CLINICAL FEATURES AND OUTCOME IN CHILDREN WITH LANGERHANS CELL HISTIOCYTOSIS. A SINGLE INSTITUTION EXPERIENCE FROM PAKISTAN

Objective: To find out the clinical manifestations, treatment given and outcome of children with diagnosis of Langerhans cell histiocytosis. Study Design: Retrospective observational study. Place and Duration of Study: Shaukat Khanum Cancer Hospital, Lahore Pakistan, from Jan 2005 to Dec 2015. Methodology: Medical charts were reviewed in detail along with the available imaging for the patients. The data included age at the time of diagnosis, extent of the disease, involvement of risk organs, treatment given, response at 6th week of chemotherapy and at the end of the treatment, and outcome in terms of disease progression during the treatment, relapse of disease on follow up and cause of death either due to treatment related mortality or disease complications. Results: There were 29 patients, 12 patients (41%) had single system and 17 (58%) had multisystem involvement. 7 patients (41%) had risk organ involvement in the multisystem group. All the patients of multisystem and 6 patients of single system were treated according to the Langerhans cell histiocytosis III protocol. Commonest sites of involvement were bone in 22 (75%), followed by lymph nodes in 18 (62%) patients. Disease relapse was seen in 6 patients and all of them had multisystem disease. Mortality was observed only in multisystem Langerhans cell histiocytosis patients and more than 50% were risk organ positive. Conclusion: Langerhans cell histiocytosis is a highly heterogeneous disease. Some forms are curable without chemotherapy, while the multisystem disease requires aggressive treatment. However, despite intensive treatment, the multisystem disease and risk organs involved have poor...........

Objective assessment of the damaging effect of glucocorticoids (toxicity index) in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multisystem disease characterized by chronic inflammation and damage to vital organs and systems. Despite the great success achieved in the treatment of SLE, glucocorticoids (GC) remain one of the main methods of therapy. The GC toxicity index is an objective method for assessing adverse events associated with their use, and in future studies can be actively used to monitor the safety of various therapy regimens. Wider introduction of this index in the management of patients with SLE will allow to optimize approaches to the selection of GC doses, to consider earlier prescription of biologic disease modifying antirheumatic drugs, before the development of severe irreversible damage.

Identification and Validation of Immune-Related Genes and Immune Cell Infiltration in Preeclampsia

Background Preeclampsia (PE) is a complex multisystem disease and its etiology remains unclear. The aim of this study was to identify potential immune-related diagnostic genes for PE, analyze the role of immune cell infiltration in PE, and explore the mechanism underlying PE-induced disruption of immune tolerance at the maternal-fetal interface. Methods We used the PE dataset GES25906 from Gene Expression Omnibus and immune-related genes from ImmPort database. The differentially expressed genes (DEGs) were identified using the “limma” package, and the differentially expressed immune-related genes (DEIGs) were extracted from the DEGs and immune-related genes using Venn diagrams. The potential functions of DEIGs were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Furthermore, the protein–protein interaction network was obtained from the STRING database, and it was visualized using Cytoscape software. Least absolute shrinkage and selection operator logistic regression was used to verify the diagnostic markers of PE and build a predicting model. The model was validated using datasets GSE66273 and GSE75010. Finally, CIBERSORT was used to evaluate the infiltration of immune cells in PE tissues. Results Six genes (ACTG1, ENG, IFNGR1, ITGB2, NOD1, and SPP1) enriched in Th17 cell differentiation, cytokine-cytokine receptor interaction, innate immune response, and positive regulation of MAPK cascade pathways were identified, and a predicting model was built. Datasets GSE66273 and GSE75010 were used to validate the model, and the area under the curve was 0.8333 and 0.8107, respectively. Immune cell infiltration analysis revealed an increase in plasma cells and gamma delta T cells and a decrease in resting natural killer cells in the high score group according to the predictive model risk values. Conclusions We developed a risk model to predict PE and proved that immune imbalance at the maternal-fetal interface plays a key role in the pathogenesis of PE.

Case Report: Early Association of Vemurafenib to Standard Chemotherapy in Multisystem Langerhans Cell Histiocytosis in a Newborn: Taking a Chance for a Better Outcome?

Langerhans cell histiocytosis (LCH) is due to aberrant monoclonal proliferation and accumulation of dendritic cells, ranging from a self-limiting local condition to a rapidly progressive multisystem disease with poor prognosis. Pathogenic cells originate from a myeloid-derived precursor characterized by an activation of the MAPK/ERK signaling pathway in about 70% of cases. In particular, BRAF V600E mutation is usually associated with a more severe clinical course and poor response to chemotherapy. We report on a newborn with multisystem LCH in life-threatening medical conditions. At diagnosis, the patient was successfully treated with the early association of BRAF inhibitor Vemurafenib to standard chemotherapy representing a new approach in first-line treatment. A rapid clinical improvement with a prompt fever regression from day 2 and complete resolution of skin lesions by week 2 were observed; laboratory data normalized as well. Vemurafenib was discontinued after 12 months of treatment. No signs of relapse occurred after 12 months of discontinuation. This case indicates that early combination of target therapy with standard treatment may induce rapid response and prolonged disease remission without significant toxicities in infants. This approach represents a valid and safe option as first-line treatment in multisystem disease, especially in high-risk patients.

