Cell non-autonomous effect of hepatic growth differentiation factor 15 on the thyroid gland.

The thyroid gland plays an essential role in the regulation of body energy expenditure to maintain metabolic homeostasis. However, to date, there are no studies investigating the morphological and functional changes of the thyroid gland due to mitochondrial stress in metabolic organs such as the liver. We used data from the Genotype-Tissue Expression portal to investigate RNA expression patterns of the thyroid gland according to the expression of growth differentiation factor 15 (GDF15) such as the muscles and liver. To verify the effect of hepatic GDF15 on the thyroid gland, we compared the morphological findings of the thyroid gland from liver-specific GDF15 transgenic mice to that of wild type mice. High GDF15 expression in the muscles and liver was associated with the upregulation of genes related to hypoxia, inflammation (TGF-α via NFκB), apoptosis, and p53 pathway in thyroid glands. In addition, high hepatic GDF15 was related to epithelial mesenchymal transition and mTORC1 signaling. Electron microscopy for liver-specific GDF15 transgenic mice revealed short mitochondrial cristae length and small mitochondrial area, indicating reduced mitochondrial function. However, serum thyroid stimulating hormone (TSH) level was not significantly different. In our human cohort, those with a high serum GDF15 level showed high fasting glucose, alanine transaminase, and alkaline phosphatase but no difference in TSH, similar to the data from our mice model. Additionally, high serum GDF15 increased the risk of lymph node metastasis to lateral neck. The hepatic GDF15 affected thyroid morphogenesis via a TSH-independent mechanism, affecting aggressive features of thyroid cancers.

Regulation of cancer stem cell activity by thyroid hormone receptor ß.

Increasing numbers of cancer stem cell markers have been recently identified. It is not known, however, whether a member of the nuclear receptor superfamily, thyroid hormone receptor ß (TRß), can function to regulate cancer stem cell (CSC) activity. Using anaplastic thyroid cancer cells (ATC) as a model, we highlight the role of TRß in CSC activity. ATC is one of the most aggressive solid cancers in humans and is resistant to currently available therapeutics. Recent studies provide evidence that CSC activity underlies aggressiveness and therapeutic resistance of ATC. Here we show that TRß inhibits CSC activity by suppressing tumor-sphere formation of human ATC cells and their tumor-initiating capacity. TRß suppresses the expression of CSC regulators, including ALDH, KLF2, SOX2, b-catenin, and ABCG2, in ATC cell-induced xenograft tumors. Single-cell transcriptomic analysis shows that TRß reduces CSC population in ATC-induced xenograft tumors. Analysis of The Cancer Genome Atlas (TCGA) database demonstrates that the inhibition of CSC capacity by TRß contributes to favorable clinical outcomes in human cancer. Our studies show that TRß is a newly identified transcription regulator that acts to suppress CSC activity and that TRß could be considered as a molecular target for therapeutic intervention of ATC.

Targeting transcriptional regulators for treatment of anaplastic thyroid cancer.

Dysregulation of genes perpetuates cancer progression. During carcinogenesis, cancer cells acquire dependency of aberrant transcriptional programs (known as "transcription addiction") to meet the high demands for uncontrolled proliferation. The needs for particular transcription programs for cancer growth could be cancer-type-selective. The dependencies of certain transcription regulators could be exploited for therapeutic benefits. Anaplastic thyroid cancer (ATC) is an extremely aggressive human cancer for which new treatment modalities are urgently needed. Its resistance to conventional treatments and the lack of therapeutic options for improving survival might have been attributed to extensive genetic heterogeneity due to subsequent evolving genetic alterations and clonal selections during carcinogenesis. Despite this genetic complexity, mounting evidence has revealed a characteristic transcriptional addiction of ATC cells resulting in evolving diverse oncogenic signaling for cancer cell survival. The transcriptional addiction has presented a huge challenge for effective targeting as shown by the failure of previous targeted therapies. However, an emerging notion is that many different oncogenic signaling pathways activated by multiple upstream driver mutations might ultimately converge on the transcriptional responses, which would provide an opportunity to target transcriptional regulators for treatment of ATC. Here, we review the current understanding of how genetic alterations in cancer distorted the transcription program, leading to acquisition of transcriptional addiction. We also highlight recent findings from studies aiming to exploit the opportunity for targeting transcription regulators as potential therapeutics for ATC.

Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers.

