Rejected

A 6-year-old girl presented with nightly fever, persistent joint pain of the knees, ankles, lower back, and hip. Her skin lesions were evanescent salmon-colored patches along with persistent pruritic light to dark pink papules and plaques on her face, post-auricular scalp, trunk, thigh, and bilateral upper extremities. Skin biopsy supported the diagnosis of fixed papules and plaques of systemic juvenile idiopathic arthritis (sJIA). We report this case to highlight diagnostic features of this exceedingly rare cutaneous presentation of sJIA presenting with typical cutaneous salmon-colored evanescent eruptions.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. Interleukin-17 (IL-17) is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS are not clear. We confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased in the prostate of EAP. Treatment of EAP mice with an IL-17-neutralizing monoclonal antibody (mAb) decreased the number of infiltrated neutrophils and CXCL1 and CXCL2 levels. Depletion of neutrophils using anti-Ly6G antibodies ameliorated the inflammatory changes and hyperalgesia caused by EAP. Fucoidan, a could potent inhibitor of neutrophil migration, also ameliorate the manifestations of EAP. Our findings suggested that IL-17 promoted the production of CXCL1 and CXCL2, which triggered neutrophil chemotaxis to prostate tissues. Fucoidan might be a potential drug for the treatment of EAP via the effective inhibition of neutrophil infiltration.

To analyze the presence of fetal myocardial dysfunction in intrahepatic cholestasis of pregnancy (ICP) at diagnosis.

The transient receptor potential cation channel 5 (TRPC5) plays an important role in numerous cellular processes. Due to this, it has gained considerable attention over the past few years as a potential therapeutic target. Recently, TRPC5 has been shown to be involved in the regulation of podocyte survival, indicating a potential treatment option for chronic kidney disease. In addition, a recent study has shown TRPC5 to be expressed in human sensory neurons and suggests that TRPC5 inhibition could be an effective treatment for spontaneous and tactile pain. To understand these processes more fully, potent and selective tool compounds are needed. Herein we report further exploration of the 2-aminobenzimidazole scaffold as a potent TRPC5 inhibitor, culminating in the discovery of 16f as a potent and selective TRPC5 inhibitor.

This study aims to compare the efficiency of Pregabalin and Ketotifen in treatment of uremic pruritus in hemodialysis (HD) patients. Thirty HD patients were randomly divided into two groups: A (Pregabalin 50 mg 3 times a day) and B (Ketotifen 1mg twice a day). Efficacy of treatment and quality of life were weekly evaluated by visual analogue scale (VAS) and Itchy Quality of life, respectively. There was no significant difference between the two groups regarding demographic features, laboratory data, quality of life, and VAS before treatment. In the second week of treatment, the pruritus intensity was significantly lower in the Pregabalin group than the Ketotifen group (p=0.026). The mean of life quality was significantly lower in Ketotifen than Pregabalin group in weeks 1, 2, and 4 (P=0.001, P=0.001, and P=0.036, respectively). There was no significant difference between the two groups regarding the side effects of drugs. This study showed that a higher dose of Pregabalin could be a more effective treatment than Ketotifen without additive side effects in improving the quality of life in dialysis patients. This article is protected by copyright. All rights reserved.

Calcitonin gene-related peptide (CGRP) signaling inhibitors have shown efficacy in both the acute and preventive treatment of migraine. Telcagepant, a first-generation CGRP receptor antagonist, was effective but failed in clinical trials due to hepatotoxicity. Subsequently, while four next-generation CGRP receptor antagonists (rimegepant, zavegepant, atogepant, and ubrogepant) were being advanced into late-stage clinical trials, due to telcagepant's failure, more confidence in the liver safety of these compounds was needed. DILIsym v6A, a quantitative systems toxicology (QST) model of drug-induced liver injury (DILI), was used to model all five compounds and thus to compare the four next-generation CGRP receptor antagonists to telcagepant. In vitro experiments were performed to measure the potential for each compound to inhibit bile acid transporters, produce oxidative stress, and cause mitochondrial dysfunction. Physiologically-based pharmacokinetic (PBPK) models were produced for each compound in order to appropriately estimate liver exposure. DILIsym predicted clinical elevations of liver enzymes and bilirubin for telcagepant, correctly predicting the observed DILI liability of the first-generation compound. By contrast, DILIsym predicted that each of the four next-generation compounds would be significantly less likely to cause DILI than telcagepant. Subsequent clinical trials have validated these predictions for each of the four compounds, and all 3 of the compounds submitted to FDA to date (rimegepant, ubrogepant and atogepant) have since been approved by the FDA with no warning for hepatotoxicity. This work demonstrates the potential for QST modeling to prospectively differentiate between hepatotoxic and non-hepatotoxic molecules within the same class.

