bluuebunny/crossref_metadata_2025 huggingface dataset:
P413 Characteristics of the stricture, not the ongoing treatment, influence the outcome of endoscopic dilatation in recurrent Crohn’s disease
Authors: Ladrón Abia P , Alonso N , Beltrán B , Minguez A , Sáez-González E , Pons-Beltrán V , Nos P , Iborra M
Published: May 2021

Background

Endoscopic balloon dilatation (EBD) is a conservative alternative for the treatment of post-surgical anastomotic strictures in Crohn’s disease (CD) that improves obstructive symptoms and could delay or avoid further surgeries. However, the usefulness of this technique and predictors of efficacy have been poorly evaluated in a homogeneous cohort.

Aim

to evaluate the efficacy of EBD in CD patients with anastomotic strictures as well as to analyze therapeutic success factors and the rate of adverse events.

Methods

Observational study in a tertiary hospital of a cohort of patients with diagnosis of CD who underwent EBD for anastomotic stricture after previous surgery and with obstructive symptoms. Clinical, demographic and disease characteristics, treatment used, surgery data, inflammatory parameters at time of dilatation, number of dilatations, complications and needed for subsequent surgery were analyzed. Technical success was defined when the endoscope was passed through the stricture after procedure. Therapeutic success per patient was considered when patient did not need surgery at the end of the follow-up.

Results

63 EBD were performed in 32 patients. Figure 1 shows the clinical and demographic characteristics of the patients. The diameters of the balloons used were 12-15 mm and 15-18 mm. Of the 63 examinations performed, 63.5% (n=40) showed technical success. The therapeutic success per patient was 62.5% (n=20) at 6 years of mean follow-up. Twelve patients required new surgery. The visualized neoileon after EBD had no significant recurrence (Rutgeerts i0-i2a) in 80% of dilatations. The adverse event rate was 3.1% (n=2) a microperforation and a major bleeding, both patients with Rutgeerts i4. The stricture length was the only predictor of technical and therapeutic success. Strictures with more than 40 mm of length were associated with poor efficacy. Neither the type of surgical anastomosis, current treatment, inflammatory parameters levels or balloon diameter were predictors of therapeutic success.

Conclusion

EBD appears to be a safe and effective technique that could avoid further surgery in up to two thirds of anastomotic strictures in CD in long-term recurrent CD. Longer stricture length and the presence of severe recurrence were associated with poor response and complications.
P444 Fecal calprotectin response to anti-tumor necrosis factor alpha induction and maintenance in Pediatric Inflammatory Bowel Disease
Authors: Matar M , Levi R , Zvuloni M , Shamir R , Assa A
Published: May 2021

Background

Fecal calprotectin (FC) is a sensitive surrogate marker of mucosal inflammation in inflammatory bowel disease (IBD). Our aim was to asses the effect of anti-tumor necrosis factor alpha (TNFα) induction and maintenance therapy on FC levels in children with IBD.

Methods

The medical records of pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 were reviewed retrospectively. We identified 63 patients who had FC levels measured prior to anti TNFα induction with sequential measurements during the first months of therapy. The main outcome measures were time to FC response according to cut-offs of 250,150,100 and 50µgr/gr. Variables affecting FC response were analyzed using multivariate analysis.

Results

Out of 63 patients, mean age 13.6 (±3) years, females 28(44.4%),54 (85.7%) had Crohn’s disease. The median (interquartile range) FC at baseline was 715 µgr/gr (312–1700). The outcomes of <250, <150, <100 and <50 µgr/gr were achieved by 52 (82%), 51 (81%), 44 (70%) and 32 (50%) patients, respectively. The mean time (± standard error) for achieving these cut-offs were 4.8 ±0.8, 7.9±1.3, 10±1.8 and 18.5±7.2 months, respectively. There was no statistically significant correlation between age, gender, type of disease, Paris classification, extra-intestinal manifestation, albumin levels, erythrocyte sedimentation rate, C-reactive protein and the pediatric disease activity indexes at baseline and FC response. Furthermore, there was no statistically significant correlation between anti TNFα trough concentration during induction and FC response.

Conclusion

In pediatric patients with IBD, FC response (<250µgr/gr) was achieved by the majority of patients within a relatively short period of time. Nevertheless, calprotectin normalization (<100µgr/gr) required an average period of approximately one year in responders.
P464 Steroid dependency in patients with Ulcerative Colitis treated with advanced therapies in a German real-world-setting
Authors: Bokemeyer B , Picker N , Wilke T , Rosin L , Patel H
Published: May 2021

Background

An important treatment goal in Ulcerative Colitis (UC) is a long-lasting corticosteroid (CS)-free remission. Avoidance of steroid dependency in these patients is essential as chronic CS use is known to be associated with an increased risk for multiple severe adverse events.

This study aimed to identify CS dependency in patients with moderate to severe UC treated with advanced therapies.

Methods

This German claims data analysis includes adult patients with ≥2 outpatient diagnoses and/or one inpatient diagnosis for UC (ICD-10: K51) in whom an advanced therapy (anti-TNF agent, vedolizumab or tofacitinib) was initiated between 01/01/2015–30/06/2019.

CS dependency was indicated by ≥2 prescriptions of systemic CS and/or oral budesonide within a median follow-up of 23.4 months. Prior CS use was evaluated by outpatient prescriptions observed in a 12-months baseline period.

Costs were assessed until the end of the study period or loss to follow-up considering all-cause expenses for inpatient and outpatient visits, and approximated indirect cost related to sick-leave days.

Exceeding the recommended dose in maintenance therapy by more than 150% was rated as an escalation of therapy. Time to the therapy discontinuation, escalation or first UC-related hospitalization from start of index therapy were estimated using Kaplan-Meier analysis.

Results

Of 574 included UC patients with a new advanced therapy, 252 (43.9%) received ≥2 prescriptions of CS while on treatment with advanced agents in the observation period up to 24 months. Altogether, 496 patients (86.4%) had prior experience with CS in the 12-months baseline-period. Among patients with ≥2 CS prescriptions, 47.0% had switched their index therapy to another advanced agent after 24 months (31.2% without CS dependency). Median time to therapy discontinuation was 17.3 months in CS-dependent patients; and 19.3 months in those without CS dependency (p = 0.639). There were no differences between naïve or advanced therapy experienced patients, but with clearly more discontinuations in patients with previously more than 1 advanced therapy (p<0.001). CS-dependent patients were more likely to require dose escalation/UC-related hospitalization within the first two years after treatment start (26.7% vs. 16.1%; p = 0.018/ 44.1% vs. 26.6%; p = 0.048; Figure 1). Total cost per patient-year was significantly higher in patients with than without CS dependency (40,884 € vs. 37,449 €; p < 0.001).

Conclusion

Most UC patients starting new advanced therapies were previously treated with CS, and more than two-fifths continue to be CS dependent even after starting such a therapy. More effective therapies are needed to achieve CS-free remission.
P550 Short term effects of a combined lifestyle intervention in patients with Inflammatory Bowel Disease
Authors: Lamers C R , de Roos N M , Heerink H H , van de Worp - Kalter L A , Witteman B J M
Published: May 2021

Background

Diet and physical activity might help to improve quality of life and maintain remission in patients with inflammatory bowel disease (IBD). In other conditions, interventions in which diet and physical activity are combined seem to be more effective than separate interventions. Therefore, we assessed the effect of a combined lifestyle intervention on the impact of disease on daily life, clinical disease activity, fatigue and quality of life in patients with Crohn’s disease (CD) or ulcerative colitis (UC).

Methods

A single arm intervention study was performed in IBD patients in remission or with mildly active disease. Participants received personal advice to improve their diet and level of physical activity by a dietician and a physiotherapist in one face-to-face and one telephone consult. These advices were supported by guidelines based on the Dutch dietary and physical activity guidelines, a recipe app and a booklet with physical activity exercises. IBD disability index (IBD-DI) to assess impact of disease on daily life, clinical disease activity questionnaires (P-HBI or P-SCCAI), IBD fatigue (IBD-F) patient self-assessment scale and IBD quality of life questionnaire (IBDQ) were completed. The Eetscore Food Frequency Questionnaire (Eetscore FFQ) and Short Questionnaire to Assess Health-enhancing physical activity (SQUASH) were used to assess diet and physical activity. Changes from baseline to 5 weeks after start were investigated by paired samples t-tests or Wilcoxon signed rank tests.

Results

We included 29 participants. At time of this preliminary analysis, 25 participants completed baseline and 5-week assessments (11 males, 11 CD, median age 36 years [IQR 29–53], median BMI 25 kg/m2 [IQR 24–28]). After 5 weeks, diet quality had significantly improved (p<0.001), but level of physical activity had not (p=0.509). Impact of disease on daily life (IBD-DI) decreased with 2.5 points (95%CI -5.5-0.4; p=0.09). Disease activity did not change significantly. There was a significant decrease in fatigue (median IBD-F 20 [IQR 8–29] to 15 [IQR 3–24; p=0.03]) and a significant increase in quality of life (median IBDQ 194 [IQR 179–206] to 196 [IQR 186–209; p=0.03]).

Conclusion

These preliminary results suggest that a combined lifestyle intervention is effective to reduce fatigue and to increase quality of life in patients with IBD, at least in the short term. Impact of disease on daily life and clinical disease activity did not improve significantly. Participants reported their level of physical activity to be restricted due to COVID-19 measures, which could explain the lack of effect on this outcome. This study is still ongoing and we expect follow-up data up till 1 year after start.
P552 Assessing adherence to objective disease monitoring and outcomes with adalimumab in a real-world IBD cohort
Authors: Xiao Y , Al Khoury A , Golovics P , Kohen R , Afif W , Wild G , Friedman G , Galiatsatos P , Hilzenrat N , Szilagyi A , Wyse J , Cohen A , Bitton A , Bessissow T , Lakatos P L
Published: May 2021

Background

Data suggests that tight objective monitoring may improve clinical outcomes in IBD.

Methods

The aim of this study is to assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015–January 1,2019 [338 Crohn’s disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms (assessed by Harvey-Bradshaw-Index, partial Mayo score), C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3, 6, 9, and 12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method

Results

Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP was also available in nearly all patients but testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months (p=0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimisation in CD and UC patients (pLogrank=0.026 for UC & p=0.09 for CD). Overall drug sustainability did not differ.