The activation of metastatic reprogramming is vital for cancer metastasis, but little is known about its mechanism. This study investigated the potential role of death-associated protein kinase 1 (DAPK1) in thyroid cancer progression. We generated knockdown (KD) DAPK1 using siRNA or shRNA in 8505C and KTC-1 cell lines, which we transiently or stably overexpressed in MDA-T32 and BCPAP cell lines. DAPK1 KD in 8505C and KTC-1 cells significantly increased cell proliferation and colony formation compared with controls. We observed significant inhibition of cancer cell invasion in cells overexpressing DAPK1, but the opposite effect in KD cells. Tumorsphere formation significantly increased after inhibition of DAPK1 expression in 8505C cells and was significantly suppressed in DAPK1-overexpressing MDA-T32 and BCPAP cells. DAPK1 overexpression inhibited mRNA and protein levels of stem markers (OCT4, Sox2, KLF4, and Nanog). Furthermore, the expression of these markers increased after KD of DAPK1 in 8505C cells. Mechanistic studies suggest that DAPK1 may modulate the expression of stem cell markers through the inhibition of ß-catenin pathways. These findings were consistent with the public data and our thyroid tissue analysis, which showed higher DAPK1 expression was associated with advanced-stage papillary thyroid cancer with a higher stemness index and lower disease-free survival.

SHMT2 expression as a diagnostic and prognostic marker for thyroid cancer.

BACKGROUND: Catabolism of serine via serine hydroxymethyltransferase2 (SHMT2) through the mitochondrial one-carbon unit pathway is important in tumorigenesis. Therefore, SHMT2 may play a role in thyroid cancer. METHODS: Thyroid tissue samples and The Cancer Genome Atlas (TCGA) database were used to evaluate SHMT2 expression in thyroid tissues and the association with clinical outcomes. RESULTS: SHMT2 protein expression was evaluated in thyroid tissues consisting of 52 benign nodules, 129 papillary thyroid carcinomas (PTC) and matched normal samples, and 20 anaplastic thyroid carcinomas (ATC). ATCs presented the highest (95.0%) positivity of SMHT2 protein expression. PTCs showed the second highest (73.6%) positivity of SHMT2 expression, which was significantly higher than that of benign nodules (19.2%, P = 0.016) and normal thyroid tissues (0%, P < 0.001). Analysis of TCGA data showed that SHMT2 messenger RNA (mRNA) expression was significantly higher in tumors than in normal tissues (P < 0.001). When we classified thyroid cancer into high and low groups according to SHMT2 mRNA expression levels, the thyroid differentiation score for the high SHMT2 group was significantly lower than that of the low SHMT2 group (P < 0.001). There was also a significant correlation between SHMT2 mRNA expression and the stemness index (r = 0.41, P < 0.001). The high SHMT2 group had more advanced TNM stages and shorter progression-free survival rates than the low SHMT2 group (P < 0.01 and P = 0.007, respectively). CONCLUSION: SHMT2 expression is higher in thyroid cancers than normal or benign tissues and is associated with de-differentiation and poor clinical outcomes. Thus, SHMT2 might be useful as a diagnostic and prognostic marker for thyroid cancer.

Traumatic Iridodialysis Associated With Hyphema Secondary to Injury From a Bungee Cord.

We present a case of an iris sphincter tear with iridodialysis, mydriasis, and hyphema secondary to a traumatic injury from a bungee cord. The correlation between the mechanism of injury and physical exam findings as well as the emergency department evaluation and management are discussed.

Flash Burn of the Eyes Caused by High-Voltage Electrical Spark.

We present a rare case of corneal abrasion with mild eyelid epitheliopathy caused by a high-voltage electrical spark. The case includes emergency department evaluation and subsequent management at the burn center with ophthalmology. The prognosis, in this case, is good, however, the potential severity of high-voltage electrical injuries can be much worse. Prevention strategies for occupational electrical injuries are discussed with an emphasis on proper personal protective equipment (PPE).

Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression.

