Overview on Juvenile Primary Fibromyalgia Syndrome

JPFS (juvenile primary fibromyalgia syndrome) is a musculoskeletal pain illness that affects children and adolescents. The intricacy of the clinical picture in JPFS has not been adequately characterized in the literature. JFMS symptoms are sometimes difficult to compare to adult fibromyalgia syndrome since many of them are "medically unexplained" and frequently overlap with other medical disorders.  The etiology of the illness is multifaceted, with impaired central pain processing being a significant contributor. Musculoskeletal pain that is severe and pervasive is the defining symptom. Other signs and symptoms include headaches, stiffness, subjective joint swelling, sleep and mood disorders, and headaches. Multiple sensitive spots might be found during a physical examination. The diagnosis has certain criteria and is clinical. Early detection and treatment are crucial. The gold standard of care combines a variety of modalities, but most significantly, exercise and cognitive behavioral therapy. The outlook varies, and symptoms might last well into adulthood. Discussing the epidemiology, etiology, pathophysiology, clinical symptoms, diagnosis, and management of JPFS is the goal of the review

Treatment of chronic or relapsing COVID-19 in immunodeficiency

BACKGROUND: Patients with some types of immunodeficiency can suffer chronic or relapsing infection with SARS-CoV-2. This leads to morbidity and mortality, infection control challenges and the risk of evolution of novel viral variants. Optimal treatment for chronic COVID-19 is unknown. OBJECTIVE: To characterise a cohort of patients with chronic or relapsing COVID-19 disease and to record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features and treatment response of immune deficient patients with chronic (at least 21 days) or relapsing (at least two episodes) of COVID-19. RESULTS: We identified 31 cases with a median age of 49 years. Underlying immune deficiency was characterised by antibody deficiency with absent or profoundly reduced peripheral B cells; prior anti-CD20 therapy and X-linked agammaglobulinemia were most common. Clinical features of COVID-19 were similar to the general population, but the median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to five episodes of illness. Remdesivir monotherapy (including when given for prolonged courses up to 20 days) was associated with sustained viral clearance in 7/23 (30.4%) clinical episodes whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 monoclonal antibodies resulted in viral clearance in 13/14 (92.8%) episodes. Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise

Treatment of chronic or relapsing COVID-19 in immunodeficiency

BACKGROUND: Patients with some types of immunodeficiency can suffer chronic or relapsing infection with SARS-CoV-2. This leads to morbidity and mortality, infection control challenges and the risk of evolution of novel viral variants. Optimal treatment for chronic COVID-19 is unknown. OBJECTIVE: To characterise a cohort of patients with chronic or relapsing COVID-19 disease and to record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features and treatment response of immune deficient patients with chronic (at least 21 days) or relapsing (at least two episodes) of COVID-19. RESULTS: We identified 31 cases with a median age of 49 years. Underlying immune deficiency was characterised by antibody deficiency with absent or profoundly reduced peripheral B cells; prior anti-CD20 therapy and X-linked agammaglobulinemia were most common. Clinical features of COVID-19 were similar to the general population, but the median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to five episodes of illness. Remdesivir monotherapy (including when given for prolonged courses up to 20 days) was associated with sustained viral clearance in 7/23 (30.4%) clinical episodes whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 monoclonal antibodies resulted in viral clearance in 13/14 (92.8%) episodes. Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise

The oxford classic links epithelial-to-mesenchymal transition to immunosuppression in poor prognosis ovarian cancers

Purpose: Using RNA sequencing, we recently developed the 52-gene-based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. Experimental Design: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n ¼ 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. Results: We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition-high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P ¼ 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. Conclusions: The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome