bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous or interrupted suture technique for hepaticojejunostomy during pancreatoduodenectomy (HEKTIK trial): study protocol of a randomized controlled multicenter trial
Authors: Brunner Maximilian , Golcher Henriette , Krautz Christian , Kersting Stephan , Weber Georg F. , Grützmann Robert 
Published: June 2022

Abstract
Background
Hepaticojejunostomy is commonly performed in hepato-bilio-pancreatic surgery, particularly during pancreaticoduodenectomy. The purpose of this study is to evaluate the safety and efficiency of two commonly applied suture techniques (the interrupted versus the continuous suture technique) in patients undergoing a hepaticojejunostomy during pancreatoduodenectomy.

Methods
The HEKTIK trial is a multicenter, randomized controlled, patient-blinded surgical explorative trial with two parallel study groups. An adaptive sample size design was chosen: First, 100 patients scheduled for surgery including a hepaticojejunostomy will be randomized 1:1 either to the interrupted suture technique or the continuous suture technique after informed consent. Based on this data, needed sample size will be adjusted.
The primary endpoint will be the occurrence of anastomotic leakage of hepaticojejunostomy, defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis (according to the definition of ISGLS). Further perioperative parameters like other morbidities as well as duration and costs of the hepaticojejunostomy will be analyzed as secondary outcomes.

Discussion
Until now there are no randomized controlled comparative data of these two suture techniques for hepaticojejunostomy. The HEKTIK trial will investigate the yet unanswered question of whether the interrupted suture or the continuous suture technique has advantages performing a hepaticojejunostomy during pancreatoduodenectomy.

Trial registration
German Clinical Trials Register DRKS00024395. Registered on 01 February 2021.
Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
Authors: Nyblade Charlotte , Parreno Viviana , Zhou Peng , Hensley Casey , Oakes Vanessa , Mahsoub Hassan M. , Kiley Kelsey , Frazier Maggie , Frazier Annie , Zhang Yongrong , Feng Hanping , Yuan Lijuan 
Published: June 2022

AbstractClostridioides difficile (C. difficile) is a gram-positive, spore-forming, anaerobic bacterium known to be the most common cause of hospital-acquired and antibiotic-associated diarrhea. C. difficile infection rates are on the rise worldwide and treatment options are limited, indicating a clear need for novel therapeutics. Gnotobiotic piglets are an excellent model to reproduce the acute pseudomembranous colitis (PMC) caused by C. difficile due to their physiological similarities to humans and high susceptibility to infection. Here, we established a gnotobiotic pig model of C. difficile infection and disease using a hypervirulent strain. C. difficile-infected pigs displayed classic signs of C. difficile infection, including severe diarrhea and weight loss. Inoculated pigs had severe gross and microscopic intestinal lesions. C. difficile infection caused an increase in pro-inflammatory cytokines in samples of serum, large intestinal contents, and pleural effusion. C. difficile spores and toxins were detected in the feces of inoculated animals as tested by anaerobic culture and cytotoxicity assays. Successful establishment of this model is key for future work as therapeutics can be evaluated in an environment that accurately mimics what happens in humans. The model is especially suitable for evaluating potential prophylactics and therapeutics, including vaccines and passive immune strategies.
Delayed hydrocephalus after excision of a colloid cyst: a case report
Authors: Gray Logan , Quig Nathan , Kang Myungsa 
Published: June 2022

Abstract
Background
In this case report we describe an unusual case of a patient who underwent resection of a colloid cyst and then presented 6 weeks postoperatively with obstructive hydrocephalus. There appear to be no prior reports of such a delayed complication after colloid cyst resection.

Case presentation
A 50-year-old Caucasian woman underwent resection of a colloid cyst with an uncomplicated perioperative course. Postoperative imaging demonstrated complete resection of the cyst. She was discharged home on postoperative day 4 but presented 6 weeks later with symptoms of obstructive hydrocephalus resulting in poor neurologic outcome and ultimately death.

Conclusion
Patients presenting with symptoms of hydrocephalus after resection of a colloid cyst should be followed closely, and timely placement of an external ventricular drain may be critical.
Time to update the Japanese standard population for comparing mortality rates
Authors: Dhungel Bibha , Wada Koji , Tanaka Hirokazu , Gilmour Stuart 
Published: June 2022

AbstractFor the last three decades, Japan has been using the population of 1985 for age standardisation to compare mortality rates over time. With the population of Japan declining and ageing rapidly every year, there is a need to update the standard population to make the comparison representative of the current scenario. This is particularly relevant owing to declining mortality rates among the super-ageing Japanese elderly population and more data availability for older age groups. The choice of one population as standard over another is arbitrary because it does not make much difference to the trends in rates. The proportion of elderly in Japan is increasing rapidly and is expected to be one-third of the total population by 2030, in contrast to the proportion of 10% in the 1980s. Using a standard population with a lower proportion of elderly may weight the rates disproportionately for this age group. It is typically suitable to change the standard population every 25 to 30 years. It is advisable to choose the population of 2015 as the new standard population as suggested by the working group of the Ministry of Health, Labour and Welfare of Japan for revising the standard population. However, it should be noted that the newly calculated age-standardised mortality rates will no longer be comparable to those calculated using the older standard populations. Updating the standard population will produce age-standardised rates for recent years closer to the crude rates and would thus reduce the extent of misinterpreting decreased mortality risks using age-standardised rates that do not closely resemble the crude rates.
How I do it: Modified Lichtenberger-Brown tracheoesophageal puncture procedure
Authors: Sapundzhiev Nikolay R. , Asenov Asen G. , Spasova Blagovesta , Genova Petya S. , Davidov Georgi I. , Ivanova Darina 
Published: June 2022

Background Tracheoesophageal puncture (TEP) with use of a prosthesis is nowadays a standard for voice restoration after laryngectomy. Different TEP approaches exist. Methods We retrospectively reviewed our series of patients who underwent TEP by a novel technique, based partially on the Lichtenberger endo-extralaryngeal needle carrier. The instrument is covered with a protective Nelaton catheter and introduced via the mouth to the neopharynx/esophagus. No rigid endoscope is used for visualization of the TEP site. The tip is palpated through the stoma at the posterior tracheal wall and incision is done to the catheter tip. The prosthesis is introduced through the mouth and the neopharynx in a retrograde fashion. Results In 14 laryngectomees with postoperative radiation voice prosthesis was successfully placed with this technique. A total of 18 procedures were performed. One misplacement occurred. No other early or late complications were observed or any other TEP or prosthesis related problems. Conclusions The rationale of our technique is to simplify the procedure, avoid risk-bearing approaches and instruments such as rigid endoscopes, simplify the armamentarium and reduce tissue trauma. The initial clinical experience in 18 TEPs confirmed it usefulness in both standard and anatomically challenging situations. The current study obtained the ethical approval from the Faculty of Medicine at Medical University “Prof. Dr. Paraskev Stoyanov”—Varna, Bulgaria (Protocol 087/24.10.2019 (retrospectively registered). Graphical Abstract
Survival of patients with neuroblastoma before versus after reduction of therapy due to the change in age cut-off from 12 to 18 months in Children’s Oncology Group (COG) risk stratification.
Authors: London Wendy B. , Bender Hannah , Irwin Meredith , Hogarty Michael D. , Castleberry Robert P. , Maris John M. , Kao Pei-Chi , Naranjo Arlene , Cohn Susan Lerner 
Published: June 2022

10013 Background: In 2006, COG reclassified subgroups of toddlers diagnosed with neuroblastoma from high-(HR) to intermediate-risk (IR), when the age cut-off for increased risk was raised from 365 days (12 mo) to 547 days (18 mo) (London, J Clin Onc 2005). The aim of this retrospective study was to determine if excellent outcome was maintained after a reduction of therapy. Methods: Children < 3 yrs old at diagnosis, enrolled on a COG biology study from 1990-2018, were eligible (n = 9,189). Therapy was reduced for two “cohorts of interest” based on the age cut-off change: 365-546 days old with INSS stage 4, MYCN not amplified, favorable INPC, hyperdiploid tumors (12-18mo/Stage4/FavBiology); and, 365-546 days old with INSS stage 3 tumors with non-amplified MYCN and unfavorable INPC (12-18mo/Stage3/NotAmp/UnfavINPC). Log rank tests compared event-free (EFS) and overall survival (OS) curves. Results: In the cohorts of interest, patient (pt) characteristics were similar for ≤2006 vs > 2006. For 12-18mo/Stage4/FavBiology, 5-year EFS and OS (± std error) before (≤2006; n = 40) versus after (> 2006; n = 55) the reduction in therapy were similar: 89±5.1% versus 87±4.6% (p = 0.7), and 89±5.1% versus 94±3.2% (p = 0.4), respectively (Table). For 12-18mo/Stage3/NotAmp/UnfavINPC, the 5-year EFS and OS were both 100%, before (n = 6) and after (n = 4) 2006. For the combined cohorts for ≤2006 versus > 2006, EFS and OS were 91±4.4% versus 88±4.3% (p = 0.6), and 91±4.5% versus 95±2.9% (p = 0.5), respectively. Within HR pts diagnosed ≤2006, EFS/OS were 91±4.4%/91±4.5% for (12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/NotAmp/UnfavINPC) vs 38±1.3%/43±1.3% for all other HR pts < 3 yrs old (p < 0.0001; Table). Within IR pts diagnosed > 2006, EFS/OS were 88±4.3%/95±2.9% for (12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/NotAmp/UnfavINPC) vs 88±0.9%/95±0.6% for all other IR pts < 3 yrs old (p = 0.9). Conclusions: Our 19 year study demonstrates that excellent outcome is maintained among toddlers with Stage4/FavBiology and Stage3/Not Amp/Unfav INPC neuroblastoma with a significant reduction of therapy from high- to intermediate-risk treatment. Importantly, pts were likely spared acute toxicity and late effects known to be associated with HR therapy. Efforts to identify additional pt cohorts who may not require HR therapy to achieve long-term survival are critical to improve the long-term health of children with neuroblastoma. [Table: see text]
Modifiable risk factors for late mortality among five-year survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Dixon Stephanie B , Liu Qi , Ehrhardt Matthew J. , Chow Eric Jessen , Oeffinger Kevin C. , Mertens Ann C. , Nathan Paul C. , Howell Rebecca M. , Leisenring Wendy M. , Krull Kevin R. , Ness Kirsten K. , Hudson Melissa M. , Robison Leslie L. , Yasui Yutaka , Armstrong Gregory T. 
Published: June 2022

10014 Background: The impact ofmodifiable lifestyle and cardiovascular risk factors (CVRFs) on risk for late mortality in adult survivors of childhood cancer is not well established. Methods: All-cause and health-related late (>5 years from cancer diagnosis) mortality (HRM; excludes death from primary cancer and external causes) were evaluated in five-year survivors diagnosed <21 years of age using the National Death Index through 2017. Modifiable lifestyle (smoking status, alcohol use, physical activity, body mass index [BMI]; combined to create a score [0-4] and categorized as unhealthy [0-2], moderate [2.5 or 3], healthy [3.5 or 4]) and CVRFs (hypertension [HTN], diabetes [DM], dyslipidemia) were assessed as time-varying covariates. Standardized mortality ratios (SMRs) and absolute excess risk of death per 1000 person-years (AER) with 95% confidence intervals (CIs) were estimated. Multivariable models estimated the relative risk (RR) of death adjusted for demographic and socioeconomic variables. Results: Among 20,051 adult survivors (median age 40.0 years, range 18.7 – 67.7), 19% reported ≥1 CVRF (13% HTN, 9% dyslipidemia, 5% DM) and few reported a healthy lifestyle (29% healthy, 40% moderate, 31% unhealthy). There were 1476 deaths due to health-related causes. While all survivors experienced an increased risk of HRM compared to the US population, risk was lower among those with a healthy vs. unhealthy lifestyle (SMR 3.5, 95% CI 3.1-3.9 vs. 6.2, 5.7-6.7) and very high among underweight survivors (11.1, 9.3-13.3) and those with both HTN and DM (13.0, 9.2-18.0). Stratified by lifestyle score, the excess risk of HRM was lowest in those with a healthy lifestyle across survival time (Table). Similar trends were seen when stratified by 0, 1 and 2 CVRFs. In multivariable models, compared to survivors with no CVRFs and healthy lifestyle, no CVRFs and unhealthy lifestyle was associated with a 50% increased risk of HRM (RR 1.5, 95% CI 1.2-1.8) and unhealthy lifestyle plus HTN a 2-fold increased risk of HRM (2.2, 1.6-2.8). Regardless of lifestyle group, ≥2 CVRF increased risk for HRM at least 2-fold (p-values <0.001). Conclusions: A reduction in excess deaths is observed among adult survivors of childhood cancer with a healthy lifestyle and no CVRFs as they age. Interventions that target improved lifestyle choices and prevention or aggressive treatment of modifiable CVRFs may reduce risk for late mortality. [Table: see text]
Outcomes of Hispanic and non-Hispanic white pediatric and young adult patients with B-cell acute lymphoblastic leukemia after commercial tisagenlecleucel.
Authors: Vandris Panayiotis , Chao Karen , Baggott Christina , Phillips Christine L. , Qayed Muna , Rossoff Jenna , Si Lim Stephanie J. , Winestone Lena E. , Stefanski Heather E. , Talano Julie-An M. , Margossian Steven , Verneris Michael R. , Myers Gary Douglas , Karras Nicole A. , Brown Patrick A. , Satwani Prakash , Mackall Crystal , Curran Kevin J. , Laetsch Theodore Willis , Schultz Liora M. 
Published: June 2022

10016 Background: Population-level data show significantly inferior outcomes for Hispanic children, adolescents, and young adults (CAYA) diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) relative to non-Hispanic whites (NHW). Here, we compare outcomes between Hispanic and NHW CAYA patients with relapsed and/or refractory (RR) B-ALL receiving tisagenlecleucel, a CD19-specific chimeric antigen receptor (CAR) T cell therapy. Methods: We used data from the Pediatric Real World CAR Consortium retrospective cohort of 200 patients who underwent cell shipment for standard-of-care tisagenlecleucel between August 2017 and March 2020 (N=15 US institutions). Race/ethnicity was identified by medical record review. Patients reported as belonging to more than one racial/ethnic group were classified as multiracial and excluded from analysis. Baseline factors, outcomes, and safety post-infusion were characterized for Hispanic vs. NHW infused patients. Outcomes included complete response (CR) rate, overall survival (OS), duration of response (DOR), and duration of B-cell aplasia (DBA). A multivariate Cox model for OS was constructed, including all baseline factors. Results: Among 185 infused patients, 90 (48.6%) were NHW and 70 (37.8%) were Hispanic. Among 15 non-infused patients, 3 (20.0%) were NHW and 5 (33.3%) were Hispanic. Hispanic patients were significantly older at diagnosis (mean: 10.7 vs. 8.3 years, p=0.02) and had significantly shorter time from diagnosis to infusion (mean: 34.4 vs. 46.4 months, p=0.04). Hispanic and NHW patients did not significantly differ across sex, leukemia type, number of prior lines of therapy, receipt of prior CD19-directed therapy, level of disease burden pre-infusion, and number of relapses pre-infusion. Hispanic and NHW patients did not significantly differ across 1-month CR, 6-month OS, 1-year OS, 18-month OS, 6-month DOR, 1-year DOR, 6-month DBA, and 1-year DBA (Table). On multivariate analysis including the above covariates, OS did not significantly differ for Hispanic patients (HR=1.04, p=0.92). Hispanic and NHW patients did not significantly differ across grade ≥ 3 cytokine release syndrome, grade ≥ 3 neurotoxicity, grade 4 neutropenia, tumor lysis syndrome, or number of infections post-infusion. Conclusions: Outcomes were similar between Hispanic and NHW CAYA RR B-ALL patients receiving tisagenlecleucel in the real-world setting. Increasing access to CAR therapy among Hispanic CAYA B-ALL patients could help mitigate population-level disparities in outcomes observed after receipt of conventional therapies. [Table: see text]
Menin inhibitors as targeted therapeutics in KMT2a rearranged infant leukemia and the identification of effective treatment combinations.
Authors: Sharma Ritul , Zhang Chunfen , Maese Luke Devon , Lacayo Norman James , Narendran Aru 
Published: June 2022

10024 Background: KMT2a rearrangements are a hallmark of infant (less than 1 year of age) leukemia and are associated with poor prognosis. Menin is a ubiquitous protein that binds to the N-terminal of the KMT2a-fusion protein to mediate the oncogenic activity of KMT2a-rearranged leukemia cells. In this study, we evaluated the effect of multiple menin inhibitors and effective drug combinations for the treatment of KMT2A-rearranged infant leukemia. Methods: FISH analysis and immunoblotting confirmed the presence of KMT2a-fusion in the primary patient samples and cell lines studied. Lymphocytes from healthy donors were used as controls. Cells were treated with various concentration of multiple menin inhibitors for 72 hours and growth inhibition was measured using alamar blue assay. Infant leukemia cells were treated with a panel of FDA-approved agents (n = 221) to identify potential synergy, additive- and antagonistic-effects with specific menin inhibitors. Therapeutic drug interaction properties were established by calculating combination indices (CI) using the Chou-Talalay method. Mode of cell death and cellular target modulations were determined by western blot analysis. The effect of targeting menin in the context of the leukemogenic bone marrow microenvironment was determined through stromal cell co-cultures. Results: A comprehensive analysis of menin inhibitors on infant leukemia cell lines and primary patient cells exhibited significant and quantitatively diverse responses in cells with distinct molecular properties. Within the panel of menin inhibitors, infant B-ALL cells were found to be more sensitive to MI-463, MI-503 and MI-136 with a mean IC50 of 5.9µM, 6.1µM and 10.2µM, respectively. On the other hand, MI-3 exhibited an IC50 of 35.6µM. The cytotoxic effect of menin inhibitors on normal lymphocytes was minimal, suggesting a favourable therapeutic window (p < 0.0001). High-throughput screening with a library of > 200 FDA-approved drugs revealed significant sensitivity of distinct infant leukemia cells to proteasome, HDAC and CDK9 inhibitors. Among these, substantial drug synergy was observed between menin and proteasome inhibitors. For example, carfilzomib synergised with menin inhibitors over a broad range of concentrations with a CI value of 0.7. Conclusions: In this study, we present and discuss the initial proof-of-concept preclinical data for the effective anti-leukemic activity of menin inhibition against KMT2A-rearranged infant leukemia cells. Furthermore, the comprehensive drug screen and drug combination studies identified a spectrum of mechanistically-validated synergies, providing usable data for the formulation of multi-agent clinical studies for this currently unmet need in pediatric oncology.
A fully automated MRI-based deep-learning algorithm for classifying germinomas and nongerminomatous germ cell tumors.
Authors: Li Yanong 
Published: June 2022

10035 Background: Intracranial germ cell tumors (iGCTs) are classified into two pathological subtypes (Germinomas [GEs] and nongerminomatous germ cell tumors [NGGCTs]), with distinct treatment strategies and prognosis. Accurate preoperative determination of iGCT subtypes is essential for clinical decision-making and prognosis assessment. We aim to develop and validate a deep-learning algorithm to automatically segment the iGCTs and classify their subtypes using preoperativeT2-weighted (T2W) images. Methods: Brain MR imaging and corresponding pathologic information were retrospectively obtained for 594 iGCTs, including 269 GEs and 325 NGGCTs from Beijing Tiantan Hospital (between January 1, 2008, and October 31, 2020). The retrospective set was subdivided into the training (n = 416) and test (n = 178) sets to develop and test a 3D nnU-Net using T2W images (here we named iGCT-net) for iGCT segmentation and its subtypes (GEs and NGGCTs) classification, simultaneously. A prospective cohort (n = 73, 56 GEs and 17 NGGCTs) was designed as a simulation set to test the model in a simulated clinical application. Dice scores were computed to assess tumor segmentation. Accuracy, sensitivity, specificity, and area under the curve (AUC) were used to assess the GEs and NGGCTs classification. Sensitivity analysis on subgroups with tumor locating at suprasellar, pineal, and basal ganglia in test and simulation set, respectively. Results: For tumor segmentation, the iGCT-net achieved a dice score of 0. 73 and 0.80 in test and simulation sets, respectively. For GEs and NGGCTs classification in the test set, the iGCT-net achieved an accuracy of 90.96%, sensitivity of 86.84% and specificity of 82.26%, and AUC of 84.87%. The iGCT-net showed 83.65% accuracy in the simulation set, with sensitivity of 83.56% and specificity of 83.72%, and AUC was 81.17%. In sensitivity analysis, the accuracies of the iGCT-net presented for the suprasellar region, pineal region, and basal ganglia region were 86.84%, 92.92%, and 61.73% in the test set, and 92.31%, 88.89%, and 72.27% for suprasellar region, pineal region, and basal ganglia region in the simulation set. Conclusions: We developed and validated a fully automatic deep learning algorithm to segment iGCT and classify GEs and NGGCTs with a high accuracy using only T2W images based on a large dataset.