Here, we investigated the potential roles of Mitofusin-2 (MFN2) in thyroid cancer progression. MFN2 regulates mitochondrial fusion/division in cells and plays an important role in various aspects of cell metabolism. MFN2 might involve in cell cycle regulation, apoptosis, and differentiation, and it might play a role as a tumor suppressor in carcinogenesis. We evaluated the prognostic impacts of MFN2 expression in thyroid cancer by analyzing TCGA data. In vitro and in vivo, MFN2 was knocked out using CRISPR/Cas9 or siRNA, and MFN2 was stably overexpressed in two thyroid cancer cell lines (Cal62 and HTH83). TCGA analysis revealed that MFN2 expression was lower in thyroid cancer than in normal tissues and significantly associated with a degree of differentiation, RAS mutations, and less lymph node metastasis. MFN2 expression was significantly correlated with cell adhesion molecules and epithelial to mesenchymal transition (EMT) in a gene-set enrichment assay. MFN2 knock-out (KO) in Cal62 and HTH83 cells using CRISPR/Cas9 or siRNA significantly promoted cell migration and invasion in vitro. The same trends were observed in MFN2 KO mouse embryonic fibroblasts (MEFs) compared to those in the controls (MFN2 WT MEFs). Conversely, MFN2 overexpression in cancer cell lines greatly inhibited cell migration and invasion. However, there was no difference in colony formation and proliferation in Cal62 and HTH83 cells after modulating MFN2, although there were significant differences between MFN KO and WT MEFs. EMT-associated protein expression was induced after MFN2 KO in both cancer cell lines. The mechanistic results suggest that MFN2 might modulate EMT through inducing the AKT signaling pathway. EMT-associated changes in protein expression were also confirmed by modulating MFN2 in xenograft tumors. Thus, MFN2 acts as a tumor suppressor in thyroid cancer progression and metastasis by modulating EMT.

Phalangeal Fracture Secondary to Hammering One's Finger.

The authors report the case of a man who smashed his finger while using a hammer, resulting in a fracture-dislocation. The description of this injury type and the emergency management is discussed.

Inflammation suppression prevents tumor cell proliferation in a mouse model of thyroid cancer.

The incidence of thyroid cancer, the most frequent endocrine neoplasia, is rapidly increasing. Significant progress has recently been made in the identification of genetic lesions in thyroid cancer; however, whether inflammation contributes to thyroid cancer progression remains unknown. Using a mouse model of aggressive follicular thyroid cancer (FTC; ThrbPV/PVPten+/- mice), we aimed to elucidate a cause-effect relationship at the molecular level. The ThrbPV/PVPten+/- mouse expresses a dominantly negative thyroid hormone receptor ß (denoted as PV) and a deletion of a single allele of the Pten gene. These two oncogenic signaling pathways synergistically activate PI3K-AKT signaling to drive cancer progression as in human FTC. At the age of 5-7 weeks, thyroids of ThrbPV/PVPten+/- mice exhibited extensive hyperplasia accompanied by 77.5-fold infiltration of inflammatory monocytes as compared with normal thyroids. Global gene expression profiling identified altered expression of 2387 genes, among which 1353 were upregulated and 1034 were down-regulated. Further analysis identified markedly elevated expression of inflammation mediators and cytokines such as, Csf1r, Csf1, SPP1, Aif1, IL6, Ccl9, Ccl3, Ccl12, and Ccr2 genes and decreased expression of Kit, Ephx2, Cd163, IL15, Ccl11, and Cxcl13 genes. These changes elicited the inflammatory responses in the hyperplastic thyroid of ThrbPV/PVPten+/- mice, reflecting early events in thyroid carcinogenesis. We next tested whether attenuating the inflammatory responses could mitigate thyroid cancer progression. We treated the mice with an inhibitor of colony-stimulating factor 1 receptor (CSF1R), pexidartinib (PLX-3397; PLX). CSF1R mediates the activity of the cytokine, colony stimulating factor 1 (CSF1), in the production, differentiation, and functions of monocytes and macrophages. Treatment with PLX decreased 94% and 62% of inflammatory monocytes in the thyroid and bone marrow, respectively, versus controls. Further, PLX suppressed the expression of critical cytokine and inflammation-regulating genes such as Csf1r, SPP1 (OPN), Aif1, IL6, Ccl9, Ccl3, Ccl12, and Ccr2 (25%-80%), resulting in inhibition of 89% tumor cell proliferation, evidenced by Ki-67 immunostaining. These preclinical findings suggest that inflammation occurs in the early stage of thyroid carcinogenesis and plays a critical in cancer progression. Importantly, attenuation of inflammation by inhibitors such as PLX would be beneficial in preventing thyroid cancer.

High Phosphoglycerate Dehydrogenase Expression Induces Stemness and Aggressiveness in Thyroid Cancer.

