bluuebunny/crossref_metadata_2025 huggingface dataset:
P475 Real world data on treatment success and drug persistence in anti-TNF therapy for ulcerative colitis
Authors: Lundekvam J A , Høivik M L , Anisdahl K , Moum B , Medhus A W
Published: May 2021

Background

The efficacy and safety of anti-TNF treatment for ulcerative colitis (UC) have been well documented in clinical trials. More data are required to increase knowledge on treatment success in a real world setting. This study reports real world data on treatment success, drug persistence and safety of anti-TNF treatment in patients with UC.

Methods

Patients with UC starting anti-TNF treatment with infliximab (IFX) or adalimumab (ADA) between January 2014 and December 2019 at Oslo University Hospital in Norway were included in a retrospective review of medical records. Eligible patients were biologically naïve adults (≥18 years) with no history of UC-related surgery. Follow-up was 12 months. Drug persistence was defined as the proportion of patients still receiving first-line anti-TNF treatment without addition of a second biologic agent. Remission was defined as i) clinical remission (six-point Mayo Score <2), ii) biochemical remission (fecal calprotectin <250 and CRP <5) or iii) a combination of the two. Treatment success was defined as drug persistence and remission. Serious adverse events (SAEs) were defined according to Good Clinical Practice guidelines.

Results

In total, 116 patients were included (mean age 35.5 ±13.9 years (SD), 58% male), of which 95 received IFX treatment and 21 ADA. Drug persistence was 74%. Treatment success by different definitions of remission and remission rates for drug persistent patients according to these definitions are reported in the table. SAEs were recorded on 18 occasions (four immediate infusion reactions, two colectomies, five infections and seven other events).

Conclusion

Treatment success by the strictest definition of remission was 40%. Of drug persistent patients, 44% were not in remission when applying the same definition. Whether these results reflect inadequacies in definitions of remission, a tendency for clinicians to let other variables guide treatment or a delay in drug switching warrants further investigation.
P507 Vulvar Crohn’s disease: A challenging diagnosis
Authors: Sahar N , Dahmani W , Nour E , Aya H , Wafa B A , Aida B S , Ahlem B , Mehdi K , Hanene J , Ali J
Published: May 2021

Background

Crohn’s disease is an inflammatory bowel disorder with several well-known extraintestinal manifestations, such as erythema nodosum, uveitis, and arthritis. Less commonly observed are cutaneous, so-called metastatic lesions of the vulva, which represent a diagnostic and therapeutic dilemma and require a multidisciplinary approach.

The objective of this study was to report a case series of patients with vulvar Crohn’s disease (VCD), describe its clinical features, histopathologic characteristics and therapeutic management.

Methods

In this retrospective study, we reviewed all cases of VCD seen in our department between 2008 and 2016. Data concerning age at diagnosis of VCD, vulval symptoms at presentation, histologic findings, and different treatment modalities were recorded. Only patients with both clinical features of VCD [knife-cut fissures, edema, ulceration] and histologic confirmation were included. A total of 3 cases were identified among 106 female patients with CD.

Results

Case 1: A 58-year-old patient, presented with a 4-year history of vulvar pain and itching. She had no bowel complaints. Clinical examination revealed hypertrophic exophytic lesions associated with linear ulcearations involving the vulva. A biopsy from the lesional skin showed non caseating gigantocellular granuloma. In view of the clinical and histopathological features, a diagnosis of Crohn’s disease of the vulva was made. Anti TNF treatment with adalimumab was started, resulting in a significant regression of the lesions.

Case 2: A 47-year-old patient presented to our department with complaints of painful, persisting vulvar ulcers, and resulting dysperunia for 2 years. On clinical examination she had unilateral vulvar oedema with multiple “knife-cut” linear ulcers. A skin biopsy was done which revealed dense inflammatory lymphocytic infiltrate with non caseating granulomas. Treatment with adalimumab was initiated. An improvement of symptoms was noted.

Case 3: A 16-year-old patient with no remarkable medical history, presented with a 2-year- history of persistent cheilitis and vulvar pain. Clinical examination of the external genitalia revealed ‘knife-cut’ vulvar fissures with important bilateral labial swelling and multiple papules on the surrounding skin. Histological analysis showed chronic inflammatory infiltrate with noncaseating tuberculoid granulomas. Anti-TNF treatment with infliximab was started with partial regression of lesions.

Conclusion

Our findings highlight the importance of keeping VCD on the differential diagnosis when faced with a range of vulvar symptoms. Anti-TNF agents seem to be an efficient treatment strategy for this particular localization.
P516 Serological biomarkers of tissue remodeling are associated with endoscopic remission in Crohn’s disease patients treated with GED-0301 (mongersen)
Authors: Mortensen J , Feagan B , Bay-Jensen A C , Karsdal M A , Horan G , Harris S , Usikin K
Published: May 2021

Background

In Crohn’s disease (CD) Smad7 is overexpressed in the intestinal mucosa, where it contributes to a sustained production of inflammatory cytokines, increased matrix metalloproteinase (MMP) activity and chronic inflammation through inhibition of the anti-inflammatory actions of TGF-beta. GED-0301, an anti-sense oligodeoxynucleaotide complementary to the mRNA of Smad7, inhibits the translation and synthesis of the Smad7 protein. We investigated exploratory biomarkers of collagen degradation by MMPs (C1M, C3M, C4M) and collagen formation (PRO-C3, PRO-C4 and PRO-C5) and their association with endoscopic remission in CD patients treated with GED-0301.

