Severity Grading Criteria Research Articles

Revisiting Latex-Fruit Syndrome after 30 Years of Research: A Comprehensive Literature Review and Description of Two Cases.

Thirty years have passed since the concept of latex-fruit syndrome (LFS) was first introduced. Since then, this phenomenon, characterized by cross-reactivity between natural latex rubber allergens and certain fruit allergens, has been extensively studied. This literature review sought to determine the prevalence of LFS in latex-allergic patients, identify the most common cross-reactions with fruit allergens in individuals with LFS, and understand the clinical manifestations of this syndrome. An extensive literature search was carried out using PubMed and Scopus databases, while applying the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology. The analysis of original studies revealed a wide variation in LFS prevalence (4-88%) influenced by diverse diagnostic tools, different geographical regions, and the size of study populations. Our findings indicate that the most prevalent allergenic fruits in patients with LFS are banana, avocado, kiwifruit, and papaya. After evaluating the symptoms of the fruit hypersensitivity of patients with LFS, the clinical manifestation of hypersensitivity constituted 73% of systemic allergy symptoms and only 27% of reported symptoms described the localized allergy. Furthermore, the clinical picture of latex-fruit syndrome is illustrated through two cases, one typical and one with an unusual presentation. Their clinical features were assessed and contrasted utilizing different anaphylaxis severity grading criteria. To properly manage LFS, it is essential to establish standardized diagnostic criteria and severity grading systems, as these are crucial for accurate diagnosis and effective treatment.

Diagnosing and Grading of Sinusoidal Obstructive Syndrome after Hematopoietic Stem Cell Transplant of Children, Adolescent and Young Adults treated in a Pediatric Institution with Pediatric Protocols

Sinusoidal obstructive syndrome (SOS), or veno-occlusive disease, of the liver has been recognized as a complex, life-threatening complication in the posthematopoietic stem cell transplant (HSCT) setting. The diagnostic criteria for SOS have evolved over the last several decades with a greater understanding of the underlying pathophysiology, with 2 recent diagnostic criteria introduced in 2018 (European Society of Bone Marrow Transplant [EBMT] criteria) and 2020 (Cairo criteria). We sought out to evaluate the performance characteristics in diagnosing and grading SOS in pediatric patients of the 4 different diagnostic criteria (Baltimore, Modified Seattle, EBMT, and Cairo) and severity grading systems (defined by the EBMT and Cairo criteria). Retrospective chart review of children, adolescent, and young adults who underwent conditioned autologous and allogeneic HSCT between 2017 and 2021 at a single pediatric institution. A total of 250 consecutive patients underwent at least 1 HSCT at UCSF Benioff Children's Hospital San Francisco for a total of 307 HSCT. The day 100 cumulative incidence of SOS was 12.1%, 21.1%, 28.4%, and 28.4% per the Baltimore, Modified Seattle, EBMT, and Cairo criteria, respectively (P < .001). We found that patients diagnosed with grade ≥4 SOS per the Cairo criteria were more likely to be admitted to the Pediatric Intensive Care Unit (92% versus 58%, P = .035) and intubated (85% versus 32%, P = .002) than those diagnosed with grade ≥4 per EBMT criteria. Age <3 years-old (HR 1.76, 95% [1.04 to 2.98], P = .036), an abnormal body mass index (HR 1.69, 95% [1.06 to 2.68], P = .027), and high-risk patients per our institutional guidelines (HR 1.68, 95% [1.02 to 2.76], P = .041) were significantly associated with SOS per the Cairo criteria. We demonstrate that age <3 years, abnormal body mass index, and other high-risk criteria associate strongly with subsequent SOS development. Patients with moderate to severe SOS based on Cairo severity grading system may correlate better with clinical course based on ICU admissions and intubations when compared to the EBMT severity grading system.

