bluuebunny/crossref_metadata_2025 huggingface dataset:
O16 Positron emission tomography - computed tomography: an important diagnostic tool in the giant cell arteritis fast track pathway
Authors: Ludwig Dalia R , Morris Vanessa , Shashidhara Anush , Voo Stefan , Reshat Reshat
Published: April 2021

Background/Aims 

Giant cell arteritis (GCA) is a systemic vasculitis affecting the temporal arteries and large vessels, including the aorta, in 25% of cases. Incidence of vertebral artery involvement is unknown likely owing to the reliance on conventional diagnostics including temporal artery biopsy (TAB) and temporal/axillary ultrasound which evade the vertebral arteries. These tests lose sensitivity soon after steroid initiation. Early specialist assessment and diagnostics, as part of a fast track pathway (FTP), can overcome this challenge. We present the first 12 months data from our FTP. To our knowledge this is the first GCA-FTP in the UK to utilise positron emission tomography - computed tomography (PET-CT) as an early diagnostic tool so we present a unique cohort of patients.

Methods 

Cohort 1: 40 patients, diagnosed between 2015-2019, before FTP implementation. Time from steroid initiation to temporal artery ultrasound (TAUS) and TAB was recorded. Cohort 2: 35 patients referred after pathway implementation. 21 had a positive diagnosis. Time from steroid initiation to diagnostic test was recorded.

Results 

Cohort 1: 26 (65%) patients had TAB; 3 (7.5%) had TAUS. The average time from starting steroid to investigation was 6 and 2 days respectively. Cohort 2: 17 (48%) had TAB, 30 (86%) had TAUS, 28 (80%) had PET-CT. In confirmed diagnoses, time from steroid initiation to investigations was 6.6 days, 1 day and 2.5 days respectively. In negative diagnoses time frames were 11.5, 1.5 and 2.3 days respectively. Table 1 shows sensitivity and specificity of these tests. Table 1. Sensitivity and specificity comparison between diagnostic tests

Conclusion 

Combining TAUS and PET-CT allows for high diagnostic accuracy without the need for invasive biopsy. 24% of patients had negative or inconclusive ultrasound and/ or negative biopsy but confirmed vasculitis on PET-CT. 50% of this cohort had vertebral involvement only. PET-CT has an important role in detecting extracranial particularly vertebral arteritis, where biopsy and ultrasound are unreliable. Our pathway design with the inclusion of PET-CT, enables us to capture all patients with GCA and satisfy NHS England criteria for tocilizumab use in refractory GCA. Continued evaluation of PET-CT and its role in predicting vascular complications is required.

Disclosure 

D.R. Ludwig: None. V. Morris: None. A. Shashidhara: None. S. Voo: None. R. Reshat: None.
O32 Serious infection with tocilizumab compared to TNF-inhibitors and other bDMARDS in rheumatoid arthritis patients: does line of therapy matter?
Authors: Lauper Kim , Kearsley-Fleet Lianne , Davies Rebecca , Watson Kath , Lunt Mark , Hyrich Kimme L
Published: April 2021

Background/Aims 

In the real-world, tocilizumab is prescribed to a population of patients different from those prescribed TNF-inhibitors, often older with longer disease duration, worse functional status and more previous b- or tsDMARDs. The aim of this study was to evaluate if and how the risk of serious infection on tocilizumab and other bDMARDs differs when stratifying by line of therapy in a real-world population of rheumatoid arthritis patients.

Methods 

We included patients registered in the BSRBR-RA treated with tocilizumab, etanercept, adalimumab, infliximab, certolizumab, abatacept or rituximab, including biosimilars. Primary outcome was the occurrence of a serious infection (defined as infection requiring hospitalisation, intravenous antibiotics or resulting in death). Primary covariate of interest was line of therapy (from first to fifth line of therapy). Every change to another b- or tsDMARD was considered a new line of therapy, but not a change between a bio-original and a biosimilar.

Hazard ratios (HR) of serious infections were estimated using an inverse probability weighted Cox regression, based on a propensity score including baseline patient and disease characteristics, and adjusting for time in study (see table). The reference group was etanercept, which included the highest number of patients. Treatment exposure was analysed without and with stratification by line of therapy.

Results 

A total of 33,916 treatment courses were included (Table) contributing to 62,532 years of follow-up. Compared to etanercept, participants starting abatacept, tocilizumab and rituximab were older, had more previous bDMARDs, longer disease duration and more comorbidities. The crude HR of serious infections were higher with infliximab and adalimumab, lower with certolizumab and rituximab, and not significantly different for abatacept and tocilizumab compared to etanercept. After adjustment, HR of serious infections were higher with tocilizumab, adalimumab and infliximab. However, when stratified by line of therapy, HR were no longer significantly different compared to etanercept for tocilizumab, adalimumab and infliximab for most lines of therapy.

Conclusion 

Whilst initially there appears to be a difference in rates of serious infections between biologic therapies, line of therapy may be a confounding factor when comparing the risk of serious infections between bDMARDs.