Methods

63 CD patients were randomized (1:1:1) to 4, 8 or 12 weeks oral, blinded GED-0301 160 mg daily (ClinicalTrials.gov no: NCT02367183). Simple endoscopic score for CD (SES-CD) (centrally read) was used to evaluate disease activity. Remission was defined as a SES-CD≤4 score at week 12. 54 CD patients completed the 12-week induction phase. Serum biomarkers measured by competitive ELISA se included C1M, C3M, C4M, PRO-C3, PRO-C4, PRO-C5 at baseline, week 4, week 8 and week 12. Spearman rho correlation was applied to evaluate the association with biomarkers and SES-CD score.

Results

Seven patients (11%) achieved a SES-CD≤4 at week 12. At baseline and at week 12 the biomarkers, C1M (baseline: r=0.36, P=0.005; wk12: r=0.47, P=0.0007), C3M (baseline: r=0.46, P=0.0002; wk12: r=0.28, P=0.047), C4M (baseline: r=0.40, P=0.002; wk12: r=0.36, P=0.011) PRO-C4 (baseline: r=0.36, P=0.004; wk12: r=0.35, P=0.013), and PRO-C5 (baseline: r=0.30, P=0.022) correlated with SES-CD (table 1). Remitters at baseline showed a numerically lower serum levels of C1M (54ng/mL vs. 65ng/mL), C3M (14.7ng/mL vs. 16.5ng/mL), PRO-C4 (241ng/mL vs. 299ng/mL) and PRO-C5 (442ng/mL vs. 660ng/mL) compared to non-remitters. The biomarkers C1M (P<0.05), C4M (P<0.05) and PRO-C5 (P<0.05) were significantly suppressed in remitters at week 12 compared to non-remitters (figure 1). The same biomarkers also demonstrated sustained suppression of serum concentrations at week 4, 8 and 12 (C1M: 21.6% decrease from baseline at week 12; C4M: 15% decrease from baseline at week 12; PRO-C5: 26.6% decrease from baseline at week 12) in remitters compared to non-remitters.

Conclusion

Biomarkers of tissue remodeling correlated with the SES-CD scores of CD patients treated with mongersen. Patients s who achieved remission based on endoscopic criteria showing greater suppression of these biomarkers relative to non-remitters. Collectively, these data suggest that biomarkers of tissue remodeling may be useful to monitoring disease activity and mucosal changes in CD patients.
P622 Comparison of midterm outcomes in Pediatric Crohn’s Disease patients treated with either Exclusive Enteral Nutrition or Corticosteroids around disease diagnosis– a population based study
Authors: Plotkin L , Focht G , Harel S , Dotan I , Greenfeld S , Kariv R , Gabay H , Loewenberg Weisband Y , Turner D
Published: May 2021

Background

Corticosteroids (CS) and exclusive enteral nutrition (EEN) are commonly used as induction therapy in pediatric Crohn’s disease (PCD). Pediatric studies showed that CS treatment is equivalent to EEN for induction of remission, and it is easier to tolerate. However, EEN may be associated with superior long-term outcomes but this remains controversial. We thus aimed in this population-based study to compare CS dependency rate in children receiving EEN vs CS as induction therapy at the time of diagnosis, and to explore additional outcomes after one and two years of follow-up: IBD-related surgery, hospitalizations, and the use of biologics.

Methods

This study was performed on data from two Israeli Health Maintenance Organizations (HMOs), covering 78% of the population. We included all PCD patients (<18 years) diagnosed between 2005 and 2017 treated with EEN or CS within the first six months of diagnosis, with at least one-year follow-up. We excluded patients who initiated biologics within the same quarter. CS dependency was defined as a systemic steroid course lasting >90 days or four purchases with 12 months.

Results

A total of 2,730 PCD were identified, of whom 669 (24.5%) received induction therapy with either EEN [n=227 (8.3%)] or CS ([n=442 (16.2%)]. Median age at diagnosis was 13.04 years (3.8). Baseline (BL) characteristics, including age at diagnosis, anthropometrics data and gender, were similar between the groups.

Steroid dependency was higher in the CS group compared to the EEN group during the 1st and the 2nd year (10% vs. 7%, p<0.001 and 14% vs. 12%, p<0.001 respectively). Use of biologics was higher in the 1st but not the 2nd year in the EEN group compared to the CS group (28% vs. 19%, p=0.0016 and 40% vs. 33%, p=0.066 respectively). Hospitalization rate was higher in the CS group in both the 1st and 2nd years (42% vs. 22%, p<0.001 and 51% vs. 30%, p<0.001 respectively). There were no differences between the groups in surgeries rate and growth during the 1st and 2nd year follow-ups.

Conclusion

The use of CS as induction therapy in PCD was associated with a higher corticosteroid dependency rate, as well as more hospitalizations during the first two years of follow-up.
P631 Food triggers in inflammatory bowel disease from the patients’ and doctors’ perspective
Authors: Cappello M , Guida L , Di Giorgio F M , Busacca A , Carrozza L , Ciminnisi S , Almasio P L
Published: May 2021

Background

Diet is receiving growing attention as a key environmental factor involved in the pathogenesis of Inflammatory Bowel Disease (IBD). Dietary components have a relevant role in triggering symptoms from the patients’perspective, but there is a gap between patients’ and doctors’ beliefs. Every patient has collected his or her own list of prohibited foods and reports a clinical benefit from avoiding such foods. Elimination of nutrients can lead to nutritional deficiencies and impact on style and quality of life. The aim of this study is to identify frequently avoided foods in a Mediterranean cohort of patients with IBD.

Methods

Consecutive patients with IBD attending our tertiary center for infusion of biologics or for follow-up visits were enrolled. Demographics and disease characteristics UC or CD) were recorded in a dedicated database. A questionnaire investigated food avoided and reasons for dietary changes, if self-driven or advised by doctors or other healthcare professionals.