Nondestructive millimeter-scale void detection for thick steel-shell–concrete interface of immersed tube tunnel: case study

The structural form of sandwich-structured immersed tunnel (SSIT) can be complex. During the casting of self-compacting concrete, creating void defects between the steel shell and concrete interface is not difficult, which can adversely affect the overall safety and service life of the structure. However, detecting millimeter-scale voids covered by a thick steel plate is a technical challenge for current engineering industries. In this study, we proposed a nondestructive millimeter-scale void detection method for SSITs with thick steel shells by combining impact imaging and neutron methods. First, based on the near-source wavefield theory and count rate of thermal neutrons, the void area and depth calculation methods were derived theoretically, and then the coupling detection method and grading criteria for void severity were proposed. Additionally, the void detection performance was validated for a full-scale SSIT model test by blind detection. Finally, the proposed method was applied to the SSIT of the Shenzhen–Zhongshan bridge. The results showed that the proposed method could quantitatively determine the location and distribution pattern of a void; however, it could not accurately determine the void depth. In contrast, the neutron method could accurately calculate the void depth but had a large minimum detectable unit area. The proposed method could effectively compensate for the limitations of both methods. Statistically, the coincidence rate of the model test was 95%, 89%, and 87.5% for the void location, void area, and void depth, respectively, when the error range was ±2 mm. Using this method, 30 tubes in the Shenzhen–Zhongshan bridge were inspected, and by summarizing the void law, suggestions to improve the casting process were proposed, such as adjusting the casting speed. Meanwhile, the void probability decreased significantly. The proposed method provides an important basis for high-quality construction in SSIT projects.

Prospective Assessment of Clinical Criteria for Diagnosis and Severity of Acute Cholangitis

Background and Aims Reliable tools to diagnose and prognosticate acute cholangitis are needed to improve patient outcomes. We assessed the accuracy of two clinical criteria, Tokyo and BILE criteria, for diagnosis and severity of acute cholangitis. Methods We identified all patients from 2020 – 21 seen at our institution with suspected cholangitis, defined as having abdominal pain or fever, and abnormal liver enzymes or biliary abnormality on imaging studies. Patient medical records were reviewed and demographics, laboratory results, imaging findings, and procedure results were collected. To ascertain clinical outcomes, patients were followed until hospital discharge or for 30-days after presentation. Results During study period, 175 patients with suspected acute cholangitis were prospectively identified. Average patient age was 69.6 years, 50.3% were women, and 115 met criteria standard for diagnosis of acute cholangitis. Intensive-care admissions in 14.3%, mortality in 5.7% and 30-day readmissions in 7.4% were observed. Tokyo diagnostic criteria for definite cholangitis had higher accuracy 64%, sensitivity 69.6% and specificity of 53.3%, when compared to BILE criteria with accuracy 48.6% (p=0.005), sensitivity 42.61% and specificity 60%. Both criteria performed better in patients with choledocholithiasis (accuracy 80% and 51%) than in patients with pre-existing biliary stents (accuracy 56% and 41%). Tokyo severity grading criteria for severe cholangitis had accuracy of 67.83% and was highly predictive of in-hospital mortality and ICU admission, but not 30-day readmission. Conclusion Tokyo criteria were more accurate than BILE criteria for acute cholangitis, however neither criteria achieved high diagnostic accuracy, especially in patients with pre-existing biliary stents.

Clinical Assessment of Fetal Well-Being and Fetal Safety Indicators.

Delivering safe clinical trials of novel therapeutics is central to enable pregnant women and their babies to access medicines for better outcomes. This review describes clinical monitoring of fetal well‐being and safety. Current pregnancy surveillance includes regular antenatal checks of blood pressure and urine for signs of gestational hypertension. Fetal and placental development is assessed routinely using the first‐trimester “dating” and mid‐trimester “anomaly” ultrasound scans, but the detection of fetal anomalies can continue throughout pregnancy using targeted sonography or magnetic resonance imaging (MRI). Serial sonography can be used to assess fetal size, well‐being, and placental function. Carefully defined reproducible imaging parameters, such as the head circumference (HC), abdominal circumference (AC), and femur length (FL), are combined to calculate an estimate of the fetal weight. Doppler analysis of maternal uterine blood flow predicts placental insufficiency, which is associated with poor fetal growth. Fetal doppler analysis can indicate circulatory decompensation and fetal hypoxia, requiring delivery to be expedited. Novel ways to assess fetal well‐being and placental function using MRI, computerized cardiotocography (CTG), serum circulating fetoplacental proteins, and mRNA may improve the assessment of the safety and efficacy of maternal and fetal interventions. Progress has been made in how to define and grade clinical trial safety in pregnant women, the fetus, and neonate. A new system for improved safety monitoring for clinical trials in pregnancy, Maternal and Fetal Adverse Event Terminology (MFAET), describes 12 maternal and 18 fetal adverse event (AE) definitions and severity grading criteria developed through an international modified Delphi consensus process. This fills a vital gap in maternal and fetal translational medicine research.

Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology.

Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life-threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n=12) and fetal (n=19) AE definitions and severity grading criteria were developed and ratified by consensus. This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety.

Discordance in Appendicitis Grading and the Association with Outcomes: A Post-Hoc Analysis of an EAST Multicenter Study

The American Association for the Surgery of Trauma (AAST) appendicitis severity grading criteria use independent subscales for radiologists (Rad), surgeons (Surg), and pathologists (Path). We reviewed the EAST Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous (MUSTANG) database to determine rates of discordance and clinical consequences of inaccuracy. A confusion matrix was constructed for pairs among Rad, Surg, and Path. Accuracy was reported using chronologically latest diagnosis as gold standard. "Concordance" (C) was achieved when both agreed on the severity grade and "Discordance"(D) when they disagreed. A composite endpoint("COMP"= 30-d incidence of surgical site infection, abscess, wound complication, Clavien-Dindo complication, secondary intervention, ED[Emergency Department] visit, hospital readmission, and mortality) was compared between C versus D groups via χ2 test with Bonferroni correction to define statistical significance(P=0.05/9=0.005). For each pair and diagnosis, subjects were categorized as C or D and compared for the incidence of COMP. Incidence of COMP for Surg and/or Path in C versus D: 16% versus. 26% (p=0.006, NS by Bonferroni) for acute (A), 39% versus 33% (p=0.39) for gangrenous (G), and 48% versus 37% (p=0.035, NS by Bonferroni) for perforated (P). For Rad and/or Path in C versus. D: 17% versus 42% (p < 0.001) for A, 27% versus 31% (p=0.95) for G, and 56% versus 48% (p=0.48) for P. For C versus D: 17% versus 40% (p < 0.001) for A, 36% versus 26% (p=0.43) for G, and 51% versus 39% (p=0.29) for P. In appendicitis treated by appendectomy, surgeons are most accurate at diagnosing acute appendicitis and least accurate at diagnosing gangrenous. Radiologists are less accurate for all categories. When the surgeon is wrong, clinical outcomes are not significantly worse. However, when the radiologist is wrong about acute appendicitis, patients have worse clinical outcomes.

Study of PA-HSOS severity grading to predict the prognosis of patients with PA-HSOS treated by transjugular intrahepatic portosystemic shunt

Objective: To explore pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) severity grading to predict the prognostic value for PA-HSOS patients treated with transjugular intrahepatic portosystemic shunt (TIPS). Methods: Clinical data of patients with PA-HSOS who were critically ill or had ineffective drug treatment and underwent TIPS treatment from December 2013 to September 2019 were retrospectively analyzed. PA-HSOS severity grading criteria in adult was quoted, revised and defined from the European Group for Blood and Marrow Transplantation (EBMT). The survival time, the rate of shunt dysfunction and the incidence of postoperative hepatic encephalopathy in different severity groups after TIPS were compared. Univariate Cox or Binomial Logistic regression analysis was used to evaluate the impact of each variable. Variables with P < 0.1 were regarded as statistically significant variables for the prognosis, and were introduced into Cox or Binomial Logistic regression hierarchical regression analysis as controlled covariates. PA-HSOS severity grading was analyzed as dummy variables. Results: A total of 102 patient data were collected, and the median follow-up time was 14.52 months. The difference in survival time of patients with different severity levels was statistically significant (P = 0.023). The mortality risk in moderate patients was 1.575 times higher than that of mild patients (95%CI: 0.216-11.457, P = 0.654). The mortality risk of severe and very severe patients was 7.424 times higher than that of mild patients (95% CI: 1.612-34.197, P = 0.010). There was no statistically significant difference in postoperative hepatic encephalopathy recurrence rate and shunt dysfunction rate (P > 0.05). Conclusion: PA-HSOS severity grading has prognostic value for PA-HSOS patients receiving TIPS treatment, and can be used as an important reference for guiding the timing of TIPS intervention.

Validation of Tokyo Guidelines 2018 for Cholangitis in an Australian Cohort

Introduction: The Tokyo Guidelines 2018 (TG18) outline diagnostic and severity grading criteria for acute cholangitis, and recommends early biliary decompression. The application of TG18 to patients with cholangitis has not been validated in an Australian setting. This study evaluates the accuracy of the TG18 diagnostic criteria, the prognostic value of severity grading, and compares outcomes based on the timing of ERCP. Methods: A retrospective review of patients undergoing emergency ERCP for cholangitis in calendar years 2016-19 was performed at our hospital – we provide a high volume, surgeon-led ERCP service in Melbourne, Australia. TG18 diagnostic criteria was applied retrospectively to patients with clinically diagnosed cholangitis. TG18 severity grade, and time to ERCP, were compared with outcomes. Data was analysed using Fisher’s and T-tests. Results: 380 patients underwent ERCP for cholangitis. 301 had a clinical diagnosis of cholangitis – the TG18 diagnostic criteria demonstrated 99% diagnostic accuracy in this cohort. We also identified 79 patients who satisfied TG18 criteria but the diagnosis of 'cholangitis' was not recognised during admission – the mortality rate in this cohort was 4%, highlighting the value of a diagnostic criteria. Grade III cases had longer length-of-stay and more ICU admissions (p<0.0001). Early ERCP (<48hrs) was associated with shorter length-of-stay (p=0.0332) but on review of cases, mortality (1.8%) did not result from delay to ERCP. Conclusion: Our study demonstrates the accuracy of TG18 diagnostic criteria in an Australian population, and validates the prognostic value of its severity gradings. We report improved outcomes with early ERCP, and low cholangitis-associated mortality.EPLB005_Table 1Grading severity VS OutcomesOverallGrade I (Mild)Grade II (Moderate)Grade III (Severe)p-value (grade I vs III)p-value (GII vs III)In-hospital mortality1.8% (7/380)1.4% (1/71)0.87% (2/229)5% (4/80)0.37110.0409Hospital LOS (mean; days)8.76.6812.40.0001<0.0001ICU admission13.4% (51/380)7.0% (5/71)6.6% (15/229)38.8% (31/80)0.0001<0.0001ICU LOS (mean; days)1.02.82.74.30.36100.1008Timing to ERCP vs Outcomes, stratified by Grading severityHospital LOS (mean)Overall8.777.77.410.10.44640.0332Grade I6.65.75.85.98.10.56450.1901Grade II86.57.36.890.51930.1354Grade III12.410.110.51115.10.46100.1156 Open table in a new tab

Treatment Duration, Symptom Resolution, and Survival in Defibrotide-Treated Patients with Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation: Analysis of a Multinational, Prospective, Observational Registry Study

Treatment Duration, Symptom Resolution, and Survival in Defibrotide-Treated Patients with Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation: Analysis of a Multinational, Prospective, Observational Registry Study

41. Banff global assessment and rejection activity index severity grading criteria for T-Cell Mediated Rejection (TCMR) in liver transplantation are strongly correlated

41. Banff global assessment and rejection activity index severity grading criteria for T-Cell Mediated Rejection (TCMR) in liver transplantation are strongly correlated

Sinusoidal Obstructive Syndrome Among Pediatric and Adolescent and Young Adult Patients: Analysis of Pediatric EBMT Diagnostic and Severity Criteria at MD Anderson

Background: Sinusoidal obstructive syndrome (SOS) is a potentially catastrophic complication of stem cell transplantation (SCT) which disproportionately affects younger patients. The incidence of SOS may vary widely depending on the diagnostic criteria (Baltimore versus Seattle), and delays in initiation of definitive treatment remains the most important predictor of outcome. Recently proposed pediatric diagnostic and severity grading criteria by the European Society of Blood and Marrow Transplantation (EBMT) may offer increased sensitivity and allow for more prompt diagnosis, but the extent to which these have been adopted and/or validated by centers in the United States is unclear. Methods: This is a retrospective analysis of all patients undergoing SCT on the Pediatric service at MD Anderson Cancer Center from 2009-2019. Patient records were reviewed for diagnosis of SOS. Among patients identified with SOS, application of Baltimore, Seattle and pediatric EBMT (pEBMT) criteria were compared. Descriptive statistics were used for data analysis where appropriate. Results: A total of 248 patients received 268 transplants during the study period. Patient characteristics are summarized in Table 1. When Baltimore criteria was used the incidence of SOS was 4.5% (n=12) as compared to 8.2% (n=22) when the Seattle or pEBMT criteria were applied. At diagnosis, the majority of these patients had moderate to very severe disease according to pEBMT criteria. The median time to diagnosis of SOS varied according to diagnostic criteria used, with a trend to earlier diagnosis with pEBMT criteria (13 days post-SCT with pEBMT versus 15 days with Seattle/Baltimore) as shown in Table II. Prior exposure to inotuzumab and gemtuzumab were associated with high rates of SOS (75% and 86% respectively). Anicteric SOS, refractory thrombocytopenia and rising bilirubin from a baseline value on 3 consecutive days or bilirubin ≥2 mg/dL within 72 hours were present in 63.6%, 77.3% and 91% of patients with SOS, when pEBMT criteria were applied. Late-onset SOS (diagnosed after 21 days post-SCT) was present in 22.7% of patients when Seattle or pEBMT criteria were applied (n=5) and could not be diagnosed per Baltimore criteria. Severe SOS was eventually observed in 95% of patients. Severe ascites requiring paracentesis (23%), impaired coagulation (77%), respiratory distress requiring supplemental oxygen and/or invasive pulmonary ventilation ( 55%), delirium (32%), acute kidney injury/KDIGO Stage 3/requiring renal replacement therapy (50%) were observed. Defibrotide treatment was initiated in 55% of patients with a median duration of treatment of 26 (3-74) days and complete resolution of SOS was observed in 42% of these patients. For patients who were initiated on defibrotide on the day of diagnosis (n=7) versus those who were not (range 1-11 days) the median time to complete resolution of SOS was 35 and 20 days respectively (p=0.2). Conclusions: To our knowledge, this is the first reported retrospective analysis of SOS among pediatric and adolescent young adult SCT patients in the United States using pEBMT SOS diagnostic and severity criteria. Our study was limited by small sample size associated with single center analyses. Use of the pEBMT criteria showed a trend to earlier time to diagnosis by a median of two days. This is a potentially clinically significant finding, as a delay in initiation of defibrotide among children with severe SOS, has been associated with statistically significant decreased rates of complete resolution. Inherent flaws of the Baltimore and Seattle criteria are the time restriction and reliance of hyperbilirubinemia for the diagnosis in children and adolescents and young adults. Our retrospective analysis suggests that pEBMT criteria for the diagnosis of SOS among children and young adults may be appropriate, especially given the rates of anicteric and late-onset SOS seen in this population. Disclosures Petropoulos: Foundation for the Accreditation of Cellular Therapy (FACT): Membership on an entity's Board of Directors or advisory committees, Other: Foundation for the Accreditation of Cellular Therapy (FACT). Kebriaei:Amgen: Research Funding; Jazz: Consultancy; Pfizer: Honoraria; Kite: Honoraria. Wierda:Xencor: Research Funding; Janssen: Research Funding; Loxo Oncology Inc.: Research Funding; KITE pharma: Research Funding; Juno Therapeutics: Research Funding; Gilead Sciences: Research Funding; Acerta Pharma Inc: Research Funding; Pharmacyclics LLC: Research Funding; Genentech: Research Funding; GSK/Novartis: Research Funding; AbbVie: Research Funding; Cyclcel: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Miragen: Research Funding; Sunesis: Research Funding. Mahadeo:Recipient of unrestricted medical education grant from Jazz: Research Funding; PI for ATARA EBV CTL Trials: Other: Other .

Standardizing Safety Assessment and Reporting for Neonatal Clinical Trials

Standardizing Safety Assessment and Reporting for Neonatal Clinical Trials

The importance of early intervention in the treatment of hepatic veno-occlusive disease.

Antonio Pagliuca is Professor of hematopoietic stem cell transplantation at King’s College London (UK) and medical director at King’s College Hospital where, until last year, he had been the transplant director for the past 24 years. He also has roles within NHS England as national clinical lead for regenerative medicine and is a trustee on both the Anthony Nolan trust (London, UK) and Leukemia UK (London, UK).Here he speaks to Commissioning Editor Jennifer Straiton and discusses the interim results of the DEFIFrance study, recently presented at the European Society for Blood and Marrow Transplant (EBMT), which looked at the real-world use of the European Society for Blood and Marrow Transplant severity grading criteria. The study investigates the use of defibrotide as a treatment of patients with post-transplant hepatic veno-occlusive disease and demonstrates how it can benefit from early intervention.

Correlation of magnetic resonance imaging grades with cytokine levels of synovial fluid of patients with temporomandibular joint disorders: a cross-sectional study

Magnetic resonance imaging (MRI) is a standardized method for assisting joint diagnosis. To validate the reliability of different imaging-based grading systems, this study examined (1) the associations between grading systems for osseous change, joint effusion, and the Wilkes classification of temporomandibular joint (TMJ) disorders and (2) the correlation between cytokines in synovial fluid and imaging-based joint scores. Twenty-seven patients, who routinely received numeric rating scale (NRS) and MRI assessment before TMJ arthrocentesis, were enrolled. Each joint was evaluated through the grading criteria for severity of osseous change and joint effusion by blinded observers using MRI. ImageJ was employed for classifying joint effusion. Joint synovial fluid, collected through arthrocentesis, was examined for cytokine expression by using a Luminex multiplex assay. All data were analyzed using the Pearson correlation analysis. The Wilkes classification was strongly correlated with osseous change scores, but not with joint effusion scores. Joint effusion scores significantly correlated with NRS scores, but not with the Wilkes classification and osseous change scores. Compared with osseous change scores, joint effusion scores had a higher correlation with the levels of inflammatory cytokines (interleukin (IL)-8 and soluble IL-6 receptor (sIL-6R)) and with anti-inflammatory cytokines (soluble tumor necrosis factor receptors I and II (sTNF-RI/II)). In patients with TMJ disorders, MRI grades are strongly correlated with NRS scores and levels of cytokines (IL-8, sIL-6R, and sTNF-RI/II) in the synovial fluid. Joint effusion scoring can be a reliable and valid indicator for pathological assessment of TMJ disorders.

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos)

Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large-scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30-day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30-day mortality among patients with Grade I or Grade III AC, but significantly lower 30-day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Clinical application and verification of the TG13 diagnostic and severity grading criteria for acute cholangitis: an international multicenter observational study.