Disclosure 

K. Lauper: Honoraria; Gilead-Galapagos. Grants/research support; AbbVie. Other; AbbVie, Pfizer. L. Kearsley-Fleet: None. R. Davies: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; AbbVie. Grants/research support; Pfizer, BMS.
P004 Rheumatologist vs pathology department: correlation of crystal identification in synovial fluid analysis
Authors: Abdalla A
Published: April 2021

Background/Aims 

Crystal arthritis is the commonest inflammatory arthritis in adults. Diagnosis relies mostly on the correct identification of crystals under red-compensated polarized microscopy with assessment of birefringence. This is done routinely in our department when opportunity arises. Failure to appropriately identify crystals may result in lengthy hospitalisations, complications, avoidable repeated urgent visits, and unnecessary cost. We aimed to examine the agreement between rheumatology vs pathology-based microscopy for crystal analysis. There is currently no standardized pathway for synovial fluid crystal analysis in our tertiary centre in Dublin.

Methods 

A prospective study at Mater Misericordiae University Hospital - Dublin, was started in Dec 2019. Synovial fluid samples were obtained from acutely inflamed joints where clinically indicated. Fresh samples which were found to contain crystals (MSU or CPP) by a rheumatology consultant or trained registrar using compensated polarized microscopy, were also simultaneously sent to our pathology laboratory to receive similar analysis. Ethical approval was granted and all patients consented for their joint fluid to receive double analysis.

Results 

33 samples have been analysed to date. 13 samples of MSU crystals and 20 CPP crystals (table 1). Both rheumatologist and pathologist agreed on all but only one MSU sample. The pathologist identified CPP crystals only on 2/20 samples. The fluid analysis was carried out within the same working day by rheumatologist Vs. median of 2.3 working days for the result by the pathologist.

Conclusion 

The study showed a high agreement between rheumatologists and pathologists on identification of MSU crystals (92%), but very poor agreement on CPP crystals (only 10%). A quality improvement project is currently underway to address this issue and bridge the gap. Majority of Rheumatologists don't routinely perform crystal analysis using polarized microscopy and rely on their local cellular pathology lab for the results. Rheumatologists need to liaise with their local pathologists to optimise and streamline the process of crystal microscopy specially CPP crystals. P004 Table 1:crystals samples analysed through rheumatology and pathologyCPPD positiveMSU positiveRheumatologist2013Pathologist212Total2013

Disclosure 

A. Abdalla: None.
P044 Tibia honest, it takes a lot of spine to diagnose DISC
Authors: Ng Wan Lin , Anjum Aqeel , Devlin Joe , Fraser Alexander
Published: April 2021

Background/Aims 

CRMO is a rare autoinflammatory condition characterised by sterile bone osteolytic lesions which is described mainly in children with a female preponderance.

Methods 

A 31 year-old male presented with a 4-week history of productive cough, abdominal pain, left sided chest pain and right hip pain. He is a smoker with a background of heroin addiction and alcohol abuse. He was homeless and no family history available as he was fostered. His chest radiography was unremarkable but he had inflammatory markers. He was treated for as chest infection and heroin withdrawal. CT abdomen and pelvis demonstrated multiple osteolytic lesions in the pelvis, sternum, thoracic and lumbar spine. His HIV, Quantiferon and blood cultures were negative. His immunoglobulins, urine Bence Jones protein and echocardiogram were normal. In-depth assessment by the Infectious Disease team failed to isolate an infective pathogen. Bone marrow aspirate and trephine were unremarkable. Two CT-guided bone biopsies done twice showed plasma cells and macrophages. His condition deteriorated rapidly over 2 months. He mobility was reduced to wheelchair-bound and had dramatic 10kg weight loss.

Results 

In the absence of an infective or malignant cause, the Rheumatology service was consulted. Having reviewed the extensive data available, he was diagnosed with a likely but unusually aggressive form of adult-onset chronic recurrent multifocal osteomyelitis (CRMO). He was commenced initially on IV methylprednisolone, zoledronic acid, methotrexate and, etoricoxib. Subsequently he was treated with, tocilizumab and teriparatide. Whole body MRI revealed numerous other lesions not evident on previous imaging including lesions of the distal right humerus, proximal right femur and both tibias. His symptoms and inflammatory markers improved substantially over several days following treatment. A repeat full body MRI demonstrated dramatic improvement in the bony lesions. Soon he was able to walk again and gained some weight before he absconded from the hospital. His treatment was changed to tocilizumab infusion and denosumab injection to facilitate compliance.

Conclusion 

This is an unusual fascinating case which posed a significant diagnostic dilemma. Ruling out infection particularly in great challenge in diagnosing CRMO in a male adult who is homeless and a heroin abuser presenting with multifocal osteolytic lesions was challenging. The severity of his condition necessitated using novel treatments such as tocilizumab.

Disclosure 

W. Ng: None. A. Anjum: None. J. Devlin: None. A. Fraser: None.
P081 Arthritis, artists and art opporunities for education
Authors: Amar Soha , Lloyd Mark
Published: April 2021

Background/Aims 

The role of art in rheumatology is under-investigated. Several well-known artists have suffered from rheumatic disease. Their insights and achievements potentially provide reassurance and encouragement to our patients. Creating art may also offer therapeutic benefits for patients. Finally, the artistic environment can affect mood and behaviour. We highlight several inspirational artists.

Methods 

Four artists offer valuable insights: Michaelangelo (d. 1564) was able to master sculpture, painting and architecture despite hand osteoarthritis and persisted in working until his death, age 89.

Pierre-Auguste Renoir (d. 1919) developed severe RA aged 50. He continued to paint for the rest of his life, being carried to outdoor scenes on a sedan and designing an innovative rolling canvas to complete some of his finest work. He painted on small pieces of wood at night to distract from his arthritic pain.

