Supplementary Material for: Risk Factors and Clinical Features in Cashew Nut Oral Food Challenges

<p><b><i>Background:</i></b> Cashew nuts (CN) are capable of causing severe allergic reactions. However, little has been reported about the details of CN oral food challenges (OFC). <b><i>Methods:</i></b> CN-specific IgE (sIgE) levels were measured for 1 year in 66 patients who underwent an OFC with >3 g CN for diagnosis or confirmation of tolerance acquisition between June 2006 and August 2014. We retrospectively analyzed the OFC and patient background. <b><i>Results:</i></b> The median (IQR) age of the 66 patients (48 boys/men and 18 girls/women) was 7.0 years (5.7-8.8). Twelve patients (18.2%) had a positive OFC result; 6 of 8 (75%) patients with a history of an immediate reaction to CN failed the OFC. Anaphylaxis was experienced by 5 of these 12 (42%) patients. A history of an immediate reaction to CN and the CN sIgE levels were significantly different for patients with a positive or negative OFC result (<i>p</i> < 0.01). Among patients without a previous immediate reaction to CN, the 95% positive predictive value (PPV) for the CN sIgE level for a positive OFC result was 66.1 kU_A/L. <b><i>Conclusions:</i></b> A history of an immediate reaction to CN and high CN sIgE were risk factors for a positive OFC result. The number of positive OFC results was relatively low, but there was a high probability of anaphylaxis. We should consider the indication of OFC carefully for patients with a history of immediate reactions to CN and avoid OFC for patients without such a history whose CN sIgE values are >66.1 kU_A/L (95% PPV).</p

Supplementary Material for: Assessment of Bronchial Obstruction Using Lateral Pressure Measurement during Bronchoscopy

<b><i>Background:</i></b> In patients with bronchial obstruction estimating the location of the maximal obstruction is crucial for guiding interventional bronchoscopy. However, flow-volume curves cannot discriminate between the right and left lungs. <b><i>Objectives:</i></b> The aim of this study was to physiologically evaluate bronchial obstruction during interventional bronchoscopy. <b><i>Methods:</i></b> We prospectively measured lateral airway pressure (P_lat) at either side of the obstruction using a double-lumen catheter (pressure-pressure [P-P] curve) simultaneously to assess the degree of bronchial obstruction in 22 patients. The shape of the P-P curve was assessed to confirm the site of maximal obstruction. <b><i>Results:</i></b> In the experimental study, P_lat was uniform between both bronchi in the normal model. For the unilateral and bilateral obstruction models, a phase shift was only seen for the more obstructed side. In healthy subjects, the angle of the P-P curve was close to 45° and linear in shape. In patients with bronchial obstruction, the angle was much smaller but approached 45° after the bronchoscopic procedure. The degree of bronchial obstruction was significantly correlated with the angle of the P-P curve (<i>r</i> = –0.51, <i>p</i> < 0.01). Dyspnea significantly increased when the airway lumen was obstructed by more than 60% (<i>p</i> < 0.0001), and when the P-P curve appeared loop-shaped (<i>p</i> < 0.01). <b><i>Conclusions:</i></b> The shape of the P-P curve could be used to detect the site of maximal obstruction for the optimal positioning of the stent and assess the need for additional procedures in real time in patients with<i></i> bronchial obstruction

Supplementary Material for: The cancer cachexia index can be used to prognostically predict patients with gastric cancer undergoing gastrectomy

Objective. Cancer cachexia occurs in cancer patients more frequently as the cancer progresses, with a negative impact on treatment outcomes. In this study, we sought to clarify the clinical impact of a cancer cachexia index CXI in patients with gastric cancer (GC) undergoing gastrectomy. Methods. Between January 2013 and December 2018, we reviewed data from 556 patients treated for GC at our hospital. CXI was calculated using skeletal muscle index (SMI), serum albumin, and neutrophil-lymphocyte ratios (NLR). Patients were divided into high (n=414) or low CXI (n=142) groups. We investigated the clinical impact of CXI in patients with GC undergoing gastrectomy. Results. Multivariate analyses of 5-year overall survival (OS) and cancer specific survival (CSS) rates indicated that a low CXI was independently associated with unfavorable outcomes for patients with GC. In multivariate analyses, SMI was independent predictor of OS but not CSS. NLR was not an independent predictor of either OS or CSS. Complication incidences [≥ Clavien Dindo (CD) 3] were non-significantly higher in the low (vs. high) CXI group. Conclusion. CXI was a more valuable prognostic biomarker when compared with SMI or NLR in GC patients undergoing gastrectomy. We suggest that patients with low CXI values should be given more comprehensive treatment, including exercise and nutritional therapy to improve clinical outcomes

Supplementary Material for: Narrow Band Imaging with Magnifying Endoscopy for Peyer's Patches in Patients with Inflammatory Bowel Disease

<b><i>Background/Aims:</i></b> Peyer's patches (PPs) play a major role in mucosal immunity, but little is known about their alterations in patients with inflammatory bowel disease (IBD). We aimed to evaluate endoscopic changes of PPs in IBD patients using narrow band imaging with magnifying endoscopy (NBI-ME). <b><i>Methods:</i></b> Images of PPs using NBI-ME by ileocolonoscopy were consecutively collected. Existence of branch-like structures and the vessel occupancy in the dome lesions of PPs were analyzed. Appearance of the surrounding villi of the domes in PPs was evaluated using a ‘villi index' consisting of irregular formation, hyperemia, and altered vascular network pattern. Vascularity of PPs was immunohistologically analyzed by anti-CD34 antibody. <b><i>Results:</i></b> 17 patients with Crohn's disease (CD), 43 with ulcerative colitis (UC), and 23 healthy control subjects (HC) were analyzed. Both CD and UC patients had a high prevalence of having branch-like structures and significantly higher vascularity in the dome lesions than HC. The villi indices and vascular widths in the villi were significantly larger in CD and UC patients than in HC. <b><i>Conclusions:</i></b> Precise examination with NBI-ME characterized alteration of vascular structure in the dome and surrounding villi lesions of PPs not only in CD but also in UC patients

Supplementary Material for: Social Anxiety/Taijin-Kyofu Scale (SATS): Development and Psychometric Evaluation of a New Instrument

<i>Background:</i> Taijin-kyofu (TK), especially the ‘convinced' subtype of TK (c-TK; also known as the ‘offensive' subtype of TK), is described as a Japanese culture-bound syndrome similar to social anxiety disorder (SAD). Recently, in Western countries, the symptoms of c-TK have been investigated in patients with SAD. We developed the Social Anxiety/Taijin-Kyofu Scale (SATS), a 12-item structured clinician-rated instrument designed to rate the severity of TK symptoms, and examined its reliability and validity. <i>Methods:</i> The SATS was administered to 15 patients with c-TK diagnosed using the traditional Japanese TK criteria. Interviews used to score patients' symptoms were recorded on videotape. Additionally, the Clinical Global Impression-Severity Scale (CGI-S) was administered to assess convergent validity. Interrater reliability was assessed on 15 videotaped interviews; the interviews were independently rated by 10 other raters. Test-retest re-liability was assessed on 15 videotaped interviews by the same rater at an interval of more than 4 weeks. <i>Results:</i> The SATS had high internal consistency (Cronbach's α = 0.97) and good interrater reliability (ICC = 0.88-0.93) and test-retest reliability (ICC = 0.94-0.99). The SATS total score correlated with the CGI-S scores (r = 0.77, p < 0.0001). <i>Conclusion:</i> The SATS appears to be a reliable and valid measure of the symptoms of TK

Supplementary Material for: Duration of Stable Disease Is Associated with Overall Survival in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