Sensorineural Hearing Loss in Rheumatoid Arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic multisystem disease of unknown etiology is characterized by persistent inflammatory synovitis, usually involving peripheral joints in a symmetric distribution. RA is well known to affect many organ systems, including the auditory system and can involve the incudomalleolar and incudostapedial joints altering the ossicular mechanics in response to static air pressure modifications. Objective: This study evaluates the degree of sensorineural hearing loss in patients with rheumatoid arthritis (RA) Material and Methods: This study was conducted in the Department of Physiology in collaboration with departments of Medicine and ENT Pt. B.D. Sharma PGIMS, Rohtak. 25 rheumatoid arthritis female patients with disease duration of more than five years as per 1987 criteria of American college of rheumatology were included in the study to study the effect of rheumatoid arthritis on hearing. 25 healthy volunteer females were included in control group. Audiological evaluation was based on pure tone audiometry. Results: We observed a high incidence of hearing loss in rheumatoid arthritis patients as compared to corresponding age and sex matched controls. Nine RA (36%) cases, were having hearing threshold more than 25 dB. Of the total of 36% patients having hearing loss 24% patients had sensorineural hearing loss. Bilateral hearing loss was seen in 8% of cases. Conclusion: Based on our study it can be postulated that patients with RA are at higher risk of hearing impairment. Key words: Rheumatoid arthritis, hearing, sensorineural, audiometry.

Rare Case of Chagas Disease

Chagas is a multisystem disease transmitted from Trypanosoma cruiz, not uncommon in Latin America. This disease causes parasympathetic failure resulting in cardiac failure, arrhythmogenic, cardiomyopathy, sudden death, mega esophagus and mega colon. In this article, we present a case of chronic Chagas disease who had extensive investigation prior to reaching a correct diagnosis. We will highlight the symptomatology and treatment.

Langerhans cell histiocytosis: an unusual cause of vesicular rashes in a neonate

The skin manifestations of Langerhans cell histiocytosis (LCH) in the neonate have a heterogenous presentation and can mimic other causes of neonatal rashes. We report an uncommon case of LCH in a term female neonate presenting with non-specific papules and vesicles from the first day of life. There was a maternal history of genital herpes simplex virus (HSV) infection in the third trimester. Blood, cerebrospinal fluid, surface swabs and vesicular fluid were negative for HSV by PCR, and a skin biopsy confirmed the diagnosis of LCH. Further investigations for systemic involvement returned negative. Our case emphasises the variable and non-specific presentation of neonatal cutaneous LCH, which can progress to or be part of multisystem disease.

Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study

The COVID-19 disease is a multisystem disease due in part to the vascular endothelium injury. Lasting effects and long-term sequelae could persist after the infection and may be due to persistent endothelial dysfunction. Our study focused on the evaluation of endothelial quality index (EQI) by finger thermal monitoring with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long-covid 19 symptoms are associated with endothelial dysfunction. This is a cross-sectional multicenter observational study with prospective recruitment of patients. A total of 798 patients were included in this study. A total of 618 patients (77.4%) had long COVID-19 symptoms. The mean EQI was 2.02 ± 0.99 IC95% [1.95–2.08]. A total of 397 (49.7%) patients had impaired EQI. Fatigue, chest pain, and neuro-cognitive difficulties were significantly associated with endothelium dysfunction with an EQI <2 after adjustment for age, sex, diabetes, hypertension, dyslipidemia, coronary heart disease, and the severity of acute COVID-19 infection. In multivariate analysis, endothelial dysfunction (EQI <2), female gender, and severe clinical status at acute COVID-19 infection with a need for oxygen supplementation were independent risk factors of long COVID-19 syndrome. Long COVID-19 symptoms, specifically non-respiratory symptoms, are due to persistent endothelial dysfunction. These findings allow for better care of patients with long COVID-19 symptoms.

Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias

The term “fibrillinopathies” gathers various diseases with a wide spectrum of clinical features and severity but all share mutations in the fibrillin genes. The first described fibrillinopathy, Marfan syndrome (MFS), is a multisystem disease with a unique combination of skeletal, thoracic aortic aneurysm (TAA) and ocular features. The numerous FBN1 mutations identified in MFS are located all along the gene, leading to the same pathogenic mechanism. The geleophysic/acromicric dysplasias (GD/AD), characterized by short stature, short extremities, and joint limitation are described as “the mirror image” of MFS. Previously, in GD/AD patients, we identified heterozygous FBN1 mutations all affecting TGFβ-binding protein-like domain 5 (TB5). ADAMTS10, ADAMTS17 and, ADAMTSL2 are also involved in the pathogenic mechanism of acromelic dysplasia. More recently, in TAA patients, we identified mutations in THSD4, encoding ADAMTSL6, a protein belonging to the ADAMTSL family suggesting that ADAMTSL proteins are also involved in the Marfanoid spectrum. Together with human genetic data and generated knockout mouse models targeting the involved genes, we provide herein an overview of the role of fibrillin-1 in opposite phenotypes. Finally, we will decipher the potential biological cooperation of ADAMTS-fibrillin-1 involved in these opposite phenotypes.

Sarcopenia: Diagnosis and Management, State of the Art and Contribution of Ultrasound

Age-related muscle loss is a phenomenon that has been extensively studied in recent decades. Sarcopenia is a multisystem disease, which predisposes to muscle weakness and frailty. At around 50 years of age, an individual begins to lose muscle strength, although this becomes more evident after 70. Sarcopenia is a condition typically found in older adults but can also affect younger people. Sarcopenia is a preventable and treatable condition. In past years, methods and tools to recognize the condition early have been researched. For the development of therapeutic interventions, agreement on diagnosis is fundamental. In recent years, a possible role of ultrasonography in the diagnosis of sarcopenia has been evaluated, compared with the best-known techniques.