Frida Kahlo (d.1954), the Mexican artist, experienced chronic generalised pain and fatigue in keeping with fibromyalgia. This was after a bus accident at eighteen resulted in multiple pelvic and vertebral fractures. Self-portraiture became the cornerstone of her bold art during the solitude of her convalescence.

Maud Lewis (d.1970), the Canadian folk painter, had JIA in early childhood resulting in a limp and severe hand changes. She spent much time indoors due to her pain and the ridicule faced from her peers. She developed an eagerness for drawing; to the extent that she painted on any surface she could find of her small cottage.

Results 

These artists’ own words reveal the resilience they gained from their art. Renoir stated: 'Out of doom and misery the most beautiful song may rise'. Lewis reported ‘As long as I’ve got a brush in front of me, I’m alright.’, whilst Kahlo was similarly quoted to say ‘I am broken. But I am happy to be alive as long as I can paint’. A small study in 2017 with 17 patients with RA showed improvement not only in hand function but also self-perception and quality of life after participating in daily art-based intervention (origami, painting and clay modelling) for four weeks.

Furthermore, a common theme between these famous artists was how they favoured bright colours in their artwork, which may have positive effects on mood. Colouring can reduce stress in children in paediatric waiting rooms. Within other settings, research suggests that visual art depicting nature can reduce anxiety in emergency department waiting rooms.

Conclusion 

Although exceptionally talented people, the artists discussed show the inspiring possibilities of creativity despite severe rheumatic disease. We suggest sharing these stories with our patients and considering further study into the therapeutic potential of creating art in rheumatic conditions. Attention should be paid to the artistic environment in which we see our patients.

Disclosure 

S. Amar: None. M. Lloyd: None.
P121 The efficacy of treatment interventions on fatigue in adolescents with juvenile idiopathic arthritis: a literature review
Authors: Moshtael Sebastian , Khanom Sonia , McDonagh Janet E
Published: April 2021

Background/Aims 

Fatigue has been reported by young people and professionals alike as a major challenge for people living with juvenile idiopathic arthritis (JIA) . It remains unclear as to how therapeutic interventions impacts on this major symptom. The aim of this review was to determine the current evidence for the effectiveness of therapeutic interventions, non- pharmacological and pharmacological, on improving fatigue in adolescents with JIA.

Methods 

Three electronic databases (MEDLINE, EMBASE, PsycINFO) were searched from 2000 to Feb 2020; in addition to manual searches. Articles were eligible for inclusion if they (i) were original research papers, (ii) had fatigue as a primary outcome measure (iii) included adolescents (10-25 years) and (iv) were available in the English language.

Results 

Of the 3,142 records identified, 31 underwent full text assessment and 4 studies were included in the qualitative synthesis including 2 from the Netherlands, 1 Germany, and 1 from Canada. The total number of participants across the 4 studies was 824. Three were randomised controlled trials of nonpharmacological interventions and one was a cohort study from a national drug registry including older adolescents JIA (mean: 19-years). Measurement tools included the Paediatric Quality of life multidimensional fatigue scale, (2 studies), the Checklist for Individual Strength CIS-20 (1 study), a numeric rating scale (1 study). In one study a visual analogue scale for energy level was also utilised. In 2 studies baseline prevalence of fatigue was reported as 60% and 76% respectively. Significant reduction in fatigue was observed in all three nonpharmacological studies. In the registry study, fatigue was noted to be prevalent in spite of the disease being in inactive or minimally active on biologic therapy. In 3 studies the relationship between health-related quality of life and fatigue was highlighted and showed a decreased quality of life in fatigued young people.

Conclusion 

Fatigue is a significant problem in JIA during adolescence and influences quality of life. Improvements in fatigue with non-pharmacological interventions have been reported. However, at present, data is insufficient to conclusively decide which treatment intervention is most efficacious in treating fatigue in young people with JIA. Fatigue should be considered as an important outcome measure for the management of JIA in future evaluations of interventions.

Disclosure 

S. Moshtael: None. S. Khanom: None. J.E. McDonagh: None.
P129 Predictors of low bone mineral density in rheumatoid arthritis
Authors: Swar Malika A , Bukhari Marwan
Published: April 2021

Background/Aims 

Osteoporosis (OP) is an extra-articular manifestation of rheumatoid arthritis (RA) that leads to increased fracture susceptibility due to a variety of reasons including immobility and cytokine driven bone loss. Bone loss in other populations has well documented risk factors. It is unknown whether bone loss in RA predominantly affects the femoral neck or the spine. This study aimed to identify independent predictors of low bone mineral density (BMD) in patients RA at the lumbar spine and the femoral neck.

Methods 

This was a retrospective observational cohort study using patients with Rheumatoid arthritis attending for a regional dual X-ray absorptiometry (DEXA) scan at the Royal Lancaster Infirmary between 2004 and 2014. BMD in L1-L4 in the spine and in the femoral neck were recorded. The risk factors investigated were steroid use, family history of osteoporosis, smoking, alcohol abuse, BMI, gender, previous fragility fracture, number of FRAX(tm) risk factors and age. Univariate and Multivariate regression analysis models were fitted to explore bone loss at these sites using BMD in g/cm2 as a dependant variable. .

