bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Gene Controls a New Structure: PiggyBac Transposable Element-Derived 1, Unique to Mammals, Controls Mammal-Specific Neuronal Paraspeckles
Authors: Raskó Tamás , Pande Amit , Radscheit Kathrin , Zink Annika , Singh Manvendra , Sommer Christian , Wachtl Gerda , Kolacsek Orsolya , Inak Gizem , Szvetnik Attila , Petrakis Spyros , Bunse Mario , Bansal Vikas , Selbach Matthias , Orbán Tamás I , Prigione Alessandro , Hurst Laurence D , Izsvák Zsuzsanna
Published: October 2022

Although new genes can arrive from modes other than duplication, few examples are well characterized. Given high expression in some human brain subregions and a putative link to psychological disorders [e.g., schizophrenia (SCZ)], suggestive of brain functionality, here we characterize piggyBac transposable element-derived 1 (PGBD1). PGBD1 is nonmonotreme mammal-specific and under purifying selection, consistent with functionality. The gene body of human PGBD1 retains much of the original DNA transposon but has additionally captured SCAN and KRAB domains. Despite gene body retention, PGBD1 has lost transposition abilities, thus transposase functionality is absent. PGBD1 no longer recognizes piggyBac transposon-like inverted repeats, nonetheless PGBD1 has DNA binding activity. Genome scale analysis identifies enrichment of binding sites in and around genes involved in neuronal development, with association with both histone activating and repressing marks. We focus on one of the repressed genes, the long noncoding RNA NEAT1, also dysregulated in SCZ, the core structural RNA of paraspeckles. DNA binding assays confirm specific binding of PGBD1 both in the NEAT1 promoter and in the gene body. Depletion of PGBD1 in neuronal progenitor cells (NPCs) results in increased NEAT1/paraspeckles and differentiation. We conclude that PGBD1 has evolved core regulatory functionality for the maintenance of NPCs. As paraspeckles are a mammal-specific structure, the results presented here show a rare example of the evolution of a novel gene coupled to the evolution of a contemporaneous new structure.
Anti-CRISPR proteins function through thermodynamic tuning and allosteric regulation of CRISPR RNA-guided surveillance complex
Authors: Patterson Angela , White Aidan , Waymire Elizabeth , Fleck Sophie , Golden Sarah , Wilkinson Royce A , Wiedenheft Blake , Bothner Brian
Published: October 2022

CRISPR RNA-guided detection and degradation of foreign DNA is a dynamic process. Viruses can interfere with this cellular defense by expressing small proteins called anti-CRISPRs. While structural models of anti-CRISPRs bound to their target complex provide static snapshots that inform mechanism, the dynamics and thermodynamics of these interactions are often overlooked. Here, we use hydrogen deuterium exchange-mass spectrometry (HDX-MS) and differential scanning fluorimetry (DSF) experiments to determine how anti-CRISPR binding impacts the conformational landscape of the type IF CRISPR RNA guided surveillance complex (Csy) upon binding of two different anti-CRISPR proteins (AcrIF9 and AcrIF2). The results demonstrate that AcrIF2 binding relies on enthalpic stabilization, whereas AcrIF9 uses an entropy driven reaction to bind the CRISPR RNA-guided surveillance complex. Collectively, this work reveals the thermodynamic basis and mechanistic versatility of anti-CRISPR-mediated immune suppression. More broadly, this work presents a striking example of how allosteric effectors are employed to regulate nucleoprotein complexes.
Effect of Blood Culture Contamination on Antibiotic Use in an Institution With Rapid Laboratory Methods and Phone-Based Clinical Follow-up of Blood Culture Results
Authors: Bloomfield Max G , O’Connor Michael J Q , Balm Michelle N D , Blackmore Tim K
Published: October 2022

In a multivariate analysis of 30 574 blood culture (BC) results, BC contamination was associated with only a small increase in antibiotic length of therapy compared to no-growth BCs (difference, 0.36 days [95% confidence interval, .05–.67]; P = .02). Stewardship processes at our institution appear to be effective in reducing the impact of BC contamination.
A new long-term measure of sustainable growth under uncertainty
Authors: Okabe Takuya , Yoshimura Jin
Published: October 2022

The trade-off between short-term success and long-term sustainability is a common subject of great importance both in the biological evolution of organisms and in the economic activities of human beings. In evolutionary biology, bet-hedging theories have described it as the trade-off between the (within-generation) arithmetic mean fitness and the (between-generation) geometric mean fitness of a genotype. Accordingly, bet-hedging strategies observed in various organisms are regarded as optimizing the geometric mean fitness. To increase the geometric mean fitness signifies to suppress the between-generation variance in the mean fitness. Thus, this view is consistent with mean-variance portfolio analysis in which the standard deviation of a portfolio is regarded as a measure of risk. In the present study, we provide yet another measure of long-term sustainability, which is based on minimization of the probability of extinction/bankruptcy that randomly varying population/asset size after a long time becomes less than a certain small value. We present results for representative examples to show that the present criterion gives a qualitatively similar but quantitatively different prediction from the traditional ones. In particular, we emphasize that maximizing survival probability (i.e. minimizing extinction probability) is equivalent neither to maximizing geometric mean fitness nor to minimizing variance in mean fitness, while these three are consistently related to each other.
Facilitating innovation diffusion in social networks using dynamic norms
Authors: Zino Lorenzo , Ye Mengbin , Cao Ming
Published: October 2022