The Tokyo Guidelines 2007 (TG07) first presented the diagnostic and severity grading criteria for acute cholangitis. Subsequently updated in 2013, the Tokyo Guidelines (TG13) have been widely adopted throughout the world as global standard guidelines. We set out to verify the efficacy of these TG13 criteria in an international multicenter study. We reviewed 6,063 patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan over a 2-year period. The TG13 diagnostic and severity grading criteria were retrospectively applied, and 30-day mortality was investigated. A diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07 criteria. The 30-day mortality rates of patients with Grade III, Grade II, and Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly along with disease severity. The mortality rate in the 1,272 Grade II cases where urgent or early biliary drainage was performed was 2.0% (n = 25), which was significantly lower than that of 3.7% (n = 28) in the other 748 cases. By using the TG13 diagnostic and severity grading criteria, more patients with possible acute cholangitis can be diagnosed, and patients whose prognosis can potentially be improved by early biliary drainage can be identified. The TG13 criteria are appropriate and useful for clinical practice.

Validation of TG13 severity grading in acute cholecystitis: Japan-Taiwan collaborative study for acute cholecystitis.

The collaborative multicenter retrospective study of acute cholecystitis (AC) was performed in Japan and Taiwan. The aim for this study was evaluation of the clinical value of TG13 severity grading for AC. The study was designed as an international multicenter retrospective study of AC from 2011 to 2013. Based on the data, we investigated the TG13 severity grading by analyzing the correlations between grade and prognosis, surgical procedures, histopathology, and organ dysfunction and prognosis. An investigation revealed that 30-day overall mortality rate was 1.1% for Grade I, 0.8% for Grade II, 5.4% for Grade III. The mortality rate for Grade III was significantly higher than lower grades (P<0.001). The greater the number of organ dysfunction, the higher the mortality rate (P<0.001). However, the mortality rate varied depending on the number of organ dysfunction (3.1-25%). With respect to the surgical procedures, laparoscopic cholecystectomy was performed for Grade I patients (P<0.001), and the higher the grade, the more likely open surgery would be selected (P<0.001). TG13 severity grading criteria for AC are providing great benefits in actual clinical settings. From this study, the position of each severity grade was obviously confirmed.

OP21.01: Developing standard maternal and fetal adverse event severity grading criteria: building a framework for obstetric and fetal therapy trials

OP21.01: Developing standard maternal and fetal adverse event severity grading criteria: building a framework for obstetric and fetal therapy trials

Clinical and bacteriological evaluation of adapalene 0.1% gel plus nadifloxacin 1% cream versus adapalene 0.1% gel in patients with acne vulgaris

This multicenter, randomized parallel group study investigated the efficacy and tolerability of adapalene 0.1% gel plus nadifloxacin 1% cream (combination therapy) compared with adapalene gel (monotherapy) during 12-week treatment of acne vulgaris. A total of 184 Japanese patients aged above 12years with moderate to severe acne as indicated by the Japanese severity grading criteria were randomized to combination therapy (n=84) and monotherapy (n=100) groups, both having comparable demographic and baseline characteristics. Adapalene was applied only to inflammatory acne lesions in order to minimize skin irritation and ensure the treatment results. Efficacy and safety evaluations, treatment compliance and satisfaction with drug application were periodically monitored. The combination therapy provided a significantly greater efficacy than adapalene in decrement of inflammatory papulopustular lesions at 4weeks and thereafter (P=0.0056). The overall judgment of the therapeutic efficacy by the physician at the end of study revealed a significant difference (P=0.02496) between the groups in favor of combination therapy. Dryness was reported in a greater proportion of patients undergoing monotherapy than combination therapy at weeks 2 and 4 (P=0.04652). The patient self-assessment in satisfaction with the drug application at the end of study revealed a significant difference (P=0.00268) between the groups in favor of combination therapy. Among 76 strains of Propionibacterium acnes isolated from 87 patients, no strain was resistant to nadifloxacin. Thus, the simultaneous use of adapalene and nadifloxacin may provide an additive and complementary effect, resulting in clinical superiority and greater patient adherence compared to adapalene monotherapy.