<b><i>Background:</i></b> Sorafenib is a molecular-targeting agent showing improved overall survival (OS) for advanced hepatocellular carcinoma (HCC). Although tumor dormancy, characterized by stable tumor status or stable disease (SD) without tumor regression, is a unique feature of sorafenib treatment, the contribution of SD to OS remains debatable. This study aimed to clarify the correlation between SD periods and OS in patients with HCC treated with sorafenib. <b><i>Methods:</i></b> From May 2009 to January 2013, 269 patients with advanced-stage HCC were treated with sorafenib at the Kinki University Hospital. The antitumor response of sorafenib was evaluated in 158 patients using the modified Response Evaluation Criteria in Solid Tumors, and patients with SD were divided into two subgroups according to the median duration of SD: short SD (<3 months) and long SD (≥3 months). The relationship between the duration of SD and OS was analyzed among patients with complete (CR) and partial response (PR), and long and short SD using the Kaplan-Meier method. <b><i>Results:</i></b> The median OS was 5.7 months in the short SD, 20.8 months in the long SD and 17.9 months in the CR + PR group. Although the duration of OS was significantly longer in the long SD group than the short SD group, no difference in OS was detected between the patients with CR + PR and patients with long SD. The impact of long SD on OS could be as strong as that of CR + PR. <b><i>Conclusion:</i></b> Achievement of long SD is one of the important goals for improving survival in patients with HCC treated with sorafenib

Supplementary Material for: Decreased Blood Flow after Sorafenib Administration Is an Imaging Biomarker to Predict Overall Survival in Patients with Advanced Hepatocellular Carcinoma

<b><i>Background:</i></b> Sorafenib is a multikinase inhibitor targeting Raf and protein tyrosine kinases, which are involved in cell growth and tumor angiogenesis. Sorafenib administration induces temporary inhibition of tumor growth and a decrease in arterial blood flow in a considerable number of hepatocellular carcinoma (HCC) patients. We retrospectively evaluated the association between decreased blood flow and the overall survival (OS) of HCC patients after the initiation of sorafenib therapy. <b><i>Patients and Methods:</i></b> Therapeutic responses of 158 advanced HCC patients with hypervascular tumors who had received sorafenib for more than 1 month were analyzed. To assess their therapeutic response, patients underwent radiological evaluation before and every 4-6 weeks after the initiation of sorafenib treatment. After the classification of patients into three groups based on the change in arterial enhancement during treatment (no change, decrease and disappearance), the OS of each group was compared using the Kaplan-Meier method. <b><i>Results:</i></b> Statistically significant differences in OS were observed among the three groups (p < 0.001). A decrease or disappearance of arterial enhancement was significantly associated with improved OS compared to patients with no change in arterial enhancement; the median OS was 19.9 months (95% confidence interval, CI, 16.4-24.5 months) and 6.0 months (95% CI, 4.0-8.8 months), respectively (p < 0.001). However, there was no difference in OS between the decrease and disappearance groups (p = 0.88). <b><i>Conclusion:</i></b> We conclude that decreased arterial enhancement during sorafenib treatment was associated with the longest OS and could therefore reflect an effective response

Supplementary Material for: Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy

<p><b><i>Objective:</i></b> The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with muscle-invasive bladder cancer (MIBC) undergoing curative radical cystectomy (RC). <b><i>Methods:</i></b> The analysis enrolled 117 patients and the variables included age, body mass index (BMI), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), Controlling Nutritional Status score, psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables were evaluated and their prognostic values after RC were tested. <b><i>Results:</i></b> Three inflammation markers (ratios of blood cell counts) were positively correlated (<i>p</i> < 0.0001). The PNI and the BMI were positively correlated (<i>p</i> = 0.04), although they were inversely correlated with the three inflammation markers (<i>p</i> < 0.0001). Age was not significantly correlated with the inflammation markers and PMI, although older age was associated with lower PNI and lower PEF. The disease-specific survival was independently predicted by T4 tumor, positive N status, and decreased PNI. Overall survival was independently predicted by T4 tumor, mGPS, and pretreatment sarcopenia status. <b><i>Conclusions:</i></b> The inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for MIBC.</p

Supplementary Material for: Endoscopic features of synchronous multiple early gastric cancers: Findings from a nationwide cohort

Introduction: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. Methods: We analyzed 8191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n=7221) and synchronous multi-lesion cases (n=970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n=832) and evaluated their localization. Results: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (OR=1.257), male sex (OR=1.385), severe mucosal atrophy (OR=1.400), tumor localization in the middle (OR=1.362) or lower region (OR=1.404), and submucosal invasion (OR=1.528 (SM1), 1.488 (SM2)). Depressed macroscopic type (OR=0.679) and pure undifferentiated histology OR=0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. Conclusion: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected