Clinical Features Research Articles

Intracapillary monoclonal IgM deposits disease with massive pseudothrombi: A clinicopathologic study of 4 cases and literature review.

Intracapillary monoclonal IgM deposits disease (ICMDD) has long been considered a hallmark of Waldenström macroglobulinemia (WM) nephropathy. Intracapillary immunoglobulin thrombi are the characteristic features of cryoglobulinemic glomerulonephritis. Here, we reported 4 cases of ICMDD with massive pseudothrombi but without WM or cryoglobulinemia. We retrospectively analyzed the clinical and pathologic features of patients diagnosed with ICMDD with massive pseudothrombi. A total of 4 patients (2 men and 2 women) aged 62 to 73 years were enrolled in this study. Microscopic hematuria, edema, and renal insufficiency were present in all patients, along with low serum C3 and C4 in 2 patients. Hematologic examination showed abnormal serum free light chain ratios in all patients and high levels of serum IgM in 3 patients. IgM-κ monoclonal band was identified by serum immunofixation electrophoresis in 3 patients. One patient was diagnosed with small B-cell lymphoma by bone marrow aspiration. Renal biopsy specimen showed massive periodic acid-Schiff-positive hyaline thrombi in the glomerular capillary lumens and also less mesangial, subendothelial, and subepithelial deposits on light microscopy. Immunofluorescence indicated positive staining for IgM (++) and κ light chain staining in the glomerular capillary lumens, capillary walls, and mesangium in all patients. By electron microscopy, the glomerular capillary lumens were filled with homogeneous high-electron-dense deposits without substructure. Two patients were treated with prednisone combined with cyclophosphamide, and 2 received plasma cell-targeted chemotherapy. One patient achieved partial renal remission. Intracapillary monoclonal IgM deposits disease is a rare disease and not always related to WM. Most patients have IgM monoclonal immunoglobulinemia; renal biopsy specimens mainly show a large number of pseudothrombi in the glomerular capillary lumens. Cyclophosphamide is effective in some patients.

Familial Bilateral Pheochromocytoma Complicated by Acute Ischemia of the Lower Limbs

Few authors have ever reported acute ischemia of the lower limbs (AILL) as a presentation of pheochromocytoma. Case Report: We present a case of familial bilaterla pheochromocytoma complicated by AILL. Discussion and Conclusion: we aim to illustrate the pathophysiological, clinical and therapeutic features of this rare case of pheochromocytoma and describe this complication (AILL), wich mainly linked to the catecholaminergic effects on the cardiovascular system, may jeopardise the functional prognosis of the locomotor system, thus affecting the quality of life of these patients.

Towards Treating Multiple Sclerosis Progression

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). In most patients, the disease starts with an acute onset followed by a remission phase, subsequent relapses and a later transition to steady chronic progression. In a minority of patients, this progressive phase develops from the beginning. MS relapses are characterized predominantly by the de novo formation of an inflammatory CNS lesion and the infiltration of immune cells, whereas the pathological features of MS progression include slowly expanding lesions, global brain atrophy and an inflammatory response predominantly mediated by macrophages/microglia. Importantly, this CNS-intrinsic pathophysiology appears to initiate early during the relapsing–remitting disease phase, while it turns into the key clinical MS feature in later stages. Currently approved disease-modifying treatments for MS are effective in modulating peripheral immunity by dampening immune cell activity or preventing the migration of immune cells into the CNS, resulting in the prevention of relapses; however, they show limited success in halting MS progression. In this manuscript, we first describe the pathological mechanisms of MS and summarize the approved therapeutics for MS progression. We also review the treatment options for progressive MS (PMS) that are currently under investigation. Finally, we discuss potential targets for novel treatment strategies in PMS.

Erythrocytic α-Synuclein in Parkinson’s Disease and Progressive Supranuclear Palsy—A Pilot Study

Background/Objectives: The current research examines the accuracy of α-synuclein in RBCs as a diagnostic biomarker for PD and PSP, despite their distinct molecular etiologies. Methods: We used ELISA to measure total, oligomeric, and p129-α-synuclein levels in erythrocytes from 8 PSP patients, 19 PD patients, and 18 healthy controls (HCs). The classification performances of RBC α-synuclein levels were investigated by receiver operator characteristic (ROC) curve. We also evaluated a possible correlation between RBC α-synuclein level and the biological and clinical features of our cohorts. Results: RBC total α-synuclein was higher in PSP patients compared to both PD patients and HCs, achieving good classification performance (AUC: 0.853) in distinguishing PSP patients from PD patients, with a sensitivity of 100% and a specificity of 70.6%; moreover, the levels of this biomarker positively correlated with disease severity in PSP group. Regarding oligomeric α-synuclein and p129-α-synuclein, the latter was slightly increased in RBCs from PSP patients compared to HCs, but no correlations were detected. Conclusions: Although these findings need to be confirmed in larger studies, our pilot work suggests that RBC total α-synuclein may represent a potential molecular biomarker for the differential diagnosis and clinical staging of PSP.

Surgical management and prognostic factors for Endolymphatic Sac Tumor: a single-institute experience with a systematic review.

To evaluate the clinical features, surgical outcomes, and predictors of progression-free survival (PFS) in patients with Endolymphatic Sac Tumors (ELSTs). This retrospective study analyzed 15 cases from Beijing Tiantan Hospital and 237 from literature (1988-2023), focusing on patients with pathologically confirmed intracranial or skull ELSTs who had comprehensive treatment and follow-up records. Univariate and multivariate Cox regression analyses were employed to identify factors influencing PFS. Cases from our institute comprised 10 males and 5 females with an average age of 39.1 years. Among these, 86.7% underwent gross total resection (GTR). During the follow-up period, two patients (13.3%) were lost to follow-up. After a mean follow-up of 74.9 months, one patient experienced recurrence and another died from unrelated causes. A review of literature identified 237 additional patients, including 134 females (56.5%), with an average age of 39.8 years; 22.8% of these patients had von Hippel-Lindau disease. The GTR rate was 69.2%. After a mean follow up of 53.2 months, 33 recurrences occurred, and the median PFS was 48 months. Additionally, eight patients died during the follow-up period, none of the deaths were attributed to ELSTs. Multivariate analysis identified GTR (HR 0.279, 95% CI 0.086-0.903, p = 0.033) as a significant protective factor against recurrence among the pooled cases. GTR is crucial for improving PFS in ELST patients, emphasizing the need for advanced surgical techniques and long-term follow-up due to potential recurrences.

Alternative polyadenylation shapes the molecular and clinical features of lung adenocarcinoma.

Alternative polyadenylation (APA) is a major mechanism of post-transcriptional regulation that affects mRNA stability, localization and translation efficiency. Previous pan-cancer studies have revealed that APA is frequently disrupted in cancer and is associated with patient outcomes. Yet, little is known about cancer type-specific APA alterations. Here, we integrated RNA-sequencing data from a Korean cohort (GEO: GSE40419) and The Cancer Genome Atlas (TCGA) to comprehensively analyze APA alterations in lung adenocarcinomas (LUADs). Comparing expression levels of core genes involved in polyadenylation, we find that overall, the set of 28 of 31 genes are upregulated, with CSTF2 particularly upregulated. We observed broad and recurrent APA changes in LUAD growth-promoting genes. In addition, we find enrichment of APA events in genes associated with known LUAD pathways and an increased heterogeneity in polyadenylation (polyA) site usage of proliferation-associated genes. Upon further investigation, we report smoking-specific APA changes are also highly relevant to LUAD development. Overall, our in-depth analysis reveals APA as an important driver for the molecular and clinical features of lung adenocarcinoma.

A Biological Perspective: Epidemiology of Acute Leukemia in Souss Massa

Acute leukemia is a type of blood cancer characterized by the rapid and uncontrolled proliferation of abnormal immature cells in the bone marrow. It is divided into two main forms: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Common symptoms include severe fatigue, paleness, easy bleeding and bruising, frequent infections, bone and joint pain, as well as swollen lymph nodes. Acute lymphoid and myeloid leukemias account for 10 to 15% of malignant hematological disorders and are rare conditions, with the majority having a poor prognosis, except for a few specific forms. Acute myeloid leukemias (AML) have a consistent incidence over time, ranging from 2.5 to 3.5 per 100,000 population per year in Western countries. We conducted a retrospective descriptive study on the medical records of patients with acute leukemia between January 2023 and June 2024 (6 months), classified according to the criteria of the Franco-American-British (FAB) group. During this period, 68 cases of acute leukemia were diagnosed. The age of the patients ranged from 4 years to 87 years, with a mean age of 26 years. The male-to-female sex ratio was 1.40, favoring males. Acute leukemias were observed across all age groups. Cytological and cytochemical examination of bone marrow smears showed a predominance of acute myeloid leukemias at 64.7% (n=44), with 24 cases of acute lymphoblastic leukemias (35.3%). The study results provide valuable insights into the demographic and clinical characteristics of patients with acute leukemias. No precise statistics on acute leukemia have been conducted to date in our region. Our study could serve as a foundation for future research in this area. Indeed, the new WHO classification utilizes a comprehensive approach that incorporates cytological, cytogenetic, immunophenotypic, and molecular biology data to classify acute leukemias with both diagnostic and prognostic objectives. Outside of these distinguishing features, ...

Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features.

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles (N = 145), and gene mutations (N = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis-free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune-depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Association of Nursing Home Residents' Demographic and Clinical Attributes and Nursing Home Characteristics With Self-Reported Ratings of Nursing Home Satisfaction.

The current study explored the association of nursing home (NH) residents' demographic and clinical attributes and NH characteristics with resident-reported satisfaction with NH communities. Pearson correlations and multiple linear regression were used to test the association of demographic and clinical attributes of residents and NH characteristics with resident-reported NH satisfaction with 197 NH residents from 28 NHs. Correlational analysis and regressions indicated an association among residents' demographic and clinical characteristics, NH characteristics, and self-reported NH satisfaction. Higher age, higher education, and race (minority status) were associated with greater resident-reported NH satisfaction. Greater NH staffing and for-profit ownership status were associated with less NH satisfaction. Greater resident depressive symptoms and dressing assistance were associated with lower resident-reported NH satisfaction. Administrators and staff should look beyond NH characteristics and consider their residents' diverse personal characteristics to create an environment that promotes satisfaction and well-being. [Journal of Gerontological Nursing, 50(11), 6-12.].

Homologous recombination deficiency score is an independent prognostic factor in esophageal squamous cell carcinoma.

Homologous recombination deficiency (HRD) represents an impairment in the homologous recombination repair (HRR) pathway, crucial for repairing DNA double-strand breaks and contributing to genomic instability in cancer. The HRD score may be a more reliable biomarker than HRR-related gene mutations for identifying patients sensitive to poly(ADP-ribose) polymerase inhibitors. Despite its relevance in various cancers, the HRD score remains underexplored in esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed HRD scores in 96 ESCC patients, examining correlations with clinical characteristics and survival outcomes, and validated our findings using the TCGA dataset. Genomic sequencing utilized a custom superHRD next-generation sequencing panel, and HRD scores were calculated from 54,000 single-nucleotide polymorphisms using Kruskal-Wallis rank-sum tests and two cut-off points for analysis. Higher HRD scores correlated with advanced tumor stages, recurrence, and mutations in TP53 and ABCB1, while APC mutations were linked to lower HRD scores. Patients with high HRD scores had significantly shorter disease-free survival (p = 0.013) and a trend toward shorter overall survival (OS) (p = 0.005), particularly those not receiving adjuvant therapy. Conversely, HRD-high patients undergoing adjuvant therapy showed a trend toward longer OS (p = 0.015). Multivariate analysis identified HRD as an independent prognostic factor (hazard ratio = 2.814 for recurrence, p = 0.015). Validation with the TCGA dataset supported these findings. This study highlights the associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, suggesting HRD as a potential prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies, warranting further investigation to validate the therapeutic implications of HRD scores in ESCC.

Clinical characteristics and decortication outcomes of bacterial, tuberculous and fungal pleural infection.

<sec><title>BACKGROUND</title>Pleural infection leading to empyema is a severe condition marked by accumulated infected fluid in the pleural space. Pneumonia with parapneumonic effusion is its most common precursor. The global incidence of pleural infections has increased significantly, with existing literature mainly focusing on bacterial empyema, leaving a gap in comparative analyses.</sec><sec><title>METHOD</title>A retrospective review was conducted on 561 cases of bacterial, tuberculous, and fungal empyema over a 10-year period. The study compared and analysed overall survival rates, 30-day mortality rates after surgery, and clinical characteristics.</sec><sec><title>RESULTS</title>The three empyema groups displayed distinct clinical characteristics. Fungal empyema had the worst overall survival compared to bacterial and tuberculous empyema, which had similar survival rates based on 30-day and 2-year mortality. Fungal empyema, advanced age, and high Charlson Comorbidity Index (CCI) score were independent predictors of poor prognosis.</sec><sec><title>CONCLUSION</title>Fungal empyema has the highest mortality rate post-decortication surgery. Advanced age and high CCI score are independent predictors of poor prognosis.</sec>.

Decrements in Morning and Evening Energy Are Associated With a Higher Symptom Burden in Patients With Gynecologic Cancers Receiving Chemotherapy.

Decrements in energy are a significant problem associated with chemotherapy. To date, no study examined the variability of energy in patients with gynecologic cancers. To identify distinct morning and evening energy profiles in patients with gynecologic cancers and evaluate for differences in demographic and clinical characteristics, other common symptoms, and quality-of-life (QOL) outcomes. A sample of 232 patients with gynecologic cancers completed questionnaires 6 times over 2 cycles of chemotherapy. Latent profile analysis was used to identify distinct morning and evening energy profiles. Differences in demographic and clinical characteristics, other common symptoms, and QOL outcomes were evaluated using parametric and nonparametric tests. Three distinct morning (ie, high [9.2%], low [63.1%], very low [27.1%]) and 2 distinct evening (moderate [30.6%], very low [69.4%]) energy classes were identified. Clinical risk factors associated with the worst morning energy profiles included lower functional status and a higher comorbidity burden. Less likely to exercise on a regular basis was the only characteristic associated with the worst evening energy profile. For both symptoms, the worst profiles were associated with higher levels of depression and sleep disturbance, lower levels of cognitive function, and poorer QOL. Approximately 70% of patients with gynecologic cancers experienced decrements in morning and evening energy. The study identified modifiable risk factors associated with more decrements in morning and evening energy. Clinicians can use these findings to identify higher-risk patients and develop individualized energy conservation interventions for these vulnerable patients.

Clinical, epidemiological, and molecular characteristics ofSARS-CoV-2 Infections among healthcare workers at a research center in the amazon region of BRAZIL from 2020 to 2022.

The coronavirus disease-2019 (COVID-19) pandemic has affected different sectors of society, and healthcare workers have been particularly impacted. This study aimed to describe the clinical, epidemiological, and molecular characteristics of SARS-CoV-2 infections among healthcare workers in Evandro Chagas Institute, a research reference center in Brazil, from October 2020 to July 2022. 845 samples were collected from individuals who presented clinical symptoms of respiratory infection. Nasopharyngeal positive samples were submitted through genome sequencing. Clinical, epidemiological, and the SARS-CoV-2 lineages (or variants) were analyzed. SARS-CoV-2 positivity was detected in 31.8% (269/845) of samples with a higher prevalence of females (60.2%). The highest SARS-CoV-2 positivity rates were reported in March 2021 (39%), January 2022 (65%), and July 2022 (56%). On clinical symptoms, arthralgia, chills, and diarrhea were statistically significantly detected in 2020; fever, runny nose, and arthralgia in 2021; runny nose, and cough in 2022. On molecular analysis of SARS-CoV-2, 66 samples (25.3%, 66/269) were sequenced and the most prevalent lineage was the Omicron, representing 57.6%. Studies on the epidemiological and clinical characteristics of HCW are essential to propose control measures and work management since research centers play a major role in surveillance to identify and monitor infectious diseases.

Vulvar lichen sclerosus in girls and adult females: A single-center retrospective study of 744 patients in China.

Vulvar lichen sclerosus (VLS) is a chronic, inflammatory disease which is accompanied by itching and pain, affecting the patient's daily life and sexual activity. However, the disease characteristics of children and adults are not completely the same. Currently, there are few studies in China that compare the characteristics of VLS between girls and adult female patients. The aim of this study was to compare the epidemiology, clinical features, and combined autoimmune diseases of VLS patients between girls and adult females, and to help clinicians better understand VLS in different age groups. We enrolled 744 female patients for analysis, divided by age into a child group (<18 years) and an adult group (≥18 years). Among girl patients, 94.6% had preadolescent onset, while among adult female patients, only 4.6% had preadolescent onset, which was a statistically significant difference. The highest percentage of adult female patients had onset during their child-bearing period (75.4%), while 20% had postmenopausal onset, with a significant difference when the three onset states were compared. White patches were equally common in both girl and adult female patients' external genital area, while mossy lesions and labia minora atrophy were more common in adult female patients. Involvement of the clitoris, labia minora, and vaginal opening area were more common in adult patients. The perianal area was more commonly involved in girl patients. We found eight cases (1.2%) of secondary squamous cell carcinoma in adult female patients. We also found that 13 patients had concurrent lichen sclerosus lesions on the vulva and extragenital region, including two girls and 11 adult females. Extragenital lichen sclerosus (EGLS) occurred mostly in the torso. Clinicians should be aware of these differences so that early diagnosis and treatment of the disease can be achieved, to avoid irreversible anatomical alterations and the risk of cancer.

Chronic Non-bacterial Osteomyelitis (CNO) In Childhood: A Review.

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder mostly affecting children and adolescents. Although it is considered a rare disease, CNO is likely to be the single most common autoinflammatory bone disease in childhood, underdiagnosed and underreported due to a lack of awareness of the condition in both medics and patients and the absence of validated diagnostic criteria. The exact underlying pathogenesis of CNO remains unknown, making targeted treatment difficult. This issue is exacerbated by the lack of any randomised control trials, meaning that treatment strategies are based solely on retrospective reviews and case series. This review summarises the current concepts in pathophysiology, the clinical features that help differentiate important differential diagnoses, and an approach to investigating and managing children with CNO. Ultimately, the timely and thorough investigation of children and young people with CNO is vitally important to exclude important mimics and initiate appropriate management that can prevent the complications of persistent inflammatory bone disease.

The association between anemia and sensorineural hearing loss: A review.

Anemia affects a third of the world's population and contributes to increased morbidity and mortality, decreased work productivity, and impaired neurological development. In recent years, many studies have found a possible association between anemia and sensorineural hearing loss (SNHL), especially in various types of nutritional deficiency and hemoglobin disorders anemia. Anemia may affect hearing through various mechanisms, including affecting microcirculation in the ear, causing tissue hypoxia in the ear, and through inflammatory and oxidative stress pathways. This review aims to comprehensively analyze the association between various types of anemia and SNHL, including possible biological mechanisms, clinical features, and treatment strategies, and clarify the importance of anemia treatment and management in preventing SNHL.

Development of fully automated models for staging liver fibrosis using non-contrast MRI and artificial intelligence: a retrospective multicenter study

Accurate staging of liver fibrosis (LF) is essential for clinical management in chronic liver disease. While non-contrast MRI (NC-MRI) yields valuable information for liver assessment, its effectiveness in predicting LF remains underexplored. This study aimed to develop and validate artificial intelligence (AI)-powered models utilizing NC-MRI for staging LF. A total of 1726 patients from Shengjing Hospital of China Medical University, registered between October 2003 and October 2022, were retrospectively collected, and divided into development (n=1208) and internal test (n=518) cohorts. An external test cohort consisting of 337 individuals from six centers, registered between June 2015 and November 2022, were also included. All participants underwent NC-MRI (T1-weighted imaging, T1WI; and T2-fat-suppressed imaging, T2FS) and liver biopsies. Two classification models (CMs), named T1 and T2FS, were trained on respective image types using 3D contextual transformer networks and evaluated on both test cohorts. Additionally, three CMs-Clinic, Image, and Fusion-were developed using clinical features, T1 and T2FS scores, and their integration via logistic regression. Classification effectiveness of CMs was assessed using the area under the receiver operating characteristic curve (AUC). A comparison was conducted between the optimal models (OMs) with highest AUC and other methods (transient elastography, five serum biomarkers, and six radiologists). Fusion models (i.e., OM) yielded the highest AUC among the CMs, achieving AUCs of 0.810 for significant fibrosis, 0.881 for advanced fibrosis, and 0.918 for cirrhosis in the internal test cohort, and 0.808, 0.868, and 0.925, respectively, in the external test cohort. The OMs demonstrated superior performance in AUC, significantly surpassing transient elastography (only for staging≥F2 and ≥ F3 grades), serum biomarkers, and three junior radiologists for staging LF. Radiologists, with the aid of the OMs, can achieve a higher AUC in LF assessment. AI-powered models utilizing NC-MRI, including T1WI and T2FS, accurately stage LF. National Natural Science Foundation of China (No. 82071885); General Program of the Liaoning Provincial Department of Education (LJKMZ20221160); Liaoning Province Science and Technology Joint Plan (2023JH2/101700127); the Leading Young Talent Program of Xingliao Yingcai in Liaoning Province (XLYC2203037).

HERC5: a comprehensive in silico analysis of its diagnostic, prognostic, and therapeutic potential in cancer.

HERC5, a vital protein in the HERC family, plays crucial roles in immune response, cancer progression, and antiviral defense. This bioinformatic study comprehensively assessed HERC5's significance across various malignancies by analyzing its gene expression, immune and molecular subtype expressions, target proteins, biological functions, and prognostic and diagnostic values in pan-cancer. We further examined its correlation with clinical features, co-expressed and differentially expressed genes, and prognosis in clinical subgroups, focusing on endometrial cancer (UCEC). Our findings showed that HERC5 RNA is expressed at low levels in most cancers and significantly differs across immune and molecular subtypes. HERC5 accurately predicts cancer and correlates with most cancer prognoses. In UCEC, HERC5 was significantly associated with age, hormonal status, clinical stage, treatment status, and metastasis. Elevated HERC5 expression was linked to worse progression-free interval, disease-specific survival, and overall survival in UCEC, particularly in diverse clinical subgroups. Significant differences in HERC5 expression were also observed in various human cancer cell line validations. In summary, HERC5 may be a critical biomarker for pan-cancer prognosis, progression, and diagnosis, as well as a promising new target for cancer therapy.

Classification of distinct tendinopathy subtypes for precision therapeutics

Rotator cuff tendinopathy is the most common tendinopathy type with the worst prognosis. Conventional treatments often elicit heterogeneous drug responses due to the diversity of tendinopathy. Hence, this study attempted a classification of 126 diseased tendons into three distinct subtypes with opposite pathogenic mechanisms based on transcriptomic and clinical features. The hypoxic atrophic subtype with white appearance (Hw) exhibits downregulated neovascularization pathways. The inflammatory proliferative subtype with white appearance (Iw) shows a moderate upregulation of inflammatory characteristics. The inflammatory proliferative subtype with red appearance (Ir) exhibits the highest levels of upregulated neovascularization and inflammatory pathways, along with severe joint dysfunction. We then established research models, including subtype-specific simulations in animal models and clinical data analysis. These revealed that glucocorticoid, a controversial commonly used drug, was only effective in treating the Ir subtype. Hence, the tendinopathy subtypes elucidated in this study have significant implications for developing precision treatment of tendinopathy.