Results

167 patients agreed to participate in the study. Eighty-one patients (48.8%) had UC, 86 (51.5%) had CD. Mean age was 48.6 ± 16 (range 18–77 years), 57.5% were males. Patients were in clinical remission or with mild activity. Most patients, about 80%, and especially patients with CD avoided certain foods considered as triggers, and this avoidance was usually practiced in both exacerbations of the disease and remission periods. This occurred upon medical advice in a minority of patients, especially for vegetable avoidance (13.2%). Foods more frequently avoided were spicy foods, seasoned foods, fried foods, milk and dairy products, carbonated drinks, spirits, vegetables, legumes, and whole grain bread. Processed meat was avoided in about 6.6% (only in 1.8% upon medical advice) and coffee in 12.6%. A lactose-free diet was advised by the treating physicians only in 14.3% of patients. 4 patients were on a glutenfree diet because of a self-reported gluten sensitivity. The role of other healthcare professionals (dietitician, nurses) was marginal in their food choices.

Conclusion

Most of the patients set diet on self-experience and give up many foods. Our results are comparable with those of previous studies. Spicy foods, seasoned and fried foods, carbonated drinks, and dairy products are on top of the list. Legumes and vegetables, the cornerstones of the Mediterranean diet, are also avoided even though the evidence that dietary fibers can induce relapse is lacking. The benefit reported could be related to the effect on IBS-related symptoms frequent in IBD in remission. Further studies and a greater involvement of doctors in providing dietary recommendations are warranted.
P683 Patients with newly diagnosed fistulizing perianal Crohn’s disease have a distinct microbial signature
Authors: Goren I , Ian W , Reshef L , Sharar Fischler T , Pauker M , Silverman J , Dotan I , Yanai H
Published: May 2021

Background

Alterations in gut bacterial microbiota are strongly associated with the pathogenesis of Crohn’s disease (CD). Up to 1/3 of patients with CD have perianal involvement (P-CD), either fistulizing (f-P-CD) or non-fistulizing (nf-P-CD). We hypothesized that alterations in fecal microbiota might drive perianal CD phenotypes.

Methods

Patients with newly diagnosed treatment naive CD were consecutively recruited. Patients were stratified into f-P-CD and nf-P-CD, and compared with CD without perianal involvement (non-P-CD). Bacterial 16S rRNA gene sequencing was performed. Microbial dysbiosis index (MDI), Shannon diversity score (H) and log ratio between anaerobic and aerobic bacteria (anaerobic index, AI) were calculated. Linear discriminant analysis effect size (LEfSe) was used to identify specific taxa discriminating between different patient groups. Fecal calprotectin (FC) was measured.

Results

We included 97 CD patients (50 males, median age 28 [IQR 22–41] years). Other than perianal involvement patients in both groups had comparable distribution of CD location and phenotype. The microbial indices MDI, H and AI as well as FC levels, did not differ between the P-CD (n=25) and non-P-CD (n=72) groups. When compared to non-P-CD, the P-CD exhibited significantly lower relative abundance in the Streptococci genera (p=0.01) and in the Ruminiclostridium_5 genera (p=0.02). Within the P-CD group, patients with f-P-CD (n=12) had significantly lower H than those with nf-P-CD (means: 2.0 vs 2.45, p=0.045), while FC levels were comparable between f-P-CD and nf-P-CD. Moreover, proportions of Coprococcus_3 and Lacnoclostridium were reduced in patients with f-P-CD vs nf-P-CD (p= 0.008, p=0.05, respectively), while Streptococcus was elevated (p=0.03).

Conclusion

Perianal CD is a spectrum with distinct microbial alterations in different phenotypes. Microbial alterations correspond to the severity of perianal involvement. This finding may suggest that the microbiome has a mechanistic role in complicated perianal CD.
Toxicity of pathogenic ataxin-2 inDrosophilashows dependence on a pure CAG repeat sequence
Authors: McGurk Leeanne , Rifai Olivia M , Shcherbakova Oksana , Perlegos Alexandra E , Byrns China N , Carranza Faith R , Zhou Henry W , Kim Hyung-Jun , Zhu Yongqing , Bonini Nancy M
Published: May 2021

Spinocerebellar ataxia type 2 is a polyglutamine (polyQ) disease associated with an expanded polyQ domain within the protein product of the ATXN2 gene. Interestingly, polyQ repeat expansions in ATXN2 are also associated with amyotrophic lateral sclerosis (ALS) and parkinsonism depending upon the length of the polyQ repeat expansion. The sequence encoding the polyQ repeat also varies with disease presentation: a pure CAG repeat is associated with SCA2, whereas the CAG repeat in ALS and parkinsonism is typically interrupted with the glutamine encoding CAA codon. Here, we asked if the purity of the CAG sequence encoding the polyQ repeat in ATXN2 could impact the toxicity of the ataxin-2 protein in vivo in Drosophila. We found that ataxin-2 encoded by a pure CAG repeat conferred toxicity in the retina and nervous system, whereas ataxin-2 encoded by a CAA-interrupted repeat or CAA-only repeat failed to confer toxicity, despite expression of the protein at similar levels. Furthermore, the CAG-encoded ataxin-2 protein aggregated in the fly eye, while ataxin-2 encoded by either a CAA/G or CAA repeat remained diffuse. The toxicity of the CAG-encoded ataxin-2 protein was also sensitive to the translation factor eIF4H, a known modifier of the toxic GGGGCC repeat in flies. These data indicate that ataxin-2 encoded by a pure CAG versus interrupted CAA/G polyQ repeat domain is associated with differential toxicity, indicating that mechanisms associated with the purity of the sequence of the polyQ domain contribute to disease.
Developing machine learning models to personalize care levels among emergency room patients for hospital admission
Authors: Nguyen Minh , Corbin Conor K , Eulalio Tiffany , Ostberg Nicolai P , Machiraju Gautam , Marafino Ben J , Baiocchi Michael , Rose Christian , Chen Jonathan H
Published: May 2021

Objective

To develop prediction models for intensive care unit (ICU) vs non-ICU level-of-care need within 24 hours of inpatient admission for emergency department (ED) patients using electronic health record data.

