compliance receive accreditation. JCI requires quality improvement on patient safety goals, but requirements may prolong the total procedure/surgery time and reduce efficiency. Here, we evaluate the impact of JCI requirements on time periods in the operating room. We included patients who received elective and emergency surgeries under general anesthesia at Juntendo University Hospital between December 2014 and June 2016. Patients were classified as before and after JCI accreditation on December 12, 2015. The primary outcome was total procedure/surgery time. Secondary outcomes include five time periods comprising the total procedure/surgery time: pre-anesthesia time, anesthesia induction time, procedure/surgery time, anesthesia awareness time and post-anesthesia time. We compared these time periods between patients before and after JCI accreditation and patients were matched for age, sex and the specific type of surgery. Although total procedure/surgery time did not change significantly, pre-anesthesia time significantly increased (8.2 ± 6.9 minutes vs. 8.5 ± 6.9 minutes, before vs. after JCI, respectively, p = 0.028) and anesthesia induction time significantly decreased (34.4 ± 16.1 minutes vs. 33.6 ± 15.4 minutes, before vs. after JCI, respectively, p = 0.037) after JCI accreditation. Other secondary study outcomes did not change significantly. Quality improvement initiatives associated with time periods in the operating room can be achieved without undermining efficiency.

The effects of a recruitment manoeuvre (RM) with positive end-expiratory pressure (PEEP) on lung compliance (CLUNG) are not well characterised in robot-assisted laparoscopic radical prostatectomy (RARP). Patients were allocated to group R (n = 10; with an RM) or C (n = 9; without an RM). An RM involved sustained inflation of 30 cmH2O for 30 s. The lungs were ventilated with volume-controlled ventilation with tidal volume of 7 mL kg−1 of predicted body weight and fraction of inspired oxygen of 0.5. End-tidal carbon dioxide pressure was maintained at normocapnia. Patients were in the horizontal lithotomy position (pre-op). After pneumoperitoneum, patients underwent RARP in a steep Trendelenburg lithotomy position at a PEEP level of 0 cmH2O (RARP0). An RM was used in the R group but not in the C group. Patients were then ventilated with 5 cmH2O PEEP for 1 h after RARP0 (RARP5.1) and 2 h after RARP0 (RARP5.2). Oesophageal pressure and airway pressure were measured for calculating CLUNG and chest wall compliance. CLUNG significantly decreased from pre-op to RARP0 and did not significantly increase from RARP0 to RARP5.1 and RARP5.2 in either group. CLUNG differed significantly between groups at RARP5.1 and RARP5.2 (103 ± 30 vs. 68 ± 11 mL cm−1 H2O and 106 ± 35 vs. 72 ± 9 mL cm−1 H2O; P LUNG was effectively increased from the horizontal lithotomy position to the steep Trendelenburg lithotomy position under pneumoperitoneum.

Background Ventilation failure commonly occurs when a standard left-sided double-lumen tube is used in patients after left upper lobectomy having remarkable angulation of the left main bronchus. We present a female without remarkable angulation, in whom ventilation failure occurred after lateral jackknife positioning. Case presentation A 73-year-old female after lingula-sparing left upper lobectomy without remarkable angulation was scheduled for robot-assisted right upper lobectomy. Ventilation failure with a standard left-sided double-lumen tube occurred when she was placed not in the lateral position but in the lateral jackknife position required for robotic surgery. After replacement by the Silbroncho® left-sided double-lumen tube, adequate one-lung ventilation became possible. Conclusions Ventilation failure with a standard tube may occur more easily when patients with bronchial angulation are placed in the lateral jackknife than lateral position due to posture-induced exacerbations of bronchial angulation. The Silbroncho® tube seems useful in such situations.

Introduction: Anticoagulation is essential during CPB in cardiac surgery. It is generally performed using heparin; however the widely used formula for its dosing is based solely on body weight. Although the formula assumes activated clotting time (ACT) to be within normal range, baseline ACT varies in each patient. Thus, we developed an original formula, which takes into account baseline ACT in addition to body weight to calculate a more proper dose for initial administration of heparin. In this study, we monitored the ACT to examine if the dose of heparin calculated using our formula can prolong the ACT to the target range, and we determined the factors which interfere with the prolongation of ACT. Methods: Between October 2010 and April 2011, 141 consecutive patients underwent cardiac surgery requiring cardiopulmonary bypass at our hospital. We measured ACT 3 minutes after the initial administration of heparin and considered ACT values >400 seconds as appropriate for safe initiation of CPB. Results: Using the proposed formula, administered heparin dose was 241 ± 27 IU/kg and target ACT was achieved in 86.4% of patients. Multivariate analysis was performed to determine the effect of patient background factors on target ACT achievement. Body weight, age, and preoperative heparin therapy, which showed significant differences, were further analyzed. Conclusions: This study demonstrated that our newly developed formula could be used to properly calculate the optimal initial dose of heparin.