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A critical evaluation of crizanlizumab for the treatment of sickle cell disease.

P-selectin is a key adhesion molecule in the pathogenesis of sickle cell disease, including acute painful event(s). Many of the mediators activated in prototypical pain crisis are also involved in other complications seen in this population. Crizanlizumab is a monoclonal antibody approved in the US in 2019 for patients of all genotypes of sickle cell disease. By blocking P-selectin, it effectively prevents acute painful event(s) and has a manageable safety profile.

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Side effects among healthcare workers from a large Milan university hospital after second dose of BNT162b2 mRNA COVID-19 vaccine.

In Italy, healthcare workers (HCWs) were among the first to receive COVID-19 vaccination. Aim of the present study is to evaluate frequency and severity of adverse events (AEs) following the second dose of BNT162b2 vaccine among HCWs of a large university hospital in Milan, Italy.

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Intra-epidermal evoked potentials: A promising tool for spinal disorders?

To test the robustness and signal-to-noise ratio of pain-related evoked potentials following intra-epidermal electrical stimulation (IES) compared to contact heat stimulation in healthy controls, and to explore the feasibility and potential added value of IES in the diagnosis of spinal disorders.

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Designing, validation, and the feasibility of a yoga module for patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes significant disability and reduced quality of life. Scientific studies on yoga have revealed its various health benefits in chronic conditions, including autoimmune diseases. However, whether yoga is feasible for AS patients or not is not studied. Further, no validated yoga module is available for AS patients.

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Photobiomodulation Delivery Parameters in Dentistry: An Evidence-Based Approach.

Dosimetry at a level of 2-8 J/cm at target cellular level has been accepted to represent the optimum range for the stimulatory benefits associated with photobiomodulation therapies. However, it has been proposed that a higher bracket of 10-30 J/cm at target tissue level may represent a good and effective range for analgesia, accompanied by at-distance regional anti-inflammatory effects. However, although this provides a useful guideline, transforming recommendations into a translatable and repeatable clinical skill have to date proven elusive. Based on prior publications of systematic reviews by the authors, key factors have been identified, associated with reported clinical and and animal studies that can support outcome success or null responses. Drawn from five recently published systematic reviews, an analysis of an extended published evidence base indicates that research methodology should embrace a mature understanding of terminology, a requirement for consistent metered energy delivery, and an appreciation of optical transport techniques. Using models derived from orthodontics and oncology, evidence-based optimal delivery parameters and techniques are presented. Within the confines of the accepted inclusion criteria, a modified Cochrane risk of bias tool has been applied and the parameters extracted from the included studies were subjected to a meta-analysis. This demonstrated a low risk of bias from the studies included with a multivariate and/or univariate statistical analysis that supports the author's evidence-based determinations. The adoption of a surface optical spot size of >1 cm demonstrated a high degree of success in managing both superficial as well as subsurface pathologies in oral care. Also, the timing of the intervention with conditioning before or at the same time as a potentially traumatic cellular event was found to be a significant signal of outcome success. An extended commentary explores the benefits and disadvantages of scanning techniques. The extracted clinical data are cross-referenced to the mechanisms suggested for photobiomodulation therapies from the authors' own current research, and proposals are made for some possible lines of approach in future research and clinical trials.

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Coronary Microvascular Disease: The “Meeting Point” of Cardiology, Rheumatology, and Endocrinology.

Exertional chest pain/dyspnea or chest pain at rest are the main symptoms of coronary artery disease (CAD), which are traditionally attributed to insufficiency of the epicardial coronary arteries. However, 2/3 of women and 1/3 of men with angina and 10% of patients with acute myocardial infarction have no evidence of epicardial coronary artery stenosis in X-ray coronary angiography. In these cases, coronary microvascular disease (CMD) is the main causative factor. The pathophysiology of CMD includes impaired microvascular vasodilatation, which leads to inability of the organism to deal with myocardial oxygen needs and, hence, development of ischemic pain. CMD has been also observed in inflammatory autoimmune rheumatic and endocrine/metabolic disorders, bringing together Cardiology, Rheumatology and Endocrinology. Causative factors in these diseases include persistent systemic inflammation and endocrine/metabolic abnormalities that influence directly the coronary microvasculature. In the past, the evaluation of microcirculation was feasible only with the use of invasive techniques, such as coronary flow reserve assessment. Currently, the application of advanced imaging modalities, such as cardiovascular magnetic resonance (CMR), can evaluate CMD non-invasively and conclusively, without exposing the patient to ionizing radiation. Although both classic and new medications have been used in the treatment of CMD, there are still many questions regarding both the pathophysiology and the treatment of this disorder. The potential effects of anti-rheumatic and endocrine medications on the evolution of CMD need further evaluation.

