bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in patients on kidney replacement therapy: observational study using the OpenSAFELY-UKRR and SRR databases
Authors: Zheng Bang , Campbell Jacqueline , Carr Edward J , Tazare John , Nab Linda , Mahalingasivam Viyaasan , Mehrkar Amir , Santhakumaran Shalini , Steenkamp Retha , Loud Fiona , Lyon Susan , Scanlon Miranda , Hulme William J , Green Amelia C A , Curtis Helen J , Fisher Louis , Parker Edward , Goldacre Ben , Douglas Ian , Evans Stephen , MacKenna Brian , Bell Samira , Tomlinson Laurie A , Nitsch Dorothea ,   OpenSAFELY Collaborative and LH&W NCS (or CONVALESCENCE) Collaborative
Published: August 2023

Background

Due to limited inclusion of patients on kidney replacement therapy (KRT) in clinical trials, the effectiveness of coronavirus disease 2019 (COVID-19) therapies in this population remains unclear. We sought to address this by comparing the effectiveness of sotrovimab against molnupiravir, two commonly used treatments for non-hospitalised KRT patients with COVID-19 in the UK.

Methods

With the approval of National Health Service England, we used routine clinical data from 24 million patients in England within the OpenSAFELY-TPP platform linked to the UK Renal Registry (UKRR) to identify patients on KRT. A Cox proportional hazards model was used to estimate hazard ratios (HRs) of sotrovimab versus molnupiravir with regards to COVID-19-related hospitalisations or deaths in the subsequent 28 days. We also conducted a complementary analysis using data from the Scottish Renal Registry (SRR).

Results

Among the 2367 kidney patients treated with sotrovimab (n = 1852) or molnupiravir (n = 515) between 16 December 2021 and 1 August 2022 in England, 38 cases (1.6%) of COVID-19-related hospitalisations/deaths were observed. Sotrovimab was associated with substantially lower outcome risk than molnupiravir {adjusted HR 0.35 [95% confidence interval (CI) 0.17–0.71]; P = .004}, with results remaining robust in multiple sensitivity analyses. In the SRR cohort, sotrovimab showed a trend toward lower outcome risk than molnupiravir [HR 0.39 (95% CI 0.13–1.21); P = .106]. In both datasets, sotrovimab had no evidence of an association with other hospitalisation/death compared with molnupiravir (HRs ranged from 0.73 to 1.29; P > .05).

Conclusions

In routine care of non-hospitalised patients with COVID-19 on KRT, sotrovimab was associated with a lower risk of severe COVID-19 outcomes compared with molnupiravir during Omicron waves.
Measurement of urinary exosomal phospholipase A2 receptor is a sensitive method for diagnosis of PLA2R-associated membranous nephropathy
Authors: Wang Bin , Fu Yu-Qi , Xie Li-jun , Cao Jin-Yuan , Yang Min , Li Min , Chen Tian-Lei , Zhang Xiao-Liang , Luo Qian , Lv Lin-Li , Liu Bi-Cheng
Published: August 2023

Background

The discovery of phospholipase A2 receptor (PLA2R) and its antibody (aPLA2Rab) has paved the way for diagnosing PLA2R-associated membranous nephropathy (PLA2R-MN) with a high specificity of 98%. However, the sensitivity was only 40% to 83.9%, and there is ongoing discussion around determining the optimal threshold for diagnosis. Recent advancements in the use of exosomes, a novel form of “liquid biopsy,” have shown great promise in identifying markers for various medical conditions.

Methods

Protein mass spectrometry and western blot were applied to verify the existence of PLA2R antigen in the urine exosome. We then evaluated the efficacy of urinary exosomal PLA2R antigen alone or combined with serum aPLA2Rab level to diagnose PLA2R-MN.

Results

The urinary exosomes contained a high abundance of PLA2R antigen as evidenced by protein mass spectrometry and western blot in 85 PLA2R-MN patients vs the disease controls (14 secondary MN patients, 22 non-MN patients and 4 PLA2R-negative MN patients) and 20 healthy controls. Of note, urinary exosomal PLA2R antigen abundance also had a good consistency with the PLA2R antigen level in the renal specimens of PLA2R-MN patients. The sensitivity of urinary exosomal PLA2R for diagnosing PLA2R-MN reached 95.4%, whereas the specificity was 63.3%. Combining detection of the urinary exosomal PLA2R and serum aPLA2Rab could develop a more sensitive diagnostic method for PLA2R-MN, especially for patients with serum aPLA2Rab ranging from 2 to 20 RU/mL.

Conclusions

Measurement of urinary exosomal PLA2R could be a sensitive method for the diagnosis of PLA2R-MN.
Examining the safety and effectiveness of a 4-week supervised exercise intervention in the treatment of frailty in patients with chronic kidney disease
Authors: Lorenz Elizabeth C , Hickson LaTonya J , Hogan Marie C , Kennedy Cassie C
Published: August 2023

Background

The optimal duration of antifrailty interventions and how best to deliver them to patients with chronic kidney disease (CKD) is unknown. The aim of this study was to examine the safety, feasibility and preliminary efficacy of a 4-week supervised exercise intervention on frailty in patients with CKD.

Methods

We conducted a prospective feasibility study involving patients with ≥stage 3 CKD (1 patient with stage 3 CKD, 7 patients with stage 4 CKD and 17 patients with stage 5 CKD) who were either frail or prefrail according to the physical frailty phenotype and/or had a Short Physical Performance Battery (SPPB) score ≤10. The exercise intervention consisted of two supervised outpatient sessions per week for 4 weeks (eight total sessions). Frailty and other study measures were assessed at baseline and after 4 weeks of exercise.

Results

Of the 34 participants who completed the baseline assessment and were included in the analyses, 25 (73.5%) completed the 4-week assessment. Overall, 64.0% of patients were on dialysis and 64.0% had diabetes mellitus. After 4 weeks of exercise, frailty prevalence, total SPPB scores and energy/fatigue scores improved. No adverse study-related outcomes were reported.

Conclusions

The 4 weeks of supervised exercise was safe, was associated with an excellent completion rate and improved frailty parameters in CKD patients with CKD. This study provides important preliminary data for a future larger prospective randomized study.

Clinical Trial.gov

registration: NCT03535584
Linguistic Intervention Strategies Speech-Language Pathologists Use With Children Using Cochlear Implants
Authors: Mieres Daniela , Losilla Josep-Maria , Pérez Encarna , Cambra Cristina
Published: August 2023

The aim of this study was to explore the strategies that speech-language pathologists (SLPs) use during their linguistic interventions on children with cochlear implants (CIs). The sample comprised 7 SLPs in interactions with 62 children, 31 with CIs and 31 with typical hearing (TH), from 5 to 7 years of age. Two linguistic activities were used: conversation and naming. With children with CIs, the SLPs used 3.8 times more adaptation strategies and 5 times more educational strategies in the conversation activity, and 1.4 times more educational strategies in the naming activity than with children with TH. Communication strategies were significantly more frequent in the conversation activity than in the naming activity while educational strategies were more frequent in the naming activity than in the conversation activity. The auditory age of children with CIs also influenced the use of these two types of strategies, increasing the use of communication strategies by 0.6% and decreasing the use of educational strategies by 1.2% for each month of increase in the auditory age. In order to foster linguistic development, the SLPs used a wide variety of strategies with the children with CIs, adjusting them to the activity and the auditory age.
CD56bright natural killer cells preferentially kill proliferating CD4+ T cells
Authors: Lee Mercede , Bell Charles J M , Rubio Garcia Arcadio , Godfrey Leila , Pekalski Marcin , Wicker Linda S , Todd John A , Ferreira Ricardo C
Published: August 2023

Human CD56br natural killer (NK) cells represent a small subset of CD56+ NK cells in circulation and are largely tissue-resident. The frequency and number of CD56br NK cells in blood has been shown to increase following administration of low-dose IL-2 (LD-IL2), a therapy aimed to specifically expand CD4+ regulatory T cells (Tregs). Given the potential clinical application of LD-IL-2 immunotherapy across several immune diseases, including the autoimmune disease type 1 diabetes, a better understanding of the functional consequences of this expansion is urgently needed. In this study, we developed an in vitro co-culture assay with activated CD4+ T cells to measure NK cell killing efficiency. We show that CD56br and CD56dim NK cells show similar efficiency at killing activated CD4+ conventional T (Tconv) and Treg cell subsets. However, in contrast to CD56dim cells, CD56br NK cells preferentially target highly proliferative cells. We hypothesize that CD56br NK cells have an immunoregulatory role through the elimination of proliferating autoreactive CD4+ Tconv cells that have escaped Treg suppression. These results have implications for the interpretation of current and future trials of LD-IL-2 by providing evidence for a new, possibly beneficial immunomodulatory mechanism of LD-IL-2-expanded CD56br NK cells.
Evaluating the representation of disaster hazards in SNOMED CT: gaps and opportunities
Authors: Lokmic-Tomkins Zerina , Block Lorraine J , Davies Shauna , Reid Lisa , Ronquillo Charlene Esteban , von Gerich Hanna , Peltonen Laura-Maria
Published: August 2023

Objective

Climate change, an underlying risk driver of natural disasters, threatens the environmental sustainability, planetary health, and sustainable development goals. Incorporating disaster-related health impacts into electronic health records helps to comprehend their impact on populations, clinicians, and healthcare systems. This study aims to: (1) map the United Nations Office for Disaster Risk Reduction and International Science Council (UNDRR-ISC) Hazard Information Profiles to SNOMED CT International, a clinical terminology used by clinicians, to manage patients and provide healthcare services; and (2) to determine the extent of clinical terminologies available to capture disaster-related events.

Materials and Methods

Concepts related to disasters were extracted from the UNDRR-ISC’s Hazard Information Profiles and mapped to a health terminology using a procedural framework for standardized clinical terminology mapping. The mapping process involved evaluating candidate matches and creating a final list of matches to determine concept coverage.

Results

A total of 226 disaster hazard concepts were identified to adversely impact human health. Chemical and biological disaster hazard concepts had better representation than meteorological, hydrological, extraterrestrial, geohazards, environmental, technical, and societal hazard concepts in SNOMED CT. Heatwave, drought, and geographically unique disaster hazards were not found in SNOMED CT.

Conclusion

To enhance clinical reporting of disaster hazards and climate-sensitive health outcomes, the poorly represented and missing concepts in SNOMED CT must be included. Documenting the impacts of climate change on public health using standardized clinical terminology provides the necessary real time data to capture climate-sensitive outcomes. These data are crucial for building climate-resilient healthcare systems, enhanced public health disaster responses and workflows, tracking individual health outcomes, supporting disaster risk reduction modeling, and aiding in disaster preparedness, response, and recovery efforts.
Evolution of Human Brain Left–Right Asymmetry: Old Genes with New Functions
Authors: Wang Jianguo , Ma Sidi , Yu Peijie , He Xionglei
Published: August 2023

The human brain is generally anatomically symmetrical, boasting mirror-like brain regions in the left and right hemispheres. Despite this symmetry, fine-scale structural asymmetries are prevalent and are believed to be responsible for distinct functional divisions within the brain. Prior studies propose that these asymmetric structures are predominantly primate specific or even unique to humans, suggesting that the genes contributing to the structural asymmetry of the human brain might have evolved recently. In our study, we identified approximately 1,500 traits associated with human brain asymmetry by collecting paired brain magnetic resonance imaging features from the UK Biobank. Each trait is measured in a specific region of one hemisphere and mirrored in the corresponding region of the other hemisphere. Conducting genome-wide association studies on these traits, we identified over 1,000 quantitative trait loci. Around these index single nucleotide polymorphisms, we found approximately 200 genes that are enriched in brain-related Gene Ontology terms and are predominantly upregulated in brain tissues. Interestingly, most of these genes are evolutionarily old, originating just prior to the emergence of Bilateria (bilaterally symmetrical animals) and Euteleostomi (bony vertebrates with a brain), at a significantly higher ratio than expected. Further analyses of these genes reveal a brain-specific upregulation in humans relative to other mammalian species. This suggests that the structural asymmetry of the human brain has been shaped by evolutionarily ancient genes that have assumed new functions over time.
Non-infectious uveitis referred for pediatric rheumatologic assessment and management: A Portuguese retrospective study
Authors: Gonçalves Hugo , Alves Sérgio , Correia-Costa Liane , Miranda Vasco , Zilhão Carla
Published: August 2023

Background

Pediatric uveitis poses challenges in diagnosis and treatment due to asymptomatic or oligosymptomatic presentations and high rates of intraocular complications.

Objectives

This study aimed to characterize clinical manifestations and treatment approaches of pediatric uveitis patients in a northern Portuguese tertiary hospital.

Methodology

A retrospective study was conducted involving 41 patients diagnosed with uveitis between 2006 and 2021. All individuals identified by the Opthalmology department were referred to Pediatric Rheumatology outpatient clinic. Demographic, clinical, treatment, and intraocular complications data were collected.

Results

Of the patients, 78% had anterior uveitis, 17% had panuveitis, and 5% had intermediate uveitis. Uveitis associated with juvenile idiopathic arthritis (JIA) was the most common cause (43.9%), predominantly in the oligoarticular, anti-nuclear antibody-positive subgroup. Complications were identified in 80.5% of the patients. Uveitis associated with JIA was diagnosed earlier [5.0 years (3.0–10.5) vs. 9.0 years (5.5–14.0), P = .036], more frequently in asymptomatic patients (71% vs. 23%, P = .010), had a more insidious installation (71% vs. 17%, P = .004), and required more tumor necrosis factor (TNF) inhibitor treatment (70% vs. 39%, P = .027).

Conclusion

The high rates of intraocular complications and systemic pathology association highlight the need for a combined approach of ophthalmology and pediatric rheumatology in the diagnosis and treatment of pediatric uveitis.
The genomic distribution of transposable elements is driven by spatially variable purifying selection
Authors: Langmüller Anna M , Nolte Viola , Dolezal Marlies , Schlötterer Christian
Published: August 2023

It is widely accepted that the genomic distribution of transposable elements (TEs) mainly reflects the outcome of purifying selection and insertion bias (1). Nevertheless, the relative importance of these two evolutionary forces could not be tested thoroughly. Here, we introduce an experimental system, which allows separating purifying selection from TE insertion bias. We used experimental evolution to study the TE insertion patterns in Drosophila simulans founder populations harboring 1040 insertions of an active P-element. After 10 generations at a large population size, we detected strong selection against P-element insertions. The exception were P-element insertions in genomic regions for which a strong insertion bias has been proposed (2–4). Because recurrent P-element insertions cannot explain this pattern, we conclude that purifying selection, with variable strength along the chromosomes, is the major determinant of the genomic distribution of P-elements. Genomic regions with relaxed purifying selection against P-element insertions exhibit normal levels of purifying selection against base substitutions. This suggests that different types of purifying selection operate on base substitutions and P-element insertions. Our results highlight the power of experimental evolution to understand basic evolutionary processes, which are difficult to infer from patterns of natural variation alone.
Binding and detoxification efficiency of albumin decline after haemodialysis
Authors: Boss Kristina , Waterstradt Katja , Schnurr Kerstin , Paar Margret , Stolpe Susanne , Ickerott Philipp , Wieneke Ulrike , Spitthöver Ralf , Oettl Karl , Kribben Andreas
Published: August 2023

Background

Albumin, as the most abundant plasma protein, represents a target structure for both drug and physicochemical therapeutic approaches to eliminate uraemic toxins more efficiently. Potentially, this approach could reduce mortality of haemodialysis patients. However, little is known about albumin functional properties in these patients and its alteration by haemodialysis treatment.

Methods

The binding and detoxification efficiency of albumin were assessed by electron paramagnetic resonance spectroscopy using a spin-labelled fatty acid. Binding efficiency (BE) reflects strength and amount of bound fatty acids under certain ethanol concentration. Detoxification efficiency (DTE) reflects the molecular flexibility of the patient's albumin molecule, thus the ability to change the conformation depending on ethanol concentration. Percentage of BE and DTE are depicted in relation to healthy individuals (100%).