Dynamic norms have recently emerged as a powerful method to encourage individuals to adopt an innovation by highlighting a growing trend in its uptake. However, there have been no concrete attempts to understand how this individual-level mechanism might shape the collective population behavior. Here, we develop a framework to examine this by encapsulating dynamic norms within a game-theoretic mathematical model for innovation diffusion. Specifically, we extend a network coordination game by incorporating a probabilistic mechanism where an individual adopts the action with growing popularity, instead of the standard best-response update rule; the probability of such an event captures the population’s “sensitivity” to dynamic norms. Theoretical analysis reveals that sensitivity to dynamic norms is key to facilitating social diffusion. Small increases in sensitivity reduces the advantage of the innovation over status quo or the number of initial innovators required to unlock diffusion, while a sufficiently large sensitivity alone guarantees diffusion.
12 Hip involvement in juvenile idiopathic arthritis: frequency and associated factors
Authors: Tbini Houssem , Rahmouni Safa , Boussaid Soumaya , Ammou Ahlem Ben , Jemmali Samia , Rekik Sonia , Zouaoui Khaoula , Sahli Hela , Elleuch Mohammed
Published: October 2022

Background

Juvenile idiopathic arthritis (JIA) is a pediatric rheumatic disease with several subgroups. The hip is frequently affected. The frequency of this involvement can reach 50% especially in the severe and destructive forms. Arthroplasty may be indicated in advanced cases.

Objectives

To assess the frequency and associated factors with hip involvement in (JIA).

Methods

We conducted a retrospective study including adults with long-standing JIA according to the International League of Associations for Rheumatology (ILAR) criteria over a period of 28 years (1994–2022). Demographic, clinical, biological, and radiographic data were collected. These parameters were compared according to the presence or absence of hip involvement.

Results

A total of 29 Patients were enrolled (12 men and 17 women), the mean age was 35.69 ± 11.72 [18–61] years. The mean age of disease onset was 11.10 ± 4.25 [2–16] years. The average diagnostic delay was 52.96 ± 95.97 [0–336] months. The average disease duration was 24.48 ± 12.76 [1–47] years.

Sixteen patients had a polyarticular form. Mean CRP values were 42.74 ± 63.37 [2–218] mg/l, a biological inflammatory syndrome was present in 19 cases. Rheumatoid factor, ACPA and anti-nuclear antibodies were observed in 12, 7 and 5 cases respectively. At least one extra-articular manifestation was noted in 16 cases.

Hip involvement was noted in 14 patients (48.3%). It was bilateral in 64.3% of cases (n = 9). Twenty-three hips were affected in total (56.9%). Hip involvement was diagnosed 14.5 ± 9.37 [1–28] years after disease onset. Arthroplasty was performed on 10 hips with a delay of 201.60 ± 104.75 [108–348] months between diagnosis of JIA and surgery.

Hip involvement was associated with male gender in our study (75% vs 29.4%; p = 0.016). On the other hand, our study showed that age, age at onset, diagnostic delay, symptoms duration, smoking, BMI, extra-articular manifestations, CRP, rheumatoid factor, antinuclear antibodies, ACPA and erosive character were not associated with hip involvement.

Conclusion

Our study showed that hip involvement is common in JIA, mainly in male patients. It usually occurs late in the disease course. Since hip involvement is a cause of disability and functional impairment, it should be assessed regularly.
14 Juvenile idiopathic arthritis: osteoporosis and fractures
Authors: Ammou Ahlem Ben , Rahmouni Safa , Boussaid Soumaya , Tbini Houssem , Jemmali Samia , Rekik Sonia , Zouaoui Khaoula , Sahli Hela , Elleuch Mohammed
Published: October 2022

Background

Juvenile idiopathic arthritis (JIA) is the most common inflammatory arthritis in children. Chronic inflammation, as well as the various treatments used during JIA increase the risk of occurrence of osteoporosis (OP) and fractures.

Objectives

The objective of this work was to determine the frequency of OP in JIA and to investigate the factors associated with its occurrence.

Methods

This was a retrospective study including adults with long-standing JIA according to the International League of Associations for Rheumatology (ILAR) criteria over a period of 28 years (1994–2022). We collected sociodemographic and anthropometric parameters, clinical data, results of biological assessments, bone densitometry results and data on prescribed therapies. We compared these variables according to the bone densitometry profile to assess the factors associated with OP in JIA.

Results

There were 29 patients (17 females and 12 males), the mean age was 35.69 ± 11.72 [18–61] years. The mean age of disease onset was 11.10 ± 4.25 [2–16] years. The average diagnostic delay was 52.96 ± 95.97 [0–336] months. The average disease duration was 24.48 ± 12.76 [1–47] years. Three patients were smokers. The mean BMI was 21.20 ± 4.88 [14.17–27.55] kg/m2, and 4 patients had a BMI ≥ 25 kg/m².

The polyarticular form was the most frequent, noted in 55.2% of cases (n = 16). NSAIDs, corticosteroids and methotrexate were prescribed in 62.1%, 69% and 79.3% of cases respectively.

OP was found in 24.1% of cases (n = 7). Mean T-score values at the lumbar and femoral sites were −2.20 ± 1.22 SD and −2.31 ± 0.97 SD, respectively. Six patients suffered at least one fracture.

Patients with OP had lower BMI than patients with normal bone density (17.02 ± 2.46 vs 23.91 ± 5.42; p = 0.046). Furthermore, absence of rheumatoid factor was associated with OP in our study (83.3% vs 16.7%; p = 0.008).

On the other hand, the following parameters were not associated with the occurrence of OP in our study: age, gender, smoking, age at onset and duration of progression of JIA, BMI, extra-articular manifestations, CRP, antinuclear antibodies, ACPA and erosive character. Regarding the treatment received (NSAIDs, corticosteroids and methotrexate), no difference was found between patients.

Conclusion

Osteoporosis in JIA is common and has a prognostic impact. It must be systematically screened throughout the follow-up. In our study, OP was associated with the absence of rheumatoid factor and was more frequent in patients with low BMI.
23 Predictive factors of hip involvement in juvenile idiopathic arthritis
Authors: Rania Ben Aissa , Hanene Ferjani , Mariam Moalla , Dorra Ben Nessib , Wafa Triki , Kaouther Maatallah , Dhia Kaffel , Wafa Hamdi
Published: October 2022

Background

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Hip involvement is a common problem in JIA patients and is associated with functional disability and poor outcomes. Intensive therapy is required to avoid replacement surgery. With few studies in the literature, the predictive factors of hip involvement are still unknown.

Objectives

To identify the clinical, biological characteristic of patients with hip involvement and determine the risk factors associated.

Methods

A cross-sectional study including children with JIA according to the International League of Associations for Rheumatology (ILAR). The recorded data included sociodemographic features, disease characteristics (subtype disease, duration, and juvenile arthritis disease activity score (JADAS) as well as treatment modalities. Regarding coxitis, we collected radiographs, ultrasound (US), and magnetic resonance imaging (MRI) of the hip when performed. Coxitis was defined by clinical (limited range of motion) and/or radiographic findings (destruction, synovitis, bone marrow oedema).

Results

Thirty-five patients (20 females) with a median age of 12 years (5–18) and disease duration 3 years (0.25–15) were recruited. The patient's distribution of JIA subtypes were oligoarticular (n = 13), enthesitis-related arthritis (n = 9), polyarticular (n = 4) (negative rheumatoid factor in 3 patients), undifferentiated (n = 4), psoriasis-arthritis (n = 4) and systemic-onset (n = 1). ESR and CRP median values were 15 mm/h (0–63) and 2 mg/l (0–47); respectively. DMARDS was admitted to 16 patients Sixteen patients [Methotrexate (n = 10), biological agent (n = 3), biological agent and methotrexate (n = 2), salazopyrine (n = 1)].

Sixteen patients (45.71%) developed coxitis (radiographic (n = 8), MRI (n = 5) and US findings (n = 3)) with limited range of movement in eight (50%) and radiological evidence of hip damage in 10 (62.5%). Hip involvement was associated with a longer disease duration (p = 0.051). JADAS of patients with coxitis was higher (Mean 8.35 vs 7.05) but not significant (p = 0.565). Higher CRP and ESR values were found in patients with coxitis (mean 8.39 mg/l vs 6.83 mg/l, 22.29 mm/h vs 16.37 mm/h respectively) but not significant (p = 0.718, p = 0.287 respectively). No associations were found between hip involvement and BMI (p = 0.233), age-onset (p = 0.496), JIA subtype (p = 0.509) and sex (p = 0.767).

Conclusion

Our study shows that long disease duration exposes to a higher risk of hip involvement in children with JIA. Active disease and biological inflammatory syndrome could be associated risk factors. Studies with larger sample size are needed to draw definite causal associations.
26 Kawasaki’s disease vs systemic juvenile idiopathic arthritis, a diagnostic dilemma
Authors: Thakkar Monali , Migowa Angela
Published: October 2022

Background

Both these conditions are separate inflammatory conditions whose clinical presentation overlap and thus make their distinction difficult. Each has a criterion that allows diagnosis but since features overlap, diagnoses may be missed.

Recent research also shows that both disease processes have similar underlying pathogenesis and involve interleukin 1; which have now raised the question of whether both these disease processes are distinct entities or conditions of a similar spectrum.

Methods

Medical records of from the inpatient admission at current and referring hospitals which included clinical history and examination, laboratory and radiological findings.

Results

13-year-old boy referred from Isiolo county with complains of unremitting fevers for 9 days with associated hip pains. Was initially treated for malaria, and started on broad spectrum antibiotics and antivirals. On further examination, was noted to have cracked lips, strawberry tongue, non-suppurative conjuctivitis and an anterior chest wall wheal like rash. Examination also revealed a left sided non tender submandibular lymph node. Initial laboratory investigations showed neutrophilia of 12.89, thrombocytosis of 431, CRP of 364 and normal joint radiographs. An ECHO done showed left ventricular enlargement with corresponding mild Mitral regurgitation. Blood cultures showed no organisms. Autoimmune markers and tropical fever markers were normal as well. He was then placed on prednisolone challenge and reported to be fever free for the first time in 12 days.