Results 

1,527 patients were included in the analysis, 1,207 (79%) were female. Mean age was 64.34 years (SD11.6). mean BMI was 27.32kg/cm2 (SD 5.570) 858 (56.2%) had some steroid exposure . 169(11.1%) had family history of osteoporosis. fragility fracture history found in 406 (26.6%). 621 (40.7%) were current or ex smokers . There was a median of 3 OP risk factors (IQR 1,3) The performance of the models is shown in table one below. Different risk factors appeared to influence the BMD at different sites and the cumulative risk factors influenced BMD in the spine. None of the traditional risk factors predicted poor bone loss well in this cohort. P129 Table 1:result of the regression modelsCharacteristicB femoral neck95% CIpB spine95%CIpAge at scan-0.004-0.005,-0.003<0.01-0.0005-0.002,0.00050.292Sex-0.094-0.113,-0.075<0.01-0.101-0.129,-0.072<0.01BMI (mg/m2)0.0080.008,0.0101<0.010.01130.019,0.013<0.01Fragility fracture-0.024-0.055,0.0060.12-0.0138-0.060,0.0320.559Smoking0.007-0.022,0.0350.650.0286-0.015,0.0720.20Alcohol0.011-0.033,0.0 5560.620.0544-0.013,0.1120.11Family history of OP0.012-0.021,0.0450.470.0158-0.034,0.0650.53Number of risk factors-0.015-0.039,0.0080.21-0.039-0.075,-0.0030.03steroids0.004-0.023,0.0320.030.027-0.015,0.0690.21

Conclusion 

This study has shown that predictors of low BMD in the spine and hip are different and less influential than expected in this cohort with RA . As the FRAX(tm) tool only uses the femoral neck, this might underestimate the fracture risk in this population. Further work looking at individual areas is ongoing.

Disclosure 

M.A. Swar: None. M. Bukhari: None.
Increasing Nursing Student Success With Early Individual Remediation
Authors: Fairchild Faye A.
Published: April 2021

With the implementation of five remediation strategies immediately after the first failed exam in a pharmacology course, this quality improvement study demonstrated an increase in retention of at-risk associate degree nursing students. Unit exam scores and course failure rates were measured before and after implementation. Twelve of 14 students who completed the remediation demonstrated a statistically significant increase in scores from the first failed exam to the last exam taken. The mean increase was 17.3 percentage points (p < .0001, 95 percent confidence interval [13.3, 20.9]). Cohen’s d, which equaled 0.604, indicated a significant increase in course pass rates.
Assisted Fluid Management Software Guidance for Intraoperative Fluid Administration
Authors: Maheshwari Kamal , Malhotra Gaurav , Bao Xiaodong , Lahsaei Peiman , Hand William R. , Fleming Neal W. , Ramsingh Davinder , Treggiari Miriam M. , Sessler Daniel I. , Miller Timothy E. ,   on behalf of the Assisted Fluid Management Study Team
Published: April 2021

Background

Excessive or inadequate fluid administration causes complications, but despite this, fluid administration during noncardiac surgery is highly variable. Goal-directed management helps optimize the amount and timing of fluid administration; however, implementation is difficult because algorithms are complex. The authors therefore tested the performance of the Acumen Assisted Fluid Management software (Edwards Lifesciences, USA), which is designed to guide optimal intravenous fluid administration during surgery.

Methods

In this multicenter, prospective, single-arm cohort evaluation, the authors enrolled 330 adults scheduled for moderate- to high-risk noncardiac surgery that required arterial catheter insertion and mechanical ventilation. Clinicians chose a fluid strategy based on a desired 10%, 15%, or 20% increase in stroke volume (SV) in response to a fluid bolus. Dedicated fluid management software prompted “test” or “recommended” boluses, and clinicians were free to initiate a “user” bolus of 100 to 500 ml of crystalloid or colloid. Clinicians were free to accept or decline the software prompts. The authors primarily compared the fraction of software-recommended boluses that produced suitable increases in SV to a 30% reference rate. On an exploratory basis, we compared responses to software-recommended and clinician-initiated boluses.

Results

Four hundred twenty-four of 479 (89%) software-recommended fluid boluses and 508 of 592 (86%) clinician-initiated fluid boluses were analyzed per protocol. Of those, 66% (95% CI, 62 to 70%) of delivered fluid boluses recommended by the software resulted in desired increases in SV, compared with the 30% reference rate, whereas only 41% (95% CI, 38 to 44%) of clinician-initiated boluses did (P < 0.0001). The mean ± SD increase in SV after boluses recommended by the software was 14.2 ± 13.9% versus 8.3 ± 12.1% (P < 0.0001) for those initiated by clinicians.

Conclusions

Fluid boluses recommended by the software resulted in desired SV increases more often, and with greater absolute SV increase, than clinician-initiated boluses. Automated assessment of fluid responsiveness may help clinicians optimize intraoperative fluid management during noncardiac surgery.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Outcomes of MPFL Reconstruction Utilizing a Quadriceps Turndown Technique in the Adolescent/Pediatric Population
Authors: Fisher Michael , Singh Satbir , Samora Walter P. , Beran Matthew C. , Klingele Kevin E.
Published: April 2021

Purpose:

Recurrent instability following a lateral patellar dislocation is a common indication for surgical intervention. Several surgical procedures are described in the literature to address recurrent patellar instability. Medial patellofemoral ligament (MPFL) reconstruction utilizing the quadriceps turndown technique attempts to restore medial stability. Results of the quadriceps turndown technique have previously only been reported in adult populations. The purpose of this study was to assess the safety, efficacy, and patient-reported outcomes following a quadriceps turndown MPFL reconstruction in the pediatric and adolescent population.

