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Objective: Pediatric orbital blowout fractures can include pathologies that seem mild but require urgent release; serious sequelae can occur with standby surgery or conservative treatment. We sought to validate an algorithm for the treatment of pediatric orbital blowout fractures. Methods: This retrospective cohort study included 61 pediatric patients, aged 18 years or younger, treated for pure orbital blowout fractures according to the algorithm from April 1, 2000, to August 31, 2020, at the Japanese Red Cross Asahikawa Hospital. Results: There were 52 males (85%). Median age was 14 years (range, 5–18 years). There were 9 patients categorized as needing urgent release, 16 as needing repair, and 36 as needing conservative treatment. Mean follow-up ocular movement was 98.0 (95% Confidence Interval [95% CI], 96.8–99.2). Postoperative diplopia was not observed in 96% (79.6%–99.9%) of patients, better than in previous studies. A higher proportion of patients aged 0–12 years needed urgent repair than those aged 13–18 years (Odds Ratio [OR] = 14.2; 95% CI 1.6–683.4; p = 0.0046). There were no differences in Hess area ratio by age group. Conclusion: Clinical results with the algorithm were satisfactory. The algorithm is suitable for treatment of pediatric orbital blowout fractures. Level of evidence: 4.

Objective: After Endoscopic Sinus Surgery (ESS), packing plays an important role in wound healing and hemostasis. However, the effect of the packing removal procedure on physician stress has not been evaluated. The purpose of this study was to evaluate physician stress during packing removal for patients treated with AQUACEL® Ag Advantage versus KALTOSTAT®. Methods: This retrospective study included 15 patients who underwent packing with ESS for chronic rhinosinusitis performed at two centers; 9 were treated with AQUACEL® Ag Advantage and 6 were treated with KALTOSTAT®. Physician stress during packing removal was evaluated with the National Aeronautics and Space Administration-Task Load Index (NASA-TLX). The time required to remove the packing and the number of instruments used in the procedure were recorded. Postoperative bleeding (Boezaart bleeding score) and wound healing were graded. Patient symptoms on the day after surgery and pain during packing removal were assessed using a visual analog scale. Results: Computed tomography scores, asthma complications, and blood eosinophil counts were significantly higher in the AQUACEL® Ag Advantage group. Patient symptoms on the day after surgery were not significantly different between the two groups. Physician stress during the task of packing removal was significantly lower in the AQUACEL® Ag Advantage group than in the KALTOSTAT® group (35.5 vs. 81.0, p = 0.016) according to the NASA-TLX scores. The number of instruments used in the procedure was significantly lower in the AQUACEL® Ag Advantage group than in the KALTOSTAT® group (3.0 vs. 6.0, p = 0.015). There were no significant differences in procedure time for packing removal, postoperative bleeding, wound healing, or patient pain at the time of packing removal between the groups. Conclusion: Physicians feel stressed about packing removal. In addition, AQUACEL® Ag Advantage is useful for packing after ESS, requiring fewer instruments for the procedure than KALTOSTAT® and reducing physician stress about the procedure. Level of evidence: Level 3.

Background: Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. Methods: We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. Results: S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1β secretion in human nasal epithelial cells. Conclusions: Our data demonstrate that S100A8 results in production of interleukin-1β in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

Hemorrhagic rupture is a very rare and life-threatening hepatic cyst complication. Several treatment methods have been used for hepatic cyst hemorrhage and/or rupture; however, transcatheter arterial embolization for hepatic cyst hemorrhage has been poorly documented. An 80-year-old man receiving dual antiplatelet therapy was diagnosed with hemorrhagic rupture of a hepatic cyst. Transcatheter arterial embolization using a coil was performed for A6 branch confirmed active extravasation. His condition improved promptly after treatment, and the hepatic cyst gradually became smaller as compared to the size before hemorrhage. Transcatheter arterial embolization is suitable for hepatic cyst hemorrhage and might be a minimally invasive treatment option for a symptomatic hepatic cyst.

Background: We examined the severity of epistaxis in patients with hereditary haemorrhagic telangiectasia (HHT) and its relationship with the performed activities of daily living. Methodology: This cross-sectional survey included 36 patients with HHT in Japan. An anonymous questionnaire survey was conducted regarding the severity of epistaxis, the measures adopted to prevent epistaxis, and the limitations in the performed activities of daily living. The latter was assessed using a visual analogue scale (VAS). The correlation between epistaxis severity and the VAS score was analysed using Spearman’s rank correlation coefficient. Results: Of the 36 participants surveyed, 94.4% had >1 episode of epistaxis/week. The mean epistaxis severity score (ESS) was 4.3 (range, 0.9–8.4). Limitations in daily life, going out (within a day), meeting with others, eating with others, and going on overnight trips were positively correlated with the ESS. To prevent nosebleeds, 44.4% and 41.7% of the participants used medications and avoided drying their nasal cavities, respectively. Conclusions: Epistaxis impacted the daily life of patients with HHT in proportion to its severity. Nonetheless, less than half of the patients used medications or took precautions. Hence, further educational activities should be considered for medical professionals and patients.

Abstract Isolated sphenoid sinus opacifications (ISSOs) are clinically important because they can lead to serious complications. However, some patients with ISSOs are asymptomatic, and not all patients are properly referred to the otolaryngology department. Because past studies of ISSOs focused only on patients who received treatment, in this study we selected ISSO cases based on radiology reports, then determined whether these patients had symptoms and were appropriately referred for specialty care. We conducted a retrospective analysis of data collected from patients who underwent computed tomography or magnetic resonance imaging from January 2007 to March 2017 at Osaka General Medical Center. We searched for the terms “sphenoid” or “sphenoidal” using F-REPORT to identify patients who had a sphenoid disease. We checked all selected images and diagnosed ISSOs. Examination of 1115 cases revealed 223 cases of ISSOs, of whom 167 (74.9%) were asymptomatic. We categorized patients with ISSOs into four groups: inflammation, mucocele, fungal diseases, and unclassifiable; the final category was used when edges were irregular or complete opacity was encountered. In the unclassifiable group, the majority of cases required otolaryngology consultation, but 37 of 47 unclassifiable patients did not have an otolaryngology visit. ISSOs are often identified by chance on imaging tests performed by non-otolaryngologists. However, our study revealed that many patients with ISSOs who should be treated by otolaryngologists were not referred to the otolaryngology department. Accordingly, it is important to promote awareness of the disease among other types of clinicians.

Background and Objectives: Teicoplanin (TEIC) is an effective drug for patients with febrile neutropenia (FN); however, it has been reported that these patients may have increased TEIC clearance compared with patients who do not have FN. The purpose of this study was to study therapeutic drug monitoring in patients with FN when the TEIC dosing design was based on the population mean method. Materials and Methods: Thirty-nine FN patients with hematological malignancy were included in the study. To calculate the predicted blood concentration of TEIC, we used the two population pharmacokinetic (population PK) parameters (parameters 1 and 2) reported by Nakayama et al. and parameter 3, which is a modification of the population PK of Nakayama et al. We calculated the mean prediction error (ME), an indicator of prediction bias, and the mean absolute prediction error (MAE), an indicator of accuracy. Furthermore, the percentage of predicted TEIC blood concentration within 25% and 50% of the measured TEIC blood concentration was calculated. Results: The ME values were −0.54, −0.25, and −0.30 and the MAE values were 2.29, 2.19, and 2.22 for parameters 1, 2, and 3, respectively. For all of the three parameters, the ME values were calculated as minus values, and the predicted concentrations tended to be biased toward smaller values relative to the measured concentrations. Patients with serum creatinine (Scr) < 0.6 mg/dL and neutrophil counts < 100/μL had greater ME and MAE values and a smaller percentage of predicted TEIC blood concentration within 25% of measured TEIC blood concentrations compared with other patients. Conclusions: In patients with FN, the accuracy of predicting TEIC blood concentrations was good, with no significant differences between each parameter. However, patients with a Scr < 0.6 mg/dL and a neutrophil count < 100/μL showed slightly inferior prediction accuracy.

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with poor survival that warrants early and precise diagnosis for timely therapeutic intervention. Despite accumulating genomic, transcriptomic, proteomic, and lipidomic data on IPF, evidence from water‐soluble metabolomics is limited. To identify biomarkers for IPF from water‐soluble metabolomic data, we measured the levels of various metabolites in bronchoalveolar lavage fluid (BALF) and serum samples from a bleomycin‐induced murine pulmonary fibrotic model using gas chromatography/mass spectrometry. Thirty‐two of 73 BALF metabolites and 29 of 74 serum metabolites were annotated. We observed that the levels of proline and methionine were higher in BALF but lower in serum than those in the control. Furthermore, analysis of public RNA‐Seq data from the lungs of patients with IPF revealed that proline‐ and methionine‐related genes were significantly upregulated compared to those in the lungs of healthy controls. These results suggest that proline and methionine may be potential biomarkers for IPF and may help to deepen our understanding of the pathophysiology of the disease. Based on our results, we propose a model capable of recapitulating the proline and methionine metabolism of fibrotic lungs, thereby providing better means for studying the disease and developing novel therapeutic strategies for IPF.

Background: Transnasal endoscopic surgery (TES) is an established procedure for the treatment of chronic rhinosinusitis, septal deviation, and paranasal benign tumours. Postoperative haemorrhage (POH) is a common complication following TES. Various studies have addressed the risk factors for intraoperative bleeding and the methods to improve the operative field by reducing bleeding. However, the factors affecting POH following TES have not been fully elucidated. Therefore, we aimed investigate the risk factors for POH following TES. Methodology: We studied 807 patients who underwent TES. The variables between cases with and without POH were compared using univariate and multivariate models. We also examined the site and timing of bleeding. Results: POH was observed in 21 cases (2.6%). Seven cases required treatment in the operation room (0.9%). The most common sites of bleeding were around sphenopalatine foramen, and the median time to POH was the 7th day after surgery. Multivariate analysis showed that anti-thrombotic medication, low platelet count, and surgical indication for sinonasal tumour were independent risk factors for POH. Conclusions: POH after TES is a relatively common complication. Careful intraoperative haemostatic procedures may be required in these cases.

Abstract Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice with a COPD-like phenotype progressively developed a syndrome resembling human aging, including cataracts, hair loss, and atrophy of various organs, including thymus, muscle, and testis, resulting in shorter survival than wild-type (WT) mice. Consistent with this, DNA microarray analysis of DKO mouse lungs revealed differential expression of genes involved in cell death, inflammation, and the sirtuin-1 (SIRT1) pathway. Accordingly, expression of SIRT1 was reduced in DKO mouse lungs. Importantly, siRNA knockdown of CD9 and CD81 in lung epithelial cells additively decreased SIRT1 and Foxo3a expression, but reciprocally upregulated the expression of p21 and p53, leading to reduced cell proliferation and elevated apoptosis. Furthermore, deletion of these tetraspanins increased the expression of pro-inflammatory genes and IL-8. Hence, CD9 and CD81 might coordinately prevent senescence and inflammation, partly by maintaining SIRT1 expression. Altogether, CD9/CD81 DKO mice represent a novel model for both COPD and accelerated senescence.

The double stapling technique has greatly facilitated intestinal reconstruction, particularly for anastomosis after anterior resection. However, anastomotic stenosis may occur, which sometimes requires surgical treatment. Redo surgery with reresection and reanastomosis presents a high risk of complications. Treatment methods need to be selected depending on the degree and location of stenosis. In an effort to propose a new resolution, reporting new cases and sharing valid experiences are necessary. An 82-year-old man diagnosed with rectal cancer had undergone laparoscopic anterior resection. Endoscopic balloon dilation performed for anastomotic stenosis had failed. Therefore, colostomy with double orifice was constructed on the oral side at 10 cm from the stenosis. Approaching from the anal and stoma side, the anastomotic stenosis was resected using a circular stapler. The colostomy was closed 1 month after surgery. Stenosis resection using a circular stapler requires the following steps: (1) passing the center shaft through the stenosis, (2) inserting the anvil head into the oral side of the stenosis, and (3) attaching the anvil head to the center shaft. This method can resect the stenosis using a circular stapler without being affected by postoperative adhesion in the pelvis. Compared to endoscopic balloon dilation, resection of the stricture by the circular stapler is thought to be reliable. This technique is particularly effective for localized stenosis, including anastomotic stenosis. It is considered that this method is minimally invasive and is low risk for complications. This method can contribute to the useful surgical option for refractory anastomotic stenosis after anterior resection.

The role of nutrient-sensing pathways in regulation of innate immune response is unexplored. Here the authors show that IL-4 activates the amino-acid sensing pathway in macrophages and leads to polarization of anti-inflammatory M2 macrophages via the transcription factor liver X receptor.

A 78-year-old woman with lumboperitoneal (LP) shunt was diagnosed with advanced cancer of the ascending colon. Laparoscopic right hemicolectomy was performed without manipulating the catheter. The patient’s postoperative course was uneventful, with no shunt-related complications or neurological deficit. The number of patients with cerebrospinal fluid (CSF) shunt who require abdominal surgery has been increasing. There are only few studies on laparoscopic surgery for patients with LP shunt, and the safety of pneumoperitoneum in the CSF shunt remains controversial. Consistent with other studies, we considered that pneumoperitoneum with a pressure of 10 mmHg has few negative effects. Our recommendations are as follows: (1) during colorectal resection, laparoscopic surgery can be performed without routine manipulation of the shunt catheter; (2) altering the location of the port is necessary to prevent both damage to the shunt tube during surgery and wound infection postoperatively; and (3) laparoscopic surgery is superior to laparotomy because it is associated with reduced surgical site infections and postoperative adhesions. However, laparoscopy should be performed at least 3 months after the construction of CSF shunt.

Background. Schwannoma arises from Schwann’s cell of the neural sheath. Schwannoma of the large intestine, particularly of the appendix, is rare. We report a case of appendiceal schwannoma resected using laparoscopic surgery. Case Presentation. A 75-year-old man was referred to our hospital for abdominal fullness and nausea since 2 months. Abdominal CT revealed a well-demarcated oval mass of 25 mm at the tip of the appendix. Contrast-enhanced CT revealed a lesion with gradually enhanced contrast from the arterial phase to the equilibrium phase. Abdominal US revealed a well-demarcated hypoechoic tumor. Preoperative diagnosis indicated appendiceal mesenchymal or neuroendocrine tumor. Ileocecal resection with D3 lymph node dissection was performed. Pathological and immunohistochemical findings confirmed the diagnosis of appendiceal schwannoma. Conclusions. For determining the surgical procedure of nonepithelial tumor of the appendix, preoperative diagnosis of mesenchymal or neuroendocrine tumors is required. However, appendiceal schwannoma is extremely rare, and its characteristic findings have not yet been established. Accumulating cases of appendiceal schwannomas is necessary for improving imaging diagnosis and surgical treatment.

Nature Communications 7 Article number: 13130 (2016); Published 12 October 2016; Updated 27 February 2017 In this Article, there are errors in the labelling of the x axis in Fig. 5g,h that were introduced during the production process. The second label on the x axis of each graph in Fig. 5g should have been ‘ΦWT’ instead of ‘ΦKO’.