Results

Fifty-eight patients (59% male, median age 68 years, median time on haemodialysis 32 months) were included in the study. Before haemodialysis treatment, albumin binding and detoxification efficiency were substantially below healthy individuals [median BE 52% (interquartile range, IQR, 45%–59%); median DTE 38% (IQR 32–49%)]. After haemodialysis treatment, median BE and DTE significantly decreased [BE 28% (IQR 20–41%); DTE 11% (IQR 7%–27%; P < .001)]. BE and DTE decline after haemodialysis was not dependent on age, sex or treatment modalities, but was to a certain extent on the level of non-esterified fatty acids.

Conclusion

Albumin binding and detoxification efficiency of fatty acids in maintenance haemodialysis patients were substantially below those in healthy individuals and even declined after dialysis treatment. These findings might be helpful when considering new therapeutic approaches in maintenance haemodialysis patients.
Cryptococcal Meningitis in Young, Immunocompetent Patients: A Single-Center Retrospective Case Series and Review of the Literature
Authors: Stack Matthew , Hiles Jon , Valinetz Ethan , Gupta Samir K , Butt Saira , Schneider Jack G
Published: August 2023

Background

Cryptococcal meningitis is an uncommon but serious infection with high mortality and morbidity. Classically described in immunocompromised patients, including those with solid organ transplants or HIV/AIDS, cryptococcosis has also been reported in young and otherwise healthy patients, albeit rarely.

Methods

We retrospectively searched for all cases of cryptococcal meningitis in young (≤50 years) and previously healthy patients with no known immunocompromising conditions from January 2015 to January 2022 at Indiana University Health (IU Health). Additionally, a PubMed literature review was performed with the keywords “cryptococcal meningitis” and “immunocompetent” from January 1988 to January 2022. Clinical courses, including outcomes and treatment regimens, were evaluated.

Results

We identified 4 local cases of cryptococcal meningitis in otherwise healthy patients age ≤50 years. Three cases were due to Cryptococcus neoformans, with 1 experiencing a postinfectious inflammatory response syndrome (PIIRS). The PubMed search identified 51 additional cases, with 32 (63%) being caused by Cryptococcus neoformans and 8 (17%) by Cryptococcus gattii. Of the 51 cases, only 2 resulted in death directly due to cryptococcosis. Fifteen (29%) had PIIRS, with steroid treatment documented in 11 of 15. Antifungal induction regimens and duration were varied but predominately consisted of amphotericin and flucytosine, with a mean induction duration of 5.0 weeks.

Conclusions

Cryptococcal meningitis in young, previously healthy patients is likely under-recognized. PIIRS (akin to immune reconstitution inflammatory syndrome observed in HIV/AIDS) with prolonged recovery should be of concern. Determining risk factors for cryptococcosis in these patients remains elusive.
Humoral Immune Response to Messenger RNA Coronavirus Disease 2019 Vaccination Among Children Aged 5–11 Years in a Multisite Prospective Cohort Study, September 2021–September 2022
Authors: Lyski Zoe L , Porter Cynthia , Uhrlaub Jennifer L , Ellingson Katherine D , Jeddy Zuha , Gwynn Lisa , Rivers Patrick , Sprissler Ryan , Hegmann Kurt T , Coughlin Melissa , Fowlkes Ashley , Hollister James , LeClair Lindsay , Mak Josephine , Beitel Shawn C , Fuller Sammantha , Grant Lauren , Newes-Adeyi Gabriella , Yoo Young M , Olsho Lauren , Burgess Jefferey L , Caban-Martinez Alberto , Yoon Sarang , Britton Amadea , Gaglani Manjusha , Lutrick Karen
Published: August 2023

Background

The PROTECT study is a longitudinal cohort study initiated in July 2021 with weekly testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 4 states: Arizona, Florida, exas, and Utah. This study aims to examine vaccine-elicited antibody response against postvaccination SARS-CoV-2 infections.

Methods

Children aged 5–11 years had serum collected 14–59 days after their second dose of monovalent Pfizer-BioNTech coronavirus disease 2019 messenger RNA vaccine. Vaccine-elicited antibodies were measured using the area under the curve (AUC) and end-point titer using enzyme-linked immunosorbent assay (receptor-binding domain [RBD] and S2) and surrogate neutralization assays against ancestral (WA1) and Omicron (BA.2).

Results

79 vaccinated participants (33 [41.7%] female; median age, 8.8 years [standard deviation, 1.9 years]), 48 (60.8%) were from Tucson, Arizona; 64 (81.0%) were non-Hispanic white; 63 (80.8%) attended school in person; 68 (86.1%) did not have any chronic conditions; and 47 (59.5%) were infected after vaccination. Uninfected children had higher AUCs against WA1 (P = .009) and Omicron (P = .02). The geometric mean and surrogate neutralization titer above the limit of detection was 346.0 for WA1 and 39.7 for Omicron, an 8.7-fold decrease (P < .001). After adjustment of covariates in the WA1-specific model, we observed a 47% reduction in the odds of postvaccination infection for every standard deviation increase in RBD AUC (aOR, 0.53 [95% confidence interval, .29–.97) and a 69% reduction in the odds of infection for every 3-fold increase in RBD end titer (0.31 [.06–1.57]).

Conclusions

Children with higher antibody levels experienced a lower incidence of postvaccination SARS-CoV-2 infection.
Day–night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics
Authors: Edelbo Beatriche Louise , Andreassen Søren Norge , Steffensen Annette Buur , MacAulay Nanna
Published: August 2023

The cerebrospinal fluid (CSF) provides mechanical protection for the brain and serves as a brain dispersion route for nutrients, hormones, and metabolic waste. The CSF secretion rate is elevated in the dark phase in both humans and rats, which could support the CSF flow along the paravascular spaces that may be implicated in waste clearance. The similar diurnal CSF dynamics pattern observed in the day-active human and the nocturnal rat suggests a circadian regulation of this physiological variable, rather than sleep itself. To obtain a catalog of potential molecular drivers that could provide the day–night-associated modulation of the CSF secretion rate, we determined the diurnal fluctuation in the rat choroid plexus transcriptomic profile with RNA-seq and in the CSF metabolomics with ultraperformance liquid chromatography combined with mass spectrometry. We detected significant fluctuation of 19 CSF metabolites and differential expression of 2,778 choroid plexus genes between the light and the dark phase, the latter of which encompassed circadian rhythm–related genes and several choroid plexus transport mechanisms. The fluctuating components were organized with joint pathway analysis, of which several pathways demonstrated diurnal regulation. Our results illustrate substantial transcriptional and metabolic light–dark phase–mediated changes taking place in the rat choroid plexus and its encircling CSF. The combined data provide directions toward future identification of the molecular pathways governing the fluctuation of this physiological process and could potentially be harnessed to modulate the CSF dynamics in pathology.
Morse numbers of function germs with isolated singularities
Authors: Maxim Laurenţiu , Tibăr Mihai
Published: August 2023

A set of Morse numbers is associated with a holomorphic function germ with stratified isolated singularity, extending the classical Milnor–Morse number to the setting of a singular base space.
OA04 Impact of pre-operative and perioperative parental preparation on the success of surgery in Tunisian children with scoliosis
Authors: Kammoun Khaled , Cherif Ines , Chaalia Malek Ben , Miladi Saoussen , Fazaa Alia , Boussaa Hiba , Makhlouf Yasmine , Jenzri Mourad , Hamdi Wafa , Abdelghani Kawther Ben , Laatar Ahmed
Published: August 2023

Background

Surgical intervention in a child represents a challenging and overwhelming event for the parents. Studies have shown that parents' preoperative preparation and satisfaction with their child's preoperative care are important components of a better clinical outcome and a stronger healthcare system.

Objective

To investigate the preoperative and postoperative preparation of parents whose children have scoliosis and have undergone surgery, and its possible association with postoperative clinical outcomes.

Methods

We conducted a cross-sectional study including children and adolescents who underwent surgery for scoliosis. Disease related characteristics were reported. Successful surgery was defined as a postoperative cobb angle less than or equal to half the initial cobb angle.

A questionnaire in the Tunisian dialect consisting of 10 Yes/No questions related to the preoperative and perioperative phase was established. The parents answered the questionnaire by telephone and informed oral consent was obtained.

An arbitrary cutoff of 7 positive answers was set to define a well-prepared parent.

Results

Thirty-six children were included (sex-ratio= 0.38, mean age at surgery = 16.05 ± 2.63 [11–23]). Etiologies of scoliosis were idiopathic (n = 29), neuromuscular (n = 4) and congenital (n = 3). Twenty-two children (61.1%) had successful surgery. Regarding the questionnaire, table 1 reports the parents’ answers to the 10 questions. Question two had the most negative response with 55.5% parents reporting that during the pre-operative phase, the medical staff didn’t mention the possible complications of the surgery. Thirty-three per cent of the parents reported that the doctor didn’t explain more about the operation and the post-operative course during the peri-operative period and about 30% revealed that, on the day of surgery, the doctor didn’t explain to them the induction of anesthesia. Forty-seven per cent of the parents mentioned that the doctor didn’t inform them about the possible restrictions in occupation for their child later. Seventy-two percent of parents had ≥7 positive answers indicating that they were well prepared for the surgery, among them 52% had children in whom surgery was successful, P = 0.14. No correlation was found between a good parental preparation and age at surgery (P = 0.736). A significant association was found between success of surgery and a positive response to Q9, P = 0.032.

Conclusion

In our series, the lack of information about the possible complications of the surgery, during the peri-operative phase and about the induction of anesthesia was noted. Interestingly, receiving sufficient information on how to provide postoperative care at home was significantly associated with a success of surgery.
E30 Sequelae of Juvenile Idiopathic Arthritis in a 20-year-old young woman
Authors: Koffi-Tessio V E S , Nouvedji K A , Oniankitan S , Diallo M , Atake A , Tagbor K C , Fianyo E , Kakpovi K , Houzou P , Oniankitan O , Mijiyawa M
Published: August 2023

Background

The long-term effects of Juvenile Idiopathic Arthritis are still largely unknown in our context. We set out to describe the long-term complications of a patient known to have Juvenile Idiopathic Arthritis who underwent follow up into adulthood.