Conclusion

Clinical and CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.
P575 Nutrition and Inflammatory Bowel Disease – a nationwide survey of patients, gastroenterologists and dietitians
Authors: McCarthy N , Schultz M , Wall C
Published: May 2021

Background

Literature indicates that Inflammatory Bowel Disease (IBD) patients (pts), who are at high risk of malnutrition, often adjust their diet following diagnosis and wish to receive specialised nutrition advice from their healthcare team. Dietitians (DTs) are health professionals (HPs) with specialist nutrition expertise. Our aim was to assess nutrition advice provided by different HPs.

Methods

Electronic surveys were disseminated to New Zealand IBD pts, DTs and gastroenterologists (GIs) asking about experience of, and practice providing, IBD nutrition advice. DTs and GIs were asked which nutrition interventions they recommend. DTs responded separately for Crohn’s disease (CD) and Ulcerative Colitis (UC) while GIs responded about IBD pts as a group.

Results

Surveys were completed by 407 pts, 79 DTs and 40 GIs.

Almost all (97%) GIs report their IBD pts ask about nutrition and 95% said they provide nutrition advice. DTs and GIs commonly recommended specific diets: modified fibre, high protein/energy and low fermentable carbohydrate diets, with occasional use of some other diet regimes (Table 1).

Half of the pts (52%) had seen a DT for advice and 31% had received nutrition advice from other HPs, commonly their GI, general practitioner or IBD nurse. Some patients (13%) received nutrition advice from other practitioners: nutritionist, naturopath, other medical doctors, counsellor, cannabis practitioner, integrated health professional, osteopath and herbalist.

Patients frequently received general nutrition advice and specific diet advice including various strict exclusion diets and herbal, probiotic and vitamin/mineral supplements from DTs and non-DT HPs (Table 1). No DTs or GIs recommended low carb, high fat, sugar free or ketogenic diets in IBD, which were recommended to pts by other HPs.

Conclusion

Pts with IBD often ask for nutrition advice but only half had seen a DT. The advice given by HPs (medical and non-medical) varies and it appears that this high-risk group of pts is not always offered advice with evidence of scientific benefit in pts with IBD. Pts would benefit from greater access to DTs with IBD expertise.
P597 Cycling Anti-TNF Therapy in Inflammatory Bowel Disease: Effectiveness and Durability of Switching from adalimumab to infliximab
Authors: Steinberg J , Andersen M , Krugliak Cleveland N , Traboulsi C , Rodriguez T , Cohen R , Dalal S , Micic D , Pekow J , Atsushi S , Rubin D
Published: May 2021

Background

Anti-TNF therapy remains the cornerstone of moderate to severe inflammatory bowel disease (IBD) treatment. There are few data regarding switching from subcutaneous (SubQ) to intravenous (IV) agents. We evaluated the clinical utility of cycling adalimumab (ADA) for infliximab (IFX) in IBD patients (pts) treated at a tertiary center.

Methods

This is a retrospective observational study where we evaluated pts with IBD who cycled from ADA to IFX from 2010 to 2018. Pts were followed for 1 year following IFX initiation. We reviewed baseline demographic and clinical data. Primary outcomes included changes in CRP and clinical disease activity indices which were statistically analyzed using Wilcoxon Signed Rank Test.

Results

24 pts with Crohn’s disease (CD) and 11 with ulcerative colitis (UC) were included. Median age at time of IFX initiation in the overall cohort was 33 years with median disease duration of 10 years. Most pts in the UC cohort had pancolitis (63.6%), while the CD cohort mostly had ileocolonic disease (79.2%). Prior to IFX initiation, median baseline CRP was 8 (IQR 15), with median HBI of 3.5 (IQR 5), and SCCAI of 3.5 (IQR 4) in the CD and UC cohorts, respectively. Additional baseline demographics are in Table 1. Following median 12 months on ADA therapy in the overall cohort, 16 pts (45.7%) discontinued ADA due to primary or secondary loss of response, 8 pts (22.8%) due to anti-drug antibody formation, and 11 pts (31.4%) due to adverse events or unclear causes. At the time of starting IFX therapy, 17 pts (48.6%) were using steroids, while 24 pts (68.6%) were on immunomodulatory therapy. In the overall cohort, after cycling to IFX, median CRP was lower at 8 weeks (4; IQR 9), 26 weeks (3; IQR 11), and 52 weeks (5; IQR 10) as compared to baseline; only the 8 week CRP reached statistical significance (P=0.0447, 0.0662, and 0.0876, respectively). In the CD cohort, median CRP was significantly lower at 8 weeks (7; IQR 6; P=0.0314) and 52 weeks (5; IQR 7; P=.0410) as compared to baseline (12.5; IQR 14). Although signals of median HBI and SCCAI scores trended lower after 8 weeks, 26 weeks, and 52 weeks of IFX therapy, these did not reach statistical significance. A total of 15 pts (43.0%) stopped IFX prior to one year. Subgroup analysis of 5 pts who developed anti-ADA antibodies demonstrated statistically significant reduction of median CRP (10; IQR 22.5; P=.043) after 52 weeks of IFX therapy. Additional results are detailed in Table 2.

Conclusion

Cycling anti-TNF therapy from ADA to IFX offers clinical utility in preserving mechanistic benefit of TNF-α blockade in IBD pts leading to improvement of CRP, particularly in CD pts and those who developed immunogenicity to ADA.
P602 Vedolizumab subcutaneous influencing disease course in Constant-care app solution
Authors: Nørgaard J , Malte R , Charlotte P L , Mette B , Eva F , Petra W , Dorit A , Lotte S , Johan B , Pia M
Published: May 2021

Background

The Constant-care app solution (CC) has been shown to empower patients with mild-moderate Ulcerative Colitis (UC) in 5-ASA treatment and improve disease specific quality of life (1). Here we present preliminary data on our study to investigate the effects of CC on quality of life in patients with moderate-severe UC or Crohns Disease (CD) treated with s.c.vedolizumab, launched in June 2020 in Denmark.

Methods

The study is an ongoing non-interventional, observational study. Patients are homemonitored via CC for 24 months. CC shows data on patient’s disease status, grouping them into three: green (remission), yellow (worsening), red (severe disease). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Greater Copenhagen. Simple Clinical Colitis Index (SCCAI), Harvey-Bradshaw Index (HB-I), Fecal calprotectin (FC) and short QoL (0–70) are measured every two months or during a flare up between fixed screenings. Serious adverse events (SAE) and adverse events (AE) are monitored.

Results

19 patients out of 40 have been included, 8 with CD and 11 with UC. None experienced SAEs. Five experienced AEs, of which four discontinued treatment. One patient experienced treatment failure during this study.

Of the 15 patients, two are in complete remission, (Q2 respectively Q3). Five of the remaining patients have not entered more than two data entries in CC (data not shown).All patients sustained remission based on FC, except for two data points for two individual patients. Good QoL ≥ 50 was almost unchanged for 6 patients.

Conclusion

IBD CC has proven a usefull tool for surveillance and maintenance of remission in IBD patients treated with s.c. vedolizumab. S.c. vedolizumab has in this patientgroup, shown to provide sustainable QoL, sustained remission, and to have few AEs.

1) Elkjaer M, Shuhaibar M, Burisch J, Bailey Y, Scherfig H, Laugesen B, et al. E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided ‘Constant-care’ approach. Gut. 2010;59(12):1652–61.
P637 Incidence rate and clinical outcome of severe COVID-19 in Inflammatory Bowel Disease patients in a population-based setting
Authors: Rezazadeh Ardabili A , Creemers R H , Jonkers D M A E , Romberg-Camps M J L , Pierik M J , van Bodegraven A A
Published: May 2021

Background

The broad use of immunosuppressants and biologicals in Inflammatory Bowel Disease (IBD) patients increases the susceptibility to severe infections, and possibly COVID-19. Recently, in a Swedish population-based study it was suggested that IBD patients are at an increased risk of hospitalization for COVID-19, although course of COVID-19 did not differ from controls. Data on the outcome of COVID-19 in IBD patients from heavily affected regions remain, however, limited. South-Limburg has the second highest COVID-19 mortality rate in the Netherlands. We aimed to determine the incidence rate and outcome of severe COVID-19 in IBD patients in a population-based setting in South-Limburg.

Methods

We identified all IBD patients who presented at the emergency department (ED) of the only two hospitals covering the whole South-Limburg region with COVID-19 associated symptoms between February 27 and November 1, 2020. Confirmed COVID-19 diagnosis was defined by a combination of COVID-19 associated symptoms and either a positive SARS-CoV-2 PCR or a CT-CORADS score ≥4. As primary outcome, the incidence rate of severe COVID-19 (i.e. confirmed COVID-19 diagnosis requiring hospitalization, and/or resulting in ICU admission or death) was determined. Baseline characteristics and data on COVID-19 course were collected. At present, the total IBD population in South-Limburg is set at 4980 patients.

Results

During a follow-up of 3384 person-years, a total of 61 IBD patients (1.22%) presented with COVID-19 associated symptoms at one of the two hospital’s ED. Of these, 18 IBD patients (0.36%; 11 UC, 7 CD) fulfilled the criteria for severe COVID-19, corresponding to an incidence rate of 5.3 per 1000 person-years. Furthermore, 12/18 patients were using immunosuppressive medication for their IBD. Mean age at time of admission was 64.5 years (SD: 10.8) and 55.6% were male. All hospitalized patients had at least one comorbidity (with ≥ 1 comorbidity in 13/18 patients (72.2%)), cardiovascular disease being most prevalent (12/18). Mean BMI at time of admission was 27.3 (SD: 4.2). Thirteen patients (72.2%) required oxygen support and three patients (16.7%) ICU admission (of which two needed mechanical ventilation), translating to an incidence rate of 0.9 per 1000 patient-years for ICU admission. Median length of hospitalization was 11 days (IQR: 5.3–18.3). No IBD patients died due to severe COVID-19.

Conclusion

The incidence rate of severe COVID-19 among IBD patients in a population-based setting in a heavily affected region was 5.3 per 1000 person-years. Despite frequent use of immunosuppressive medication and high region-specific mortality rates, clinical outcomes of severe COVID-19 were comparable to the general population and in line with recent literature.
P647 Awareness, knowledge and use of mesenchymal stem cells – a global survey among gastroenterologists and colorectal surgeons
Authors: Williams P , Klersy C , Karki C , Bennett D , Rodríguez A M , Ciccocioppo R
Published: May 2021

Background

This study aimed to understand awareness, knowledge, and perception of mesenchymal stem cells (MSCs) among physicians, with particular focus on the complex perianal fistula (CPF) in Crohn’s disease (CD) indication.