Discussion and conclusion

A persistent fever unremitting with parenteral antipyretics can have a multitude of differentials. In a tropical nation the likelihood of an infectious cause is more common than other aetiologies. Hence, it should always be investigated for thoroughly. In the case highlighted above, malaria, TB, osteomyelitis, septic arthritis and other infectious causes were investigated. Childhood malignancy can also present with the same. But of note is autoimmune conditions need to be considered. With history of arthritic like pain, quotidian pattern of fevers, evanescent salmon coloured chest wall rash and cervical lymphadenopathy, a diagnosis of Systemic Juvenile Arthritis needs to be considered. Often this may be overlooked or misinterpreted as Kawasaki’s; which is a close differential; or Still’s disease. There is a criterion for SJIA by the International League of Associations for Rheumatology, however, there can be an incomplete presentation as well. This adds on to the diagnostic challenge and hence, SJIA may remain undiagnosed for a long time.
28 Osteoarticular manifestations simulating JIA in acute leukemia: case report and literature review
Authors: Benmouffok N , Boudouaa F. Z , Tari S , Nemmar R , Boulainine A , Rouabeh S , Ouatah S , Zeroual Z
Published: October 2022

Background

The osteoarticular manifestations are proven during hematological malignancies in children, they can be the revealing symptom of the disease, and they may simulate a full clinical picture of Juvenile Idiopathic Arthritis (JIA), especially if no blasts are found in blood smear. Some therapies are common to both diseases, which commonly delay diagnosis for a couple of months and worsens the prognosis of these malignancies. We report three observations of patients treated for JIA which turned out to be acute leukaemia.

Clinical caises

The first patient is a 7-year-old male followed in pediatric rheumatology consultation for a monoarticular onset JIA. Since the patient did not respond to indomethacin, a bone marrow examination (BME) was performed before corticosteroid therapy (CST), no blasts were found. The patient received 01 month of CST which led to the amendment of clinical and biological signs, however, joint pain and bicytopenia reappeared after we started CST reduction. Blood and blood marrow smear were performed, leading to the diagnosis of acute B-lymphoblastic leukaemia.

The second patient is a 4 years old male admitted for exploration of polyarthritis with cervical lymphadenopathy, the initial assessment allowed the diagnosis of JIA with polyarticular onset. Indomethacin is prescribed, without any improvement. Radiological assessment was performed, as well as a complete blood count (CBC) which found neutropenia with lymphopenia, and blasts were discovered in the second BME.

The third patient is a 6-year-old female admitted for exploration of arthralgia and pathological fractures. Radiological signs in favor of leukaemia and normochromic aregenerative normocytic anaemia were revealed, allowing the diagnosis of ALL B to be made after several consultations in rheumatology.

Discussion

Joint damage during leukaemia, called leukaemic arthritis, is frequent, complicating 12% to65% of pediatric leukaemia, most often ALL. It is linked to specific damage by leukaemic infiltration of the synovium or less likely to a synovial reaction to adjacent periosteal or capsular infiltration. In JIA there are incomplete or atypical forms, the differential diagnoses to be sought are numerous and depend on age, personal and family anamnesis and clinical, biological, hematological and radiological signs. The dread of a haematological malignancy must constantly be sought and excluded before the use of CST, which is one of the therapeutic weapons in ALL, thus causing the blasts to disappear and delaying the diagnosis.

Conclusion

The diagnosis of JIA must be made with caution, raise the possibility of haematological malignancy in children in the absence of response to usual treatments, in the presence of systemic signs such as fever or a persistent biological syndrome or atypical radiological lesions, hence the correct analysis of the CBC and the blood and marrow smears is clearly important.
29 Juvenile idiopathic arthritis and osteogenesis imperfecta: an exceptional association
Authors: Emna Hannech , Soumaya Boussaid , Sonia Rekik , Samia Jemmali , Safa Rahmouni , Houda Ajlani , Hela Sehli , Mohamed Elleuch
Published: October 2022

Background

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. Osteogenesis imperfecta (OI) is an autosomal dominant inherited disease defined by bone fragility due to abnormal collagen synthesis. It affects the entire skeleton, predisposing the patient to fractures.

We report an uncommon association between osteogenesis imperfecta and juvenile idiopathic arthritis.

Case presentation

A 15-year-old child presented to our rheumatology department with medical history of recurrent bone fractures due to low-energy trauma since the age of five years. The patient was born from a consanguineous marriage. He has been diagnosed with a polyarticular JIA since the age of eight years-old. The initial clinical presentation was a symmetric, cumulative, large and small joint polyarthritis. The rheumatoid factor was negative. No other autoantibodies were detected.

The patient was treated initially with methotrexate which was inefficient. He developed joint deformities. Then, biologic therapy was associated with a good response.

Clinical examination on entry showed severe joint deformities touching elbows, wrists and interphalangeal joints. Arms and thighs were curved and an unequal leg length was noted. There was no arthritis. The patient has bluish sclera. Neurological and dental examination was normal. There was no hearing loss. Laboratory findings showed a normal C-reactive protein. Calcium and phosphate serum levels were within normal ranges. On radiological investigations, radiographs showed excessive trabecular bone transparency, cortical bone thinning and incomplete bone fractures. Bone densitometry revealed a Z-score of the lumbar spine of -4.2 SD.

According to clinical, biological, and radiological investigations, the diagnosis of JIA associated with OI was confirmed clinically. Treatment with Pamidronate was initiated intravenously.

Conclusion

We reported an exceptional association between JIA and OI which occurred in a young Tunisian patient. We emphasize that this association should be considered when severe joints and extremities deformities occur.

Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this abstract.