Methods:

Records of all patients who underwent MPFL reconstruction using a quadriceps turndown technique between 2011 and 2018 were reviewed for demographics, risk factors, complications, mechanism of injury, and concomitant procedures. Return to activities of daily living (ADLs), return to presurgery level of sport, length of bracing, and recurrent instability were assessed with the administration of the Kujala Anterior Knee Pain Score. All analyses were completed using IBM SPSS Statistics 26.

Results:

Thirty-six knees [14 female (39%), 22 male (61%)] from 34 patients met inclusion/exclusion criteria. The average follow-up length was 35.9±15.2 months. The average age was 16.3±1.8 years at the time of surgery. The average time for resumption of ADLs was 8.1±6.0 weeks after surgery. Ninety-four percent of patients returned to preinjury level of sport at an average of 23.6±12.0 weeks after surgery. Mean Kujala Anterior Knee Pain Score was 90.7±10.3. Female patients (P<0.001) reported significantly lower Kujala scores. Three patients (8%) experienced recurrent instability during ADLs and an additional 4 (11%) reported subjective feelings of instability only during sport or elevated activity. One knee required a return to the operating room for irrigation and debridement due to infection.

Conclusion:

This study demonstrates that the quadriceps turndown technique for MPFL reconstruction is a safe and effective procedure for the management of recurrent patellar instability in pediatric and adolescent patients.

Level of Evidence:

Level III—therapeutic.
Posterior Instrumentation and Fusion in Multiple-segment Adolescent Congenital Scoliosis: When Are Posterior Column and Concave Rib Osteotomies Needed?
Authors: Yucekul Altug , Ramazanov Rafik , Olgun Zeynep D. , Ayvaz Mehmet , Demirkiran Gokhan , Bekmez Senol , Yazici Muharrem
Published: April 2021

Background:

No clear guidelines exist for appropriate surgical treatment of congenital scoliosis. The spectrum varies from isolated posterior instrumentation and fusion (PIF-only) to vertebral column resections. Multiple posterior column osteotomies (PCOs) with and without concave rib osteotomies have previously been suggested as an alternative to invasive 3-column osteotomies. The aim of the study is to analyze outcomes of spinal surgery in congenital scoliosis patients for a new treatment algorithm based on a traction radiograph under general anesthesia (TruGA).

Methods:

Surgical intervention was determined according to flexibility with TruGA: patients with >40% correction underwent PIF-only; patients with <40% of correction underwent PCO. Patients, who had <30% of correction in TruGA and/or more than 5 vertebral levels with failure of segmentation, underwent additional concave rib osteotomies. The radiologic and clinical results were compared.

Results:

Forty-three patients met inclusion criteria (14M). The mean age was 13.8 (10 to 17) years, average follow-up 67 (24 to 107) months. Fourteen patients were in the PIF-only group, 29 in the PCO group. PCO patients were significantly older (14.5 vs. 12.3, P=0.001). Mean operative time and blood loss of PCO group were significantly greater than those of PIF-only group. Nine patients required concave rib osteotomies. While the curve magnitude of patients in the PIF-only and PCO groups did not differ significantly (54.6 vs. 63 degrees, P=0.067), curve rigidity was significantly higher in the patients of PCO group (51.2% vs. 32%, P=0.001). Despite this, postoperative correction rates for 2 groups were similar (51.1% vs. 47.8%, P=0.545).

Conclusions:

The number of anomalous segments and the curve flexibility on TruGA play important roles in the decision-making process in congenital scoliosis and <40% flexibility of the major curve could be an important indicator of the need for PCO. Curves with more than 5 anomalous vertebral segments might be more likely to need additional concave rib osteotomies for adequate correction.

Level of Evidence:

Level III.
Discoid Lupus Erythematosus Presenting With Disfiguring Acneiform Plaques: A Diagnostic Challenge
Authors: Prieto-Torres Lucía , Morales-Moya Ana L. , Garcia-Garcia Mar , Aldea-Manrique Beatriz , Ara Mariano , Requena Luis
Published: April 2021

Hypertrophic and acneiform forms are very rare variants of discoid lupus erythematosus (DLE), which can suppose a diagnostic and therapeutic challenge. We present a South American woman with facial disfiguring lesions of 7 years of evolution with clinical and histopathological characteristic of both hypertrophic and acneiform DLE. No criteria for systemic lupus erythematosus were present in the patient. To the best of our knowledge, no patients with concomitant hypertrophic and acneiform DLE have been previously reported in the literature.
Primary Cutaneous Monomorphic Post-transplant Lymphoproliferative Disorder Mimicking Squamous Cell Carcinoma In Situ
Authors: Craddock Ashley P. , Gru Alejandro A. , Mannschreck Diana , Wilson Barbara B. , Raghavan Shyam S.
Published: April 2021

Post-transplant lymphoproliferative disorder (PTLD) is a term used to describe a range of lymphoproliferative disorders that occur after solid organ transplant. Although the clinical presentation is variable, primary cutaneous PTLD typically presents as isolated nodules that appear as dermal-based proliferations. We present a case of a 70-year-old woman with a history of a kidney transplant who presented with a 2-month history of an asymptomatic, erythematous plaque on the right shin, clinically suspected to be squamous cell carcinoma in situ. Histomorphology demonstrated a dermal proliferation of atypical plasma cells with dense chromatin, variable nucleoli, and irregular nuclear borders. The atypical plasma cells were positive for Epstein-Barr virus by in situ hybridization and markedly kappa-restricted by RNAscope in situ hybridization. A diagnosis of cutaneous monomorphic PTLD, plasma cell neoplasm variant, was rendered, a rare diagnosis in the skin. Treatment for PTLD typically involves reduction of immunosuppression, although our patient progressed and developed new lesions despite this intervention. In this study, we present an atypical presentation of cutaneous PTLD, plasma cell neoplasm variant, presenting as squamous cell carcinoma in situ.
Emerging follicular activation strategies to treat women with poor ovarian response and primary ovarian insufficiency
Authors: Reig Andres , Herraiz Sonia , Pellicer Antonio , Seli Emre
Published: April 2021

Purpose of the review

Female reproductive aging remains one of the key unsolved challenges in the field of reproductive medicine. This article reviews three of the most recent and cutting-edge strategies that are currently being investigated to address the issues of poor ovarian response (POR) and primary ovarian insufficiency (POI).

Recent findings

Publications revealing the mechanism of mechanical disruption of the Hippo signaling pathway paved the way to studies on its potential application for fertility treatments. This, in combination with Akt stimulation, resulted in live births and ongoing pregnancies in women with POI. Building on previous reports on the effects of bone marrow transplants on fertility after chemotherapy, another approach involved autologous stem cell ovarian transplantation (ASCOT). The method proved effective in achieving live births in women previously diagnosed with POR. A third approach, intraovarian injection of autologous platelet-rich plasma, resulted in live births and ongoing pregnancies both spontaneously and via in vitro fertilization (IVF) in women with POI and POR.

New paths are being charted to address the issues of POI and POR. Although these are preliminary studies that should be interpreted with caution, they represent great promise for the women affected by these conditions and the physicians treating them.
Circulating biomarkers to assess cardiovascular function in critically ill
Authors: van Lier Dirk , Pickkers Peter
Published: April 2021

Purpose of review

Circulatory shock is one of the most common reasons for ICU admission. Mortality rates in excess of 40% necessitate the rapid identification of high-risk patients, as well as the early assessment of effects of initiated treatments. There is an unmet medical need for circulating biomarkers that may improve patient stratification, predict responses to treatment interventions and may even be a target for novel therapies, enabling a better biological rationale to personalize therapy.

Recent findings

Apart from established biomarkers such as lactate, ScvO2 or NT-pro-BNP, novel biomarkers, including adrenomedullin, angiopoietins, angiotensin I/II ratios, renin and DPP3 show promise, as they are all associated with well defined, therapeutically addressable molecular pathways that are dysregulated during circulatory shock. Although some of the therapies related to these biomarkers are still in preclinical stages of development, they may represent personalized treatment opportunities for patients in circulatory shock.

From a molecular perspective, shock represents a highly heterologous syndrome, in which multiple unique pathways are dysregulated. Assessment of the status of these pathways with circulating biomarkers may provide a unique opportunity to detect specific phenotypes and implement personalized medicine in the treatment of circulatory shock.
What Ever Happened to Nostalgia (the Diagnosis)?
Authors: Weiss Kenneth J. , Dube Anish Ranjan
Published: April 2021

Nostalgia and homesickness are not currently regarded as mental disorders. The psychic pain associated with longing to return home had been considered a mental disorder for centuries, especially in Europe, where it was a sign of moral weakness between nations. Nostalgia's effects on American Civil War soldiers—anxiety, depression, and sleep and appetite disturbances, for example—were described by clinicians and linked to significant morbidity and mortality. Since then, although these effects of combat have been of interest, focus has shifted to psychic trauma, relegating the concept of nostalgia to an unclassified but commonly encountered condition. Besides wartime trauma, symptomatic conditions related to nostalgia have been described among displaced persons and refugees living in the diaspora longing for their homelands (e.g., social displacement syndrome). More recently, nostalgia has pervaded culture as a benign pastime, with no implications for psychopathology. Finally, the longing for return to an idyllic or imagined lifestyle has returned amid worldwide quarantining and isolation during the COVID-19 pandemic. In this new sense, nostalgia has become a remedy rather than a disease. We identify four major iterations of nostalgia: the medical condition of homesickness, the condition studied in wartime, the application to migration and social displacement, and as a remedy for existential anxiety. We conclude that nostalgia per se is neither pathological nor normative, but a consistent phenomenon in human existence that should not be overlooked in cultural assessment and psychotherapy.
Emotion Regulation Difficulties and Depression Among Individuals With Dermatological and Body Dysmorphic Concerns
Authors: Boullion Gina Q. , Witcraft Sara M. , Schadegg Mary J. , Perry Megan M. , Dixon Laura J.
Published: April 2021

Existing literature demonstrates strong links between emotion regulation (ER) difficulties and depression. Although high rates of depression are observed among individuals with body dysmorphic disorder and skin disease, little is known about these co-occurring syndromes. To advance our understanding of a vulnerable population, this study examined facets of ER difficulties in relation to depression among adults with skin disease symptoms and body dysmorphic concerns (N = 97). Participants were recruited online and completed self-report measures. The overall hierarchical regression model accounted for 61.6% of the variance in depression. After controlling for anxiety and stress, ER difficulties added 9.9% unique variance. In particular, limited access to ER strategies was the only ER dimension significantly associated with depression. This study integrates divergent literatures and suggests the important role of ER difficulties in depression in this unique sample, thereby highlighting directions for future investigation.
Recurrent YAP1-TFE3 Gene Fusions in Clear Cell Stromal Tumor of the Lung
Authors: Agaimy Abbas , Stoehr Robert , Michal Michael , Christopoulos Petros , Winter Hauke , Zhang Lei , Stenzinger Albrecht , Michal Michal , Mechtersheimer Gunhild , Antonescu Cristina R.
Published: April 2021

