AVASCULAR NECROSIS OF THE FEMORAL HEAD – NOT TO BE OVERLOOKED SEQUELA AFTER COVID 19 INFECTION

BackgroundCOVID 19 infection could lead to different sequelae in survivors, known as post-COVID or long COVID 19 syndromes. Some of them are thought to be due to the thrombophylic changes observed in COVID 19 infection, but some are thought to be caused by the administrated (especially high dose) corticosteroid treatment. Avascular necrosis of the femoral head (AVNFH) is a multifactorial disease which leads to compromised vascular supply, ischemia and finally necrosis of the femoral head. As corticosteroids usage and thrombophylic states are among the main known risk factors for the development AVNFH [1], it could be presumed that the frequency of this disease will increase with the COVID 19 pandemic. The exact corticosteroid dose needed for the development of AVNFH is not clear, but it has been stated that a higher daily dose and a larger total cumulative dose increase substantially the risk for the development of osteonecrosis [2].ObjectivesTo describe in detail the characteristics of AVNFH diagnosed in patients after COVID 19 infection.MethodsThe study was done in a tertiary university rheumatological clinic. Data was extracted from the records of patients who have been referred to the clinic because of hip pain between June and December 2022. Inclusion criteria were: - a new onset of uni-or bilateral hip pain that started after a documented COVID 19 infection;and an MRI scan of the hip joints showing osteonecrosis of one or both femoral heads. Exclusion criteria were the presence of hip pain prior to the COVID 19 infection, anamnesis of traumatic injuries of the hips or pelvis, personal history of hypercoagulable states.ResultsNine patients (4 women and 5 men) with an average age 59.1 years (range 38-72) were included in the study. Four patients had been diagnosed with bilateral and five – with unilateral AVNFH, thus 13 hip joints were analysed in total (8 left and 5 right sided). The mean time lap between the COVID 19 infection and the start of the hip pain was 26.2 weeks (range 10-48 weeks). All patients had limited and painful movement in their symptomatic hip(s), especially internal rotation and four of the patients had also elevated CRP levels (mean 11.7 mg/L). The stage of the AVNFH was evaluated according to the Ficat-Arlet classification (0-IV stage). In four hips the AVNFH was stage I, five hips were classified as stage II and the remaining four joints - as stage III. All symptomatic hip joints exhibited effusion/synovitis on both ultrasound examination and the corresponding MRI scan. It should be noted that the presence of hip effusion was found to be related with a worse prognosis in AVNFH [1]. In three patients the amount of the effusion required arthrocentesis and fluid aspiration. The analysis of the joint fluid was consistent with a degenerative disease (i.e., low WBC count with predominant lymphocytes and no crystals). All patients included in our study had received corticosteroids during their COVID19 infection, while 6 of the patients had also been hospitalized due to more severe disease. According to the patients' documentation, the mean cumulative dose of the received corticosteroids was 936.2 mg prednisolone equivalent per patient (range 187-2272 mg).ConclusionAVNFH must not be overlooked in a new onset hip pain after COVID 19 infection. Our results show that corticosteroids administrated during the infection and the presence of hip joint effusion on ultrasound are especially suggestive for the development of osteonecrosis, as they were registered in all of our patients. The presence of these two factors necessitates patient referral for an MRI scan of the hips, in order that AVNFH be detected timely.References[1]Petek D, Hannouche D, Suva D. Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment. EFORT Open Rev. 2019 Mar 15;4(3):85-97.[2]Kerachian MA, Séguin C, Harvey EJ. Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):121-8.Acknowledgements:NIL.Disclosur of InterestsPLAMEN TODOROV Speakers bureau: speaker at national level for AbbVie, Novartis and UCB, Lily Mekenyan: None declared, Anastas Batalov Speakers bureau: Speaker at national level for AbbVie, Novartis, Pfizer, Stada, Elly Lilly.

NEUTROPHIL TO LYMPHOCYTE RATIO (NLR) PREDICTS FRACTURE IN PATIENTS ON LONG-TERM GLUCOCORTICOID

BackgroundLong-term glucocorticoid (GC) exposure leads to systemic bone loss and fracture. In addition, GC is known to increase white blood cell (WBC) amount and change the distribution of differential count (DC). Neutrophil-to-Lymphocyte ratio (NLR) has been studied as an optimal marker of subclinical inflammation, predicting the prognosis of cardiovascular diseases, cancers and even covid-19 infection. For patients under long-term GC exposure, the hemogram change might be a potential parameter to predict prognosis.ObjectivesThis pilot study aims to investigate if GC related WBC-DC change, including NLR, is associated with future fractures during 3 years follow-up.MethodsThis retrospective study is based on a registry, conducted in Kaohsiung Chang Gung Memorial Hospital, Taiwan, from September 2014 till April 2021, aimed to monitor bone mineral density (BMD) changes and fractures in patients with autoimmune diseases. All recruited patients were followed at least 3 years and took X-ray images annually to capture new fragility fracture, including morphometric vertebral fractures. We screened participants who used GC continuously at least 3 months before the index day. We recorded the complete blood count (CBC) and WBC-DC values at least twice during the period of 3 months before and after the index day, and excluded patients who were febrile, under infection status, diagnosed as cancers or cardiovascular diseases at the index day. The NLR was calculated by the absolute neutrophil count divided by absolute lymphocyte count individually.ResultsA total of 346 participants were enrolled in current study, and 101 (29.2%) suffered from new fragility fracture in 3 years. Among patients with fracture and non-fracture, conventional fracture risk factors, such as age, BMD, and previous fracture remained significantly different, while the WBC revealed no difference (Table 1). Nevertheless, the absolute neutrophil and lymphocyte count were significantly higher and lower in the fracture group, respectively, and no difference in the monocyte, eosinophil, and basophil count. We compared different WBC ratio, and NLR is significantly higher in the fracture group, providing the odds ratio of 1.24 (95% confidence interval 1.07-1.44, p=0.005). Figure 1 showed that the observed fracture risk raised as the NLR values increased.ConclusionIn patients under long-term GC, NLR might be a helpful marker to predict fracture, and higher NLR indicates higher fracture risks.Figure 1.Observed fracture rate is associated with baseline NLR[Figure omitted. See PDF]Table 1.Demographic characteristics of enrolled patients on long-term glucocorticoid.Fracture N=101No-Fracture N=245p-valueAge63.7 ± 9.056.5 ± 9.6<0.001*Sex(women)89(88.1)210(85.7)0.55BMI24.1 ± 3.923.4 ± 3.90.14Previous Fracture64(63.4)55(22.4)<0.001*Total hip BMD0.738 ± 0.1330.790 ± 0.1220.001*Femoral neck BMD0.575 ± 0.1130.626 ± 0.109<0.001*Lumbar BMD0.841 ± 0.2000.855 ± 0.1500.49WBC7.3 ± 2.16.9 ±1.70.14Hemoglobin12.8 ± 1.512.9 ± 1.40.33Platelet239.2 ± 64.7247.9 ± 71.40.30Neutrophil67.3 ± 9.764.3 ± 9.70.009*Lymphocyte24.3 ± 8.726.6 ± 9.50.04*Monocyte6.2 ± 1.86.3 ± 1.60.52Eosinophil1.8 ± 1.81.9 ± 1.30.77Basophil0.4 ± 0.20.4 ± 0.20.18NLR (Neutrophil to lymphocyte)3.3 ± 1.72.8 ± 1.40.004*NMR (Neutrophil to monocyte)11.9 ± 4.511.0 ± 3.60.04*LMR (Lymphocyte to monocyte)4.2 ± 1.74.5 ± 1.90.20AcknowledgementsThis work was supported by funding grant CMRPG8J0331 from the Chang Gung Memorial Hospital (https://www.cgmh.org.tw).Disclosure of InterestsNone Declared.

The effect of COVID-19 on 30-day mortality rates amongst fragility hip fracture patients

Aim: Fragility hip fracture patients have always been vulnerable to high rates of short term mortality, an issue that may have been exacerbated by the ongoing COVID-19 pandemic. To date, published data regarding Irish hip fracture patients in the era of COVID-19 is limited. This study aims to assess the effect of COVID-19 on 30-day mortality rates amongst a group of Irish hip fracture patients. Additionally, patient demographics, length of stay, admission haematological parameters, fracture type and surgical procedure will be assessed. Methods: A multicentre, observational, retrospective study of hip fracture patients (n = 1,017) admitted to six Dublin teaching hospitals during the COVID-19 pandemic (4th February to 9th July 2020) was performed. For comparative purposes, equivalent data was retrospectively collected relating to hip fracture patients admitted to the same six teaching hospitals during the same time period in 2019. Results: 481 patients were admitted during the specified timeframe in 2020, compared with 536 in 2019. The mean patient age was 77.6 years and 65.9% of patients were female. There was no statistically significant overall difference in 30-day mortality rates between the study and control groups, at 5.4% in 2020 and 4.3% in 2019 (p=0.338). There was an insignificant decrease in mean length of stay (17.85 days in 2020 vs. 18.82 days in 2019;p=0.106). Advancing age (p=0.021), male gender (p=0.019), low admission haemoglobin (p=0.024) and high admission white cell count (p=0.019) were all associated with increased 30-day mortality. Conclusion: We found no significant difference in 30-day mortality rates amongst our cohort of hip fracture patients at the height of the COVID-19 pandemic in Ireland. Advancing age, male gender, anaemia at admission and leucocytosis at admission were associated with increased 30-day mortality. The continuation of COVID-19 related safety protocols in the treatment of hip fracture patients is essential in maintaining a safe hip fracture service.