Methods

A cross-sectional, web-based survey of currently practicing and registered gastroenterologists (GIs) and colorectal surgeons (CRs) across 15 countries in North America, Europe and Asia Pacific was undertaken. Descriptive analyses of data on awareness, knowledge, and perception of MSCs, willingness to use them in clinical practice and potential concerns were conducted overall and by medical specialty. Missing responses were allowed, thus denominators differed among questions (N values reported throughout). Multivariable logistic regression was used to examine factors associated with moderate/strong awareness of MSCs.

Results

Of 146 physicians, 115 (79%) were aware of MSCs (63% strong/moderate; 37% limited awareness), including 101 GIs (88%) and 14 CRs (12%). Of these, 21 physicians (19%, N=112) had treated ≥1 patient with MSCs.

Among the aware physicians, the majority were moderately/largely interested in MSCs (87%, N=113), were willing to use them for patients with CD and CPF (82%, N=108) and believed MSCs address an unmet need for these patients (93%, N=101). However, there was a marked heterogeneity as to the assumed definition and mechanism of action (MoA) of MSCs (Figure 1). By specialty group, more CRs (50%) than GIs (31%) defined correctly MSCs as an immunomodulatory therapy.

The majority of the physicians aware of MSCs stated that they have limited/no knowledge of this therapy (64%), its efficacy (51%), safety (53%) and MoA (65%) in patients with CPF in CD (N=105 for all questions). Many physicians (46%; N=107) also expressed concerns about using MSCs in these patients.

In physicians with concerns, long-term efficacy, long-term safety, and cost were the most frequently reported concerns, both overall (Figure 2) and by each specialty group (data not shown).

The multivariable logistic regression showed that attendance at discussions or presentations on MSCs in the past 2 years (p<0.0001) and seeing more patients with CD per year (p=0.0002) were associated with increased awareness of the therapy.

Conclusion

In this study, the majority of physicians demonstrated interest and willingness to use MSCs in clinical practice. However, the survey showed a perceived lack of knowledge of what MSCs are and how they work in patients with CPF in CD. This may explain physicians’ concerns about using MSCs in this indication. Increased communication and education regarding MSCs are required to alleviate physicians’ concerns and increase the uptake of this therapy in routine practice.

Sponsor: Takeda Pharmaceuticals USA, Inc.
P690 Changes of intestinal microbiota in patients with inflammatory bowel diseases
Authors: Baryshnikova N , Uspenskiy Y , Suvorova M , Lyudyno V , Suvorov A
Published: May 2021

Background

Normal microbiota is one of the main topic controling normal function of human organism. Microbiota changes and dysbiosis are the important factors in the pathogenesis of different digestive diseases, including inflammatory bowel diseases (IBD). The aim: estimation the intestinal microbiota changes in patients with IBD.

Methods

We investigated fecal samples to determine features of intestinal microbiota in 17 patients with IBD in acute phase of diseases: 10 patients with ulcerative colitis and 7 patient with Crohn’s disease, four patients received therapy with immunodiological agents. For feces analysis we used real-time polymerase chain reaction with fluorescent detection. Statistical processing was performed using the SPSS8.0 software package.

Results

100% of patients showed some changes in gut microbiota. These disorders were different in patients but no any significant changes in ulcerative colitis and Crohn’s disease patients. We saw the most frequent and significant changes:

1. decrease of Lactobacillus spp. level was determined in 59% of those examined

2. increase of Bifidobacterium spp. level was determined in 47% of patients

3. changing of the ratio of Bacteroides spp./Faecalibacterium prausnitzii towards increase of Bacteroides - in 24% of patients

4. frequency of occurrence of C. difficile was 24% of patients

5. frequency of occurrence of Candida spp. was in 35% of patients.

In a number of patients, increased growth of opportunistic bacteria was detected: Proteus vulgaris/mirabilis - 24%, Citrobacter spp. - 29%, Enterobacter spp. - 12%.

Microboal indirect microbial markers of colon oncopathology Fusobacterium nucleatum was identified in 18% and Parvimonas micra - in 24%. F. nucleatum and P. micra have higher frequency in patient who received immimmunodiological agents.

Conclusion

Patients with IBD show a downward trend in Lactobacillus spp. and increasing Bifidobacterium spp., whereby lacto-containing probiotics may be recommended for such patients and Bifidobacteria-containing probiotic may be not recommended. There is also a relatively high incidence of F. nucleatum and P. micra in IBD patients, which dictates the need for dispensary surveillance of these patients not only for the purpose of controlling the onset and maintenance of remission, but also for the purpose of early detection of colorectal cancer and IBD-associated malignancies.
Benchmarking and scalability of machine-learning methods for photometric redshift estimation
Authors: Henghes Ben , Pettitt Connor , Thiyagalingam Jeyan , Hey Tony , Lahav Ofer
Published: May 2021