Materials and Methods

Using records of 41 654 ED visits to a tertiary academic center from 2015 to 2019, we tested 4 algorithms—feed-forward neural networks, regularized regression, random forests, and gradient-boosted trees—to predict ICU vs non-ICU level-of-care within 24 hours and at the 24th hour following admission. Simple-feature models included patient demographics, Emergency Severity Index (ESI), and vital sign summary. Complex-feature models added all vital signs, lab results, and counts of diagnosis, imaging, procedures, medications, and lab orders.

Results

The best-performing model, a gradient-boosted tree using a full feature set, achieved an AUROC of 0.88 (95%CI: 0.87–0.89) and AUPRC of 0.65 (95%CI: 0.63–0.68) for predicting ICU care need within 24 hours of admission. The logistic regression model using ESI achieved an AUROC of 0.67 (95%CI: 0.65–0.70) and AUPRC of 0.37 (95%CI: 0.35–0.40). Using a discrimination threshold, such as 0.6, the positive predictive value, negative predictive value, sensitivity, and specificity were 85%, 89%, 30%, and 99%, respectively. Vital signs were the most important predictors.

Discussion and Conclusions

Undertriaging admitted ED patients who subsequently require ICU care is common and associated with poorer outcomes. Machine learning models using readily available electronic health record data predict subsequent need for ICU admission with good discrimination, substantially better than the benchmarking ESI system. The results could be used in a multitiered clinical decision-support system to improve ED triage.
Daśanāmīsamādhisin West Bengal: Preliminary Observations
Authors: Hatcher Brian A
Published: May 2021

This essay provides a summary of research on the history and material legacy of a Daśanāmī monastic network established in modern Bengal. Centred on the pilgrimage centre of Tārakeśvar, at its peak this network area covered much of southwestern Bengal, integrating disparate temples and economic centres. The essay calls special attention to the role of samādhis (burial monuments) in anchoring Daśanāmī monasteries (maṭhas) in the local landscape and also illustrates the challenge of documenting sites when these material markers have deteriorated, vanished, or been renovated.
Dark Energy Survey Year 3 results: Curved-sky weak lensing mass map reconstruction
Authors: Jeffrey N , Gatti M , Chang C , Whiteway L , Demirbozan U , Kovacs A , Pollina G , Bacon D , Hamaus N , Kacprzak T , Lahav O , Lanusse F , Mawdsley B , Nadathur S , Starck J L , Vielzeuf P , Zeurcher D , Alarcon A , Amon A , Bechtol K , Bernstein G M , Campos A , Rosell A Carnero , Kind M Carrasco , Cawthon R , Chen R , Choi A , Cordero J , Davis C , DeRose J , Doux C , Drlica-Wagner A , Eckert K , Elsner F , Elvin-Poole J , Everett S , Ferté A , Giannini G , Gruen D , Gruendl R A , Harrison I , Hartley W G , Herner K , Huff E M , Huterer D , Kuropatkin N , Jarvis M , Leget P F , MacCrann N , McCullough J , Muir J , Myles J , Navarro-Alsina A , Pandey S , Prat J , Raveri M , Rollins R P , Ross A J , Rykoff E S , Sánchez C , Secco L F , Sevilla-Noarbe I , Sheldon E , Shin T , Troxel M A , Tutusaus I , Varga T N , Yanny B , Yin B , Zhang Y , Zuntz J , Abbott T M C , Aguena M , Allam S , Andrade-Oliveira F , Becker M R , Bertin E , Bhargava S , Brooks D , Burke D L , Carretero J , Castander F J , Conselice C , Costanzi M , Crocce M , da Costa L N , Pereira M E S , De Vicente J , Desai S , Diehl H T , Dietrich J P , Doel P , Ferrero I , Flaugher B , Fosalba P , García-Bellido J , Gaztanaga E , Gerdes D W , Giannantonio T , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Hoyle B , Jain B , James D J , Lima M , Maia M A G , March M , Marshall J L , Melchior P , Menanteau F , Miquel R , Mohr J J , Morgan R , Ogando R L C , Palmese A , Paz-Chinchón F , Plazas A A , Rodriguez-Monroy M , Roodman A , Sanchez E , Scarpine V , Serrano S , Smith M , Soares-Santos M , Suchyta E , Tarle G , Thomas D , To C , Weller J ,   DES Collaboration
Published: May 2021

We present reconstructed convergence maps, mass maps, from the Dark Energy Survey (DES) third year (Y3) weak gravitational lensing data set. The mass maps are weighted projections of the density field (primarily dark matter) in the foreground of the observed galaxies. We use four reconstruction methods, each is a maximum a posteriori estimate with a different model for the prior probability of the map: Kaiser–Squires, null B-mode prior, Gaussian prior, and a sparsity prior. All methods are implemented on the celestial sphere to accommodate the large sky coverage of the DES Y3 data. We compare the methods using realistic ΛCDM simulations with mock data that are closely matched to the DES Y3 data. We quantify the performance of the methods at the map level and then apply the reconstruction methods to the DES Y3 data, performing tests for systematic error effects. The maps are compared with optical foreground cosmic-web structures and are used to evaluate the lensing signal from cosmic-void profiles. The recovered dark matter map covers the largest sky fraction of any galaxy weak lensing map to date.
Insights into xanthine riboswitch structure and metal ion-mediated ligand recognition
Authors: Xu Xiaochen , Egger Michaela , Chen Hao , Bartosik Karolina , Micura Ronald , Ren Aiming
Published: May 2021

