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Postoperative nausea and vomiting (PONV) is a commonly encountered problem in surgical practice. It delays discharge from the post-anesthesia care unit, requires additional resources to treat, and may increase the morbidity in some patients. Many effective drugs are available to treat or prevent PONV, however many of these drugs have the potential to prolong the QTc on the electrocardiogram (EKG) and increase the risk of serious ventricular arrhythmias, in particular, torsade de pointes. The QTc prolongation may be a manifestation of a genetic mutation resulting in abnormal myocyte repolarization or it may be acquired and associated with the use of various medications, electrolyte disorders, and physiological conditions. Patients predisposed to QTc prolongation presenting for surgery constitute a challenging group, since many drugs commonly used for PONV management will put them at risk for perioperative serious arrhythmias. This is an important topic, and our mini-review is an attempt to highlight the problem, summarize the existing experience, and generate recommendations for safe management of PONV for patients, who are at increased risk of QTc prolongation and arrhythmias. Focused prospective studies will help to find definitive answers to the discussed problems and challenges and develop specific guidelines for clinical application.

Abstract  Positron emission tomography (PET) with epidermal growth factor receptor (EGFR) kinase-specific radiolabeled tracers could provide the means for noninvasive and repetitive imaging of heterogeneity of EGFR expression and signaling activity in tumors in individual patients before and during therapy with EGFR signaling inhibitors. We developed the synthesis and 124I-radiolabeling of the (E)-But-2-enedioic acid [4-(3-[124I]iodoanilino)-quinazolin-6-yl]-amide-(3-morpholin-4-yl-propyl)-amide (morpholino-[124I]-IPQA), which selectively, irreversibly, and covalently binds the adenosine-triphosphate-binding site to the activated (phosphorylated) EGFR kinase, but not to the inactive EGFR kinase. The latter was demonstrated using in silico modeling with crystal structures of the wild type and different gain-of-function mutants of EGFR kinases. Also, this was demonstrated by selective radiolabeling of the EGFR kinase domain with morpholino-[131I]-IPQA in A431 human epidermoid carcinoma cells and Western blot autoradiography. In vitro radiotracer accumulation and washout studies demonstrated a rapid accumulation and progressive retention postwashout of morpholino-[131I]-IPQA in A431 epidermoid carcinoma and in U87 human glioma cells genetically modified to express the EGFRvIII mutant receptor, but not in the wild-type U87MG glioma cells under serum-starved conditions. Using morpholino-[124I]-IPQA, we obtained noninvasive PET images of EGFR activity in A431 subcutaneous tumor xenografts, but not in subcutaneous tumor xenografts grown from K562 human chronic myeloid leukemia cells in immunocompromised rats and mice. Based on these observations, we suggest that PET imaging with morpholino-[124I]-IPQA should allow for identification of tumors with high EGFR kinase signaling activity, including brain tumors expressing EGFRvIII mutants and nonsmall-cell lung cancer expressing gain-of-function EGFR kinase mutants. Because of significant hepatobiliary clearance and intestinal reuptake of the morpholino-[124I]-IPQA, additional [124I]-IPQA derivatives with improved water solubility may be required to optimize the pharmacokinetics of this class of molecular imaging agents. [ABSTRACT FROM AUTHOR]

Proceeding from the measurements of the lightning occurrences, slow and fast electric-field disturbances, particle flux enhancements and their abrupt terminations, we formulate a lightning origination model. Registration of the extensive air shower simultaneously with lightning detection allows us to propose a solution to the long-standing problem of its role in the lightning initiation. Our analysis is based on the numerous Thunderstorm Ground Enhancements detected in 2012–2014 at Mt. Aragats in Armenia. [ABSTRACT FROM AUTHOR]

The mechanisms of oxygen diffusion in brain capillaries have not been fully clarified to date. According to the laws of physics, the well-documented phenomenon of hyperoxemia-induced excessive increases in brain tissue oxygen pressure (PbtO2) contradicts traditional models of cerebral capillary oxygen diffusion. Circulating models predict a significant drop in oxygen pressure (PO2), and some of them foresee the presence of hypoxic or anoxic corners near the capillary end, regardless of high PbtO2 levels. We propose that the cerebral intracapillary transformation of hemoglobin from the relaxed (R) to the tense (T) quaternary conformational state, driven by deoxygenation and an overload of negative allosteric effectors, and characterized by a lower, more hyperbolic dissociation curve, mitigates the oxygen pressure difference across cerebral capillaries, ensuring a homogeneous pericapillary distribution of oxygen. The hemoglobin R to T state transition is responsible for the high PbtO2 levels observed in viable cerebral tissue during hyperoxemia., Competing Interests: Declarations. Competing interests: On behalf of all authors, the corresponding author states that there are no conflicts of interest. The authors declare that they have no competing interests., (© 2024. The Author(s).)

Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain. However, over- or underdelivery of the SCS may occur because the spacing between the stimulating electrodes and the spinal cord is not fixed; spacing changes with motion and postural shifts may result in variable delivery of the SCS dose and, in turn, a suboptimal therapy experience for the patient. The evoked compound action potential (ECAP)-a measure of neural activation-may be used as a control signal to adapt SCS parameters in real time to compensate for this variability. In this prospective, multicenter, randomized, single-blind, crossover trial, reduction in overstimulation intensity was used as a perceptual measure to evaluate a novel ECAP-controlled, closed-loop (CL) SCS algorithm relative to traditional open-loop (OL) SCS. The primary outcome used a Likert scale to assess sensation during activities of daily living with CL versus OL SCS. Of the 42 subjects in the intent-to-treat analysis set, 97.6% had a reduction in sensation with CL versus OL SCS. The primary objective was met as the lower confidence limit (87.4%) exceeded the performance goal of 50% (P < .001). A total of 88.1% (37/42) of subjects preferred CL and 11.9% (5/42) preferred OL SCS. SCS dose consistency during CL SCS was demonstrated by the reduced variability in ECAP amplitude with CL SCS (standard deviation: 8.72 µV) relative to OL SCS (standard deviation: 19.95 µV). Together, these results demonstrate that the ECAP-controlled, CL algorithm reduces or eliminates unwanted sensation, and thereby provides a more preferred and consistent SCS experience. PERSPECTIVE: Patients with chronic pain need durable and dependable options for pain relief. SCS is an important therapy option, and new technology advancements could improve long-term therapy use. CL SCS offers a preferred and more consistent therapy experience for patients that could lead to increased therapy utilization and reliable therapy outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Postoperative sore throat (POST) is one of the most reported complications after general anesthesia with an incidence of as high as 60% which may impact patient satisfaction and increase the cost of treatment. The aim of this review is to summarize the currently accepted approaches and new trends intended to reduce the risk and increase the treatment efficacy of POST. Difficult intubation, traumatic intubation, and several other factors contribute to the development of POST. Endotracheal intubation using a stylet-loaded tube exerts excessive pressure on the anterior tracheal wall predisposing to mucosal trauma and contributing to development of POST. Pharmacological interventions are aimed at prevention, amelioration of symptoms, and treatment of POST. Medications suggested for this purpose include corticosteroids, topical sprays and creams, non-steroidal anti-inflammatory drugs (NSAID), and N-methyl-D-aspartate (NMDA) receptor antagonists. The use of video-laryngoscopes (VL) for endotracheal intubation improves the glottic view and increases the success rates with less force required to ensure adequate laryngoscopic view. Nevertheless, despite advances in laryngoscopic devices, the incidence of POST remains high. A novel intubation technique with endotracheal tube (ETT) rotation 180 degrees (ETT 180°) has been suggested to overcome stylet related injury and, possibly, decrease the POST. To date, no clinical trials have been conducted to test the efficacy of ETT 180° in reducing the incidence of POST. Undoubtedly, the suggested method deserves further investigation to determine its role in patient care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Mazzotta, Soghomonyan and Hu.)

Postoperative nausea and vomiting (PONV) is a commonly encountered problem in surgical practice. It delays discharge from the post-anesthesia care unit, requires additional resources to treat, and may increase the morbidity in some patients. Many effective drugs are available to treat or prevent PONV, however many of these drugs have the potential to prolong the QTc on the electrocardiogram (EKG) and increase the risk of serious ventricular arrhythmias, in particular, torsade de pointes. The QTc prolongation may be a manifestation of a genetic mutation resulting in abnormal myocyte repolarization or it may be acquired and associated with the use of various medications, electrolyte disorders, and physiological conditions. Patients predisposed to QTc prolongation presenting for surgery constitute a challenging group, since many drugs commonly used for PONV management will put them at risk for perioperative serious arrhythmias. This is an important topic, and our mini-review is an attempt to highlight the problem, summarize the existing experience, and generate recommendations for safe management of PONV for patients, who are at increased risk of QTc prolongation and arrhythmias. Focused prospective studies will help to find definitive answers to the discussed problems and challenges and develop specific guidelines for clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BR declared a shared affiliation with the authors to the handling editor at time of review., (Copyright © 2021 Soghomonyan, Stoicea, Ackermann and Bhandary.)