Methods

Retrospective chart review

Results

We report a case of a female patient, now 20 years’ old who was diagnosed with Juvenile Idiopathic Arthritis since the age of 8 years. The patient initially received symptomatic treatment with paracetamol and non-steroidal anti-inflammatory drugs administered during flare-ups. After 12 years of follow up, she has failure to thrive (BMI 15.43 kg/m2) and delayed secondary sexual characteristics (menarche at 17, poorly developed chest). Other sequelae include bilateral boutonniere deformation of the 2nd and 3rd fingers, camel back deformity of the wrists, flexion contractures of the elbows, and bilateral coxopathy. She has tenderness and limited range of motion of shoulders, knees and ankles with bilateral thigh atrophy. She has a tender cervical spine painful and limited movement (C7-wall at 4.5 cm, tragus-acromion at 9 cm on the right and on the left).

Conclusion

This case highlights the importance of early control of the disease to mitigate against sequelae with negative impact on the academic and social life of the patient.

The implication to policy, practice, research and advocacy

The case illustrates the consequences of sub-optimal management of chronic inflammatory rheumatism in Africa, especially among children, due to lack of expertise and resources across the continent.

Ethics

We have no conflict of interest
E40 Chronic recurrent multifocal osteomyelitis: management disease in Tunisian child population
Authors: Kamoun Khaled , Arfa Wajdi , Oueslati Wajih , Maatallah Kawthar , Hamdi Wafa , Jenzri Mourad
Published: August 2023

Introduction

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease especially in Tunisian population and occurs more often in children. It is a bone non-microbial inflammatory disease that frequently involves long bones, pelvis and spine. The autoimmune origin seems to be the most suggested pathogenic theory. It often manifests by multifocal bone pain with insidious onset and recurrent course

Objectives

The aim of the study was to highlight specific symptoms, frequent localization, investigations, imaging and multidisciplinary management of CRMO

Methods

We retrospectively reviewed five children on follow up for CRMO in our institution on both pediatric orthopedic and rheumatology department between 2012 and 2022. We have noted epidemiology features, symptoms, clinical manifestations, medical and orthopedic management, sequallae and outcome at last follow up for each case in order to identify specificities and correlations

Results

Five children, including 3 female and 2 males, were treated for such disease during this period. The mean age at diagnosis was 13.2 years (9–16). Duration of symptoms prior to diagnosis was 1–6 months. Inflammatory bone pain was present in all cases and isolated swelling in one case (clavicle). CRMO involves spine, femur, foot, humerus and clavicle and only two children present more than two locations. No correlation between age and location was noted. Radiographs were normal at presentation in four cases and showed reactive hyperostosis during the course of the disease in two cases. Whole-body MRI revealed some clinically non symptomatic localizations in three cases. The differential diagnoses were osteomyelitis, inflammatory arthritis, vertebral fracture and Ewing's sarcoma in one case. Microbiological examinations were negative in all cases. Biopsy, performed in two cases (spine, clavicle) showed non-specific inflammatory bone involvement. Non-steroidal anti-inflammatory drugs were used in four cases and salazopyrine in one case with durable remission at last follow up.

CRMO involved spine in two cases where brace has been used for a 6-month period. A mild progression of thoraco-lumbar kyphosis was noted in one case (local kyphosis from 6 to 10°).

Conclusion

Even if CRMO remains diagnosis of exclusion, it should be managed early to prevent functional sequellae especially in spine where orthosis is essential to prevent kyphosis and vertebrae collapses. Asymptomatic bone involvement can be revealed by whole body MRI. Non steroid anti-inflammatory drugs and salazopyrin in second intention seems to be effective to stabilize bone lesion.

Ethics

Informed consent was obtained for each patient for diffusing their imaging file in scientific congress
E42 Severe infectious adverse events in children treated with biological agents
Authors: Lotfi S , Benbrahim G , Aboufariss H , Sakhi A , Bouayed K
Published: August 2023

Background

Since the 90’s, biologics, as a novel class of drugs, have revolutionized the therapeutic field of autoimmune and inflammatory diseases in children by providing effective treatment options. Biologics aim to modify targeted pathways to interfere with the immunologic aberration creating the clinical disease, However, alteration of the pathways increase the risk of infection. We report a series of severe infectious adverse events (SIAE) in children treated with biologics.

Objectives and Methods

This is a retrospective study over a period of 10 years (January 2012-October 2022) conducted in the Department of Pediatric Rheumatology and internal Medicine, A. Harouchi Mother and Child Hospital CHU Ibn Rochd, Casablanca, Morocco. The aim of our study is to assess SIAE in children treated with

Results

The study included 76 patients on biologics with different diseases dominated by systemic juvenile idiopathic arthritis. Six patients developed SIAE, sex-ratio was 1, four patients received TNF-alpha inhibitors (Infliximab, Adalimumab, Etanercept), 1 on Tocilizumab and 1 on Rituximab. Our 6 patients were on other immunosuppressive agents simultaneously (Corticosteroids, MMF, Azathioprine, Methotrexate). The delay of occurrence of SIAE after the initiation of biologics ranged from 10 days to 7 years. We report 3 cases of Tuberculosis, 2 of which were treated with anti-TNF agents, 1 case of CMV hepatitis, 1 case of Herpes zoster and 1 case of orbital cellulites. Treatment consisted of temporary discontinuation of biologic with specific management of the SIAE by an appropriate anti-infectious agent. The evolution was favorable except one case of death.

Discussion and Conclusion

Biologics have become an important component of effective management of patients with autoimmune and inflammatory diseases. However, there is an increased risk of SIAE for those patients, especially the risks of Tuberculosis and viral infections, even though systematic screening is performed prior to the start of biotherapy, requiring physician vigilance.
E44 Differences of hematological abnormalities between COVID-19 infection and multisystemic inflammatory syndrome (MIS-C)
Authors: Glai M , Guedri R , Fitouri Z , Becher S Ben
Published: August 2023

Introduction

SARS-CoV-2 virus was associated with hypercoagulability and hematological abnormalities.

Objectives

We aim to compare hematological findings in acute COVID-19 and MIS-C syndrome.

Methods

This was a retrospective cohort study conducted for one year (March 2020 to March 2021) in the isolation unit of the children’s hospital. Children with confirmed COVID-19 infection and those who met the criteria for MIS-C by the World Health Organization definition were included. Laboratory results were collected through patients ‘files.

Results

We enrolled 99 children in our case series. Sixty-seven (68%) had COVID-19 infection (median age: 3.8 years) and 32 (32%) had MIS-C syndrome (median age: 7.5 years). Sex ratio was 1.8 (64 boys’ vs 35 girls). In COVID-19 infection, 24 patients (35.8%) had anaemia (median value: 11 g/dl). Leucocytosis was found in 13 cases (19.4%) (median value: 18 187/mm3, range: 6540–86 250) vs leucopenia in two cases. Lymphopenia was detected in 22 (32.8%) (median value: 1317 109/l, range: 800–3500). In MIS-C syndrome cohort, anaemia was detected in 20 (62.5%) with a median value of 10.8 g/dl (range : 6–12.8). Leucocytosis and leukopenia were in 7 (21.9%) and 1 (3.1%) cases respectively (median value: 20 650 cells/ml vs 3620 cells/ml). Lymphopenia was marked in 24 (75%) (median value : 896x109/l) and thrombocytopenia was present in 10 (31.3%) (median value : 125 200 cells/ml). Raised level of D-dimers was found in 21 (65.6%, range: 500-20 780 ng/ml) but no one had thrombosis.

Conclusions

Anaemia, lymphopenia and hypercoagulopathy were more related to MIS-C syndrome rather to acute COVID-19 form.

Ethics

no conflicts of interest
E60 Localized scleroderma and venous thrombosis: an uncommon association in a case report
Authors: Mehaba N , Gacem O , Bakkar B , Tenkout K , Ouahbi K , Guers S , Boukandoura F , Ayad N , Mansouri N , Laboune L , Ladj M S
Published: August 2023

Introduction

Morphea or localized scleroderma is a rare paediatric inflammatory disease. It causes sclerosis of the skin and subcutaneous tissues. The condition does not have serious systemic implications, except in rare cases. However, it can cause functional and aesthetic sequelae. There is no truly effective consensus treatment, hence the importance of correctly assessing the extent and severity of the disease before any therapeutic approach.

Objective

Through the case of a girl presenting with linear scleroderma, revealed at the exploration of a superficial venous thrombosis; we report the diagnostic and therapeutic difficulty.

Results

Hadjer, a 14 years old girl, with no particular personal or family history, presented with thrombosis of the great saphenous vein. Thrombophilia work-up and anti-phospholipid antibodies were normal. She was treated by stripping; then she was lost to follow-up. One year later, hadjer’s clinical examination revealed thickened, inflamed skin on the left lower limb, extending from the dorsal surface of the ankle to the upper third of the thigh along its inner surface, suggesting linear scleroderma in the inflammatory phase. There was also a varicose vein sequelae of the thrombosis. The patient had no Raynaud's phenomenon or systemic damage. The skin biopsy confirmed the diagnosis. The search for multi-visceral involvement was non-contributory: capillaroscopy, chest X-ray, cardiac ultrasound, ophthalmological examination, liver, kidney and haematological tests. Muscle enzymes and magnetic resonance imaging for deep involvement were also normal. The autoimmune assessment revealed the positivity of Antinuclear Antibodies. The patient benefited from oral corticosteroid therapy and physiotherapy. After three months of partial remission, methotrexate was started.

Discussion and conclusion

Morphea is a rare autoimmune condition in paediatrics. A correlation between antinuclear antibody positivity and the severity of Morphea has been suggested. Certain risk factors have been incriminated. The linear form is by far the most frequent. The presence of venous thrombosis suggests the probable association of other autoimmune diseases, hence the interest of a rigorous follow-up, to watch for other clinical signs. The treatment and prognosis of morphea depend on the clinical form and the time to diagnosis; functional and aesthetic sequelae can be observed in the deep forms which require treatment with corticoids and immune modulators.

Ethics

this work is ethically approved.
Deficiency of Pdk1 drives heart failure by impairing taurine homeostasis through Slc6a6
Authors: Li Chen , Zhou Yi , Niu Yan , He Wenting , Wang Xinyi , Zhang Xi , Wu Yali , Zhang Wenli , Zhao Liangcai , Zheng Hong , Song Weihong , Gao Hongchang
Published: August 2023