Riboswitches are conserved functional domains in mRNA that mostly exist in bacteria. They regulate gene expression in response to varying concentrations of metabolites or metal ions. Recently, the NMT1 RNA motif has been identified to selectively bind xanthine and uric acid, respectively, both are involved in the metabolic pathway of purine degradation. Here, we report a crystal structure of this RNA bound to xanthine. Overall, the riboswitch exhibits a rod-like, continuously stacked fold composed of three stems and two internal junctions. The binding-pocket is determined by the highly conserved junctional sequence J1 between stem P1 and P2a, and engages a long-distance Watson–Crick base pair to junction J2. Xanthine inserts between a G–U pair from the major groove side and is sandwiched between base triples. Strikingly, a Mg2+ ion is inner-sphere coordinated to O6 of xanthine and a non-bridging oxygen of a backbone phosphate. Two further hydrated Mg2+ ions participate in extensive interactions between xanthine and the pocket. Our structure model is verified by ligand binding analysis to selected riboswitch mutants using isothermal titration calorimetry, and by fluorescence spectroscopic analysis of RNA folding using 2-aminopurine-modified variants. Together, our study highlights the principles of metal ion-mediated ligand recognition by the xanthine riboswitch.
U–Pb Dating of Apatite, Titanite and Zircon of the Kingash Mafic–Ultramafic Massif, Kan Terrane, Siberia: from Rodinia Break-up to the Reunion with the Siberian Craton
Authors: Marfin Alexander E , Radomskaya Tatiana A , Ivanov Alexei V , Kamenetsky Vadim S , Kamenetsky Maya B , Yakich Tamara Yu , Gertner Igor F , Kamo Sandra L , Ernst Richard E , Bryanskiy Nikolay V , Glazunov Oleg M , Belozerova Olga Yu
Published: May 2021

The initial stage of Rodinia supercontinent break-up occurred at about 750 Ma. It preceded formation of the Irkutsk and Franklin large igneous provinces (LIPs) at 712 ± 2 to 739 ± 8 Ma. These LIPs were emplaced within the formerly connected Laurentian and Siberian cratons. The Kingash massif is located in the Precambrian Kan terrane in direct contact with the Siberian Craton at its southwestern boundary. It has been linked to an important suite of mafic–ultramafic intrusions that border the southern margin of the Siberian craton, and that have been inferred to belong to the Irkutsk LIP. The massif is also significant, because it hosts platinum group element (PGE)–Cu–Ni-rich mineralization and is the only large deposit in the region. However, despite numerous dating attempts, the age of the massif had not been resolved. A significant difficulty is post-magmatic recrystallization at amphibolite facies that affected the rocks of the massif. In this study we used U–Pb dating of zircon, titanite and apatite from rocks of the Kingash massif and cross-cutting granite and monzonite veins. The oldest igneous zircon grain of the Kingash massif analysed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) yields an age of c. 750 Ma, taken as a tentative age of magmatism. Dating of multiple grains of metamorphic zircon by chemical abrasion isotope dilution thermal ionization mass spectrometry yielded 564·8 ± 2·2 Ma, which is in agreement with LA-ICP-MS titanite ages of 557 ± 19, 565 ± 35 and 551 ± 17 Ma. Apatite of two different samples showed ages of 496·4 ± 7·9 and 497·0 ± 1·8 Ma (LA-ICP-MS), which are interpreted as the time when the terrane cooled below the closure temperature of apatite. Using our new data we suggest that at the time of the Irkutsk–Franklin LIP event the Kan terrane was a part of Rodinia, then it separated from either Siberia or Laurentia during the break-up of Rodinia and finally collided with Siberia at 560 Ma, the time of regional amphibole-facies metamorphism.
Reliability of Trigger Point Evaluation in the Lower Leg Muscles
Authors: Rozenfeld Evgeni , Strinkovsky Asia , Finestone Aharon S , Kalichman Leonid
Published: May 2021

Background

Myofascial trigger point diagnosis is a clinical palpatory skill dependent on the patient’s subjective response. The inter- and intra-rater reliability of trigger point physical evaluation in the lower leg muscles has rarely been reported. Previous reliability studies suffered from the Kappa paradox.

Objective

To evaluate the inter- and intra-rater reliability of trigger point recognition in the lower leg muscles implying a specific method to overcome the first Kappa paradox.

Design

A reliability study with pre-second examiner exclusion to correct prevalence index.

Setting

Physical therapy outpatient clinic, Beer-Sheva, Israel.

Subjects

In sum, 86 soldiers aged 18–30 referred for physical therapy with a diagnosis of musculoskeletal pain consented to take part in this study; 26 were excluded for lacking trigger points, leaving 60 subjects for analysis (31 women, 29 men).

Methods

Both legs were evaluated, and the results were analyzed separately for symptomatic (N = 87) and asymptomatic legs (N = 31). Each subject was evaluated three times, twice by one examiner, and once by a second examiner. Dichotomous findings including palpable taut-band, tenderness, referred pain, and relevance of referred pain were recorded.

Results

Inter-rater reliability for active trigger points ranged from 0.49 to 0.75 (median: 0.52) and intra-rater reliability ranged from 0.41 to 0.84 (median: 0.65) and. For total trigger points intra-rater reliability ranged from 0.52 to 0.79 (median: 0.67), and inter-rater reliability ranged from 0.44 to 0.77 (median: 0.66).

Conclusions

Physical examination is a reliable method of trigger point evaluation in lower leg muscles, and it can be used as a diagnostic method for trigger point evaluation.
The Cognitive Load of Inpatient Consults: Development of the Consult Cognitive Load Instrument and Initial Validity Evidence
Authors: Brondfield Sam , Blum Alexander Mario , Lee Kewchang , Linn Marcia C. , O’Sullivan Patricia S.
Published: May 2021

Purpose

Fellows and residents provide inpatient consultations. Though consults vary considerably, measuring the associated cognitive load (CL) is key to guiding faculty on how to optimize learning during consults. However, existing CL instruments, such as the unidimensional Paas scale, cannot separate the 3 components of CL and may miss the nuances of consult CL. Therefore, the authors developed the Consult Cognitive Load (CCL) instrument to measure the 3 CL components during consults.