Effect of COVID-19 on severity of signs and symptoms of autoimmune diseases

It is an observational cross-sectional study, the data collected by convenience sampling method from 33 patients in the Ranya General Hospital and private clinics for follow-up patient's autoimmune diseases state in the Ranya city from the 10th November 2020 to the 20th May 2021 and the study included all the patients had autoimmune diseases that recovered from the COVID-19 disease. For the study materials, the data was collected by a questionnaire form that included demographic and autoimmune disease questions also questions about the patient's intensity of their autoimmune disease's signs and symptoms before and after they recovered from COVID-19. Determine patient's autoimmune disease signs and symptoms intensity based on the prescribed drug for a treat the autoimmune diseases which are changed by special doctors. Furthermore, the data were analysed by SPSS software to produce descriptive statistic measures and to find the difference between dependent categorical variables Sign tests were used but the Chi-square test was used for the categorical independent variables with regarding 0.05 as a significant critical value. The result reveals that the range of their age started from 42 to 74 years old with mean..standard deviation (57.3 .. 8.06) and most of the cases 15(45.5%) were between (55-65) years old, followed by less than 55 years old 13(39.4%) and more than 65 years old age 5(3.8%) cases respectively. Rheumatoid arthritis was a major type 16 (48.5%) of the autoimmune disease compared to other types, Ankylosing Spondylitis 8(24.2%) cases, and Ulcerative Colitis 6(18.2%) cases respectively while Crohn's disease was the minimum 3(9.1%) cases and before the got COVID-19 most of the cases 25(75.8%) had moderate intensity signs and symptoms of their autoimmune diseases and 8(24.2%) cases had severe signs and symptoms but after they recovered from the COVID-19 disease the rate of their signs and symptoms changed to mild 19(57.6%) and moderate 14(42.4%) intensity while severe intensity signs and symptoms were zero with highly significant differences (P-value 0.0001). Despite the current study concluded autoimmune disease patients recovered from the COVID-19 their autoimmune diseases signs and symptoms intensity decreased significantly but still further studies are needed with a bigger sample size to determine and explain this association.

Clinical research of pre-hospital emergency care, nursing, infection prevention and control for senile osteoporotic vertebral compression fracture during epidemic period

Background: Novel coronavirus pneumonia (NCP) and osteoporotic vertebral compression fractures (OVCF) are the high incidences of diseases in the elderly. During the epidemic period, if not treated in time, the complications are high and the mortality is high. If we do not pay attention to infection prevention and control in pre-hospital emergency care, it will lead to the first time infection of medical staff and in-hospital cross infection in emergency outpatient receiving area. The correct consideration of both and the establishment of perfect pre-hospital emergency treatment and infection prevention and control synchronous strategy is an important premise to ensure the stable, orderly and safe medical treatment. Background: To explore the effect of synchronous implementation of pre-hospital emergency care, nursing and infection pre-vention and control for senile OVCF during the epidemic. In order to improve the efficiency of pre-hospital emergency care and prevent the spread of infection. Method: A total of 92 elderly patients with OVCF who received pre-hospital treatment in 18 hospitals in Zhangjiakou City during the epidemic prevention and control period from January 2020 to November 2022 and met the inclusion criteria were selected as research objects, including 24 males and 68 females, aged 65 - 82 (74.2 +or- 2.2) years. All patients were associated with concomitant injuries and underlying diseases. All patients in this group underwent predictive pre-hospital rescue and infection prevention and control procedures. Results: All the 92 elderly patients with OVCF received timely pre-hospital treatment during the epidemic period, and no aggravation occurred of the 92 patients, 35 were in the high risk area, 10 were in the medium risk area, and 47 were in the low risk area. Exclude OVCF for NCP Patients were treated according to the conventional diagnosis and treatment principles. Suspected and confirmed cases are transferred to designated surgical hospitals for treatment. All patients were followed up 3 months, 6 months and 12 months after treatment. There was no death rate, high satisfaction of pre-hospital first aid, high diagnostic accuracy, and good curative effect. None of the rescue personnel had any infection rate, and no hospital infection transmission and nosocomial cross infection occurred. Conclusion: It is the first step to safely treat patients and prevent cross infection to establish a perfect synchronous strategy of pre-hospital first aid and infection prevention and control.

Life quality and its influencing factors in patients with Kashin-Beck disease

Objective: To evaluate the life quality of patients with Kashin-Beck disease (KBD), and to analyze its influencing factors.