3‐Phosphoinositide‐dependent protein kinase‐1 (Pdk1) as a serine/threonine protein kinase plays a critical role in multiple signaling pathways. Analysis of the gene expression omnibus database showed that Pdk1 was significantly downregulated in patients with heart diseases. Gene set enrichment analysis of the proteomics dataset identified apoptotic‐ and metabolism‐related signaling pathways directly targeted by Pdk1. Previously, our research indicated that Pdk1 deletion‐induced metabolic changes might be involved in the pathogenesis of heart failure; however, the underlying mechanism remains elusive. Here, we demonstrated that deficiency of Pdk1 resulted in apoptosis, oxidative damage, and disturbed metabolism, both in vivo and in vitro. Furthermore, profiling of metabonomics by 1H‐NMR demonstrated that taurine was the major differential metabolite in the heart of Pdk1‐knockout mice. Taurine treatment significantly reduced the reactive oxygen species production and apoptosis, improved cardiac function, and prolonged the survival time in Pdk1 deficient mice. Proteomic screening identified solute carrier family 6 member 6 (Slc6a6) as the downstream that altered taurine levels in Pdk1‐expression cells. Consistently, cellular apoptosis and oxidative damage were rescued by Slc6a6 in abnormal Pdk1 expression cells. These findings collectively suggest that Pdk1 deficiency induces heart failure via disturbances in taurine homeostasis, triggered by Slc6a6.
Technical Factors Contributing to Nonunion in Supracondylar Distal Femur Fractures Treated with Lateral Locked Plating: A Risk-Stratified Analysis
Authors: Stockton David J. , O’Hara Nathan N. , Brodke Dane J. , McKibben Natasha , Healey Kathleen , Goch Abraham , Demyanovich Haley , Devana Sai , Hernandez Adolfo , Burke Cynthia E. , Gupta Jayesh , Marchand Lucas S. , Dekeyser Graham J. , Steffenson Lillia , Shymon Stephen J. , Fairres Marshall J. , Perdue Paul W. , Barber Colby , Atassi Omar H. , Mitchell Thomas W. , Working Zachary M. , Black Loren O. , El Naga Ashraf N. , Roddy Erika , Hogue Matthew , Gulbrandsen Trevor , Morellato John , Gillon W. Hunter , Walters Murphy M. , Hempen Eric , Slobogean Gerard P. , Lee Christopher , O’Toole Robert V.
Published: August 2023

Objective:

To identify technical factors associated with nonunion after operative treatment with lateral locked plating.

Design:

Retrospective cohort study.

Setting:

Ten Level 1 trauma centers.

Participants:

Six hundred fifteen adult patients with supracondylar distal femur fractures (OTA/AO Type 33A or C).

Intervention:

Lateral locked plating.

Main Outcome Measurements:

Surgery for nonunion.

Results:

We observed nonunion rates of 2% in a low-risk of nonunion group (n = 129), 4% in a medium-risk group (n = 333), and 14% in a high-risk group (n = 153). Varus malreduction with an anatomic lateral distal femoral angle (aLDFA) greater than 84 degrees, was associated with double the odds of nonunion (OR, 2.1; 95% CI, 1.1 to 4.2; P = 0.03). Malreduction by medial translation of the articular block increased the odds of nonunion, with 30% increased odds per 4 mm of medial translation (95% CI, 1.0 to 1.6; P = 0.03). Working length increased the odds of nonunion primarily in the medium risk group, with an 18% increase in nonunion per 10 mm increase in working length (95% CI, 1.0 to 1.4; P = 0.01). Proximal screw density was protective against nonunion (OR, 0.71; 95% CI, 0.53 to 0.92; P = 0.02). Lateral plate length and type of plate material were not associated with nonunion.

Conclusions:

Malreduction is a surgeon-controlled variable associated with nonunion after lateral locked plating of supracondylar distal femur fractures. Longer working lengths were associated with nonunion, suggesting that simple bridge plating may be less likely to succeed for longer fractures.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Surgeon Learning Curve for the Sinus Tarsi Approach to Intra-articular Calcaneus Fractures – Improvement with Experience
Authors: Joseph Noah M. , McCaskey Meghan , Bhatt Fenil R. , Watson David T. , Sanders Roy W. , Mir Hassan R.
Published: August 2023

Objective:

To analyze the relationship between surgeon experience with the sinus tarsi approach (STA) and outcomes in the treatment of displaced intra-articular calcaneus fractures (DIACF).

Setting:

Single level 1 trauma center

Design:

Retrospective.

Patients/Participants: 103 consecutive DIACF (OTA/AO 82C; Sanders II-IV) treated operatively using STA from 2015 to 2021.

Intervention:

Open management using the STA performed by two fellowship-trained orthopaedic traumatologists.

Main Outcome Measurement:

Quality of anatomic reduction based on postoperative CT scans and standard radiographs.

Results:

Sixty-six patients met inclusion criteria. Patients were primarily men (75.8%) with mean age 41 years (range 20-71 years), including 14 smokers (21.2%), 9 diabetics (13.6%), and 10 open fractures (15.2%). Sanders III fractures were most common (68.2% vs 28.5% and 6.1% Sanders II/IV respectively). Reduction quality was predominantly Good (59.1%, n=39) or Excellent (25.8%, n=17). Complications included wound necrosis (1), superficial infection (1), deep infection (1), and symptomatic posttraumatic arthritis requiring arthrodesis (3). There was a 29.3% reduction in likelihood of surgical complication with each year in surgeon experience with the STA and an 8.9% reduction per case (p<0.001). The likelihood of achieving a Good or Excellent reduction was 1.8 and 2.3 times greater than achieving a Fair reduction, respectively, for each year increase in surgeon experience with the STA (p=0.012 and 0.007, respectively). For each successive case, there was a 1.2 times greater likelihood of achieving a Good reduction (p=0.03).

Conclusion:

Surgeon experience plays a critical role in outcomes. We found that outcomes (reduction, complications) improve with each cumulative case and year of experience with the STA to treat DIACF.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.