Background: Surgery on posterior cranial fossa (PCF) and pineal region (PR) carries the risks of intraoperative trauma to the brainstem structures, blood loss, venous air embolism (VAE), cardiovascular instability, and other complications. Success in surgery, among other factors, depends on selecting the optimal patient position. Our objective was to find associations between patient positioning, incidence of intraoperative complications, neurological recovery, and the extent of surgery. Methods: This observational study was conducted in two medical centers: The Ohio State University Wexner Medical Center (USA) and The Burdenko Neurosurgical Institute (Russian Federation). Patients were distributed in two groups based on the surgical position: sitting position (SP) or horizontal position (HP). The inclusion criteria were adult patients with space-occupying or vascular lesions requiring an open PCF or PR surgery. Perioperative variables were recorded and summarized using descriptive statistics. The post-treatment survival, functional outcome, and patient satisfaction were assessed at 3 months. Results: A total of 109 patients were included in the study: 53 in SP and 56 in HP. A higher proportion of patients in the HP patients had >300 mL intraoperative blood loss compared to the SP group (32 vs. 13%; p = 0.0250). Intraoperative VAE was diagnosed in 40% of SP patients vs. 0% in the HP group ( p < 0.0001). However, trans-esophageal echocardiographic (TEE) monitoring was more common in the SP group. Intraoperative hypotension was documented in 28% of SP patients compared to 9% in HP group ( p = 0.0126). A higher proportion of SP patients experienced a new neurological symptom compared to the HP group (49 vs. 29%; p = 0.0281). The extent of tumor resection, postoperative 3-months survival, functional outcome, and patient satisfaction were not different in the groups. Conclusions: The SP was associated with, less intraoperative bleeding, increased intraoperative hypotension, VAE, and postoperative neurological deficit. More HP patients experienced macroglossia and increased blood loss. At 3 months, there was no difference of parameters between the two groups. Clinical Trial Registration: ClinicalTrials.gov: registration number NCT03364283., (Copyright © 2020 Mavarez-Martinez, Israelyan, Soghomonyan, Fiorda-Diaz, Sandhu, Shimansky, Ammirati, Palettas, Lubnin and Bergese.)

Purpose of the article: To determine whether intraoperative ventilation with pure oxygen during the last stage of surgery reduces the occurrence and volume of postoperative pneumocephalus when compared to conventional air/oxygen mixture in patients undergoing craniotomy., Material and Methods: prospective randomized single-blinded study to compare the rate of occurrence and volume of postoperative pneumocephalus in patients undergoing craniotomy receiving intraoperative ventilation with pure oxygen (Group B) versus a conventional air/oxygen 1:1 mixture (Group A) during the last stage of surgery. This trial was registered in ClinicalTrials.gov #NCT02722928, protocol number 2015H0032., Results: One hundred patients were randomized into group 'A' and group 'B'. Seventy patients were included in the final analysis with 39 patients allocated in group 'A' and 31 patients in group 'B'. Median and IQR were used for postoperative penumocephalus volume. Group A: 9.65 [3.61-23.20]; Group B: 7.06 [2.70-20.1]. Our study showed no prophylactic effect on postoperative pneumocephalus volume when using mechanical ventilation with higher oxygen concentrations than the standard FiO 2 during the last stage of surgery in patients undergoing craniotomy (p = .47). No statistical difference was found in SICU LOS between groups (median 1,380 min [group A] versus 1,524 min [group B]; p = .18)., Conclusion: The use of intraoperative mechanical ventilation with pure oxygen was not associated with a prophylactic effect on the occurrence and extent of postoperative pneumocephalus in our patient setting. Published literature describing the extent of postoperative pneumocephalus is limited or highly variable among institutions.