Method

In 2018–2019, the authors developed the CCL at the University of California, San Francisco, using Wilson’s constructive approach to measurement. To generate content and response process validity evidence, the authors consulted the literature and experts to generate construct maps, items, and a scoring rubric and conducted cognitive interviews. They administered the CCL to internal medicine and psychiatry trainees across 5 University of California campuses and used Rasch family and linear regression models to assess internal structure validity and relationships to key predictor variables. They compared the CCL with the Paas scale using Wright maps and used latent correlations to support separating CL into 3 components.

Results

Analysis revealed appropriate fit statistics, appropriate mean respondent location increases across all levels, threshold banding, and expected relationships with key predictor variables. The CCL provided more coverage of the 3 CL components compared with the Paas scale. Correlations among the 3 CL components were not strong, suggesting that the CCL offers more nuance than a unidimensional measure of CL in the context of consults.

Conclusions

This study generated initial validity evidence to support the CCL’s use as a measure of consult CL and supports measuring the 3 CL components separately rather than as a single construct in the context of consults. Learners and faculty could compare learner CCL scores with reference scores to promote reflection, metacognition, and coaching.
Cat Scratch Disease and Bartonellaceae
Authors: Zangwill Kenneth M.
Published: May 2021

Since the early 1900s, Bartonella species were known only to cause human disease resulting from very restricted geographic (bartonellosis) or environmental influences (“trench fever”). In the 1990s, and in parallel, cat scratch disease and bacillary angiomatosis were definitively linked to Bartonella species. Subsequently, widespread use of modern diagnostic methods revealed the broad ecologic niche of this organism and greatly expanded our knowledge of the epidemiology and clinical presentations associated with this genus. A large number of reservoirs and vectors involved with Bartonella propagation and transmission to humans have been identified; cats and various arthropods remain the most well-studied to date. Though not completely understood, it appears that specific immune-modulated interactions between the infecting species and host-related factors play a major role in the observed breadth of human clinical syndromes associated with Bartonellae, the large differences in immunopathologic features of tissue samples among different syndromes and potentially the varied responses to antimicrobial therapy. Further, the clinical management for cat scratch disease in particular is quite variable among clinicians, reflecting a poor evidence base. No preventive measures have been developed beyond suggestions to avoid at-risk behavior with known vectors.
Quality of Life and Mid-Term Survival in Patients Receiving Extracorporeal Membrane Oxygenation After Cardiac Surgery
Authors: Shao Chengcheng , Wang Liangshan , Yang Feng , Wang Jinhong , Wang Hong , Hou Xiaotong
Published: May 2021

There is a lack of data regarding mid-term outcomes of extracorporeal membrane oxygenation (ECMO) for refractory postcardiotomy cardiogenic shock (PCS). In this context, this research aimed to assess the mid-term survival and quality of life of PCS patients who receive ECMO by comparing them with cardiac surgery patients who do not receive ECMO. A retrospective analysis was performed on the clinical data of patients who had undergone ECMO treatment after cardiac surgery from January 2013 to June 2017 in a tertiary hospital (n = 102); non-ECMO patients who had undergone cardiac surgery and were discharged successfully were selected as the control group (n = 102). Survival and mid-term quality of life were assessed and compared through the Short-Form 36 (SF-36). Both groups were followed up by telephone, and SF-36 scores were obtained from the surviving patients. The data were available for 89 patients (87.3%) and 88 patients (86.3%) in the ECMO group and the control group, respectively. After discharge, the control group outperformed the ECMO group in survival (93.1% vs. 82.4%; p = 0.013). No significant differences in complications, all-cause mortality, first readmission for any cause, or work condition between the ECMO group and the control group were observed. The SF-36 scores in general health (GH) and vitality (VT) were significantly lower among the ECMO survivors (p < 0.05). The results of this study indicate that ECMO can provide acceptable mid-term survival with good quality of life for patients with refractory cardiogenic shock.
Pediatric Heart Transplant Recipients Bridged with Biventricular Assist Device Have Worse 1 Year Graft Survival
Authors: Watanabe Kae , Joong Anna , Thrush Philip T. , Srdanovic Nina , Monge Michael C. , Pahl Elfriede
Published: May 2021

There are little data on postheart transplant (HT) outcomes for pediatric patients that were supported to HT with biventricular assist device (BiVAD). The United Network for Organ Sharing database was queried for patients <18 years old at time of HT between January 2005 and March 2018, excluding patients bridged with total artificial hearts and right ventricular assist device (VAD). Of 4,904 pediatric HT recipients, patients were grouped by no VAD support (3,934; 80.2%), left ventricular assist device only (736; 15%), and BiVAD (234; 4.8%). Overall graft survival analysis indicates crossing hazard rates between groups over time with the BiVAD group having a significantly lower graft survival at 1 year post-HT. A Cox model adjusted for age, era, diagnosis, and time by group interaction demonstrated increased 1 year hazard ratio (HR) of 8.5 (95% confidence intervals [CI]: 6.15–11.79) comparing BiVAD to no VAD. Comparable hazard between BiVAD and no VAD groups were found at 5 years (HR 1.01; 95% CI: 0.67–1.51), while lower hazard for the BiVAD group was found at 10 years post-HT (HR 0.07; 95% CI: 0.03–0.18). Although pre-HT BiVAD support leads to worse graft survival 1 year post-HT, long-term survival is acceptable.
Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Metabolic Associated Fatty Liver Disease
Authors: Jianping Wu , Xuelian Zheng , Anjiang Wang , Haiying Xiao
Published: May 2021

Background:

Clinical trials examining the therapeutic benefits of glucagon-like peptide-1 receptor agonists (GLP-1RA) on patients with metabolic associated fatty liver disease (MAFLD) have reported inconsistent results. The aim of this meta-analysis was to verify the role of GLP-1RA in the treatment of MAFLD patients.