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An empirical study on quality of life and related factors of Pakistani breast cancer survivors.

A comprehensive understanding of the quality of life (QoL) is essential to establish long-term survivor care plans. The present study was aimed at the assessment of QoL of BC survivors with special emphasis on post-treatment physical, emotional, social, and spiritual challenges. We have assessed the QoL of 250 female BC survivors of all age groups through demographic factors. Volunteer BC survivors were registered in the present study who had got treatment from the Institute of Nuclear Medicine and Oncology (INMOL) hospital and Mayo hospital Lahore. An informed consent form was signed by each participant. The physical, psychological, and spiritual well-being was evaluated by a questionnaire filled with the help of respondents. The average age of BC survivors was 52 ± 7.8 years. Most of them (83%) complained of fatigue during daily life activities, 75.1% body pain or headache, 77.1% had problems with appetite, 63.2% reported weight loss, 77.1% had sleep problems, and 90.5% were feeling general weakness. Only 16.2% were satisfied with their physical health and 2% were not satisfied with their medication. Psychologically, 74.4% were feeling different levels of anxiety, only 10% of them were hoping to achieve a desired life. Age group 21 to 40 years reported better physical health, those with 40-50 years of age and family history of BC have shown better mental strength. The physical and psychological health of survivors from rural areas was comparatively better than those from urban areas. The BC survivor women have to face several physical, psychological and social challenges. The majorities of them complain of anxiety, body pain, fatigue, sleep problems, general weakness, and fear about the future. Our findings suggest the need for psychological support, physical activity a comprehensive post-diagnosis and post-treatment physical and mental health assistance plan for all BC survivors. Implications for Cancer Survivors. Survivors of breast cancer experience various challenges including anxiety, sleep problems, body pain, fatigue, and fear about the future. The psychological, physical and social factors make a great difference in their quality of life.

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Clinical Reasoning: Longitudinally Extensive Spinal Cord Lesions in a Middle-aged Man.

An immunocompetent 47-year-old man presented with a five-month history of progressive lower limb weakness, back pain, sphincter dysfunction, and intermittent fever, suggesting myelopathy in a chronic deteriorating course. A comprehensive analysis comprising of blood tests, neuroimaging, CSF profiling, molecular analysis, and histopathology was performed. Notably, enhanced spinal cord MRI revealed longitudinally extensive intradural-extramedullary lesions involving the cervical, thoracic, and lumbosacral spinal cord, with homogeneous enhancement and spinal cord compression. Serum TPHA and RPR tests were positive. CSF profiling showed pleocytosis, significant protein elevations, hypoglycorrhachia, and positive TPHA test. 18F-FDG-PET/CT indicated slightly increased intraspinal FDG uptake. Spinal cord biopsy further showed small round blue cells in poorly differentiated tissues. Immunostaining was positive for NKX2.2, CD56, CD99, Synaptophysin, and Ki67 (50%). Molecular analysis detected a novel MALAT-CYSLTR1 fusion protein and variants in oncogenic genes including and The diagnosis of intraspinal extraosseous Ewing's sarcoma (ES) was confirmed. Briefly, our case details the diagnosis of a patient with intradural-extramedullary ES and highlights the value of spinal cord biopsy in progressive myelopathy of unknown causes.

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Prognostic factors for work disability in patients with chronic widespread pain and fibromyalgia: protocol for a cohort study.

The association between chronic widespread pain (CWP) and disability is well established. Although research support large interindividual differences in functional outcomes, limited studies are available on the socio-economic consequences of offering stratified treatment based on prognostic factors. Identification of predictors of long-term functional outcomes such as work disability as a critical consequence, could assist early and targeted personalised interventions. The primary objective of this cohort study is to identify prognostic factors for the primary endpoint work status (employed and working vs not working) in patients with CWP assessed 3 years from baseline, that is, at referral for specialist care.

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Incidental Findings of Appendiceal Diverticulitis Presenting as Acute Appendicitis.

Diverticulosis of the appendix (DA) is a rare pathological finding that clinically imitates acute appendicitis and is most commonly found in adult males with chronic abdominal pain. It has a higher rate of perforation compared to acute appendicitis (84% vs 12%, P<0.01), and is consequently associated with a higher rate of mortality. Appendiceal diverticulitis has been found to have a significant association with incidental appendiceal neoplasms, therefore elective prophylactic appendectomy is recommended to prevent the risk of complications and to rule out the possibility of a coexisting neoplasm. Meticulous gross examination in addition to thorough histological examination of the entire appendectomy specimen by pathologists is essential in order to identify diverticula. We present two female patients with signs and symptoms consistent with acute appendicitis, they were found to have appendiceal diverticulitis on pathologic evaluation.

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