P34 A case of haemophagocytic lymphohistiocytosis triggered by primary Epstein–Barr virus infection

Abstract Introduction Haemophagocytic lymphohistiocytosis (HLH) is an uncommon systemic hyperinflammatory state characterised by uncontrolled activation of the immune system. HLH may occur in a primary (familial) form, but more commonly occurs secondary to another disease process. Such triggers include infections, autoimmune disease and malignancy. We present the case of a 24-year-old female who was previously fit and well, who was diagnosed with HLH secondary to primary Epstein-Barr virus (EBV) infection. Case description The patient was admitted with a 10-day history of fever, sore throat and abdominal pain. On examination she had bibasal crackles and epigastric and right upper quadrant tenderness. There was pharyngeal erythema but no exudate. No rash or joint inflammation. Admission blood tests showed WBC 11.7 x109/L, neutrophils 6.5 x109/L, lymphocytes 4.3 x109/L, platelets 142 x109/L, CRP 179 mg/L, ALT 330 U/L, ALP 1022 U/L, bilirubin 37 mmol/L and lactate 1.81 mmol/L. A CT chest/abdomen/pelvis showed bibasal consolidation with small bilateral pleural effusions and mild splenomegaly. The patient was hypotensive and tachycardic, and was spiking temperatures greater than 39 °C. She subsequently developed type 1 respiratory failure and was transferred to the intensive care unit. She was treated with broad-spectrum antibiotics for suspected sepsis secondary to pneumonia. She remained unwell with high spiking fevers. HLH was suspected and ferritin was &amp;gt;100,000 mg/L with triglycerides 6.19 mmol/L, fibrinogen 1.1 g/L and LDH &amp;gt;1800 U/L. Her HScore was 200, indicating a high probability of HLH. Autoimmune screen including rheumatoid factor, ANCA and ANA were negative. A comprehensive infection screen identified a strongly positive EBV viral capsid antigen (VCA) IgM, positive EBV VCA IgG and negative EBV nuclear antigen (EBNA) with a viral load of 49,600 copies/ml. These results were consistent with acute primary EBV infection. Bone marrow biopsy confirmed haemophagocytosis. A diagnosis of HLH triggered by primary EBV infection was made. The patient was discussed with the specialist HLH service at University College Hospital and was commenced on intravenous methylprednisolone and anakinra 200 mg twice daily. She was additionally given antivirals, antibiotics and antifungals as prophylaxis against secondary infection. The patient improved clinically and biochemically. The dose of anakinra was reduced and eventually discontinued, and the patient was discharged on a tapering course of prednisolone. Discussion HLH carries a high mortality rate and early recognition and treatment is vital. However, diagnosis is often delayed as HLH may resemble other conditions such as sepsis. Signs and symptoms of HLH include fever, hepatosplenomegaly, cytopenias, hyperferritinaemia, hypertriglyceridaemia, liver dysfunction and coagulopathy. There may be multi-organ dysfunction. The characteristic histopathological finding is haemophagocytosis on biopsy of bone marrow, lymph node, liver or spleen, however this may initially be absent. EBV is the most common infective trigger for HLH, but it may occur with other viral and bacterial infections including tuberculosis. The most common autoimmune conditions associated with HLH include adult-onset Still’s disease (AOSD), systemic juvenile idiopathic arthritis and lupus. Haematological malignancy, in particular lymphoma, is another important cause and can sometimes be challenging to identify. The initial presentation of AOSD can share many of the same clinical features as EBV infection, including fever, rash, sore throat, hepatosplenomegaly, lymphadenopathy and liver dysfunction. The rash of AOSD is classically salmon-pink coloured and comes and goes with the fever, and the fever typically occurs at the same time each day. In our patient, the absence of arthralgia, rash and leucocytosis meant AOSD was felt to be unlikely, but this was kept under review. Key learning points • Early recognition and treatment of HLH is crucial to reducing mortality • The HScore tool can be used to assess the probability of HLH • Management of HLH involves supportive care, immunosuppression and treatment of the underlying cause • Agents that may be used include steroids, cyclosporine, etoposide, anakinra and intravenous immunoglobulin