Materials and Methods:

We searched PubMed, Embase, Medline, and the Cochrane Library for randomized controlled trials published that compared GLP-1RA with the control treatment in patients with MAFLD till to July 30, 2020. The effects of GLP-1RA on liver histology, body mass index, waist circumference (WC), aspartate aminotransferase, total cholesterol, triglycerides (TG), low-density lipoprotein and high-density lipoprotein were evaluated.

Results:

Thirteen trials involving 704 patients were included in the meta-analysis. Compared with the control treatment, GLP-1RA treatment induced a greater resolution of steatohepatitis [RR=2.87; 95% confidence interval (CI): 0.89 to 9.23], delayed the progression of liver fibrosis (RR=3.83, 95% CI: 0.91 to 16.07) and reduced liver fat deposition (MD: −1.40; 95% CI: −2.75 to −0.05). In addition, it reduced the body mass index (MD: −1.15; 95% CI: −2.26 to −0.04), WC (MD: −3.33; 95% CI: −6.31 to −0.35) and improved serum aspartate aminotransferase (MD: −3.04; 95% CI: −5.93 to −0.16) and total cholesterol (MD: −0.20; 95% CI: −0.28 to −0.13).

Conclusion:

GLP-1RA improves liver steatosis and fibrosis. It is also beneficial to metabolic syndrome as it reduces BMI, WC, and hyperlipidemia.
Treatment options for managing obesity in chronic kidney disease
Authors: Parvathareddy Vishnu P. , Ella Krishiv M. , Shah Maulin , Navaneethan Sankar D.
Published: May 2021

Purpose of review

Obesity is a risk factor for the development and progression of chronic kidney disease (CKD). In this review, we provide a comprehensive overview of various management options (lifestyle intervention, medications, and bariatric surgery) to address obesity in those with CKD.

Recent findings

Few clinical trials have examined the benefits of lifestyle modifications in those with preexisting CKD and suggest potential renal and cardiovascular benefits in this population. Yet, superiority of different dietary regimen to facilitate weight loss in CKD is unclear. Although medications could offer short-term benefits and assist weight loss, their safety and long-term benefits warrant further studies in this high-risk population. Observational studies report that bariatric procedures are associated with lower risk of end stage kidney disease. Clinicians should also recognize the higher risk of acute kidney injury, nephrolithiasis, and other complications noted with bariatric surgical procedures.

Lifestyle modifications and some weight loss medications may be recommended for facilitating weight loss in CKD. Referral to bariatric centers should be considered among morbidly obese adults with CKD.
Case Report: Management of Refractory Filamentary Keratitis with N-acetylcysteine
Authors: Crist Andrew J.
Published: May 2021

SIGNIFICANCE

Filamentary keratitis is frequently a recurrent corneal condition characterized by the presence of filaments attached to the cornea. This condition can be challenging to manage because the clinician must treat the underlying cause and filament formation. N-acetylcysteine, a mucolytic agent, should be considered as adjunctive therapy to manage refractory cases.

PURPOSE

This case demonstrates the utility of a mucolytic agent, N-acetylcysteine, to treat and manage filamentary keratitis when conventional therapies failed to provide long-term symptomatic relief and reduction of further filament formation.

CASE REPORT

A 70-year-old man with recurrent filamentary keratitis (first occurrence 8 years prior) presented to the clinic with worsening red and painful eyes for 2 days. Prior treatment and management included artificial tears and ointments, punctal plugs, topical corticosteroids, contact lenses, and eyelid hygiene. Slit-lamp examination revealed multiple corneal filaments that were removed with forceps. He was diagnosed with recurrent filamentary keratitis secondary to dry eye disease and treated with preservative-free ophthalmic ointment, oral doxycycline, and 10% N-acetylcysteine ophthalmic solution. The patient had complete resolution of corneal filaments with significant relief of symptoms at 3-week, 5-month, and 10-month follow-up examinations.

CONCLUSIONS

N-acetylcysteine is not commercially available in an ophthalmic solution and must be compounded by a local pharmacist for patient use. Because filamentary keratitis can be challenging to manage because of frequent recurrences, addition of N-acetylcysteine to the treatment regimen should be considered a viable option in refractory cases when other therapies have failed to provide sustained symptomatic relief and resolution of filaments.
Case Report: Pentosan Polysulfate Sodium Maculopathy Originally Diagnosed as Pattern Macular Dystrophy
Authors: Case Aaron W. , Anderson Matthew J. , Sayomac Lovelee E.
Published: May 2021

SIGNIFICANCE

Pentosan polysulfate sodium (PPS) maculopathy is a clinical entity characterized by a pigmentary maculopathy in the setting of chronic exposure to PPS. Pentosan polysulfate sodium is indicated for discomfort related to interstitial cystitis/painful bladder syndrome. Given a reported interstitial cystitis/painful bladder syndrome prevalence up to 2%, recognition is critical to mitigate visual sequelae.

PURPOSE

We present an observational case report demonstrating typical findings of PPS maculopathy in a patient originally diagnosed with a pattern macular dystrophy. We demonstrate the importance of medical history, medication profile review, and multimodal imaging in the diagnosis and management. The patient provided written informed consent for medical information and images to be published.