Background: Clopidogrel is an irreversible antagonist of P2Y 12 receptors (P2Y 12 Rs) used as an antiplatelet drug to reduce risk of thrombosis. P2Y 12 Rs are expressed in gastrointestinal (GI) tract where they might regulate GI function., Aim: To evaluate if blockade of P2Y 12 Rs by clopidogrel is associated with higher incidence of GI symptoms in patients with irritable bowel syndrome (IBS)., Methods: A retrospective analysis of our institutional database was conducted for a 13-year period. IBS patients were identified, and their demographics, GI symptoms and clopidogrel therapy were collected. Logistic regression models were used to characterize symptoms in clopidogrel versus no-clopidogrel IBS-groups, adjusting for Age and Sex differences. An additional study characterized the P2Y 12 R distribution in human gut., Results: The search identified 7217 IBS patients (6761 no-clopidogrel/456 clopidogrel). There were a higher proportion of patients with GI symptoms on clopidogrel (68%) compared to controls (60%, p = 0.0011) that were Females (70 vs. 60%, p = 0.0003) not Males (61 vs. 60%; p = 0.8312). In Females, clopidogrel was associated with higher incidence of GI symptoms (Age adjusted; p < 0.0001) for pain, constipation, gastroparesis (p ≤ 0.0001) and psychogenic pain (p = 0.0006). Age or Sex (adjusted models) influenced one or more GI symptoms (i.e., pain, p < 0.0001; constipation, p < 0.0001/p = 0.008; diarrhea, flatulence, p = 0.01). P2Y 12 R immunoreactivity was abundant in human ENS; glial-to-neuron ratio of P2Y 12 Rs expressed in Females ≫ Males., Conclusions: Irreversible blockade of P2Y 12 R by clopidogrel is associated with higher incidence of GI symptoms in Female IBS patients, although Age or Sex alone contributes to symptomatology. Prospective studies can determine clinical implications of P2Y 12 Rs in IBS.

The relationship of lightning and elementary particle fluxes in the thunderclouds is not fully understood to date. Using the particle beams (the so-called Thunderstorm Ground Enhancements - TGEs) as a probe we investigate the characteristics of the interrelated atmospheric processes. The well-known effect of the TGE dynamics is the abrupt termination of the particle flux by the lightning flash. With new precise electronics, we can see that particle flux decline occurred simultaneously with the rearranging of the charge centers in the cloud. The analysis of the TGE energy spectra before and after the lightning demonstrates that the high-energy part of the TGE energy spectra disappeared just after lightning. The decline of particle flux coincides on millisecond time scale with first atmospheric discharges and we can conclude that Relativistic Runaway Electron Avalanches (RREA) in the thundercloud assist initiation of the negative cloud to ground lightning. Thus, RREA can provide enough ionization to play a significant role in the unleashing of the lightning flash.

Simulation of the actual procedure is a simple and yet effective method of increasing patient safety and reducing the rate of unexpected adverse effects. We present our experience with 2 cases of preprocedural simulation on healthy volunteers that were performed in the intraoperative magnetic resonance imaging suite. During one of the cases, we also simulated a scenario of sudden cardiac arrest. Such an approach helped us to refine the procedures and coordinate the work of different teams within the intraoperative magnetic resonance imaging suite as well as improve the quality of patient management.