Clear cell (hemangioblastoma-like) stromal tumor of the lung (CCST-L) is a recently described distinctive rare pulmonary neoplasm of unknown histogenesis and molecular pathogenesis. Only 7 cases have been reported in 2 recent studies, although additional cases might have been reported under the heading of extraneural pulmonary hemangioblastoma. We herein describe 4 CCST-L cases, 3 of them harboring a YAP1-TFE3 fusion. The fusion-positive tumors occurred in 3 women, aged 29, 56, and 69 years. All presented with solitary lung nodules measuring 2.3 to 9.5 cm. Histologically, all tumors showed similar features being composed of relatively uniform medium-sized epithelioid to ovoid cells with clear cytoplasm and small round monomorphic nuclei. Scattered larger cells with enlarged hyperchromatic nuclei and marked pleomorphism were noted in 2 cases. The tumors were associated with a hypervascularized stroma with variable but essentially subtle resemblance to capillary hemangioblastoma and perivascular epithelioid cell tumor (PEComa). Immunohistochemistry was negative for all lineage-specific markers. Targeted RNA sequencing showed a YAP1-TFE3 fusion in 3 of 4 cases. All 3 tumors showed homogeneous nuclear TFE3 immunoreactivity. Two patients were disease free at 36 and 12 months. The third patient had biopsy-proven synchronous renal and hepatic metastases, but extended follow-up is not available (recent case). The fourth case lacking the fusion affected a 66-year-old woman and showed subtle histologic differences from the fusion-positive cases, but had comparable TFE3 immunoreactivity. CCST-L represents a distinctive entity unrelated to hemangioblastoma and likely driven by recurrent YAP1-TFE3 fusions in most cases. The relationship of our cases to the recently reported “hemangioblastoma-like” CCST-L remains to be determined. Analysis of larger series is paramount to delineate the morphologic spectrum and biological behavior of this poorly characterized entity.
Structured illumination microscopy and image scanning microscopy: a review and comparison of imaging properties
Authors: Sheppard Colin J. R.
Published: April 2021

Structured illumination microscopy and image scanning microscopy are two microscopical tech- niques, rapidly increasing in practical application, that can result in improvement in transverse spatial resolution, and/or improvement in axial imaging performance. The history and principles of these techniques are reviewed, and the imaging properties of the two methods compared.

This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 1)’.
Improving axial resolution in Structured Illumination Microscopy using deep learning
Authors: Boland Miguel A. , Cohen Edward A. K. , Flaxman Seth R. , Neil Mark A. A.
Published: April 2021

Structured Illumination Microscopy (SIM) is a widespread methodology to image live and fixed biological structures smaller than the diffraction limits of conventional optical microscopy. Using recent advances in image up-scaling through deep learning models, we demonstrate a method to reconstruct 3D SIM image stacks with twice the axial resolution attainable through conventional SIM reconstructions. We further demonstrate our method is robust to noise and evaluate it against two-point cases and axial gratings. Finally, we discuss potential adaptions of the method to further improve resolution.

This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 1)’.
Zygotorulaspora dagestanica sp. nov., a novel ascomycetous yeast species associated with the Georgian honeysuckle (Lonicera iberica M. Bieb.)
Authors: Kachalkin Aleksey V. , Abdullabekova Dinakhanum A. , Magomedova Elena S. , Yurkov Andrey M.
Published: April 2021

During an investigation of the yeast communities associated with wild fruit shrubs in Dagestan (Caucasus, Russia), four fermenting ascospore-producing yeast strains were isolated from leaves of the Georgian honeysuckle (Lonicera iberica M. Bieb.) and from soil underneath this plant. Phylogenetic analyses based on concatenated sequences of the ITS region and D1/D2 domains of the large subunit rRNA gene and concatenated sequences of the ribosomal DNA cystron, RPB2 and TEF1 genes showed that the isolated strains represented a new species of the genus Zygotorulaspora. The new species was placed in the basal position to other species of the clade and close to Zygotorulaspora mrakii. Based on the results of phylogenetic analyses and the phenotypic characteristics of the four studied strains, a novel species is described, for which the name Zygotorulaspora dagestanica sp. nov. is proposed. The holotype is KBP Y-4591T, three metabolically inactive cryopreserved isotype cultures are DSM 100088, VKM Y-3060 and VKPM Y-4318. The MycoBank number is MB 838285.
Risk factors associated with severe outcomes of COVID-19: A systematic rapid review to inform national guidance on vaccine prioritization in Canada
Authors: Gates Michelle , Pillay Jennifer , Wingert Aireen , Guitard Samantha , Rahman Sholeh , Zakher Bernadette , Gates Allison , Hartling Lisa
Published: April 2021

Background

To inform vaccine prioritization guidance in Canada, we systematically reviewed evidence on the magnitude of association between risk factors and severe outcomes of COVID-19. The urgent nature of this review necessitated an adapted methodology, which may serve as an exemplar for reviews undertaken under strict timelines.