CASE REPORT

A 55-year-old White woman presented with a painless, bilateral loss of vision and bilateral pigmentary maculopathy that was initially diagnosed as pattern macular dystrophy. Detailed review of medical history, medication profile, and subsequent studies, including optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence, fluorescein angiography, and genetic studies, ultimately led to the diagnosis of PPS maculopathy. Pentosan polysulfate sodium was discontinued, and ongoing surveillance with multimodal imaging was encouraged.

CONCLUSIONS

Because toxic maculopathies are an uncommon diagnosis, screening and recognition of PPS maculopathy are critical in the primary eye care setting. Discontinuation of the insulting agent may be necessary to prevent potentially severe and irreversible vision loss in the at-risk population.
Modeling transmission of pathogens in healthcare settings
Authors: Stachel Anna , Keegan Lindsay T. , Blumberg Seth
Published: May 2021

Purpose of review

Mathematical, statistical, and computational models provide insight into the transmission mechanisms and optimal control of healthcare-associated infections. To contextualize recent findings, we offer a summative review of recent literature focused on modeling transmission of pathogens in healthcare settings.

Recent findings

The COVID-19 pandemic has led to a dramatic shift in the modeling landscape as the healthcare community has raced to characterize the transmission dynamics of SARS-CoV-2 and develop effective interventions. Inequities in COVID-19 outcomes have inspired new efforts to quantify how structural bias impacts both health outcomes and model parameterization. Meanwhile, developments in the modeling of methicillin-resistant Staphylococcus aureus, Clostridioides difficile, and other nosocomial infections continue to advance. Machine learning continues to be applied in novel ways, and genomic data is being increasingly incorporated into modeling efforts.

As the type and amount of data continues to grow, mathematical, statistical, and computational modeling will play an increasing role in healthcare epidemiology. Gaps remain in producing models that are generalizable to a variety of time periods, geographic locations, and populations. However, with effective communication of findings and interdisciplinary collaboration, opportunities for implementing models for clinical decision-making and public health decision-making are bound to increase.
Development and evaluation of a new non-competitive Luminex immunoassay detecting antibodies against human papillomavirus types 6, 11, 16 and 18
Authors: Trevisan Andrea , Wissing Michel D. , Dagenais Carole , Forest Pierre , Ramanakumar Agnihotram V. , Burchell Ann N. , Franco Eduardo L. , Coutlée François , Couillard Michel
Published: May 2021

Serum antibody levels can be used to measure the humoral immune response against human papillomaviruses (HPV). We developed and validated a rapid, technically simple and relatively inexpensive multiplex non-competitive Luminex-based immunoassay (ncLIA) to measure total IgG antibody levels against four HPV types. For the assay’s solid phase, virus-like particles (VLPs) of HPV6, 11, 16 and 18 were bound to heparin-coated beads. HPV serum antibody levels binding to the VLPs were quantified using a phycoerithrin-conjugated secondary polyclonal donkey anti-human IgG antibody. Standardization and validation of the ncLIA were performed using 96 paired serum and genital samples from participants in the HITCH cohort study, including young women (aged 18–24 years) and their male sexual partners (aged 18+) in Montreal, Canada. Results from the ncLIA were compared to a validated Luminex immunoassay from PPD laboratories using Pearson’s correlation coefficients, receiver operating characteristic curves and logistic regression. Our assay had good inter- and intra-assay variability. The correlation of serum antibody levels between the ncLIA and validation assay was highest for HPV16 and HPV11 (r=0.90), followed by HPV6 (r=0.86) and HPV18 (r=0.67). The ncLIA was better able to predict HPV DNA positivity in genital samples than the validation assay for HPV16 [area under the curve (AUC) 0.65 versus 0.52, P=0.001] and HPV18 [AUC 0.71 versus 0.57, P=0.024]. AUCs for HPV6 and HPV11 were similar between the two assays (0.70 versus 0.71, P=0.59, and 0.88 versus 0.96, P=0.08, respectively). The developed ncLIA is useful for measuring total IgG antibody response following natural infection or vaccination against four HPV VLPs included in the quadrivalent vaccine.
Chemical structure elucidation of the carotenoids in the extremely radiation-resistant bacterium Deinococcus radiodurans R1
Authors: Zhang Xiao-ling , Yang Qiao
Published: May 2021

The main carotenoid in the extremely radiation-resistant bacterium Deinococcus radiodurans is deinoxanthin. In this paper, based on UV-Vis, MS/MS spectra as well as the chemical properties, the other main two carotenoids in this bacterium were identified as ((all-E)-1’-hydroxy-3’,4’-didehydro-1’,2’-dihydro-β,Ψ-carotene- 4-one-1), and ((all-E)-1’-hydroxy-3’,4’-didehydro-1’,2’,2,3-quahydro-β,Ψ-carotene- 4-one-1), respectively. The fully structure elucidation for the carotenoids should help to gain a better understanding of the radiation-resistant mechanisms in this remarkable bacterium.
Establishment, verification and application of rapid detection of baculovirus infectious titer by flow cytometry
Authors: Qingsheng Wu , Yuanyuan Li
Published: May 2021

Titer detection of baculovirus usually is time-consuming.It is important to establish a rapid detection method for baculovirus titer. In this report, Staining of cells with a fluorescently labeled anti-gp64 antibody allows for identification of infected insect cells. By inoculating cultures with a series of log dilutions of virus, and staining of the cultures 13-22 hours post inoculation, the ratio of infected to un-infected insect cells can be determined by flow cytometry. Statistical analysis of the percentage of infected cells in the virus dilution series enables accurate infectious titer determination. The culture time, cell growth state, the concentration of GP64-APC antibody and the concentration of inactivated FBS in diluent were optimized.The generality, repeatability and intermediate precision of the method were verified. The FCM method has the advantages of simplicity, accuracy, low cost and good repeatability.