Obtaining accurate photometric redshift (photo-z) estimations is an important aspect of cosmology, remaining a prerequisite of many analyses. In creating novel methods to produce photo-z estimations, there has been a shift towards using machine-learning techniques. However, there has not been as much of a focus on how well different machine-learning methods scale or perform with the ever-increasing amounts of data being produced. Here, we introduce a benchmark designed to analyse the performance and scalability of different supervised machine-learning methods for photo-z estimation. Making use of the Sloan Digital Sky Survey (SDSS – DR12) data set, we analysed a variety of the most used machine-learning algorithms. By scaling the number of galaxies used to train and test the algorithms up to one million, we obtained several metrics demonstrating the algorithms’ performance and scalability for this task. Furthermore, by introducing a new optimization method, time-considered optimization, we were able to demonstrate how a small concession of error can allow for a great improvement in efficiency. From the algorithms tested, we found that the Random Forest performed best with a mean squared error, MSE = 0.0042; however, as other algorithms such as Boosted Decision Trees and k-Nearest Neighbours performed very similarly, we used our benchmarks to demonstrate how different algorithms could be superior in different scenarios. We believe that benchmarks like this will become essential with upcoming surveys, such as the Vera C. Rubin Observatory’s Legacy Survey of Space and Time (LSST), which will capture billions of galaxies requiring photometric redshifts.
Health Care Needs of Deaf Signers: The Case for Culturally Competent Health Care Providers
Authors: Jacob Sabrina A. , Palanisamy Uma Devi , Napier Jemina , Verstegen Daniëlle , Dhanoa Amreeta , Chong Elizabeth Yie-Chuen
Published: May 2021

There is a need for culturally competent health care providers (HCPs) to provide care to deaf signers, who are members of a linguistic and cultural minority group. Many deaf signers have lower health literacy levels due to deprivation of incidental learning opportunities and inaccessibility of health-related materials, increasing their risk for poorer health outcomes. Communication barriers arise because HCPs are ill-prepared to serve this population, with deaf signers reporting poor-quality interactions. This has translated to errors in diagnosis, patient nonadherence, and ineffective health information, resulting in mistrust of the health care system and reluctance to seek treatment. Sign language interpreters have often not received in-depth medical training, compounding the dynamic process of medical interpreting. HCPs should thus become more culturally competent, empowering them to provide cultural- and language-concordant services to deaf signers. HCPs who received training in cultural competency showed increased knowledge and confidence in interacting with deaf signers. Similarly, deaf signers reported more positive experiences when interacting with medically certified interpreters, HCPs with sign language skills, and practitioners who made an effort to improve communication. However, cultural competency programs within health care education remain inconsistent. Caring for deaf signers requires complex, integrated competencies that need explicit attention and practice repeatedly in realistic, authentic learning tasks ordered from simple to complex. Attention to the needs of deaf signers can start early in the curriculum, using examples of deaf signers in lectures and case discussions, followed by explicit discussions of Deaf cultural norms and the potential risks of low written and spoken language literacy. Students can subsequently engage in role plays with each other or representatives of the local signing deaf community. This would likely ensure that future HCPs are equipped with the knowledge and skills necessary to provide appropriate care and ensure equitable health care access for deaf signers.
Optimal Anchor at the Uppermost Instrumented Vertebra in Long Fusion From the Pelvis to the Lower Thoracic Spine in Elderly Patients With Degenerative Spinal Deformity
Authors: Tsutsui Shunji , Hashizume Hiroshi , Yukawa Yasutsugu , Minamide Akihito , Nakagawa Yukihiro , Iwasaki Hiroshi , Takami Masanari , Yamada Hiroshi
Published: May 2021

Study Design:

This was a retrospective cohort study.

Objective:

The objective of this study was to compare pedicle screws (PSs) and transverse process hooks (TPHs) as anchors at the uppermost instrumented vertebra (UIV) in the lower thoracic spine in elderly patients with adult spinal deformity.

Summary of Background Data:

Less-rigid fixation using hooks at the UIV are thought to best prevent proximal junctional kyphosis (PJK) in long spinal fusion surgery. Although adult spinal deformity is commonly treated via spinal fusion from the pelvis to the lower thoracic spine, few studies have focused on UIV anchors in the lower thoracic spine.

Materials and Methods:

We retrospectively reviewed 53 patients aged 65 years and above who underwent spinal fusion from the pelvis to T9 or T10, with a minimum follow-up of 1 year. Radiographic outcomes including the incidence of PJK and implant failure were compared between 28 patients with TPHs and 25 patients PSs at the UIV.

Results:

The TPH and PS groups had similar radiographic values for pelvic incidence-lumbar lordosis (preoperative: 42.8 vs. 49.0 degrees, postoperative: 9.9 vs. 7.3 degrees) and the sagittal vertical axis (preoperative: 109.3 vs. 106.8 mm; postoperative: 21.9 vs. 11.2 mm). However, the incidence of PJK was significantly higher in the TPH group (35.7%) than that in the PS group (8.0%) at the 1-year follow-up (P=0.012). PJK in the TPH group was associated with UIV or UIV±1 fracture accompanied by posterior dislodgement of the TPH.

Conclusion:

Rigid fixation using PSs at the UIV in the lower thoracic spine produced better radiographic outcomes than did TPHs in elderly patients undergoing spinopelvic fusion.

Level of Evidence:

Level III.
The role of osteopontin in the development and metastasis of melanoma
Authors: Zhao Yun , Huang Changzheng
Published: May 2021

Melanoma is a highly heterogeneous tumor. The incidence of melanoma increases with age and its long-term prognosis is poor. The treatment of melanoma includes surgical removal, chemotherapy and immunotherapy; however, the effect of these treatments is limited on mutated melanoma. Osteopontin is an extracellular protein which is expressed in numerous kinds of cells; it is related to the proliferation and invasion of cancer cells as well as the development of tumor microenvironment. The relationship between osteopontin and metastasis of melanoma has been clarified in recent years. This review focuses on the expression of osteopontin in patients with melanoma and associated signaling pathways involved in development and metastasis of melanoma; the potential role of osteopontin in immune modulation and prognosis prediction is also discussed here.
Eliminating HIV reservoirs for a cure: the issue is in the tissue
Authors: Busman-Sahay Kathleen , Starke Carly E. , Nekorchuk Michael D. , Estes Jacob D.
Published: May 2021

Purpose of review

Advances in antiretroviral therapy have saved numerous lives, converting a diagnosis with human immunodeficiency virus 1 (HIV-1) from a death sentence into the possibility for a (nearly) normal life in many instances. However, the obligation for lifelong adherence, increased risk of accumulated co-morbidities, and continued lack of uniform availability around the globe underscores the need for an HIV cure. Safe and scalable HIV cure strategies remain elusive, in large part due to the presence of viral reservoirs in which caches of infected cells remain hidden from immune elimination, primarily within tissues. Herein, we summarize some of the most exciting recent advances focused on understanding, quantifying, and ultimately targeting HIV tissue viral reservoirs.

Recent findings

Current studies have underscored the differences between viral reservoirs in tissue compartments as compared to peripheral blood, in particular, the gastrointestinal (GI) tract. Additionally, several novel or modified techniques are showing promise in targeting the latent viral reservoir, including modifications in drug delivery platforms and techniques such as CRISPR.

Elimination of tissue viral reservoirs is likely the key to generation of an effective HIV cure. Exciting studies have come out recently that reveal crucial insights into topics ranging from the basic biology of reservoir seeding to effective drug targeting. However, there are still many outstanding questions in the field about the relative importance of specific reservoirs, such as the GI tract, that may alter the final strategy pursued.
Visualization of HIV-1 reservoir: an imaging perspective
Authors: Chapon Catherine , Moysi Eirini , Naninck Thibaut , Mayet Celine , Petrovas Constantinos
Published: May 2021

Purpose of review

The persistence of HIV-1-infected cells, despite the introduction of the combinatorial antiretroviral therapy, is a major obstacle to HIV-1 eradication. Understanding the nature of HIV reservoir will lead to novel therapeutic approaches for the functional cure or eradication of the virus. In this review, we will update the recent development in imaging applications toward HIV-1/simian immunodeficiency virus (SIV) viral reservoirs research and highlight some of their limitations.

Recent findings

CD4 T cells are the primary target of HIV-1/SIV and the predominant site for productive and latent reservoirs. This viral reservoir preferentially resides in lymphoid compartments that are difficult to access, which renders sampling and measurements problematical and a hurdle for understanding HIV-1 pathogenicity. Novel noninvasive technologies are needed to circumvent this and urgently help to find a cure for HIV-1. Recent technological advancements have had a significant impact on the development of imaging methodologies allowing the visualization of relevant biomarkers with high resolution and analytical capacity. Such methodologies have provided insights into our understanding of cellular and molecular interactions in health and disease.

Imaging of the HIV-1 reservoir can provide significant insights for the nature (cell types), spatial distribution, and the role of the tissue microenvironment for its in vivo dynamics and potentially lead to novel targets for the virus elimination.
Environmental impact on reproductive health and risk mitigating strategies
Authors: Giudice Linda C.
Published: May 2021

Purpose of review

The purpose of this review is to increase awareness among reproductive health professionals and trainees about the impact of environmental toxicants and climate change on women's health and mitigation strategies at the individual, professional and governmental levels.

Recent findings

Global health indicators reveal a meteoric rise of noncommunicable diseases over the past 50 years, which threaten reproductive health directly and indirectly. Evolutionary genetic mutations as contributors are unlikely in this timeframe, and environmental causes have been invoked. Notably, the past 75 years have witnessed marked increases in industrial chemical production, and global warming has rendered a ‘climate crisis’ with extreme temperatures and compromised food, water, and air quality. There is now strong experimental and epidemiologic evidence for endocrine disrupting chemicals and particulate matter and chemical components of air pollution in the pathophysiology of human reproductive disorders during development and across the lifespan, especially among vulnerable populations.

Environmental impacts on fertility, pregnancy outcomes, childhood neurodevelopment, and reproductive tract development are significant, not widely appreciated, and may be preventable. In light of the evidence, education and advocating economical mitigations of toxic environmental chemicals and alternative energy strategies are imperatives to assure quality reproductive health for this and future generations.
Aldosterone contributes to hypertension in male mice inducibly overexpressing human endothelin-1 in endothelium
Authors: Berillo Olga , Coelho Suellen C. , Mahjoub Nada , Offermanns Stefan , Paradis Pierre , Schiffrin Ernesto L.
Published: May 2021

Objective:

Mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells are complex and remain unclear. Long-term exposure to human ET-1 (hET-1) in mice inducibly overexpressing hET-1 in the endothelium (ieET-1) caused sustained BP elevation. ET-1 has been shown to stimulate the release of aldosterone. Whether aldosterone plays a role in hET-1 overexpression-induced BP elevation and vessel injury is unknown.