Background: We examined the changes in glucose metabolites of papillary thyroid cancer (PTC) and identified phosphoglycerate dehydrogenase (PHGDH) as a potential target. The role of PHGDH in the proliferation and tumorigenesis of thyroid cancer cells and its clinical significance were analyzed. Methods: Glucose metabolites of various thyroid tissues were analyzed via targeted metabolomics analysis. In vitro experiments using shPHGDHs, inhibitor (NCT503), or PHGDH overexpression in thyroid cell lines (BCPAP, 8505C, and Nthy-Ori) were performed. In vivo experiments were performed by using shPHGDH. Human tissue samples and The Cancer Genome Atlas (TCGA) data were used to validate the experimental findings. Results:PHGDH knockdown in BCPAP and 8505c cell lines significantly inhibited cell viability, colony formation, and tumor spheroid formation compared with the control. In addition, treatment with NCT503 showed similar results. PHGDH inhibition by both knockdown and treatment with NCT503 significantly inhibited the expression of embryonic cancer stemness markers (Oct4, Sox2, KLF4, and Nanog). PHGDH overexpression in Nthy-Ori cells significantly increased cell viability and colony formation. The stemness markers were significantly increased after PHGDH overexpression. PHGDH knockdown significantly inhibited tumor growth in an in vivo mouse xenograft study using 8505c cells. The protein expression of Oct4 in tumors was significantly reduced after PHGDH knockdown. The associations between PHGDH expression and stemness markers were confirmed in the TCGA data and human thyroid tissue samples. Positive PHGDH protein expression was associated with metastases of PTC. Conclusions:PHGDH expression is induced in thyroid cancer and is associated with stemness and aggressiveness of PTC.

Steroid receptor coactivator-3 as a target for anaplastic thyroid cancer.

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy without effective therapeutic options to improve survival. Steroid receptor coactivator-3 (SRC-3) is a transcriptional coactivator whose amplification and/or overexpression has been identified in many cancers. In this study, we explored the expression of SRC-3 in ATCs and the effects of a new class of SRC-3 inhibitor-2 (SI-2) in human ATC cells (THJ-11T and THJ-16T cells) and mouse xenograft models to assess therapeutic potential of SI-2 for the treatment of ATC. SRC-3 protein abundance was significantly higher in human ATC tissue samples and ATC cells than in differentiated thyroid carcinomas or normal controls. SI-2 treatment effectively reduced the SRC-3 expression in both ATC cells and ATC xenograft tumors induced by these cells. Cancer cell survival in ATC cells and tumor growth in xenograft tumors were significantly reduced by SI-2 treatment through induction of cancer cell apoptosis and cell cycle arrest. SI-2 also reduced cancer stem-like cells as shown by an inhibition of tumorsphere formation, ALDH activity, and expression of stem cell markers in ATC. These findings indicate that SRC-3 is a potential therapeutic target for treatment of ATC patients and that SI-2 is a potent and promising candidate for a new therapeutic agent.

Cardiac Arrest Following Treatment With Diltiazem for Atrial Fibrillation With Rapid Ventricular Response.

We present the case of a 43-year-old man with a history of atrial fibrillation and poor medical compliance who presented to the emergency department with palpitations for three hours. Electrocardiogram (ECG) revealed atrial fibrillation with rapid ventricular response at 119 beats per minute. Following administration of diltiazem 10 mg IV, the patient became bradycardic with a rate of 30 beats per minute and complete atrioventricular node block. A subsequent ECG revealed asystole, and the patient became unresponsive. Chest compressions were administered, and the rhythm changed to ventricular tachycardia. There was spontaneous return of circulation without any further intervention. The patient eventually converted to sinus rhythm and was started on anticoagulation to prevent a thrombotic event. He was discharged the next day with apixaban and propafenone.