First person – Aikta Sharma

First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Aikta Sharma is first author on ‘Multiscale molecular profiling of pathological bone resolves sexually dimorphic control of extracellular matrix composition’, published in DMM. Aikta is a PhD student in the lab of Dr Claire E. Clarkin at the University of Southampton, Southampton, UK, investigating the role of osteoblast-derived vascular endothelial growth factor in bone matrix formation.

Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer.

Vitamin D has received considerable optimistic attention as a potentially important factor in many pathological states over the past few decades. However, the proportion of the active form of vitamin D metabolites responsible for biological activity is highly questionable in disease states due to flexible alterations in the enzymes responsible for their metabolism. For instance, CYP3A4 plays a crucial role in the biotransformation of vitamin D and other drug substances. Food-drug and/or drug-drug interactions, the disease state, genetic polymorphism, age, sex, diet, and environmental factors all influence CYP3A4 activity. Genetic polymorphisms in CYP450-encoding genes have received considerable attention in the past few decades due to their extensive impact on the pharmacokinetic and dynamic properties of drugs and endogenous substances. In this review, we focused on CYP3A4 polymorphisms and their interplay with vitamin D metabolism and summarized the role of vitamin D in calcium homeostasis, bone diseases, diabetes, cancer, other diseases, and drug substances. We also reviewed clinical observations pertaining to CYP3A4 polymorphisms among the aforementioned disease conditions. In addition, we highlighted the future perspectives of studying the pharmacogenetics of CYP3A4, which may have potential clinical significance for developing novel diagnostic genetic markers that will ascertain disease risk and progression.

Evaluating Explainable Artificial Intelligence for X-ray Image Analysis

The lack of justification of the results obtained by artificial intelligence (AI) algorithms has limited their usage in the medical context. To increase the explainability of the existing AI methods, explainable artificial intelligence (XAI) is proposed. We performed a systematic literature review, based on the guidelines proposed by Kitchenham and Charters, of studies that applied XAI methods in X-ray-image-related tasks. We identified 141 studies relevant to the objective of this research from five different databases. For each of these studies, we assessed the quality and then analyzed them according to a specific set of research questions. We determined two primary purposes for X-ray images: the detection of bone diseases and lung diseases. We found that most of the AI methods used were based on a CNN. We identified the different techniques to increase the explainability of the models and grouped them depending on the kind of explainability obtained. We found that most of the articles did not evaluate the quality of the explainability obtained, causing problems of confidence in the explanation. Finally, we identified the current challenges and future directions of this subject and provide guidelines to practitioners and researchers to improve the limitations and the weaknesses that we detected.

India and COVID-19: the changing trends in epidemiology of fracture distal end radius

Background: Distal radius fractures (DRF) are one of the most common fractures seen in the emergency department. The aim of our study was a thorough assessment of impact of COVID-19 pandemic on epidemiological trends of DRF. There is limited data on possible changes in epidemiology of DRF in both adults and children.

Quality of life and experiences of sarcoma trajectories (the QUEST study): protocol for an international observational cohort study on diagnostic pathways of sarcoma patients.

INTRODUCTION: Sarcomas are rare tumours with considerable heterogeneity. Early and accurate diagnosis is important to optimise patient outcomes in terms of local disease control, overall survival (OS) and health-related quality of life (HRQoL). Time to diagnosis is variable in bone as well as soft tissue sarcoma. Possible factors for a long time from first symptom to diagnosis (the total interval) include patient, tumour and healthcare characteristics, but until now the most relevant risk factors and its association with outcomes remain unknown. Our study aims to (1) quantify total interval, the time interval from first symptom until (histological) diagnosis; (2) identify factors associated with interval length and (3) determine the association between total interval and HRQoL, stage and tumour size at diagnosis, progression-free survival (PFS) and OS. METHODS AND ANALYSIS: We will conduct a longitudinal, prospective, international, multicentre cohort study among patients aged ≥18 years with newly diagnosed bone or soft tissue sarcoma at eight centres (three in UK, five in The Netherlands). Patients will be asked to complete questionnaires at five points in time; one at diagnosis and at follow-up points of 3, 6, 12 and 24 months. Questionnaire data is collected within the Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship (PROFILES) registry: an international data management system for collection of patient-reported outcomes. Clinical data will be extracted from patient records. The primary endpoint is HRQoL at diagnosis, measured with the EORTC QLQ-C30. Secondary endpoints are stage and tumour size at diagnosis, PFS, OS, additional patient-reported outcomes, such as quality-adjusted life years and psychological distress. ETHICS AND DISSEMINATION: Ethical approval was given by the Health Research Authority and Research Ethics Committee for the United Kingdom (18/WA/0096) and medical ethical committee of Radboudumc for The Netherlands (2017-3881). Results will be presented in peer-reviewed journals and presented at meetings. TRIAL REGISTRATION NUMBER: NCT03441906.

Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic.

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care.