Objective: To evaluate the perioperative dynamics of hematologic changes and transfusion ratio in patients undergoing a major spinal surgery accompanied with massive bleeding defined as blood loss >5 liters., Design: Retrospective cohort study., Setting: Operating room of a university-affiliated hospital., Patients: Adult patients who underwent elective neurosurgical, orthopedic, or combined spinal surgical procedure between 2008 and 2012., Methods: Patients who underwent a major spinal or orthopedic surgery and who experienced major bleeding (>5 L) during surgery were identified and selected for final analysis. The following information was analyzed: demographics, clinical diagnoses, hematologic parameters, estimated intraoperative blood loss, blood product transfusions, and survival 1 year after surgery., Results: During the study period, 25 patients, who underwent 28 spinal procedures, experienced intraoperative blood loss >5 L. Mean patient age was 50.5 years and 56.4% were males. The majority of patients underwent procedures to manage spinal metastases. Median estimated intraoperative blood loss was 11.25 L (IQR 6.35-22 L) and median number of units (U) transfused was 24.5 U (IQR 14.0-32.5 U) of packed red blood cells (RBCs), 24.5 U (IQR 14.0-34.0 U) of fresh frozen plasma (FFP), and 4.5 U (IQR 3.0-11.5 U) of platelets (PLTs). The blood product transfusion ratio was 1 and 4 for RBC:FFP, and RBC:PLT, respectively. Hematocrit, hemoglobin, PLTs, partial thromboplastin, prothrombin time, INR, and, fibrinogen varied significantly throughout the procedures. However, acid-base status did not change significantly during surgery. Patients' survival at 1 year was 79.17%., Conclusion: Our results indicate that a 1:1 RBC:FFP and 4:1 RBC:PLT transfusion ratio was associated with significant intraoperative variations in coagulation variables but stable intraoperative acid-base parameters. This transfusion ratio helped clinicians to achieve postoperative coagulation parameters not significantly different to those at baseline. Future studies should assess if more liberal transfusion strategies or point of care monitoring might be warranted in patients undergoing spinal surgery at risk of major blood loss., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The objective of this narrative review is to provide an overview of the problem of non-opioid anesthetic drug abuse among anesthesia care providers (ACPs) and to describe current approaches to screening, therapy, and rehabilitation of ACPs suffering from non-opioid anesthetic drug abuse., Source: We first performed a search of all literature available on PubMed prior to April 11, 2016. The search was limited to articles published in Spanish and English, and the following key words were used: anesthesiology, anesthesia personnel, AND substance-related disorders. We also searched Ovid MEDLINE ® databases from 1946-April 11, 2016 using the following search terms: anesthesiology OR anesthesia, OR nurse anesthetist OR anesthesia care provider OR perioperative nursing AND substance-related disorders., Principal Findings: Despite an increased awareness of drug abuse among ACPs and improvements in preventive measures, the problem of non-opioid anesthetic drug abuse remains significant. While opioids are the most commonly abused anesthesia medications among ACPs, the abuse of non-opioid anesthetics is a significant cause of morbidity, mortality, and professional demise., Conclusion: Early detection, effective therapy, and long-term follow-up help ACPs cope more effectively with the problem and, when possible, resume their professional activities. There is insufficient evidence to determine the ability of ACPs to return safely to anesthesia practice after rehabilitation, though awareness of the issue and ongoing treatment are necessary to minimize patient risk from potentially related clinical errors.

Background: Induced hypotension (IH) had been used for decades in neurosurgery to reduce the risk for intraoperative blood loss and decrease blood replacement. More recently, this method fell out of favor because of concerns for cerebral and other end-organ ischemia and worse treatment outcomes. Other contributing factors to the decline in its popularity include improvements in microsurgical technique, widespread use of endovascular procedures, and advances in blood conservation and transfusion protocols. Permissive hypotension (PH) is still being used occasionally in neurosurgery; however, its role in current anesthesia practice remains unclear. Our objective was to describe contemporary utilization of IH and PH (collectively called PH) in clinical practice among members of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC)., Methods: A questionnaire was developed and distributed among SNACC members that addressed practice patterns related to the use of PH. The responses were analyzed based on the number of individuals who responded to each specific question., Results: Of 72 respondents, 67.6% reported over 10 years of clinical experience, while 15.5% reported 5-10 years of post-training experience. The respondents admitted to providing anesthesia for 300 (median) neurosurgical cases per year. PH was applied most commonly during open interventions on cerebral aneurysms (50.8%) and arteriovenous malformations (46%). Seventy-three percent of respondents were not aware of any complications in their practice attributable to PH., Conclusion: PH is still being used in neuroanesthesia practice by some providers. Further research is justified to clarify the risks and benefits of PH in modern neuroanesthesia practice.

Enterochromaffin (EC) cells synthesize 95% of the body 5-HT and release 5-HT in response to mechanical or chemical stimulation. EC cell 5-HT has physiological effects on gut motility, secretion and visceral sensation. Abnormal regulation of 5-HT occurs in gastrointestinal disorders and Inflammatory Bowel Diseases (IBD) where 5-HT may represent a key player in the pathogenesis of intestinal inflammation. The focus of this review is on mechanism(s) involved in EC cell "mechanosensation" and critical gaps in our knowledge for future research. Much of our knowledge and concepts are from a human BON cell model of EC, although more recent work has included other cell lines, native EC cells from mouse and human and intact mucosa. EC cells are "mechanosensors" that respond to physical forces generated during peristaltic activity by translating the mechanical stimulus (MS) into an intracellular biochemical response leading to 5-HT and ATP release. The emerging picture of mechanosensation includes Piezo 2 channels, caveolin-rich microdomains, and tight regulation of 5-HT release by purines. The " purinergic hypothesis" is that MS releases purines to act in an autocrine/paracrine manner to activate excitatory (P2Y 1 , P2Y 4 , P2Y 6 , and A 2A /A 2B ) or inhibitory (P2Y 12 , A 1 , and A 3 ) receptors to regulate 5-HT release. MS activates a P2Y 1 /G α q/PLC/IP 3 -IP 3 R/SERCA Ca 2+ signaling pathway, an A 2A /A 2B -Gs/AC/cAMP-PKA signaling pathway, an ATP-gated P2X 3 channel, and an inhibitory P2Y 12 -G i/o /AC-cAMP pathway. In human IBD, P2X 3 is down regulated and A 2B is up regulated in EC cells, but the pathophysiological consequences of abnormal mechanosensory or purinergic 5-HT signaling remain unknown. EC cell mechanosensation remains poorly understood.

Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 ( HSVtk ) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC., Competing Interests: Conflict of interest statement: W.A. and R.P. are founders of AAVP BioSystems, which has licensed intellectual property related to the adeno-associated virus/phage (AAVP) technology, and they are inventors on patent applications and entitled to standard royalties if commercialization occurs. The University of Texas M. D. Anderson Cancer Center and the University of New Mexico Health Sciences Center currently manage these arrangements in accordance with their established institutional conflict of interest policy.

Many trauma patients present with a combination of cranial and thoracic injury. Anesthesia for these patients carries the risk of intraoperative hemodynamic instability and respiratory complications during mechanical ventilation. Massive air leakage through a lacerated lung will result in inadequate ventilation and hypoxemia and, if left undiagnosed, may significantly compromise the hemodynamic function and create a life-threatening situation. Even though these complications are more characteristic for the early phase of trauma management, in some cases, such a scenario may develop even months after the initial trauma. We report a case of a 25-year-old patient with remote thoracic trauma, who developed an intraoperative tension pneumothorax and hemodynamic instability while undergoing an elective cranioplasty. The intraoperative patient assessment was made even more challenging by unexpected massive blood loss from the surgical site. Timely recognition and management of intraoperative pneumothorax along with adequate blood replacement stabilized the patient and helped avoid an unfavorable outcome. This case highlights the risks of intraoperative pneumothorax in trauma patients, which may develop even months after injury. A high index of suspicion and timely decompression can be life saving in this type of situation.

The word "glia" is derived from the Greek word "γλoια," glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the "reactive glial phenotype" is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor-α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential.

The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

Purpose: The literature and clinical data support the use of intravenous (IV) infusions of ibuprofen to control pain and reduce the opioid requirements associated with surgical pain. According to current guidelines, IV ibuprofen can be administered via a slow IV infusion performed during a 30-minute period. Although recent studies indicate that more rapid infusions may yield additional benefits for patients, the safety of such an approach needs further evaluation. The main purpose of this study was to determine the safety of single and multiple doses of IV ibuprofen (800 mg) administered over 5 to 10 minutes at the induction of anesthesia and after the surgical procedure for the treatment of postoperative pain., Methods: This was a Phase IV, multicenter, open-label, clinical surveillance study. It was conducted at 21 hospitals in the United States, and 300 adult hospitalized patients undergoing surgery were enrolled. The exclusion criteria for the study were: inadequate IV access; hypersensitivity to any component of IV ibuprofen, aspirin, or related products; and any active, clinically significant bleeding. Also excluded were patients who had taken NSAIDs <6 hours before administration of IV ibuprofen; pregnant or breastfeeding female patients; and patients in the perioperative period of coronary artery bypass graft surgery. Patients received 800 mg of IV ibuprofen administered over 5 to 10 minutes preoperatively. Vital signs, adverse events, and pain scores were assessed., Findings: Approximately 22% (65 of 300) of patients reported adverse events (serious and nonserious). The most common adverse event was infusion site pain (34 of 300 [11%]). No deaths were reported. Nine subjects reported serious adverse events, 8 of which occurred during the first 6 hours. All serious events reported were judged unrelated to ibuprofen. Of the 300 total patients, 2 (0.67%) discontinued the study drug due to an adverse event (1 patient discontinued the study because of infusion site pain, and 1 patient withdrew due to a hypersensitivity reaction after drug administration)., Implications: Our study found that IV ibuprofen infused over 5 to 10 minutes at induction of anesthesia is a safe administration option for surgical patients. ClinicalTrials.gov identifier: NCT01334957., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)