Potentiated anti-tumor effects of BETi by MEKi in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited treatment options. We explored novel treatment modalities by targeting epigenetic modifications using inhibitors of BET (e.g. BRD4) activity. We evaluated the efficacy in the treatment of ATC of a novel BET inhibitor, PLX51107 (PLX), currently in clinical trials for other solid tumors and hematologic malignancies, alone or combined with a MEK inhibitor, PD0325901(PD). To elucidate the effects of these inhibitors on growth of ATC, we treated ATC cells derived from patient tumors (THJ-11T and THJ-16T cells) and mouse xenograft tumors with inhibitors. We found PLX and PD inhibitors singly inhibited proliferation of both human ATC cells lines, but together exhibited stronger inhibition of proliferation. In mouse xenografts, the combination treatment almost totally blocked growth in xenograft tumors derived from both ATC cells. PD effectively attenuated MEK-ERK signaling, which was further enhanced by PLX in the combined treatment in cultured cells and tumors. Importantly, the combination of PLX and PD acted synergistically to suppress MYC transcription to increase p27 in decreasing tumor cell proliferation. PLX and PD cooperated to upregulate pro-apoptotic proteins to promote apoptosis. These two inhibitors converged to reduce the binding of BRD4 to the MYC promoter to suppress the MYC expression. These findings indicate that combined treatment of BET and MEK-ERK inhibitors was more effective to treat ATC than single targeted treatment. Synergistic suppression of MYC transcription via collaborative actions on chromatin modifications suggested that targeting epigenetic modifications could provide novel treatment opportunities for ATC.

Chemistries for Making Additive Nanolithography in OrmoComp Permissive for Cell Adhesion and Growth.

Two-photon lithography allows writing of arbitrary nanoarchitectures in photopolymers. This design flexibility opens almost limitless possibilities for biological studies, but the acrylate-based polymers frequently used do not allow for adhesion and growth of some types of cells. Indeed, we found that lithographically defined structures made from OrmoComp do not support E18 murine cortical neurons. We reacted OrmoComp structures with several diamines, thereby rendering the surfaces directly permissive for neuron attachment and growth by presenting a surface coating similar to the traditional cell biology coating achieved with poly-d-lysine (PDL) and laminin. However, in contrast to PDL-laminin coatings that cover the entire surface, the amine-terminated OrmoComp structures are orthogonally modified in deference to the surrounding glass or plastic substrate, adding yet another design element for advanced biological studies.

Peripheral location and infiltrative margin predict invasive features of papillary thyroid microcarcinoma.

OBJECTIVE: Tumor location in papillary thyroid microcarcinoma (PTMC) might determine tumor outgrowth from the thyroid gland. However, the clinical implications of tumor location and minimal extrathyroid extension (mETE) have not been well elucidated. We aimed to investigate the relationship between tumor location and mETE to predict the aggressiveness of PTMC. METHODS: A total of 858 patients with PTMC were grouped according to tumor location on ultrasonography: central (cPTMC) and peripheral PTMC (pPTMC). PTMC without mETE (PTMC-mETE(-)) was divided further according to margin shape: encapsulated (E-) or infiltrative (I-). To understand the molecular biologic characteristics of PTMC presenting with an I-margin and mETE, transcriptome data from TCGA-THCA were analyzed using Gene Set Enrichment Analysis (GSEA). RESULTS: pPTMC (n = 807, 94.1%) accounted for the majority of cases; mETE was identified only in pPTMC (403/807; 49.9%). pPTMC-mETE(+) showed aggressive clinical characteristics that increased the odds ratio (OR) for lymph node metastasis (LNM). Interestingly, subgroup analysis of PTMC-mETE(-) revealed that the I-margin also increased the OR for LNM, independent of other clinical factors. GSEA of TCGA-THCA data suggested coordinated upregulation of genes related to epithelial-mesenchymal transition (EMT) in PTC with mETE. Immunohistochemical staining for laminin subunit gamma 2 (LAMC2), CD59, E-cadherin and vimentin showed that these markers of EMT were associated with progressive changes in E-margin PTMC-mETE(-), I-margin PTMC-mETE(-) and pPTMC-mETE(+). CONCLUSION: mETE related to peripheral location of PTMC is an important predictor of tumor invasiveness, as is the I-margin, which presents with EMT features similar to mETE. I-margin PTMC-mETE(-) and pPTMC-mETE(+) might reflect the pattern of invasive PTMC.

Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer.

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide 'A' at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.

Long-term oncologic outcomes of papillary thyroid microcarcinoma according to the presence of clinically apparent lymph node metastasis: a large retrospective analysis of 5,348 patients.