Acknowledgements: declared none.
40 Arthralgia and celiac disease
Authors: Boutrid N , Rahmoune H , Bioud B , Amrane M
Published: October 2022

Background

In a large cohort of 2125 children followed in rheumatology, 2% had celiac disease (CD) (about 3 times the rate in the general population). Inversely, CD was reported in up to 2–3% of children with juvenile idiopathic arthritis

Objectives

Reporting joint damage such as arthrlagia in a celiac pediatric cohort

Material and method

We collected 58 celiac children and reported those with arthralgia and studied their clinical aspects

Results

Arthralgia was reported in 10/58 children (i.e. 17.24%) of the entire cohort studied (n = 58), including 09 children with positive HLA DQ2/DQ8 typing, potentially with an autoimmune background. The arthralgia was not accompanied by arthritis, and had an apyretic, labile and transient character. Only one case of episodic spinal pain was reported in the history

Conclusion

More than a sixth of the pediatric celiac cohort presents with arthralgia. These joint pains can be caused by vitamin D deficiency, osteoporosis, associated juvenile idiopathic arthritis (JIA), in particular HIV-positive. They can also be isolated and respond to the gluten-free diet.
54 Kawasaki disease: experience in a general paediatric department of the CHU de Annaba Algeria
Authors: Belamri D. J , Sehab H , Bouglouf S , Boutalbi N , Boustil L , Bouchair N
Published: October 2022

Background

Kawasaki disease (adeno-cutaneous-mucosal syndrome) is an acute febrile systemic vasculitis, affecting with predilection infants. Of unknown aetiology, its diagnosis is based on clinical criteria validated by the CDC and updated by the American Heart Association. Its prognosis is linked to the presence of coronary complications. Its prevalence in Algeria remains unknown, the increase in the number of cases in recent years has raised questions about its situation in our department.

Objective

To study the epidemiological, diagnostic, therapeutic, biological and evolutionary aspects of this disease.

Materials and methods

The authors report the results of a retrospective study of 2 years and 4 months, concerning 15 cases of Kawasaki disease hospitalized and treated in the pediatric department of the University Hospital of Annaba. The information was obtained from the hospitalization records.

Results

15 cases of Kawasaki disease were identified during the study period. Almost half of the patients were between 2 and 5 years of age, with an average age of 26.3 months (range: 11 months-9 years). A clear male predominance was noted (SR: 2). The reasons for hospitalization were dominated by fever (73%), skin involvement (66%) and stomatitis (40%). The clinical examination showed the frequency of the classical criteria of the disease with almost constant fever (100%), polymorphous skin rash 93.33%, oral-pharyngeal involvement 93.33%, involvement of hands and feet 40%, conjunctivitis 53.33% and adenopathies 46.67%. Biologically, the blood count showed anaemia (93.33%), hyperleukocytosis (66.67%) and hyperplateletosis (46.67%); an accelerated blood count in all our patients and an elevated CRP in 86.67% of cases. Doppler ultrasound performed in all patients returned normal in 73.33% of cases and found 2 cases of mitral insufficiency and 1 case of 8 mm coronary aneurysm. All our patients were treated with human immunoglobulins (2 g/kg IV) associated with aspirin 80–100 mg/kg/d in 4 doses. The evolution was favorable for all our patients.

Conclusion

Kawasaki disease is a pediatric vasculitis whose severity is related to coronary complications, which are prevented by early administration of IG and aspirin. It is therefore imperative to think of the disease in front of a prolonged fever associated with cutaneous and mucosal clinical signs and a biological inflammatory syndrome.
60 Childhood Behçet disease: clinical features, management and outcome of 13 cases
Authors: El Qadiry R , Nassih H , Bourrahouat A , Ait Sab I
Published: October 2022

Background

Behçet disease is a rare vasculitis that involves medium and small calibre arteries. Multisystem involvement is possible. Few are the papers that provide information about its clinical course, and outcome in the pediatric population. Also, the management is mainly based on adult guidelines.

Objectives

To shed light on the clinical course and outcome of juvenile Behçet disease.

Methods

A single center retrospective descriptive study of 13 children with Bechet disease. The mean follow-up period was for 3 years.

Results

We had 8 boys and 5 girls. Four of our patients were consanguineous. The mean age was 9 years. The mean interval between onset and diagnosis was 3 months. All of our patients had recurrent aphthous stomatitis with a median of 6 episodes per year. The other symptoms at diagnosis were concomitant genital ulcers in 4 cases, pseudo-folliculitis in 7 cases, urticarial rush in 4 cases, severe headache in 2 patients, stroke in one patient, prolonged and/or recurrent fever in 9 patients, uveitis in 4 cases, episcleritis in one case, arthritis in 5 cases, pulmonary hemorrhage in one case, and pyoderma gangrenosum in one case. The pathergy test was performed in all the patients, and was positive in 3 of them. Diagnosis was based on the International Criteria for Behcet's Disease. Acute phase reactants (ESR and CRP) were high in all patients. Meanwhile, granulocytosis was found in 10 patients. HLA 51 was positive in 8 patients, from whom three were siblings. All our patients were on steroids, five had colchicine, seven had azathioprine, two had methotrexate, two had cyclophosphamide, three had etanercept and one had tocilizumab. Complete remission was obtained in 8 cases in a mean time of 15 months, while five children had partial remission, and one boy lost sight of his left eye after a severe retinitis.