Methods

We updated our existing review by searching online databases and websites for cohort studies providing multivariate adjusted associations. After piloting, one author screened studies and extracted data. Two authors estimated the magnitude of association between exposures and outcomes as little-to-no (odds, risk, or hazard ratio <2.0, or >0.50 for reduction), large (2.0-3.9, or 0.50-0.26 for reduction), or very large (≥4.0, or ≤0.25 for reduction), and rated the evidence certainty using GRADE.

Results

Of 11,734 unique records we included 134 reports. There is probably (moderate certainty) at least a large increase in mortality from COVID-19 among people aged 60-69 vs. <60 years (11 studies, n=517,217), with ≥2 vs. no comorbidities (4 studies, n=189,608), and for people with (vs. without): Down syndrome (1 study, n>8 million), type 1 and 2 diabetes (1 study, n>8 million), end-stage kidney disease (1 study, n>8 million), motor neuron disease, multiple sclerosis, myasthenia gravis, or Huntington’s disease (as a grouping; 1 study, n>8 million). The magnitude of association with mortality is probably very large for Down syndrome and may (low certainty) be very large for age 60-69 years, and diabetes. There is probably little-to-no increase in severe outcomes with several cardiovascular and respiratory conditions, and for adult males vs. females.

Conclusion

There is strong evidence to support at least a large increase in mortality from COVID-19 among older adults aged 60 to 69 years versus <60 years; people having two or more versus no comorbidities; and for people affected by several pre-existing conditions. The methodology employed in this review may provide an important exemplar for future syntheses undertaken under urgent timelines.

Systematic review registration

PROSPERO #CRD42021230185.
Hierarchical chromatin regulation during blood formation uncovered by single-cell sortChIC
Authors: Zeller Peter , Yeung Jake , de Barbanson Buys Anton , Gaza Helena Viñas , Florescu Maria , van Oudenaarden Alexander
Published: April 2021

Post-translational histone modifications modulate chromatin packing to regulate gene expression. How chromatin states, at euchromatic and heterochromatic regions, underlie cell fate decisions in single cells is relatively unexplored. We develop sort assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in hematopoietic stem and progenitor cells (HSPCs), and mature blood cells in the mouse bone marrow. During differentiation, HSPCs acquire distinct active chromatin states that depend on the specific cell fate, mediated by cell type-specifying transcription factors. By contrast, most regions that gain or lose repressive marks during differentiation do so independent of cell fate. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin-repressed states. This suggests hierarchical chromatin regulation during hematopoiesis: heterochromatin dynamics define differentiation trajectories and lineages, while euchromatin dynamics establish cell types within lineages.
New red phosphor Na3EuB8O15 with an open-window tubular structure
Authors: Bi Wen-Yan , Wang Wei , Zhang Rui-Juan
Published: April 2021

A new rare-earth polyborate, trisodium europium octaborate, Na3EuB8O15, was prepared using the high-temperature molten-salt method and structurally determined by single-crystal X-ray diffraction analysis. It crystallizes in the triclinic space group P-1 and contains a one-dimensional [B8O15]∞ tube structure that is constructed from BO3 and BO4 polyhedra. The Eu3+ and Na+ cations reside in this structure to ensure cohesion and neutrality. The excitation spectra, emission spectra, decay time and Commission Internationale de l'Éclairage (CIE) chromaticity index of Na3EuB8O15 were studied. Under near-UV light excitation (393 nm), the polyborate shows an intense red emission, which mainly originates from the highest intensities of the 5D0→7F1 and 5D0→7F2 transitions.
Predicting intraspecific trait variation among California's grasses
Authors: Sandel Brody , Pavelka Claire , Hayashi Thomas , Charles Lachlan , Funk Jennifer , Halliday Fletcher W. , Kandlikar Gaurav S. , Kleinhesselink Andrew R. , Kraft Nathan J. B. , Larios Loralee , Madsen‐McQueen Tesa , Spasojevic Marko J.
Published: April 2021

Plant species can show considerable morphological and functional variation along environmental gradients. This intraspecific trait variation (ITV) can have important consequences for community assembly, biotic interactions, ecosystem functions and responses to global change. However, directly measuring ITV across many species and wide geographic areas is often infeasible. Thus, a method to predict spatial variation in a species’ functional traits could be valuable.

We measured specific leaf area (SLA), height and leaf area (LA) of grasses across California, covering 59 species at 230 sampling locations. We asked how these traits change along climate gradients within each species and used machine learning to predict local trait values for any species at any location based on phylogenetic position, local climate and that species’ mean traits. We then examined how much these local predictions alter patterns of assemblage‐level trait variation across the state.

Most species exhibited higher SLA and grew taller at higher temperatures and produced larger leaves in drier conditions. The random forests predicted spatial variation in functional traits very accurately, with correlations up to 0.97. Because trait records were spatially biased towards warmer areas, and these areas tend to have higher SLA individuals within each species, species means of SLA were upwardly biased. As a result, using species means over‐estimates SLA in the cooler regions of the state. Our results also suggest that height may be substantially under‐predicted in the warmest areas.

Synthesis. Using only species mean traits to characterize the functional composition of communities risks introducing substantial error into trait‐based estimates of ecosystem properties including decomposition rates or NPP. The high performance of random forests in predicting local trait values provides a way forward for estimating high‐resolution patterns of ITV without a massive data collection effort.