Method:

Nine- to 12-week-old male ieET-1 mice and control mice expressing a tamoxifen-inducible Cre recombinase (CreERT2) in the endothelial cells (ieCre) were treated with tamoxifen for 5 days and studied 3 months later.

Results:

Endothelial hET-1 overexpression increased plasma aldosterone levels, which was reversed by 2-week treatment with atrasentan, an endothelin type A receptors blocker. Aldosterone synthase and cryptochrome 2 adrenal cortex mRNA expression was decreased in ieET-1 mice. Two-week treatment with eplerenone, a mineralocorticoid receptor antagonist, reduced systolic BP by 10 mmHg in ieET-1 mice during rest time. Saline challenge-induced sodium excretion and renal cortex thiazide-sensitive sodium-chloride cotransporter mRNA expression were decreased in ieET-1 mice. The sensitivity of mesenteric arteries to contraction by norepinephrine was increased in ieET-1 mice, and was abrogated by eplerenone treatment, whereas sensitivity of endothelium-independent relaxation responses to sodium nitroprusside was enhanced. Resistance artery remodeling was reduced in eplerenone-treated ieET-1 vs. ieET-1 and ieCre mice.

Conclusion:

These results demonstrate that aldosterone contributes to BP elevation and vascular norepinephrine sensitivity and remodeling caused by hET-1 overexpression in endothelium in mice.
Maternal Intervention to Prevent Mother-to-Child Transmission of HIV: Moving Beyond Antiretroviral Therapy
Authors: Mangold Jesse F. , Goswami Ria , Nelson Ashley N. , Martinez David R. , Fouda Genevieve G. , Permar Sallie R.
Published: May 2021

Widespread availability of antiretroviral therapy among pregnant women living with HIV has greatly reduced the rate of mother-to-child transmission (MTCT) of HIV across the globe. However, while Joint United Nations Programme on HIV/AIDS has set targets to reduce the annual number of new pediatric HIV infections to fewer than 40,000 in 2018 and fewer than 20,000 in 2020, progress towards these targets has plateaued at an unacceptably high global estimate of greater than 160,000 children newly infected with HIV in 2018. Moreover, it has become clear that expansion of maternal antiretroviral therapy alone will not be sufficient to close the remaining gap and eliminate MTCT of HIV. Additional strategies such as maternal or infant passive and/or active immunization that synergize with maternal antiretroviral therapy will be required to end the pediatric HIV epidemic. In this review, we outline the landscape of existing maternal interventions and emerging maternal immune-based approaches to prevent MTCT of HIV.
Monoclonal Antibodies for Prevention of Respiratory Syncytial Virus Infection
Authors: Rodriguez-Fernandez Rosa , Mejias Asuncion , Ramilo Octavio
Published: May 2021

Respiratory syncytial virus (RSV) is the leading cause of hospitalizations in infants worldwide. Palivizumab, a humanized monoclonal antibody against the RSV F protein, is the only licensed agent for prevention of severe RSV infection in high-risk infants. Palivizumab is administered intramuscularly, every month during the RSV season, usually 5 doses are required. In recent years, the resolution of the structure of the RSV F protein, with identification of potent neutralizing epitopes, and new technologies for production of monoclonal antibodies (mAbs) have facilitated the development of new alternative strategies for the prevention of RSV infections. One promising approach is a new generation of mAbs directed to new neutralizing epitopes and with prolonged half life. These enhanced mAbs are expected to provide adequate protection during the complete RSV season with a single intramuscular (IM) dose. The long-term goal of this approach is to provide passive immunization for the prevention of RSV lower respiratory tract infection to all infants (preterm and full term) in the first months of life before their initial exposure to RSV.
Heart Transplantation in Adult Congenital Heart Disease with the Organ Care System Use: A 4-Year Single-Center Experience
Authors: Verzelloni Sef Alessandra , Sef Davorin , Garcia Saez Diana , Trkulja Vladimir , Walker Christopher , Mitchell Jerry , McGovern Ian , Stock Ulrich
Published: May 2021

Recent advances in the management of patients with adult congenital heart disease (ACHD) have led to an increased number of patients who may develop heart failure and require heart transplantation (HTx). The purpose of this study was to evaluate early and mid-term postoperative outcomes after HTx with the use of Organ Care System (OCS) in a cohort of ACHD patients transplanted at our tertiary center. All consecutive HTx performed from January 2015 to January 2019 at our institution were analyzed. Donor and recipient preoperative characteristics, intraoperative course, and perioperative clinical outcomes were evaluated. Nine patients with median age of 44 years (range 17–61 years) underwent isolated HTx for end-stage ACHD during the study period. Mean cold ischemic time was 84 ± 17 minutes. Postoperatively, four patients (44%) needed venoarterial extracorporeal membrane oxygenation (1–7 days). One patient (11%) required surgical re-exploration for bleeding. Thirty-day and 1-year mortality were 11% and 22%, respectively. In our experience, despite the challenges of transplantation in ACHD, these patients can be successfully transplanted with the use of the OCS in a highly specialized center. Careful donor and recipient selection are of paramount importance.