bluuebunny/crossref_metadata_2025 huggingface dataset:
P324 Predictors of corticosteroid-free remission after initiation of ustekinumab for ulcerative colitis: a real-world, multicenter cohort study in the United States
Authors: Dalal R , Esckilsen S , Barnes E , McClure E , Goodrick H , Allegretti J
Published: May 2021

Background

Clinical trial data has demonstrated the efficacy of ustekinumab (UST) for the treatment of ulcerative colitis (UC), however real-world clinical outcomes data are limited. We therefore performed a real-world multicenter cohort study to identify predictors of corticosteroid-free clinical remission after initiation of ustekinumab for UC.

Methods

This is a retrospective cohort study of adult UC patients initiating UST between 1/1/2016 and 11/1/2020 at three large IBD referral centers in the United States. Patients with prior colectomy and those receiving UST for primarily non-UC indications were excluded. Electronic health records were reviewed to obtain clinical data. Independent variables present at UST induction included demographics, disease duration, extraintestinal manifestations, current/prior IBD medications, substance use (cigarettes, cannabis, or opioids), last endoscopic extent/severity, last serum albumin and C-reactive protein (within 3 months prior to induction), and daily bowel frequency. The primary outcome was corticosteroid-free remission (i.e. simple clinical colitis activity index [SCCAI] or 9-point Mayo score of <3) 12-16 weeks after induction. Secondary outcomes included clinical response (reduction of SCCAI or Mayo score by >2 points from baseline) 12-16 weeks after induction and UST failure (i.e. UST discontinuation or colectomy due to uncontrolled disease) within 52 weeks after induction. Multivariable logistic regression was used to identify factors associated with remission.

Results

We identified 108 UC patients who initiated UST. Median age at induction was 39 years (IQR 30-56 years), 91.7% (99/108) of patients had prior anti-TNF exposure, and 60.2% (65/108) had prior anti-TNF and anti-integrin exposure (Table 1). Of 101 patients with available clinical follow-up data, 39.6% achieved remission and 51.5% had clinical response 12-16 weeks after induction. UST failure occurred in 41.1% (23/56 with sufficient follow-up) within 52 weeks. Adverse events were reported in 3.0% (3/101; rash, urinary tract infection, and C. difficile infection). After multivariable logistic regression, prior anti-TNF and anti-integrin exposure (OR 0.31, 95% CI 0.11-0.86), Mayo endoscopic severity >1 (OR 0.30, 95% CI 0.10-0.88), and bowel frequency (OR 0.84, 95% CI 0.72-0.98) were inversely associated with remission (Table 2).

Conclusion

In this multicenter cohort, nearly 40% of UC patients achieved corticosteroid-free remission 12-16 weeks after UST induction. Prior exposure to both anti-TNF and anti-integrin therapies, endoscopic severity, and daily bowel frequency were associated with failure to achieve remission. Prospective studies are needed to optimize management strategies for UC patients with failure of two biologic classes.
P416 Use of DXA in children with Inflammatory Bowel Disease – a large single centre study
Authors: Jois A , Perera S , Simm P , Alex G
Published: May 2021

Background

Low bone mineral density (BMD) is a complication in children with Inflammatory Bowel Disease (IBD). Dual-energy X-ray absorptiometry (DXA) is an established screening tool for BMD, yet there are limited data to guide its use in children with IBD. We performed a single site retrospective analysis of the use of DXA and evaluated factors associated with low BMD.

Methods

Children 3-18 years with IBD diagnosed between 2013-2018 at The Royal Children’s Hospital, Melbourne, Australia, were included. Patient, disease and treatment demographics were collected alongside vitamin D, calcium, CRP, ESR, albumin and faecal calprotectin (FCP) (averaged over 6 months before and after DXA). Rates of corticosteroid use, vitamin D and calcium supplementation, bisphosphonate use and fractures were also collected. Mann-Whitney and Fisher exact tests were used for continuous and categorical group comparison, respectively. Data are presented as median (interquartile range).

Results

239 children diagnosed at a median age of 12 (9.1-14.2) were followed for 5.1 (4-6.4) years. 72/239 (30%) children had at least one DXA at 11 (1.25-28.8) months post diagnosis. 28/72 (39%) children had a follow-up DXA 2.3 (1.9-2.9) years post diagnosis. Children referred for DXA had a lower weight centile (48.7 (17.1-78.2) vs 59.7 (31.4-84.7), p=0.03), and were more likely to have Crohn’s disease (OR 2.18, p=0.01). At first DXA, median lumbar spine (LS) Z score was -0.80 (-1.65-0.08), height adjusted LS Z score was -0.65 (-1.18-0.10), hip Z score was -1.30 (-1.80--0.35) and total body less head Z score was -1.40 (-2.55--0.70). 18/72 children had LS Z score > 0. Children with LS Z score < -2.0 (n=14) had lower weight (6.57 (1.78-23.7) vs 51.1 (26.5-68.7), p=0.0002) and height centiles (3.62 (1.17-17.1) vs 42 (16.9-67.1), p<0.0001), higher FCP (3041 (1182-4192) vs 585 (139-2419), p=0.009) (Figure 1), and higher odds of calcium supplementation (OR 16 (95% CI 2.93-89.1), p=0.003) and endocrinology review (OR 9.61 (95% CI 2.65-31.0), p=0.001). No fractures were reported. Of the 28 children with serial DXAs, there was no significant change in Z scores. When comparing children with a worse (16/28) Z score at second DXA to those with improvement (12/28), there was a trend toward lower vitamin D levels (37 (25.2-58.3) vs 62 (46.3-87), p=0.06) at first DEXA, and higher ESR at second DEXA (23.4 (19.3-29) vs 8.20 (3.5-21.9), p=0.02).

Conclusion

Almost one third of children with IBD at a tertiary referral centre underwent DXA, with lower BMD than age and sex matched controls. Disease activity markers FCP and ESR were associated with lower BMD. There was no significant change in DXA score over time. No fractures were identified over the study period.
P454 Treatment with biologics improves disability from Inflammatory Bowel Disease in therapy responders
Authors: Castillo G , Sultan K , Kwah J , Chen L A , Axelrad J
Published: May 2021

Background

The IBD-Disability Index (IBD-DI) is a quantitative measure of disease impact on physical activity and social participation, with higher sores indicating greater disability. Prior studies have been cross-sectional, but few studies have longitudinally measured disability with IBD treatment.

Methods

Patients with Crohn’s disease (CD) and ulcerative colitis (UC) starting a new biologic or small molecule therapy were surveyed using the IBD-DI at induction, and 2- and 6-months. Surveys also included the Harvey Bradshaw Index (HBI), Simple Clinical Colitis Activity Index (SCCAI), partial Mayo score (pMayo), depression index (PHQ-9), quality of life index [Short IBD Questionnaire (SIBDQ)], and illness perception scale [Brief Illness Perception Questionnaire (BIPQ)]. Clinical data included endoscopic scores, biomarkers (ESR, CRP, calprotectin), comorbidities, and IBD history. Therapy response was defined as a reduction in HBI, pMayo, SCCAI ≥3 or total HBI ≤ 4, pMayo < 2, SCCAI ≤2 at survey 3.

Results

111 patients (65 males and 46 females) completed survey 1, 79 completed survey 2, and 63 completed survey 3. There were no significant differences in baseline demographic, disease activity, or psychosocial scores between participants who completed only survey 1, and those who completed all 3 surveys. The median age was 31 years, 58% had CD, 42% had UC, and 32% were non-white (Table 1). At induction, the median IBD-DI score was 34.0 out of 100. IBD-DI scores did not correlate with age, race, sex, comorbidities, IBD-type, or surgery, but there was a weak correlation with prior biologic use, specifically anti-TNF therapy (Table 1). There was a moderate correlation between clinical disease activity scales and the IBD-DI [HBI, pMayo, and SCCAI (r=0.63, r= 0.56, r=0.55; p <0.001)] (Table 2). Endoscopic scores and biomarkers did not correlate with the IBD-DI. Psychosocial scales correlated strongly with the IBD-DI: SIBDQ, PHQ-9, and the wellbeing and emotional domains of the BIPQ (r=-0.83, r=0.78, r= 0.60, p <0.0001, respectively). Among therapy responders, there was a significant improvement in IBD-DI scores from survey 1 to 3 [median 32 (IQR, 20–43) to 24 (IQR, 14–38), p =0.04] (Table 3). This difference was not observed in treatment non-responders.

Conclusion

Disability is not commonly measured in clinical studies, but it plays a large role in patients’ overall wellbeing. In this longitudinal cohort, there was a strong correlation between IBD-DI, clinical disease activity, depression, and quality of life indices. Among therapy responders, there was a significant improvement in IBD-DI from a moderate to mild degree of disability. These findings further clarify the relationship between disability, disease activity, and therapeutic response in IBD.
P506 The Impact of Anxiety in Patients With Inflammatory Bowel Diseases Treated With Biologics during COVID Lockdown. A Comparative Study between Hospitalized and non-hospitalized patients
Authors: Bertani L , Barberio B , Zanzi F , Maniero D , Ceccarelli L , Marsilio I , Minciotti M , Coppini F , Lorenzon G , Mumolo M G , Zingone F , Costa F , Savarino E V
Published: May 2021

Background

The first wave of COVID-19 pandemic management implied to remain at home in order to reduce the spread of the infection. Several patients with inflammatory bowel diseases (IBD) treated with biologics had to go to the hospital to perform intravenous (i.v.) therapies, whereas patients treated with subcutaneous (s.c.) ones could remain at home. Since immumodulatory therapies as well as the access to high-risk places like hopitals have been associated to an increased risk of infections, we have investigated whether patients hospitalized or treated at home showed similar levels of anxiety related to the pandemic situation.

Methods

We conducted a survey including consecutive IBD patients treated with biologics at three Italian referral centers referring to the first lockdown period. We included consecutive adult patients in clinical and biochemical remission treated with biologics, administered i.v. or s.c. Patients experiencing a disease flare during these months were excluded from the study, in order to avoid potential biases related to disease activity. Patients underwent the normally scheduled clinical visits, performed at home by using phone or video calls for patients treated with s.c. drugs and only in specific cases (i.e. suspected COVID symptoms) for patients treated with i.v. ones. We administered to all patients the Hospital Anxiety and Depression Scale (HADS) questionnaire and other 11 questions, specifically related to COVID and its implications. Group differences in continuous and nominal variables were tested by Kruskal–Wallis test and Fisher exact test, respectively.

Results

A total of 189 IBD patients were recruited, 112 (59.3%) treated with i.v. drugs and 77 (40.7%) with s.c. ones. The two groups of patients had similar scores in the 14 single items of the HADS questionnaire (p>0.10 for all). The total HADS score obtained by the sum of all items was also almost identical between groups (37.1 ± 2.8 vs 37.2 ± 2.8; p=0.98). In patients treated with i.v. drugs receiving a televisit (n=17), the rates of satisfaction about telemedicine (58.8%) and the lack of in-person care (33.3%) were significantly lower compared with those treated with s.c. drugs (94.8% and 92.2%, respectively; both p<0.0005).

Conclusion

Our results suggest that there is no need to convert patients from i.v. to s.c. therapy, since the risk of infection as well as of disease relapse due to stressful events are similar in both groups. Moreover, the hospitalization for drug administration does not affect the the psychological status of the patients. Interestingly, patients used to coming to the hospital have more need for in-person contact than patients used to be treated at home, suggesting that the choice of telemedicine should be personalized.
P532 Delay of maintenance infliximab increases the risk of relapse in Crohn’s disease during the COVID-19 pandemic
Authors: Guo H , Tang J , Huang Z , Li B , Yang Q , Chao K , Gao X
Published: May 2021

Background

Scheduled maintenance infliximab (IFX) therapies were frequently delayed during the COVID-19 pandemic. The unusual situation allowed us to study the influence of decreased treatment adherence on Crohn’s disease (CD). This retrospective study aimed to evaluate the effect of IFX delay on relapse in Crohn’s disease (CD) patients.

Methods

166 CD patients with maintenance IFX between January 25, 2020, and April 25, 2020, were retrospectively enrolled. Demographic and clinical characteristics were recorded. Relapse was defined as clinical disease relapse or biochemical disease relapse (C-reactive protein (CRP) level ≥5 mg/L without other, non-IBD related explanation). Associations between relapse and IFX delay were analyzed.

Results

A retrospective cohort study was conducted, including 166 CD patients receiving maintenance IFX infusion during the COVID-19 pandemic. Of all, 135 (81.3%) had delayed their IFX infusion. Only 31 (18.7%) followed the schedule infusion during the COVID-19 pandemic. The median time of the IFX delay was 18.6±17.1 days. The relapse rate in the IFX-delay group was significantly higher than the group without delay (25.9% versus 5.5%, P＜0.02). During a median IFX delay interval of 46 days (95% CI 20.9–71.1), the ratio of relapse increased with the increase of IFX delay intervals. Delay interval had a cumulative effect on disease recurrence. We proposed interval prolongation resulted in a

significant IFX trough concentration reduction.

Conclusion

Our study provided real-world evidence of influence on relapse of IFX delay in CD patients undergone maintenance therapy. It might help the IBD specialists arrange reasonable IFX treatment intervals for patients.
P590 Which biomarkers have an effect on therapeutic vedolizumab drug levels? A retrospective analysis from a London Tertiary Centre
Authors: Bancil A , Stevens M , Kok K
Published: May 2021

Background

Vedolizumab is a humanised monoclonal antibody that binds to the α 4β 7 integrin and is an established treatment for both Crohn’s Disease (CD) and Ulcerative Colitis (UC). Drug levels for anti-tumour necrosis factor-α inhibitors such as infliximab and adalimumab have been used routinely for therapeutic drug monitoring (TDM). Target therapeutic levels for vedolizumab are yet to be established. Correlations with vedolizumab levels have been found in prospective and retrospective studies with a number of biomarkers such as C-Reactive Protein (CRP), albumin and Body Mass Index (BMI). However, these have failed to replicate consistently among studies of vedolizumab drug levels.

Methods

Trough serum vedolizumab drug levels were taken for 81 patients through a period of 3 months. These were analysed using a drug tolerant assay (IDKMonitor Drug level ELISA and IDKMonitor vedolizumab Free anti-drug antibody ELISA) run on a Dynex DS2 ELISA processor. These were collected from 33 CD patients, 46 UC patients and 2 patients with unclassified Inflammatory Bowel Disease (IBD-U). Faecal calprotectin (FCP) was collected in a subset of patients. Serum CRP, albumin, and haemoglobin (Hb) levels were also taken alongside levels. BMI was recorded at our infusion unit before receiving the infusion.

Results

81 patients had drug levels taken: CD patients (mean drug level Q8w - 7.8 mcg/ml, Q4w - 18.6 mcg/ml, 9 patients with concomitant immunomodulators (CIM)), UC patients (mean drug level Q8w - 9.4 mcg/ml, Q4w – 22.0 mcg/ml, 5 patients with CIM), IBD-U (mean drug level Q8w - 15.2 mcg/ml, no patients with CIM). One patient developed anti-drug antibodies. Correlation was analysed using simple linear regression. A positive correlation was found with vedolizumab levels and albumin (correlation coefficient (r) = 0.11; p=0.03) but not with CRP (p=0.49), Hb (p=0.56), BMI (p=0.33) or FCP (p=0.08).

Conclusion

Our results indicate that albumin positively correlates with a higher vedolizumab drug level, which suggests that drug levels will be lower and perhaps less effective in patients with a low albumin level. Further studies should look at larger numbers of patients to identify whether the correlations identified with other biomarkers are significant and identify therapeutic target levels for vedolizumab. These will help guide TDM for patients and inform clinicians of when to switch as well as recognising likely non-responders and thus provide a personalised approach to biologic choice.
P638 Changes in the management of IBD patients since the onset of COVID-19 pandemic. A path towards the implementation of telemedicine in Spain?
Authors: Del Hoyo Francisco J , Millán M , Garrido-Marín A , Nos P , Barreiro-de Acosta M , Bujanda L , de la Portilla F , Aguas M
Published: May 2021

Background

COVID-19 pandemic increased medical services demand aside from interrupting daily clinical practice for other diseases such as Inflammatory Bowel Disease (IBD). Here we present the results of a survey to gain the perception of IBD specialists in their patient-management using telemedicine in their daily practice.

Methods

This was an observational survey study among physicians focused on IBD (gastroenterologist, surgeons, and pediatricians) members of the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU), the Spanish Association of Gastroenterology (AEG), and the Spanish Association of Coloproctology (AECP), regarding changes of management of IBD patients.

Results

We received a total of 269 responses to the survey (from May to June 2020). Before the pandemic, nearly all the respondents reported performing very frequently their visits face-to-face (n=251, 93.3%) while, during the pandemic, the telephone visits were the most frequent visits performed (n=138, 51,3%). Regarding communication difficulties, 157 (58.4%) respondents reported the impossibility of performing a proper examination as the most relevant issue. Also, 114 (42.4%) respondents considered remote visits more time-consuming than face-to-face visits. Most gastroenterologists (n=188, 83.2%) considered patients with active perianal disease in special need of face-to-face consultation and more than half of the surgeons (n=35, 50.7%) reported having performed an immediate postoperative follow-up remotely.

Conclusion

Most IBD units have implemented remote visits during the pandemic, but most professionals found them more time-consuming and unsuitable for some disease profiles. Therefore, there is a need for the development of better telemedicine systems that can meet professionals’ and patients′ requirements.
P667 Characterization of a large Hispanic cohort with Inflammatory Bowel Disease across a 25-year span
Authors: Torres E A , Ramos L , Sanchez A , Amaya C , Perez-Gilbe A
Published: May 2021

Background

Inflammatory Bowel Disease (IBD) in Hispanics has increased, but characterization of this population is limited. We describe the demographic and clinical characteristics of a large Hispanic population with IBD and compare it among two periods, 1995- 2009 and 2010–2019.

Methods

The Registry of IBD has been recruiting patients with IBD continuously since 1995. Data is obtained from the subject and the medical record. This study includes 1365 Hispanics recruited between 1995 and 2019. Variables include age, gender, age at onset and diagnosis, IBD type, family history, smoking, extraintestinal manifestations (EIM), medications, and surgery for IBD. Descriptive statistics included frequency, median, mean, and standard deviation. SPSS software was used for comparison analysis utilizing Chi square and Fisher′s test. The protocol is approved by the IRB.

Results

712 were males and 653 females. Crohn’s disease (CD) was more prevalent in males (479/836, 57.3%) and ulcerative colitis (UC) in females (288/517, 55.7%). The mean age at diagnosis was 34.1 + 15.4 for UC and 24.4 + 12 for CD (p<.001). History of smoking was infrequent (24.3%). Interval between onset of symptoms and diagnosis was 1.8 + 4.7 yrs. for UC and 2.5 + 5.3 yrs. for CD (p=.012). At recruitment, duration of disease was 7.4 + 8.4 yrs. for UC and 5.6 + 7.3 yrs. for CD (p<.001). Family history of IBD was present in 23% of CD and UC participants. The most frequent EIM was arthropathy in 37.9% and 25.9 % of UC and CD (p=.670), followed by skin manifestations in 13.2% and 18.9% respectively (p=.070). Aminosalicylates (94.9%) and corticosteroids (81.6%) were more frequent in UC, and immunomodulators (23%) and anti-TNF drugs (aTNF) (46.2%) in CD (p<.001). At the time of recruitment, 54.5% of CD and 23.7% of UC patients had previous surgery for IBD.

Stratification of subjects into two groups by date of recruitment,1995–2009 and 2010–2019, showed similar ages at onset and diagnosis, but the time to diagnosis decreased for UC (2 vs 1.55 yrs.) and increased for CD (2.2 vs 2.6 yrs.) in the later interval. Medications varied between decades, with aTNF increasing markedly in CD and UC (p<.001) and aminosalicylates decreasing in CD (p<.001) in the later years. Surgery for UC decreased from 25.2% to 20.7%, whereas surgery for CD remained the same (52.2% vs 52.5%).

Conclusion

We describe a large cohort of Hispanics with IBD studied over two decades. Differences over time may reflect changes in disease phenotypes, environmental influences and the impact of physician awareness and new management guidelines and therapies. Further studies are needed to better characterize this population and explore outcomes.
P681 Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn’s disease patients
Authors: Becker H , Kameli N , Rustichelli A , Britt H , Stassen F , Penders J , Jonkers D
Published: May 2021

Background

Crohn’s disease (CD) is a chronic inflammatory gastro-intestinal condition with a variable disease course. Impaired intestinal integrity and microbial dysbiosis are associated with disease onset and exacerbations. We hypothesized that a perturbed microbial activity in CD patients may contribute to the impaired barrier function. Therefore, this study aimed to examine the impact of faecal bacterial products of active CD patients, CD patients in remission, and healthy controls (HC) on mucin degradation and intestinal epithelial barrier function in vitro.

Methods

Six HC and twelve CD patients were included. Faecal samples were obtained within one week prior to endoscopy processed within 6 hours after collection. Disease activity was determined by the short endoscopic score for CD (SES-CD). Faecal water (FW) and bacterial membrane vesicles (MVs) were applied on mucin agar to determine mucin degradation. Further, differentiated Caco-2 cell monolayers were exposed to FW and MVs to assess transepithelial electrical resistance (TEER) and paracellular junction stability using permeation of fluorescein isothiocyanate-labelled dextran of 4 kDa. Relative abundances of faecal bacterial genera were evaluated by 16S rRNA gene amplicon sequencing.

Results

FW-induced mucin degradation was higher in CD samples as compared to HC (p<0.01), but was not linked to specific bacterial relative abundances. FW resulted in 78–87% decrease of TEER in three of the remissive (p<0.001) but not the active CD or HC samples. The decrease of TEER was not linked to increased paracellular permeability. MVs did not induce mucin degradation or epithelial barrier disruption.

Conclusion

The higher mucin degradation capacity of CD patient-derived FW might indicate contributions of microbial products to CD pathophysiology and warrants further investigation. Moreover, the altered epithelial resistance in some individuals is not due to paracellular alterations.
P689 Aeromonas infection and Inflammatory Bowel Disease: a single tertiary center analysis
Authors: Alves Da Silva J , Pereira Guedes T , Falcão D , Neves S , Costa P , Lago P , Pedroto I , Salgado M
Published: May 2021

Background

Aeromonas genus consists of gram-negative rods known to cause a spectrum of diseases in humans. Inflammatory bowel disease (IBD) is an idiopathic complex condition where multiple factors contribute to its development and progression. The association of Aeromonas infection with IBD manifestation have been proposed by other authors and is still largely unknown. We aim to look for the significance of Aeromonas infection and for significant differences between IBD and non-IBD patients.

Methods

A retrospective observational data retrieval and analysis was performed of all patients positive for Aeromonas in stool cultures, during a 10-year period, from a Portuguese tertiary and university setting hospital.

Results

Fifty patients, 56% of male sex and with a mean age of 42.1 years-old were included. Thirty-eight (76%) were non-IBD and 12 (24%) were IBD patients. IBD patients were more frequently under immunosuppressors. Two patients were asymptomatic and 44% develop mild, 44% moderate and 16.7% severe infection. The main Aeromonas strains isolated were Aeromonas hydrophila/caviae. Co-isolation with other bacteria was found in 4 non-IBD patients and histological findings compatible with Cytomegalovirus were found in 2 IBD patients. Non-IBD patients presented more frequently with fever and IBD patients with bloody diarrhea and abdominal pain. There was higher tendency for severe infection rate in IBD patients with higher antimicrobial therapy use. Steroids were exclusively used in IBD group. No significant differences were observed for isolation of Aeromonas resistant strains. From the IBD, 4 patients had the diagnosis of Ulcerative Colitis and 9 of Crohn’s Disease with colonic involvement. Of them 5 patients received the diagnosis after the acute episode of Aeromonas infection.

Conclusion

Clinical presentation of Aeromonas infection differ between IBD and non-IBD patients. Non-IBD patients had milder severity of infection with less use of antibiotics. Aeromonas infection seem to play an important role on the contribution of IBD manifestation.
Characterization of a Sex-Determining Region and Its Genomic Context via Statistical Estimates of Haplotype Frequencies in Daughters and Sons Sequenced in Pools
Authors: Cordaux Richard , Chebbi Mohamed Amine , Giraud Isabelle , Pleydell David Richard John , Peccoud Jean
Published: May 2021

Sex chromosomes are generally derived from a pair of autosomes that have acquired a locus controlling sex. Sex chromosomes may evolve reduced recombination around this locus and undergo a long process of molecular divergence. At that point, the original loci controlling sex may be difficult to pinpoint. This difficulty has affected many model species from mammals to birds to flies, which present highly diverged sex chromosomes. Identifying sex-controlling loci is easier in species with molecularly similar sex chromosomes. Here we aimed at pinpointing the sex-determining region (SDR) of Armadillidium vulgare, a terrestrial isopod with female heterogamety (ZW females and ZZ males) and whose sex chromosomes appear to show low genetic divergence. To locate the SDR, we assessed single-nucleotide polymorphism (SNP) allele frequencies in F1 daughters and sons sequenced in pools (pool-seq) in several families. We developed a Bayesian method that uses the SNP genotypes of individually sequenced parents and pool-seq data from F1 siblings to estimate the genetic distance between a given genomic region (contig) and the SDR. This allowed us to assign more than 43 Mb of contigs to sex chromosomes, and to demonstrate extensive recombination and very low divergence between these chromosomes. By taking advantage of multiple F1 families, we delineated a very short genomic region (∼65 kb) that presented no evidence of recombination with the SDR. In this short genomic region, the comparison of sequencing depths between sexes highlighted female-specific genes that have undergone recent duplication, and which may be involved in sex determination in A. vulgare.
The Axes of Life: A Roadmap for Understanding Dynamic Multiscale Systems
Authors: Chandrasekaran Sriram , Danos Nicole , George Uduak Z , Han Jin-Ping , Quon Gerald , Müller Rolf , Tsang Yinphan , Wolgemuth Charles
Published: May 2021

Synopsis

The biological challenges facing humanity are complex, multi-factorial, and are intimately tied to the future of our health, welfare, and stewardship of the Earth. Tackling problems in diverse areas, such as agriculture, ecology, and health care require linking vast datasets that encompass numerous components and spatio-temporal scales. Here, we provide a new framework and a road map for using experiments and computation to understand dynamic biological systems that span multiple scales. We discuss theories that can help understand complex biological systems and highlight the limitations of existing methodologies and recommend data generation practices. The advent of new technologies such as big data analytics and artificial intelligence can help bridge different scales and data types. We recommend ways to make such models transparent, compatible with existing theories of biological function, and to make biological data sets readable by advanced machine learning algorithms. Overall, the barriers for tackling pressing biological challenges are not only technological, but also sociological. Hence, we also provide recommendations for promoting interdisciplinary interactions between scientists.
Examining the expansion of qualitative network models towards integrating multifaceted human dimensions
Authors: Szymkowiak Marysia , Rhodes-Reese Melissa
Published: May 2021

Qualitative network models (QNMs) have become a popular tool to assess how ecosystems respond to a perturbation within ecosystem-based fisheries management strategies. Yet, the incorporation of humans into these models is often rudimentary, potentially limiting the accuracy and reliability of the model results. We developed QNMs focusing solely on the social components, derived from content analysis of the literature on the effects of the US Pacific halibut Individual Fishing Quota (IFQ) Program and evaluated how the QNMs performed with respect to simulating the programmatic effects on individual well-being components. The QNMs were effective at reproducing IFQ programmatic effects and demonstrating how well-being heterogeneity across user groups can be incorporated into network models. However, key mechanistic variables were omitted to maintain model stability, reducing our ability to fully replicate the IFQ system. We conclude that QNMs require improvement to incorporate human dimensions that reflect broader social realities. Yet, given the current structural limitations of these modelling frameworks coupled with the complexity of human decision making, there are likely to be continued issues with integrating humans accurately and representatively into these models.
A case of endovascular management to gain control of a lower gastrointestinal haemorrhage caused by appendiceal artery bleeding
Authors: Smith Eleanor J , Coventry Charles , Taylor Jeremy , De’ath Henry , Haque Ali
Published: May 2021

Bleeding from the appendix is a rare cause of lower gastrointestinal haemorrhage. Previous publications have noted diagnosis via colonoscopy or computed tomography angiogram and treatment via surgical or endoscopy. We report a case of large volume per rectal bleeding from the appendix, with diagnosis and treatment via angiography and coil insertion, which is the first of its kind reported in the literature.
Synaptomys cooperi(Rodentia: Cricetidae)
Authors: Rose Robert K , Linzey Alicia V
Published: May 2021

This account represents a thorough update of Mammalian Species 210 on the subject species by A. V. Linzey, incorporating 102 relevant references published since 1983. Synaptomys cooperi Baird, 1857, the southern bog lemming, is an arvicoline rodent. This compact snub-nosed rodent has a thick grayish coat, small eyes and ears, gray or silver venter, and a stubby tail as long as the hind foot. It occurs from Canadian maritime provinces to southeastern Manitoba, southward to Arkansas and northeastern North Carolina. This cold-adapted species lives in mesic grasslands in the Great Plains states, in wet meadows in some eastern states, and often in wet coniferous and other forest types in the north. Its presence often can be detected by distinctive green droppings. One of two species in the genus, S. cooperi is sometimes difficult to capture and study, leading to its status of conservation concern in some states and provinces.
Patient perspectives on treatment decision-making under clinical uncertainty: chemotherapy treatment decisions among stage II colon cancer patients
Authors: Brotzman Laura E , Crookes Danielle M , Austin Jessica D , Neugut Alfred I , Shelton Rachel C
Published: May 2021

The decision to use adjuvant chemotherapy (ACT) after surgical resection for stage II colon cancer remains an area of clinical uncertainty. Many patients diagnosed with stage II colon cancer receive ACT, despite inconclusive evidence of long-term clinical benefit. This study investigates patient experiences and perceptions of treatment decision-making and shared decision making (SDM) for ACT among patients diagnosed with stage II colon cancer. Stage II colon cancer patients engaged in treatment or follow-up care aged >18 years were recruited from two large NYC health systems. Patients participated in 30–60-min semi-structured interviews. All interviews were transcribed, translated, coded, and analyzed using a thematic analysis approach. We interviewed 31 patients, of which 42% received ACT. Overall, patient perspectives indicate provider inconsistency in communicating ACT harms, benefits, and uncertainties, and poor elicitation of patient preferences and values. Patients reported varying perceptions and understanding of personal risk and clinical benefits of ACT. For many patients, receiving a clear treatment recommendation from the provider limited their participation in the decision-making process, whether it aligned with their decisional support preferences or not. Findings advance understanding of perceived roles and preferences of patients in SDM processes for cancer treatment under heightened clinical uncertainty, and indicate a notable gap in understanding for decisions made using SDM models in the context of clinical uncertainty. Educational and communication strategies and training are needed to support providers in communicating uncertainty, risk, treatment options, and implementing clinical guidelines to support patient awareness and informed decisions.
Creating a family communication program during a pandemic
Authors: Donohue-Ryan Mary Ann , DeLuca Anna
Published: May 2021

The Family in Touch Program
Review of Genotype-Phenotype Correlations in Usher Syndrome
Authors: Nisenbaum Eric , Thielhelm Torin P. , Nourbakhsh Aida , Yan Denise , Blanton Susan H. , Shu Yilai , Koehler Karl R. , El-Amraoui Aziz , Chen Zhengyi , Lam Byron L. , Liu Xuezhong
Published: May 2021

Usher syndrome (USH) encompasses a group of clinically and genetically heterogenous disorders defined by the triad of sensorineural hearing loss (SNHL), vestibular dysfunction, and vision loss. USH is the most common cause of deaf blindness. USH is divided clinically into three subtypes—USH1, USH2, and USH3—based on symptom severity, progression, and age of onset. The underlying genetics of these USH forms are, however, significantly more complex, with over a dozen genes linked to the three primary clinical subtypes and other atypical USH phenotypes. Several of these genes are associated with other deaf-blindness syndromes that share significant clinical overlap with USH, pointing to the limits of a clinically based classification system. The genotype-phenotype relationships among USH forms also may vary significantly based on the location and type of mutation in the gene of interest. Understanding these genotype-phenotype relationships and associated natural disease histories is necessary for the successful development and application of gene-based therapies and precision medicine approaches to USH. Currently, the state of knowledge varies widely depending on the gene of interest. Recent studies utilizing next-generation sequencing technology have expanded the list of known pathogenic mutations in USH genes, identified new genes associated with USH-like phenotypes, and proposed algorithms to predict the phenotypic effects of specific categories of allelic variants. Further work is required to validate USH gene causality, and better define USH genotype-phenotype relationships and disease natural histories—particularly for rare mutations—to lay the groundwork for the future of USH treatment.
Responsiveness and Minimal Clinically Important Difference of the 6-minute Walk Distance in Patients Undergoing Lumbar Spinal Canal Stenosis Surgery
Authors: Takenaka Hiroto , Kamiya Mitsuhiro , Sugiura Hideshi , Nishihama Kasuri , Ito Atsuki , Suzuki Junya , Hanamura Shuntaro
Published: May 2021

Study Design:

This was a retrospective review of prospectively collected data.

Objective:

We aimed to evaluate the responsiveness of the 6-minute walk distance (6MWD) and determine the threshold of the minimal clinically important difference (MCID) in the 6MWD in patients who underwent surgery for lumbar spinal canal stenosis (LSS) surgery.

Summary of Background Data:

The 6MWD rapidly and objectively assesses the walking distance in patients with LSS. To date, no study has assessed the MCID in the 6MWD in patients who underwent LSS surgery.

Materials and Methods:

A total of 41 patients (16 women; average age: 69.4 y, SD: 7.8 y) were included and assessed preoperatively and at 6 months postoperatively. We evaluated the 6MWD and Oswestry Disability Index (ODI), which is a health-related patientrReported outcome, used as an anchor to calculate the MCID for in the 6MWD. We used 2 different approaches to examine the responsiveness of the 6MWD: internal and external responsiveness. The external responsiveness was assessed in 2 ways: one based on the anchoring questionnaire and the other based on the scale distribution of the scale. The anchor-based approach was evaluated using the Spearman rank correlation coefficient and the receiver operating characteristic curve. The distribution-based approach was evaluated using the minimal detectable change.

Results:

The ODI scores and 6MWD for each anchor significantly improved postoperatively. The correlation coefficient between changes in the 6MWD and ODI was r=−0.58. The area under the receiver operating characteristic curve for the ODI anchor was 0.70 (95% confidence interval: 0.52–0.89), and the cutoff value for the ODI anchor was 50 m (sensitivity=0.57, specificity=0.71). In the distribution-based approach, the minimal detectable change for the 6MWD was 105.9 m.

Conclusions:

Both the internal and the external responsiveness of the 6MWD were validated using the ODI. Therefore, the MCID in the 6MWD in patients undergoing LSS surgery ranges from 50 to 105.9 m.

Level of Evidence:

Level III.
Computed tomography image fusion, Coaxial guidewire technique, Fast intraprocedural cortisol testing technique improves success rate and decreases radiation exposure, procedure time, and contrast use for adrenal vein sampling
Authors: Liu Zhenjie , He Minzhi , Song Xiaoxiao , Xu Fangfang , Zhang Binna , Chen Bin , Yu Peng , Zhou Hanlei , Shan Lizhen , Wang Hongya , Gu Zheng , Zhong Shan , Xu Xiaohong , Tao Zhihua , Chen Bing , Gu Wei
Published: May 2021

Background:

Adrenal vein sampling (AVS) is recommended for discriminating patients with unilateral primary aldosteronism from bilateral disease. However, it is a technically demanding procedure that is markedly underused. We developed a computed tomography image fusion, coaxial guidewire technique, fast intraprocedural cortisol testing (CCF) technique to improve AVS success rate, which combines CT image fusion, coaxial guidewire technique, and fast intraprocedural cortisol testing.

Objective:

To evaluate the effectiveness and safety of the AVS--CCF technique.

Methods:

We retrospectively evaluated 105 patients who undervent AVS from June 2016 to October 2020. There were 51 patients in the AVS--CCF group and 54 patients in the AVS group. We compared two groups with technical success rate, procedure time, radiation exposure, volume of contrast medium, and complications (adrenal vein rupture, dissection, infarction, or thrombosis; intraglandular or periadrenal hematoma; and contrast-induced nephropathy).

Results:

The technical success rate was higher for AVS--CCF than for AVS without CCF (98 vs. 83.3% for bilateral adrenal veins, P = 0.016). AVS--CCF was associated with a shorter procedure time (63.6 ± 24.6 vs. 94.8 ± 40.8 min, P < 0.001), shorter fluoroscopy time (15.6 ± 12.6 vs. 20.4 ± 15.0 min, P = 0.043), and lower contrast medium volume (25.10 ± 21.82 vs. 44.1 ± 31.0 ml, P < 0.001). There were no significant differences between groups with respect to the time for cannulating the left or right adrenal vein or the peak skin radiation dose. Adrenal vein rupture occurred in 14 patients and intraglandular hematoma in 1 patient.

Conclusion:

The CCF technique during AVS not only contributed to improved technical success rates but also associated with decreased procedure time, radiation exposure, and contrast medium volume.
Centrifugal and Roller Pumps in Neonatal and Pediatric Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis of Clinical Outcomes
Authors: Papadimas Evangelos , Leow Lowell , Tan Ying Kiat , Shen Liang , Ramanathan Kollengode , Choong Andrew M.T.L. , MacLaren Graeme
Published: May 2021

Extracorporeal membrane oxygenation (ECMO) is an invaluable means of supporting critically ill children with refractory respiratory or cardiac failure. Controversy remains; however, whether roller or centrifugal pumps are superior, particularly in infants. We performed a comprehensive search on PubMed, Embase, and Scopus for studies comparing the use of centrifugal and roller pumps in the pediatric and neonatal population from 1973 until March 1, 2020. All prospective and retrospective comparative studies were screened. Single-arm studies and those that included adult patients were excluded. The primary endpoint was survival to discharge. Secondary endpoints were complications (mechanical, cardiac, pulmonary, neurologic, renal, and hemolytic) and requirements for inotropic support. Random effects meta-analyses across all clinical endpoints were conducted. A total of four studies with 9111 patients were included. There was a statistically significant difference in in-hospital mortality, favoring the groups where roller pumps were used. Roller pumps were associated with fewer episodes of hemolysis, mechanical complications, cardiac complications, renal complications, and less inotropic support. ECMO with roller pumps may be associated with lower mortality in children. Roller pumps were associated with fewer complications, as well as reduced hemolysis and use of inotropes.
Significant variations across European centres in implementing recommended guidelines for the paediatric gastroenterology endoscopy suite during the COVID-19 pandemic
Authors: Athiana Ilektra , Légeret Corinne , Bontems Patrick , Dall’Oglio Luigi , De Angelis Paola , Dias Jorge Amil , Hauser Bruno , Homan Matjaž , Narula Priya , Norsa Lorenzo , Oliva Salvatore , Papadopoulou Alexandra , Romano Claudio , Thomson Mike , Vila-Miravet Victor , Furlano Raoul I.
Published: May 2021

Background:

The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published recommendations regarding protection for the paediatric endoscopist during the coronavirus 2019 (COVID-19) pandemic.The aim of this survey was to investigate whether European paediatric gastroenterology centres applied the recommendations and how this extraordinary situation was handled by the different centres.

Results:

Twelve paediatric European gastroenterology centres participated. Nine centres (75%) screened their patients for possible COVID-19 infection before the procedure, the same amount of hospitals changed their practice based on the ESPGHAN recommendations. Six-seven percentage of the centres reduced the staff in the endoscopy suite, 83% of the units used FFP2/3 masks and protective goggles during the procedure and 75% wore waterproof gowns.

Conclusion:

Uniform guidelines could not be applied by all European hospitals at a certain time point of the viral spread, as different regions of Europe were not only affected differently by COVID-19, but also had different access to personal protective equipment.
Venous thromboembolic risk stratification in pediatric trauma: A Pediatric Trauma Society Research Committee multicenter analysis
Authors: Labuz Daniel F. , Cunningham Aaron , Tobias Joseph , Dixon Alexandra , Dewey Elizabeth , Marenco Christopher W. , Escobar Mauricio A. , Hazeltine Max D. , Cleary Muriel A. , Kotagal Meera , Falcone Richard A. , Fallon Sara C. , Naik-Mathuria Bindi , MacArthur Taleen , Klinkner Denise B. , Shah Aashka , Chernoguz Artur , Orioles Alberto , Zagel Alicia , Gosain Ankush , Knaus Maria , Hamilton Nicholas A. , Jafri Mubeen A.
Published: May 2021

BACKGROUND

Venous thromboembolism (VTE) in injured children is rare, but its consequences are significant. Several risk stratification algorithms for VTE in pediatric trauma exist with little consensus, and all are hindered in development by relying on registry data with known inaccuracies. We performed a multicenter review to evaluate trauma registry fidelity and confirm the effectiveness of one established algorithm across diverse centers.

METHODS

Local trauma registries at 10 institutions were queried for all patients younger than 18 years admitted between 2009 and 2018. Additional chart review was performed on all “VTE” cases and random non-VTE controls to assess registry errors. Corrected data were then applied to our prediction algorithm using 10 real-time variables (Glasgow Coma Scale, age, sex, intensive care unit admission, transfusion, central line placement, lower extremity/pelvic fracture, major surgery) to calculate VTE risk scores. Contingency table classifiers and the area under a receiver operator characteristic curve were calculated.

RESULTS

Registries identified 52,524 pediatric trauma patients with 99 episodes of VTE; however, chart review found that 13 cases were misclassified for a corrected total of 86 cases (0.16%). After correction, the algorithm still displayed strong performance in discriminating VTE-fated encounters (sensitivity, 69%; area under the receiver operating characteristic curve, 0.96). Furthermore, despite wide institutional variability in VTE rates (0.04–1.7%), the algorithm maintained a specificity of >91% and a negative predictive value of >99.7% across centers. Chart review also revealed that 54% (n = 45) of VTEs were directly associated with a central line, usually femoral (n = 34, p < 0.001 compared with upper extremity), and that prophylaxis rates were underreported in the registries by about 50%; still, only 19% of the VTE cases had been on prophylaxis before diagnosis.

CONCLUSION

The VTE prediction algorithm performed well when applied retrospectively across 10 diverse pediatric centers using corrected registry data. These findings can advance initiatives for VTE screening/prophylaxis guidance following pediatric trauma and warrant prospective study.

LEVEL OF EVIDENCE

Clinical decision rule evaluated in a single population, level III.