A previously healthy 24-year-old male patient was referred to our clinic with bilateral lower extremity pain and dark urine, which developed two weeks after receiving the second dose of BNT162b2 vaccine against SARS-CoV-2. Laboratory tests indicated rhabdomyolysis. Lower extremity magnetic resonance imaging was compatible with myositis. Myositis-related antibodies were negative. Biopsy taken from gastrocnemius muscle revealed muscle necrosis and striking expression of major histocompatibility complex class I antigen. He was successfully treated, and his complaints resolved. One week later at follow-up, he reported new-onset exertional dyspnea with palpitations. ST-segment depressions were spotted on electrocardiography. Troponin T was found elevated as 0.595 ng/mL (normal <0.014 ng/mL). Echocardiography showed hypokinetic left ventricle with ejection fraction of 40%, and pericardial effusion of 2mm. An appropriate treatment plan was formulated for the diagnosis of myocarditis, eventually the patient recovered within ten days. BNT162b2 mRNA vaccine was felt to cause the aforementioned condition since no other etiology could be identified. Although it is known that BNT162b2 may induce myocarditis, myositis concomitant myocarditis appears to be a very rare adverse effect of this vaccine.

(1) Objective: This review paper aims to discuss multiple aspects of cerebral venous thrombosis (CVT), including epidemiology, etiology, pathophysiology, and clinical presentation. Different neuroimaging methods for diagnosis of CVT, such as computer tomography CT/CT Venography (CTV), and Magnetic Resonance Imaging (MRI)/MR Venography (MRV) will be presented. (2) Methods: A literature analysis using PubMed and the MEDLINE sub-engine was done using the terms: cerebral venous thrombosis, thrombophilia, and imaging. Different studies concerning risk factors, clinical picture, and imaging signs of patients with CVT were examined. (3) Results: At least one risk factor can be identified in 85% of CVT cases. Searching for a thrombophilic state should be realized for patients with CVT who present a high pretest probability of severe thrombophilia. Two pathophysiological mechanisms contribute to their highly variable clinical presentation: augmentation of venular and capillary pressure, and diminution of cerebrospinal fluid absorption. The clinical spectrum of CVT is frequently non-specific and presents a high level of clinical suspicion. Four major syndromes have been described: isolated intracranial hypertension, seizures, focal neurological abnormalities, and encephalopathy. Cavernous sinus thrombosis is the single CVT that presents a characteristic clinical syndrome. Non-enhanced CT (NECT) of the Head is the most frequently performed imaging study in the emergency department. Features of CVT on NECT can be divided into direct signs (demonstration of dense venous clot within a cerebral vein or a cerebral venous sinus), and more frequently indirect signs (such as cerebral edema, or cerebral venous infarct). CVT diagnosis is confirmed with CTV, directly detecting the venous clot as a filling defect, or MRI/MRV, which also realizes a better description of parenchymal abnormalities. (4) Conclusions: CVT is a relatively rare disorder in the general population and is frequently misdiagnosed upon initial examination. The knowledge of wide clinical aspects and imaging signs will be essential in providing a timely diagnosis.

To compare the effectiveness of a single exercise session with manual therapy techniques in the segments of the upper cervical spine (C0-1, C1-2 and C2-3), against a single exercise session in patients with chronic neck pain and mobility deficits in the upper cervical spine.

The aim of this randomized, controlled trial was to determine whether children undergoing otolaryngological procedures (adenoidectomy, adenotonsillotomy, or tonsillectomy) benefit from pre-emptive analgesia in the postoperative period.