PURPOSE: Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PTMC) may reduce the risk of overtreatment of clinically insignificant cancer. However, the absence of predictor for the progression of PTMC resulted in treatment delay and potentially compromising cure of aggressive disease. Therefore, to anticipate potential damage of delayed surgery, we investigated the oncologic outcomes of patients with low-risk PTMC initially eligible for AS except clinically apparent lymph node metastasis (LNM), imitating delayed surgery with neck dissection. MATERIALS AND METHODS: A total of 5,348 patients, enrolled between 1987 and 2016, with low-risk PTMC initially eligible for AS were included regardless of LNM. We classified our study patients into two groups: Group I, lobectomy with prophylactic central cervical node dissection; Group II, total thyroidectomy with modified radical neck dissection for LNM. In addition, we investigated the oncological outcomes of patients with second-wave surgery due to lateral lymph node recurrence (Group III, subgroup of Group I). RESULTS: Group I showed more favorable clinicopathological characteristics compared with Group II. In Group I, only 29 (0.58%) of 4,927 patients underwent second-wave surgery with neck dissection for lateral lymph node recurrences, whereas in Group II, all 22 (5.23%) of 421 patients underwent second-wave selective node dissection because of nodal recurrence. Disease-free survival rates were significantly different between Groups I and II (P<0.05). Of note, the recurrence rate of Group II was still significantly higher than that of Group III (5.2% vs 0%, respectively; P=0.021). In addition, Kaplan-Mayer survival analysis indicated poor disease-free survival rates in Group II compared with Group III (P<0.05). CONCLUSION: The long-term treatment outcome of PTMC without LNM was favorable even if the recurrence occurs during follow-up period compared with that of PTMC with LNM. It should be noted that AS might be able to cause poor prognosis due to clinically apparent LNM.

Accidental intracerebral injection and seizure during scalp nerve blocks for awake craniotomy in a previously craniotomized patient -a case report.

A 34-year-old man who previously underwent a craniotomy due to oligodendroglioma was admitted with a diagnosis of recurrent brain tumor. An awake craniotomy was planned. Approximately 15 minutes after completing the scalp nerve block, his upper torso suddenly moved and trembled for 10 seconds, suggesting a generalized clonic seizure. He recovered gradually and fully in 55 minutes without any neurological sequelae. The emergency computed tomography scan revealed a localized fluid collection and small intracerebral hemorrhage nearby in the temporoparietal cortex beneath the skull defect. He underwent surgery under general anesthesia at 8 hours after the seizure and was discharged from the hospital after 10 days. This report documents the first case of generalized seizure that was caused by the accidental intracerebral injection of local anesthetics. Although the patient recovered completely, the clinical implications regarding the scalp infiltration technique in a patient with skull defects are discussed.

Application of intraoperative lung-protective ventilation varies in accordance with the knowledge of anaesthesiologists: a single-Centre questionnaire study and a retrospective observational study.

BACKGROUND: The benefits of lung-protective ventilation (LPV) with a low tidal volume (6 mL/kg of ideal body weight [IBW]), limited plateau pressure (< 28-30 cm H2O), and appropriate positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome have become apparent and it is now widely adopted in intensive care units. Recently evidence for LPV in general anaesthesia has been accumulated, but it is not yet generally applied by anaesthesiologists in the operating room. METHODS: This study investigated the perception about intraoperative LPV among 82 anaesthesiologists through a questionnaire survey and identified the differences in ventilator settings according to recognition of lung-protective ventilation. Furthermore, we investigated the changes in the trend for using this form of ventilation during general anaesthesia in the past 10 years. RESULTS: Anaesthesiologists who had received training in LPV were more knowledgeable about this approach. Anaesthesiologists with knowledge of the concept behind LPV strategies applied a lower tidal volume (median (IQR [range]), 8.2 (8.0-9.2 [7.1-10.3]) vs. 9.2 (9.1-10.1 [7.6-10.1]) mL/kg; p = 0.033) and used PEEP more frequently (69/72 [95.8%] vs. 5/8 [62.5%]; p = 0.012; odds ratio, 13.8 [2.19-86.9]) for laparoscopic surgery than did those without such knowledge. Anaesthesiologists who were able to answer a question related to LPV correctly (respondents who chose 'height' to a multiple choice question asking what variables should be considered most important in the initial setting of tidal volume) applied a lower tidal volume in cases of laparoscopic surgery and obese patients. There was an increase in the number of patients receiving LPV (VT < 10 mL/kgIBW and PEEP ≥5 cm H2O) between 2004 and 2014 (0/818 [0.0%] vs. 280/818 [34.2%]; p <  0.001). CONCLUSIONS: Our study suggests that the knowledge of LPV is directly related to its implementation, and can explain the increase in LPV use in general anaesthesia. Further studies should assess the impact of using intraoperative LPV on clinical outcomes and should determine the efficacy of education on intraoperative LPV implementation.