Nationwide Multicenter Study Research Articles

Prognostic value of preoperative protein induced vitamin K absence or antagonist II after hepatectomy for hepatitis B related hepatocellular carcinoma: Nationwide multicenter study

The prognostic value of PIVKA-II has been insufficiently elucidated. This study is aimed to determine the prognostic value of preoperative serum PIVKA-II after hepatectomy for hepatitis B related HCC. The nationwide multicenter database of the Korean Liver Cancer Association was reviewed. Patients with hepatitis B related HCC who underwent liver resection as a first treatment after initial diagnosis between 2008 and 2014 were selected. Comparative analysis between low versus high PIVKA-II was performed. Survival outcomes of propensity score-matched groups were compared. Kaplan-Meier and multivariable analyses were performed to identify risk factors for disease-specific survival. Univariable and multivariable Cox proportional hazards regression were used. Among 6,770 randomly selected patients with hepatitis B related HCC, 987 patients were included. The disease-specific 5-year survival rate was 84.6% in patients with PIVKA-II of 106.5 mAU/mL or less compared with 76.3% for those with a level exceeding 106.5 mAU/mL (p = 0.041). After propensity score matching, the two groups were well balanced (n = 263, each). In univariable analysis, high PIVKA-II (> 106.5 mAU/mL) was a significant predictor for worse survival (hazard ratio [HR], 1.527; p = 0.047). In multivariable analysis, lymph node positivity (HR, 6.123; p = 0.023), hyponatremia (< 135 mEq/L) (HR, 4.187; p = 0.002), tumor size ≥ 5.0 cm (HR, 3.399; p < 0.001), preoperative ascites (HR, 3.874; p = 0.001), microvascular invasion (HR, 2.639; p = 0.001), thrombocytopenia (< 100 × 103/µL) (HR, 2.620; p = 0.001), and multiple HCC (HR, 2.068; p = 0.007) were independent predictors for worse disease-specific survival, but not preoperative high PIVKA-II. Preoperative high PIVKA-II is significantly associated with worse disease-specific survival after hepatectomy for hepatitis B related HCC, nonetheless, not a strong prognostic factor.

Myocardial involvement in idiopathic inflammatory myopathies: a multi-center cross-sectional study in the CRDC-MYO Registry.

This study aimed to investigate the associated factors of myocardial involvements (MIs) in patients with idiopathic inflammatory myopathies (IIMs). In this multi-center cross-sectional study, 1946 patients with IIMs were enrolled from Chinese Rheumatism Data Center-Myositis Registry (CRDC-MYO). A total of 108 (5.5%) patients were identified with MIs, including congestive heart failure (n = 67, 62.0%), and severe arrhythmias (n = 61, 56.5%). The other 1838 IIM patients without IMs were set as the control group. Clinical features were collected including age, gender, comorbidities, clinical symptoms, clinical signs of both IIMs and MIs, lab findings including myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs), echocardiogram, and radiological exams. Multivariate logistic analysis was used to explore independent associated factors of MIs in patients with IIMs. Several independent associated factors were identified in multi-variate logistic regression, including positivity for anti-mitochondrial antibody-subtype 2 (AMA-M2) (OR 5.194, 95% CI 2.509-10.753, P < 0.001), elevation of creatine kinase (CK) (OR 2.611, 95% CI 1.312-5.198, P = 0.006), elevation of C-reactive protein (CRP) (OR 2.150, 95% CI 1.211-3.818, P = 0.001), and pulmonary hypertension (OR 4.165, 95% CI 1.765-9.882, P = 0.009). AMA-M2 and pulmonary hypertension were the most consistent associated factors in the polymyositis subgroup and the dermatomyositis/clinically amyopathic dermatomyositis subgroup. MIs are rare but serious complication of IIMs could lead to congestive heart failure and severe arrhythmias. IIM patients with AMA-M2 positivity, elevation of CK and CRP, and pulmonary hypertension are more likely to develop MI complications. Key Points • This study investigated the independent associated factors for clinically significant myocardial involvements among idiopathic inflammatory myopathies in a large-scale, nation-wide multi-center cross-sectional study.

Baseline Assessment of Patients with Newly-Diagnosed Acquired Bone Marrow Failure Enrolled in a Prospective Observational Study, “Search for Unidentified Links between PNH Clone Size and the Related Clinical Manifestations By High Precision Flow Cytometry (SUPREMACY)”

Baseline Assessment of Patients with Newly-Diagnosed Acquired Bone Marrow Failure Enrolled in a Prospective Observational Study, “Search for Unidentified Links between PNH Clone Size and the Related Clinical Manifestations By High Precision Flow Cytometry (SUPREMACY)”

Comorbidities and treatment patterns in adult patients with atopic dermatitis: results from a nationwide multicenter study

Adult atopic dermatitis (adult AD) is a systemic inflammatory disorder, whose relationship with immune-allergic and metabolic comorbidities is not well established yet. Moreover, treatment of mild-to-moderate and severe atopic dermatitis needs standardization among clinicians. The aim of this study was to evaluate the distribution of comorbidities, including metabolic abnormalities, rhinitis, conjunctivitis, asthma, alopecia and sleep disturbance, according to severity of adult AD, and describe treatments most commonly used by Italian dermatologists. Retrospective, observational, nationwide study of adult patients over a 2-year period was performed. Clinical and laboratory data were obtained through review of medical records of patients aged ≥ 18 years, followed in 23 Italian National reference centres for atopic dermatitis between September 2016 and September 2018. The main measurements evaluated were disease severity, atopic and metabolic comorbidities, treatment type and duration. Six-hundred and eighty-four adult patients with AD were included into the study. Atopic, but not metabolic conditions, except for hypertension, were significantly associated with having moderate-to-severe AD in young adult patients. Disease duration was significantly associated with disease severity. Oral corticosteroids and cyclosporine were the most widely used immunosuppressant. Our study seems confirm the close relationship between adult AD and other atopic conditions, further long-term cohort studies on patients affected by adult AD need to be performed to evaluate the complex relationship between adult AD disease severity and metabolic comorbidities.

Validation of MALDI-TOF for the early detection of the ST175 high-risk clone of Pseudomonas aeruginosa in clinical isolates belonging to a Spanish nationwide multicenter study

IntroductionPseudomonas aeruginosa causes severe infections, particularly in healthcare settings and immunocompromised patients in whom MDR and XDR isolates are more prevalent. The aim of this study is to validate a method based on MALDI-TOF spectra analysis for early detection of the ST175 high-risk clone (HRC). MethodsThe MALDI-TOF spectra of the first 10 P. aeruginosa clinical isolates from each of the 51 participating Spanish hospitals were analyzed (n=506). Resistance profiles were determined by broth microdilution, and clonal epidemiology was assessed by PFGE analysis and multilocus sequence typing (MLST) in a previous study. ResultsAmong all the isolates, 14.2% were XDR and 26.9% were non-susceptible to meropenem, while rates of resistance to ceftolozane/tazobactam (3.6%) and colistin (5.7%) were low. Up to 41.7% of all XDR isolates belonged to the ST175 clone, and most of them were only susceptible to ceftolozane/tazobactam and colistin. However, most of the resistance to ceftolozane/tazobactam among isolates belonging to this HRC was observed in carbapenemase-producing isolates. A model based on the presence of two MALDI-TOF biomarker peaks at m/z 6911 and 7359 yielded a negative predictive value (NPV) and a positive predictive value (PPV) of 99.8% and 91.9%, respectively, and sensitivity and specificity values of 97.1% and 99.4%, respectively. ConclusionsMALDI-TOF spectra analysis using a model based on the presence of two biomarker peaks proved to maintain high sensitivity and specificity for early detection of the ST175 HRC in a large collection of isolates from all Spanish regions. These data support the use of this model in a clinical setting; however, the consequences of detection of the ST175 HRC, such as choice of empirical antibiotic therapy, must be consistent with local epidemiology and the prevalence of certain resistance patterns of this HRC, such as carbapenemase production, in a given geographical area.

1017-P: Association between Death at Day 28 and Components of Microvascular Disease of with Diabetes Hospitalized for Coronavirus Disease-2019 (COVID-19): The CORONADO Study

The prognostic role of microvascular complications (MVC) for all-cause death in patients with diabetes hospitalized for COVID-19 has been suggested. However, no detailed analysis of the microvascular burden is available so far. The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalized for COVID-19. The patients were enrolled after hospital admission from 03/10/2020 to 04/10/2020. MVC were defined as severe diabetic retinopathy (DR) and/or diabetic kidney disease (DKD, eGFR 300mg/g) and/or diabetic foot ulcer (DFU). We analysed the association of MVC with death within 28 days after admission. The status for all 3 MVC was ascertained for 1755 participants including 1048 (60%) free of MVC. Patients with MVC were older, had lower BMI, HbA1c, AST/ALT concentration, lymphocyte and platelet counts, while sex, type of diabetes and CRP were not significantly different. Patients with any MVC had a sex- and age-adjusted OR for death of 2.54 (95%CI: 1.94-3.31, P Disclosure P. Saulnier: None. S. Hadjadj: Advisory Panel; Self; Valbiotis, Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi. L. Kessler: None. M. Marre: Board Member; Self; Merck Sharp & Dohme Corp., Consultant; Self; Novo Nordisk. J. Halimi: None. M. Wargny: None. P. Gourdy: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Research Support; Self; Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Sanofi. B. Cariou: Board Member; Self; Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Sanofi, Research Support; Self; Amgen Inc., AstraZeneca, Regeneron Pharmaceuticals Inc., Speaker’s Bureau; Self; Abbott Diabetes, Akcea Therapeutics. For the coronado study group: n/a.

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett\u2019s esophagus-related neoplasms: a nationwide multicenter study

BackgroundCurrently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett’s esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society—Barrett’s esophagus working group (JES-BE) for superficial Barrett’s esophagus-related neoplasms.MethodsThe JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter.ResultsThe sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found.ConclusionThe JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician’s experience level.

P276 Influence of vedolizumab on extraintestinal manifestations in Inflammatory Bowel Disease: a nationwide multicenter study of the GETECCU Eneida registry

Abstract Background Evidence regarding vedolizumab (VDZ) influence on extraintestinal manifestations (EIMs) in inflammatory bowel disease patients (IBD) is scarce. Our aim was to analyze the effectiveness of VDZ in pre-existing EIMs and the occurrence of de novo EIMs during VDZ therapy in IBD. Methods We performed an observational, multicenter, retrospective cohort study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified 551 patients from 20 centers. The co-primary outcomes were to evaluate the response of EIMs to VDZ and to assess the frequency of de novo EIMs during therapy. Secondary outcomes were to analyze associated factors with EIMs response to VDZ, time from VDZ initiation to occurrence of de novo EIMs and the discontinuation rate of VDZ because of worsening/de novo EIMs. Response and worsening of IBD and EIMs were defined by clinical and laboratory criteria according to the physician’s assessment. Results The median age of the cohort was 49.7 years (IQR 38-60), 50.8% were female, 50.8% had Crohn’s disease and 90.4% had prior biologic exposure (more than 1 biologic drug in 57.9%). At baseline 133 patients (24.1%) had pre-existing EIMs of whom 21 showed more than 1 EIM; 76.7% of EIMs were articular and 31% cutaneous. Regarding 77 patients with active EIMs at baseline, response of EIMs to VDZ at 3 months was observed in 23 (29.9%), worsening in 13 (16.9%) and no change in 41 (53.2%). Response rates for active EIMs were 35.4% for peripheral arthritis (PA), 11.8% for axial arthropathy (AA), 35.7% for cutaneous EIMs and 33.3% for ocular EIMs. Response of IBD at 3 months was the only associated factor with response of EIMs to VDZ (OR=3.72; CI 95% [1.08-12.83]). Among 56 patients with inactive EIMs at baseline, worsening of EIMs was observed in 5 patients after 12 months of VDZ therapy (13.5%) (3 cases of PA and 2 of AA). During follow-up 25 patients (4.5%) developed 27 de novo EIMs (17 cases of PA, 4 of AA, 4 of erythema nodosum, 1 of pyoderma gangrenosum and 1 of episcleritis). Median time from VDZ initiation to onset of de novo EIMs was 244 days (IQR 115-693). Presence of more than 1 pre-existing EIM was the only associated factor with de novo EIM onset during first year of VDZ therapy (OR=14.5; 95% CI [3.3-62]). Worsening of pre-existing EIMs or de novo EIMs was the cause of VDZ discontinuation in 15 patients (5.8% of all patients who discontinued VDZ). Conclusion VDZ achieved clinical response of active EIMs in nearly a third of patients after 3 months of therapy, being the response of IBD to VDZ the only associated factor. Worsening of inactive EIMs or de novo EIMs during VDZ therapy was infrequent.

P183 Risk of eating disorders in italian children and adolescents with Inflammatory Bowel Disease: results of a multicenter nationwide study

Abstract Background The prevalence and risk of Eating Disorders (ED) in IBD, despite the potential overlap of these two conditions, have been rarely reported. ED diagnosis should be considered in patients with IBD and multidisciplinary approach would be recommended in these complex cases to provide an adequate therapeutic intervention. Screening tools to evaluate eating attitudes and behaviours in patients with IBD could be used in daily practice, as for example the Eating Attitude Test – 26 Methods Children and adolescents (8–18 years) with IBD and age and gender matched healthy controls were prospectively enrolled in 5 italian pediatric IBD units between June 2019 and August 2020. Subjects with an existing diagnosis of ED were excluded. The risk of ED was assessed using a 26 points Likert scale screening tool (CH-EAT-26 and EAT-26 for children &amp;lt; and &amp;gt; 14 years respectively), with a total score of 20 or above indicating a risk for ED. Correlations between clinical and disease’s parameters and the CH-EAT-26/EAT-26 score were calculated Results 110 patients with IBD and 110 age and matched healthy controls were screened with the CH-EAT26/EAT-26 questionnaire. The total EAT26 scores and the prevalence of an at-risk score (score&amp;gt;20) did not differ in IBD subjects compared to controls. IBD patients were more frequently on an exclusion diet with lactose free-diet being the most common regimen. Furthermore, 8.1% of IBD children was on a partial enteral nutrition (PEN). In IBD subjects elevated scores on the Ch-EAT26/EAT-26 were associated with being younger (r=-0,2226, p=0.002), following an exclusion diet (r=0.25, p=0.009) and a partial enteral nutrition (PEN: r=0,2507, p=0.009). Type, duration and activity of disease, gender, weight, height and BMI z-scores were not significantly correlated to the CHEAT26/EAT-26 score. Being on a PEN and following an exclusion diet were the only independents factors influencing the EAT26 score at the multiple regression analysis (p= 0,004; p= 0,034; R2 = 0,25) Conclusion Our results indicate that 5.45% of IBD children have a behavior at risk for developing an ED, a percentage that is not statistically different compared to healthy controls. A particular follow-up should be reserved to patients on restricted diets and on partial enteral nutrition, that can develop maladaptive attitudes toward eating. The development of a disease specific tool or a validation of pre-existing questionnaires would help to identify a robust screening instrument and ultimately to correctly classify the risk of patients. Once the risk is correctly assessed it is mandatory to address the patient to a specific multidisciplinary follow-up.

The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study.

Simple SummaryThe first-line systemic therapy for advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab therapy in many guidelines for HCC, however, there are no established therapeutic strategies in patients with intermediate stage and beyond the combination therapy. The aim of our retrospective study was to assess the real-world efficacy and safety of lenvatinib in Japanese patients with unresectable hepatocellular carcinoma. The results including median OS and PFS according to Barcelona Clinic Liver Cancer (BCLC) stage, liver function, and treatment history would be useful for making treatment strategies for patients with intermediate and beyond the combination therapy.Background: Lenvatinib (LEN) has been approved for patients with unresectable hepatocellular carcinoma (u-HCC) since March 2018 in Japan. We performed a retrospective nationwide multicenter study to clarify the clinical characteristics of LEN in real-world practice. Methods: A total of 343 u-HCC patients who received LEN from March 2018 to May 2020 at 23 sites in Japan were registered. Results: During the median observation period of 10.5 months, 143 patients died. In Child-Pugh A (n = 276) and Child-Pugh B (n = 67) patients, the median overall survival (OS) was 21.0 and 9.0 months. The median progression-free survival (PFS) was 8.8 months in Child-Pugh A patients. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors (RECIST criteria) were 42.1% and 82.1%. The independent pretreatment factors associated with mortality in all patients were AFP ≥ 400 ng/mL (hazard ratio (HR) 2.00, 95% confidential interval (95% CI) 1.08–2.09, p < 0.0001), modified albumin-bilirubin (ALBI) grade 2b or 3 (HR 1.56, 95% CI 1.09–2.17, p = 0.012), major vascular invasion (HR 1.91, 95% CI 1.26–2.89, p = 0.0022), PS > 0 (HR 1.50, 95% CI 1.09–2.08, p = 0.014), and MTT (molecular targeted therapy) experience (HR 2.22, 95% CI 1.56–3.13, p = 0.00038). In the MTT naïve patients with ALBI grade 1 or modified ALBI 2a and BCLC stage B (n = 68), median OS and PFS were 25.3 and 12.3 months. Liver-related adverse events during LEN were the only significant adverse event associated with OS (HR 2.74, 95% CI 1.93–3.88, p < 0.0001). Among the Child-Pugh A patients with extrahepatic metastasis and no major vascular invasion, median PFS in the patients with bone metastasis was significantly shorter than those with lung or adrenal grand metastasis (6.3 vs. 12.5 months, p = 0.0025). Conclusion: LEN showed a high response rate in real-world practice. Pretreatment factors, including ALBI score, AFP, and major vascular invasion are important in making a treatment strategy for patients with u-HCC. The patients with bone metastasis would be candidates for new therapeutic approaches.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study

BackgroundMechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome.MethodsThis retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan–Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality.ResultsA total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18–1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03–1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12–1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52–0.76).ConclusionsA high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

Evaluation of treatment satisfaction misalignment between Japanese psoriasis patients and their physicians – Japanese psoriasis patients and their physicians do not share the same treatment satisfaction levels

Objectives High treatment satisfaction in both patients and physicians is an important factor in improving quality of life in psoriasis patients. This study aimed to evaluate treatment satisfaction alignment between psoriasis patients and physicians and to identify factors associated with satisfaction misalignment, especially “physician-predominant” misalignment. Methods This is a nationwide multicenter cross-sectional study. Subjects were paired moderate to severe psoriasis outpatients and their physicians. Treatment satisfaction was evaluated on a scale from 0 to 10. Subjects were defined as “misaligned” when the difference in treatment satisfaction was over ±1 between the patient–physician pair. Results A total of 425 pairs were collected from 54 facilities in Japan. The mean patient age and disease duration were 56.5 years and 18.7 years, respectively. The mean physician age was 50.6 years and 69.6% of physicians specialized in psoriasis. Treatment satisfaction misalignment was found in 49.9% of the patient–physician pairs. Among misaligned pairs, 43.6% were “physician-predominant” pairs. In the multivariate logistic regression analyses, “treatment is effective” was the most important reason for treatment satisfaction (odds ratio [OR]: 35.5; 95% confidence interval [CI]: 5.43, 231.78). Symptoms in the genital area (OR: 10.2; 95% CI: 2.55, 40.93) and lack of understanding of treatment options by patients (OR: 7.5; 95% CI: 2.19, 25.94) were key factors leading to “physician-predominant” status. Conclusions The results suggest that genital psoriasis plays an important role in treatment satisfaction from the patient perspective, and illustrate the importance of communication between patients and physicians which potentially resolves these factors and improves misalignment.

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real‐world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life‐threatening complications occurred in 0.5%, but there were no treatment‐related deaths. During a median follow‐up period of 46.1 months (range 1–113), the 3‐year overall survival rate, relapse‐free survival rate, cause‐specific survival rate, and larynx‐preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.

IMPACT-Scot 2 report on COVID-19 in hip fracture patients.

The primary aim was to determine the influence of COVID-19 on 30-day mortality following hip fracture. Secondary aims were to determine predictors of COVID-19 status on presentation and later in the admission; the rate of hospital acquired COVID-19; and the predictive value of negative swabs on admission. A nationwide multicentre retrospective cohort study was conducted of all patients presenting with a hip fracture to 17 Scottish centres in March and April 2020. Demographics, presentation blood tests, COVID-19 status, Nottingham Hip Fracture Score, management, length of stay, and 30-day mortality were recorded. In all, 78/833 (9.4%) patients were diagnosed with COVID-19. The 30-day survival of patients with COVID-19 was significantly lower than for those without (65.4% vs 91%; p < 0.001). Diagnosis of COVID-19 within seven days of admission (likely community acquired) was independently associated with male sex (odds ratio (OR) 2.34, p = 0.040, confidence interval (CI) 1.04 to 5.25) and symptoms of COVID-19 (OR 15.56, CI 6.61 to 36.60, p < 0.001). Diagnosis of COVID-19 made between seven and 30 days of admission to hospital (likely hospital acquired) was independently associated with male sex (OR 1.73, CI 1.05 to 2.87, p = 0.032), Nottingham Hip Fracture Score ≥ 7 (OR 1.91, CI 1.09 to 3.34, p = 0.024), pulmonary disease (OR 1.68, CI 1.00 to 2.81, p = 0.049), American Society of Anesthesiologists (ASA) grade ≥ 3 (OR 2.37, CI 1.13 to 4.97, p = 0.022), and length of stay ≥ nine days (OR 1.98, CI 1.18 to 3.31, p = 0.009). A total of 38 (58.5%) COVID-19 cases were probably hospital acquired infections. The false-negative rate of a negative swab on admission was 0% in asymptomatic patients and 2.9% in symptomatic patients. COVID-19 was independently associated with a three times increased 30-day mortality rate. Nosocomial transmission may have accounted for approximately half of all cases during the first wave of the pandemic. Identification of risk factors for having COVID-19 on admission or acquiring COVID-19 in hospital may guide pathways for isolating or shielding patients respectively. Length of stay was the only modifiable risk factor, which emphasizes the importance of high-quality and timely care in this patient group. Cite this article: Bone Joint J2021;103-B(5):888-897.

Validation of sepsis-induced coagulopathy score in critically ill patients with septic shock: post hoc analysis of a nationwide multicenter observational study in Japan.

Coagulation disorder is a major cause of death in sepsis patients. Recently, sepsis-induced coagulopathy (SIC) scoring was developed as a new criterion for coagulopathy-associated sepsis. We aimed to evaluate the accuracy of the SIC score for predicting the prognosis of septic shock. We analyzed data from a multicenter observational study conducted from 2011 to 2013. We grouped the participants into those who did and did not use vasopressors, and compared the in-hospital mortality rates of SIC and non-SIC patients. Patients who needed vasopressors were considered to have septic shock. We performed survival analysis adjusted by factors independently associated with mortality. SIC developed in 66.4% of patients who used vasopressors and 42.2% of patients who did not. The in-hospital mortality difference between the SIC and non-SIC groups was statistically significant in those who needed vasopressors (35.8% vs 27.9%, p < 0.01). Cox regression analysis indicated that SIC was significantly correlated with mortality risk in patients who used vasopressors (hazard ratio [HR] 1.39; 95% confidence interval [CI] 1.13–1.70; p < 0.01), but not in those who did not (HR 1.38; 95% CI 0.81–2.34; p = 0.23). In conclusion, the SIC score might be a good diagnostic indicator of fatal coagulopathy among sepsis patients who need vasopressors.

Post-transplantation maintenance with sorafenib or midostaurin for FLT3 positive AML patients – a multicenter retrospective observational study

The role of post allogeneic stem-cell transplantation (AlloSCT) FLT3 inhibition for acute myeloid leukemia in the real-world setting is unclear, especially in the era of widespread pre-transplant use of tyrosine kinase inhibitors (TKIs). In a multicenter nationwide study, we assessed 41 patients who were treated with post-transplant TKIs (sorafenib, n = 23, midostaurin, n = 18). The majority also received TKIs pre-transplant (n = 32, 79%). After a median follow up of 10 months post-transplant (range 3–53.6), 29 patients (71%) were alive and in complete remission. Similar results were seen in a subgroup analysis of pre-transplant TKI recipients (78%). In Univariate analysis, HCT-CI score < 4 and Type of TKI (sorafenib versus midostaurin) predicted longer overall survival. Seventeen patients (41%) suffered from side effects and seven patients (17%) stopped TKI therapy due to adverse events. Overall, our data suggest that post-transplant use of TKIs is safe and effective in an era of their widespread use prior to AlloSCT.

Association between age and neurological outcomes in out-of-hospital cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation: a nationwide multicentre observational study.

Little is known about the difference in outcomes between young and old patients who received extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate the differences in outcomes between those aged ≥75 years and <75 years who experienced OHCA and were resuscitated with ECPR. We performed a secondary analysis of a nationwide prospective cohort study using the Japanese Association for Acute Medicine OHCA registry. We identified patients aged ≥18 years with OHCA who received ECPR. The patients were classified into three age groups (18-59 years, 60-74 years, and ≥75 years). The primary outcome was a 1-month neurological outcome. To examine the association between age and 1-month neurological outcome, we performed logistic regression analyses fitted with generalized estimating equations. From 2014 to 2017, we identified 875 OHCA patients aged ≥18 years who received ECPR. The proportion of patients who survived with favourable neurological outcome in the patients aged 18-59 years, 60-74 years, and ≥75 years were 15% (64/434), 8.9% (29/326), and 1.7% (2/115), respectively. In the multivariable analysis, compared with the age of 18-59 years, the proportions of favourable neurological outcomes were significantly lower in patients aged 60-74 years [adjusted odds ratio (OR), 0.44; 95% confidence interval (CI), 0.32-0.61] and those aged ≥75 years (adjusted OR, 0.26; 95% CI, 0.11-0.59). Advanced age (age ≥75 years in particular) was significantly associated with poor neurological outcomes in patients with OHCA who received ECPR.

Preterm Birth and Birth Weight and the Risk of Type 1 Diabetes in Chinese Children.

AimsFindings from previous studies about the association of preterm birth as well as birth weight with the risk of T1DM were still inconsistent. We aimed to further clarify these associations based on Chinese children and explore the role of gender therein.MethodsA nationwide multicenter and population-based large cross-sectional study was conducted in China from 2017 to 2019. Children aged between 3 and 18 years old with complete information were included in this analysis. Multiple Poisson regression models were used for evaluating the associations of birth weight as well as preterm birth with T1DM in children.ResultsOut of 181,786 children, 82 childhood T1DM cases were identified from questionnaire survey. Children with preterm birth (<37 weeks) had higher risk of type 1 diabetes (OR: 3.17, 95%CI: 1.76-5.71). Children born with high birth weight (≥4,000g) had no statistically significant risk of T1DM (OR:1.71, 95%CI: 0.90-3.22). However, children’s gender might modify the effect of high birth weight on T1DM (girls: OR: 3.15, 95%CI: 1.33-7.47; boys: OR: 0.99, 95%CI: 0.38-2.55, p for interaction=0.065). In addition, children with low birth weight were not associated with T1DM (OR: 0.70, 95%CI: 0.24-2.08). The findings from matched data had the similar trend.ConclusionsIn China mainland, preterm birth increased the risk of childhood T1DM, but high birth weight only affected girls. Therefore, early prevention of T1DM may start with prenatal care to avoid adverse birth outcomes and more attention should be paid to children with preterm birth and girls with high birth weight after birth.

Real-world treatment results for ruptured blood-blister aneurysm of the internal carotid artery: analysis of a Japanese nationwide multicenter study

Ruptured blood-blister aneurysm (BBA) of the internal carotid artery (ICA) remains a challenging lesion, even in the age of modern neurosurgery and endovascular treatment. This retrospective multicenter study aimed to investigate the real-world treatment choice and treatment results. We included 182 ruptured BBAs of the ICA treated at 51 neurosurgical centers in Japan between 2013 and 2017. The baseline patient characteristics, radiological features of the aneurysm, treatment modality, details of treatment, complications of treatment, and treatment results were retrospectively collected. The treatment strategy was divided into deconstructive and reconstructive procedures. Primary clinical outcomes were evaluated using the modified Rankin scale (mRS) at final follow-up. Direct surgery was performed in 144 (79%) cases, and the remaining 38 (21%) cases received endovascular treatment. The majority of treatment selections were deconstructive and reconstructive procedures in the direct surgery group and endovascular treatment group, respectively. Overall, favorable clinical outcomes (mRS 0 to 2) were achieved in 66% of cases, and the mortality rate was 15% at the final follow-up (mean 23months). There was no significant difference in clinical outcome between direct and endovascular treatment groups. Our large nationwide study compared the real-world treatment options for ruptured BBAs and their results. Our findings may offer beneficial information for treatment decision and for future studies investigating ruptured BBAs.

Adenoma detection by Endocuff-assisted versus standard colonoscopy in an organized screening program: the “ItaVision” randomized controlled trial

The Endocuff Vision device (Arc Medical Design Ltd., Leeds, UK) has been shown to increase mucosal exposure, and consequently adenoma detection rate (ADR), during colonoscopy. This nationwide multicenter study assessed possible benefits and harms of using Endocuff Vision in a fecal immunochemical test (FIT)-based screening program. Patients undergoing colonoscopy after a FIT-positive test were randomized 1:1 to undergo Endocuff-assisted colonoscopy or standard colonoscopy, stratified by sex, age, and screening history. Primary outcome was ADR. Secondary outcomes were ADR stratified by endoscopists' ADR, advanced ADR (AADR), adenomas per colonoscopy (APC), withdrawal time, and adverse events. 1866 patients were enrolled across 13 centers. After exclusions, 1813 (mean age 60.1 years; male 53.8 %) were randomized (908 Endocuff Vision, 905 standard colonoscopy). ADR was significantly higher in the Endocuff Vision arm (47.8 % vs. 40.8 %; relative risk [RR] 1.17, 95 % confidence interval [CI] 1.06-1.30), with no differences between arms regarding size or morphology. When stratifying for endoscopists' ADR, only low detectors (ADR < 33.3 %) showed a statistically significant ADR increase (Endocuff Vision 41.1 % [95 %CI 35.7-46.7] vs. standard colonoscopy 26.0 % [95 %CI 21.3-31.4]). AADR (24.8 % vs. 20.5 %, RR 1.21, 95 %CI 1.02-1.43) and APC (0.94 vs. 0.77; P = 0.001) were higher in the Endocuff Vision arm. Withdrawal time and adverse events were similar between arms. Endocuff Vision increased ADR in a FIT-based screening program by improving examination of the whole colonic mucosa. Utility was highest among endoscopists with a low ADR.