Conclusion

Behcet’s disease can cause severe sequalae if not diagnosed and treated on time. More studies are needed to establish management guidelines for pediatric population.
75 Juvenile systemic sclerodermas: a case report
Authors: Remilaoui A , Hafirassou H , Ferhat A , Dahou-Makhloufi C
Published: October 2022

Background

Systemic scleroderma (SSc) is a rare generalized connective tissue disorder of poorly understood aetiology resulting in systemic fibrosis. It affects mainly women, usually in adulthood, but can occur at any age, although it is rare in children. Its prognosis is conditioned by cardiopulmonary involvement, which is the primary cause of mortality. Some innovative therapies have improved the management of this orphan disease.

We report an observation of a 14-year-old child with systemic scleroderma.

Observation

Child B.Z, 14 years old, without any particular history, consulted for a Raynaud's phenomenon that had appeared 4 months earlier. Clinical examination reveals localized skin sclerosis on the face and extremities of the upper limbs (Rodnan score = 11), associated with inflammatory-type arthralgias. Biologically: SV = 38 mmH1, CRP = 87 mg/l, FAN at 1/320 and positive Anti-Scl70. Periungual capillaroscopy showed megacapillaries with altered capillary architecture. The frontal chest X-ray did not reveal any interstitial syndrome, the cardiac ultrasound was without abnormalities (no PAH). The diagnosis of SSc was retained, the patient was put on calcium channel blockers (Diltiazem at a dose of 120 mg/d) associated with dietary rules and NSAIDs on demand with good improvement.

Conclusion

Very few cases of juvenile SSc have been reported in the literature. Its diagnosis should be based on the same ACR-EULAR 2013 criteria as those for adults. Its prognosis is conditioned by visceral damage which must be diagnosed and treated early.
87 Intracerebral inflammatory pseudotumor in Behçet’s disease: a pediatric case report
Authors: Hadef Djohra , Slimani Samy , Nezzar Mouna , Tahrour Issam
Published: October 2022

Introduction

Behçet's disease is a chronic, relapsing, multisystem vasculitis. The diagnosis is essentially clinical, due to the absence of specific biological criteria, which remains very difficult to establish in pediatric age because of often insidious or atypical disease onset. The association of Pseudo Inflammatory Non-Specific Tumors (PTINS) and Behcet's disease (BD) is exceptionally reported. We report the case of a 12-year-old boy with Behçet's disease who presented with an inflammatory pseudotumor during the course of his disease.

Methods and results

A 12-year-old boy, from Batna (Algeria), with no relevant past medical history, admitted in 2010 for the management of a venous thrombosis of the right lower limb without any obvious cause and which responded well to anticoagulant treatment.

A year later, the child was readmitted for polymorphic clinical signs made up of joint damage (inflammatory arthralgia of the large joints), digestive (glairo-bloody diarrhea) and ocular (decreased visual acuity) and skin and mucous membranes (oral-genital apthosis and erythema nodosum of the 4 limbs).

Lab work-up showed significant inflammatory syndrome with erythrocyte sedimentation rate (ESR) of 100 mm at the first h, C-reactive protein (CRP) up to 400 mg/l and thrombocytosis (700 000–900 000 elements/mm2). HLA B51 was negative.

The patient was treated with Colchicine, Steroids, and Aspirin with partial response. Subsequently, a treatment with azathioprine was started, with clinical improvement (despite occasional digestive crises) but with persistent biologic inflammation.

In 2012 the patient presented with a unilateral decrease in visual acuity. A CT scan was performed showing an intracranial tumor compressing the right optic nerve with all the criteria of a malignant tumor (rupture of the cortex, increase in volume on 2 successive CT scans). A transsphenoidal biopsy of the mass revealed a non-specific inflammation. Biological treatment with anti-TNF alpha (Infliximab) was associated with a spectacular tumor regression, allowing retrospectively the diagnosis of an inflammatory granulomatous lesion related to Behçet's disease rather than a malignant tumor. The outcomes were favorable with clinical and biological improvement for the first time since the onset of the disease.

Conclusion

Behcet is rare in the pediatric age group and it is difficult to diagnose. Nonspecific inflammatory pseudotumors can be associated with Behçet's disease and constitute a real diagnostic and therapeutic challenge.

Disclosure of Interest

None declared
88 Tubulointerstitial nephropathy and uveitis (TINU syndrome): a paediatric case report
Authors: Mouffouk Hassan , Hadef Djohra , Hezzil Widad , Bahamma Nacera , Guedjiba Asma , Rougui Mohamed Fateh
Published: October 2022

Introduction

TINU (Tubulo-interstitial Nephritis and Uveitis) or oculo-renal syndrome was first described by Dobrin et al. in 1975. >100 cases (mostly paediatric) have been reported since then. It should be considered as diagnosis of elimination, as some iatrogenic, infectious, or systemic diseases may cause similar oculo-renal manifestations. There is no clear therapeutic consensus. However, the rapid initiation of high-dose corticosteroid therapy was associated with favorable outcome in the majority of published cases, as well as in our patient.

Case report

We report the case of an acute tubulointerstitial nephritis associated with uveitis in 11-year-old girl who presented with abdominal pain, vomiting and asthenia of one month. Laboratory tests revealed acute renal failure with proteinuria and aseptic leucocyturia. An inflammatory syndrome was found with erythrocyte sedimentation rate of 92 mm and inflammatory anaemia. Hypoproteinemia and polyclonal hypergamma-globulinaemia was found. No aetiology was found. The renal biopsy revealed a tubulo-nephritis with an interstitial inflammatory infiltrate of lymphoid cells and normal glomeruli. The patient was treated with high-dose of steroids (Methylprednisolone pulse followed by oral Prednisone 1 mg/kg/d with gradual weaning). We noted a progressive improvement of the renal function and the appearance of ocular pain and a decrease in visual acuity. The ophthalmological examination revealed bilateral uveitis. The diagnosis of TINU syndrome was confirmed and the patient received steroids with progressive resolution of the uveitis.

Conclusion

In the presence of any uveitis of unknown cause associated with disturbed renal function the diagnosis of TINU syndrome should be considered. This syndrome requires more precise diagnostic criteria and standardized management.

Disclosure of Interest

None declared
‘I turned in my man card’: a qualitative study of the experiences, coping styles and support needs of men with systemic sclerosis
Authors: Flurey Caroline A , Pauling John D , Saketkoo Lesley Ann , Denton Christopher P , Galdas Paul , Khanna Dinesh , Williams Adrian , Hughes Michael
Published: October 2022

Objectives

Men with SSc have a more severe clinical phenotype and reduced survival compared with women. No previous psychosocial studies have focused solely on men with SSc. This study aimed to explore experiences, coping strategies and support preferences of men with SSc.

Material and methods

An international qualitative research study comprising seven focus groups (three USA, four UK) of 25 men with SSc. Transcripts were analysed using reflexive thematic analysis.

Results

Three overarching themes and one underpinning theme were identified. In ‘impact of SSc on masculinity’, the men described an ‘impact on roles and activities’, reported ‘sex, intimacy, and erectile dysfunction’ as a salient issue that may be overlooked by clinicians, and experienced challenges to ‘masculine self-image’. ‘Dealing with SSc’ meant ‘always being prepared’, ‘becoming an expert’ and ‘balancing priorities’ in responsibilities, activities and symptom management. In ‘support for living with SSc’ men were selective in ‘(Not) talking about SSc’, would ‘(reluctantly) accept help’ and described ‘preferences for support’. Underpinning these experiences was ‘facing an uncertain future’ with some participants preferring not to focus on an unpredictable future, and others worrying about disease progression.

Conclusion

These novel data suggest SSc impacts male patients’ masculine identity and roles, and although they will accept practical help, they may mask the full emotional impact. Sex and intimacy are important overlooked issues with erectile dysfunction often not discussed at diagnosis. Further research should develop a self-management intervention for men with rheumatic diseases with a combination of disease-specific and common core components.
A scoping review of implementation of health-focused interventions in vulnerable populations
Authors: Daniels Sarah I , Cheng Hannah , Gray Caroline , Kim Bo , Stave Christopher Donald , Midboe Amanda M
Published: October 2022

Vulnerable populations face significant challenges in getting the healthcare they need. A growing body of implementation science literature has examined factors, including facilitators and barriers, relevant to accessing healthcare in these populations. The purpose of this scoping review was to identify themes relevant for improving implementation of healthcare practices and programs for vulnerable populations. This scoping review relied on the methodological framework set forth by Arksey and O’Malley, and the Consolidated Framework for Implementation Research (CFIR) to evaluate and structure our findings. A framework analytic approach was used to code studies. Of the five CFIR Domains, the Inner Setting and Outer Setting were the most frequently examined in the 81 studies included. Themes that were pertinent to each domain are as follows—Inner Setting: organizational culture, leadership engagement, and integration of the intervention; Outer Setting: networks, external policies, and patients’ needs and resources; Characteristics of the Individual: knowledge and beliefs about the intervention, self-efficacy, as well as stigma (i.e., other attributes); Intervention Characteristics: complexities with staffing, cost, and adaptations; and Process: staff and patient engagement, planning, and ongoing reflection and evaluation. Key themes, including barriers and facilitators, are highlighted here as relevant to implementation of practices for vulnerable populations. These findings can inform tailoring of implementation strategies and health policies for vulnerable populations, thereby supporting more equitable healthcare.
Multi-stakeholder perspectives on the implementation of a clinic-based food referral program for patients with chronic conditions: a qualitative examination
Authors: DePuccio Matthew J , Garner Jennifer A , Hefner Jennifer L , Coovert Nicolette , Clark Aaron , Walker Daniel M
Published: October 2022

Clinic-based food referral programs (FRPs) may help alleviate food insecurity and improve access to nutritious foods by systematically identifying and referring food-insecure primary care patients to community-based food resources. The purpose of this study was to examine

the barriers to and facilitators of implementation of an FRP offered to primary care patients who screen positive for food insecurity and have a qualifying chronic condition. we used a multi-stakeholder approach to conduct semi-structured interviews with healthcare providers and administrators from an academic medical center (AMC) (n = 20), representatives of a regional foodbank and its affiliated pantries (n = 11), and patients referred to the FRP (n = 20), during the initial phase of FRP implementation from April to September 2020. Interviews were audio-recorded, transcribed verbatim, and coded using a deductive dominant approach that allowed for the identification of emergent themes. Seven major themes emerged across the two domains of analysis: barriers to and facilitators of FRP implementation. Key barriers were (a) provider time constraints and competing demands; (b) inadequate physician feedback regarding patient use of the program; (c) patient transportation barriers; and (d) stigma associated with food pantry use. Key facilitators of implementation included (a) program champions; (b) screening and referral coordination; and (c) addressing food pantry-related stigma. This study identifies factors that deter and facilitate the implementation of an AMC-based FRP. Our findings highlight opportunities for healthcare and community-based organizations to refine and optimize FRP models toward the ultimate aim of advancing health equity for food-insecure patients.
Provider discussion of genetic counseling among high-risk Spanish-preferring Latina breast cancer survivors
Authors: Conley Claire C , Rivera Rivera Jessica N , Castro-Figueroa Eida M , Moreno Laura , Dutil Julie , García Jennifer D , Ricker Charité , Quinn Gwendolyn P , Soliman Hatem , Vadaparampil Susan T
Published: October 2022

Among high-risk breast cancer (BC) survivors, genetic counseling (GC) and genetic testing (GT) may inform cascade testing and risk management. Compared to non-Hispanic White BC survivors, Spanish-preferring Latina BC survivors are less likely to report discussing GC with a healthcare provider. However, few studies have examined Latinas’ experiences with GC/GT, particularly outside of the mainland USA. This study aimed to compare frequency of provider discussion of GC between Spanish-preferring Latina BC survivors living in Florida (FL) and Puerto Rico (PR). We conducted secondary data analysis of baseline assessments from a randomized pilot of an educational intervention for Spanish-preferring Latina BC survivors. Participants (N = 52) were GC/GT-naive, but met clinical criteria for GC/GT referral. Participants self-reported sociodemographic, clinical, and cultural variables, including previous provider discussion of GC. Descriptive statistics characterized frequency of GC discussion. Logistic regression examined the relationships between sociodemographic, clinical, and cultural characteristics and GC discussion. Only 31% of participants reported previous GC discussion. More participants from PR reported having GC discussions (43% vs. 21% in the mainland USA). In multivariable analyses, greater likelihood of GC discussion was associated with PR (vs. mainland USA) residence (odds ratio [OR] = 6.00, p = .03), older age at baseline (OR = 1.19, p = .04), and younger age at BC diagnosis (OR = 0.80, p = .03). Few high-risk Spanish-preferring Latina BC survivors in the mainland USA and PR had discussed GC with their providers. These results highlight a gap in the implementation of evidence-based genetics guidelines. Provider-directed interventions may be needed to increase uptake of GC/GT among Latina BC survivors.
Emerging research areas and contributions of NIH in violence research across the lifespan and throughout different settings
Authors: Burgdorf Caitlin E , Maholmes Valerie , O’Connor Stephen , Blachman-Demner Dara R
Published: October 2022

This commentary provides background for NIH’s interest in research designed to better understand the causes and consequences of violence and the development, evaluation, and implementation of preventive and treatment interventions to address the resulting trauma, injuries, and mortality from violence. The manuscript describes the context that contributed to a range of initiatives from the NIH focused on violence research, with a particular emphasis on firearms violence prevention research, and opportunities and gaps for future research.
It is time to Go All In: a call to action
Authors: Baskin Monica L
Published: October 2022

Lay Summary

Even though there have been numerous advances in medicine and technology in the past few decades, the length and quality of life vary significantly based on a person’s race, ethnicity, gender identity, sexual orientation, disability status, geographic residence, and/or socioeconomic status. In fact, membership in one or more marginalized sociodemographic groups is particularly associated with worse healthcare access and health outcomes. Behavioral medicine is uniquely equipped to advance health equity through inclusive and innovative research and practice and exerted influence on policies and practices that contribute to health disparities.
Transitioning to Telehealth: The Multifaceted Impact of a Midcareer Transition in Practice
Authors: Stoynova Valeria , Eva Kevin W.
Published: October 2022

Purpose

The medical education continuum is interrupted by several transition periods that can adversely affect performance. Most of what has been learned about such periods focuses upon movement from one stage of training to another and movement from training to practice. Established physicians, however, experience transitions throughout their careers at idiosyncratic times and with little assistance. Better understanding how physicians experience transition, where they struggle and how they adapt, would enable better support to be provided. We investigated the COVID-19-forced transition in clinical practice to virtual care, particularly its effect on physician roles and the ways that established physicians faced challenges they encountered when transitioning to virtual care.

Method

Ten semistructured interviews were conducted between November 2020 and February 2021 with physicians across different specialties and practice contexts who transitioned their practice to virtual care during the COVID-19 pandemic. Interview data were analyzed iteratively using “generic qualitative methodology” with constant comparison to identify themes in relation to observations.

Results

The transition to telehealth had implications that extended beyond the patient encounter, appearing to affect all aspects of the physician’s practice. To reflect that, CanMEDS was chosen as a useful organizing framework. The effects, captured in the theme “changes to the physician’s roles,” were nuanced, illustrated a consistent need to adapt to context, and could be framed positively or negatively or both. Additionally identified themes were labeled “physicians’ mental health” and “strategies to mitigate challenges.” These themes highlighted that, despite the effort involved and novelty of the situation, all participants found remarkably similar ways of grappling with the challenges faced.

Conclusions

While the basic roles of the physician do not appear to have changed through the transition to telehealth, our findings indicated that these roles were redefined in fundamental ways in response to changing societal needs.