Rejected

X-linked hypophosphatemia (XLH) causes significant burden in pediatric patients in spite of maintained treatment with phosphate supplements and vitamin D derivatives. Administration of burosumab has shown promising results in clinical trial but studies assessing its effect in the everyday practice are missing. With this aim, we analyzed the response to one-year treatment with burosumab, injected subcutaneously at 0.8 mg/kg every 2 weeks, in five children (three females) aged from 6 to 16 years, with genetically confirmed XLH. Patients were being treated with phosphate and vitamin D analogs until the beginning of burosumab treatment. In all children, burosumab administration led to normalization of serum phosphate in association with marked increase of tubular reabsorption of phosphate and reduction of elevated serum alkaline phosphatase levels. Baseline height of patients, from -3.56 to -0.46 SD, increased in the three prepubertal children (+0.84, +0.89, and +0.16 SD) during burosumab treatment. Growth improvement was associated with reduction in body mass index (-1.75, -1.47, and -0.17 SD, respectively), suggesting a salutary effect of burosumab on physical activity and body composition. Burosumab was well-tolerated, mild local pain at the injection site and transient and mild headache following the initial doses of burosumab being the only reported undesirable side effects. No patient exhibited hyperphosphatemia, progression of nephrocalcinosis, worsening of metabolic control or developed hyperparathyroidism. Mild elevation of serum PTH present at the beginning of treatment in one patient 4 was not modified by burosumab administration. These results indicate that in the clinical setting, beyond the strict conditions and follow-up of clinical trials, burosumab treatment for 1 year exerts positive effects in pediatric patients with XLH without major adverse events.

Pharmacological interventions remain the cornerstone of chronic pain treatment; however, nearly 40% of the prescription medicines are not taken as prescribed. The present study aims at understanding and describing non-adherence from the perspective of chronic pain patients during a 1-year follow-up study.

Hydatid disease (HD) is caused by Echinococcus granulosus and is endemic in many parts of the world. This parasitic tapeworm can produce cysts in almost every organ of the body, with the liver and lung being the most frequently targeted organs. The spleen and mesentery are unusual locations. We report a case of simultaneous huge splenic and mesenteric hydatid cyst in a 91-year-old male patient. The patient was presented with chronic abdominal pain, increased frequency of defecation, and typical history of animal contact (cattle, sheep, and dogs). After performing imaging studies, he was diagnosed with a simultaneous huge spleen and pelvic mesentery hydatid cyst that was managed surgically by splenectomy, pelvic mesenteric cyst deroofing, and partial cystectomy.

Currently, the only approved hepatitis C virus (HCV) treatment for children aged <12 years is pegylated-interferon plus ribavirin. In an open-label study, we evaluated the safety and efficacy of sofosbuvir plus ribavirin for 12 weeks in children aged 3 to <12 years chronically infected with genotype 2 or for 24 weeks in patients with genotype 3. Patients aged 3 to <6 years weighing <17 kg received sofosbuvir 150 mg, and patients aged 3 to <6 years weighing ≥17 kg and all patients aged 6 to <12 years received sofosbuvir 200 mg once daily. Intensive pharmacokinetic sampling conducted in each age group confirmed the appropriateness of sofosbuvir doses. For all patients, ribavirin dosing was determined by baseline weight (up to 1400 mg/day, two divided doses). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). 54 patients were enrolled (41 aged 6 to <12 years and 13 aged 3 to <6 years). Most were treatment-naive (98%) and infected perinatally (94%). All but one patient achieved SVR12 (53/54, 98%, 95% CI 90-100%). The patient who did not achieve SVR12 was a 4 year-old who discontinued treatment after three days due to 'abnormal drug taste'. The most commonly reported adverse events in patients aged 6 to <12 years were vomiting (32%) and headache (29%) and in patients aged 3 to <6 years, vomiting (46%) and diarrhea (39%). One 3 year-old patient had a serious adverse event of accidental ribavirin overdose requiring hospitalization for monitoring; this patient completed treatment and achieved SVR12. CONCLUSION: Sofosbuvir plus ribavirin was well-tolerated and highly effective in children aged 3 to <12 years with chronic HCV genotype 2 or 3 infection. This article is protected by copyright. All rights reserved.

The peak prevalence of migraine occurs in women of reproductive age, and women experience a higher burden of migraine symptoms and disability compared to men. This increased burden of migraine in women is related to both developmental and temporally variable activational effects of female sex hormones. Changing levels of female sex hormones affect the expression of migraine during pregnancy, and, to a lesser degree, lactation, and are the mechanism underlying menstrual migraine. This review describes the evidence for sex differences in the expression of migraine across the reproductive epoch; reviews the epidemiology of migraine during pregnancy, lactation, and menses; and summarizes the available evidence for safety and efficacy of acute treatments during pregnancy and lactation and for menstrual migraine. Areas of controversy in treatment of migraine during pregnancy, including the use of magnesium, triptans vs butalbital combination medications, and onabotulinum toxin, are also explored.

In this systematic review and meta-analysis of psoriatic arthritis (PsA) studies, we pooled data from existing literature to (1) estimate the prevalence of mental health disorders in PsA patients and (2) compare disease activity in PsA patients with and without these comorbidities.

Neutrophils are peripheral immune cells that represent the first recruited innate immune defense against infections and tissue injury. However, these cells can also induce overzealous responses and cause tissue damage. Although the role of neutrophils activating the immune system is well established, only recently their critical implications in neuro-immune interactions are becoming more relevant. Here, we review several aspects of neutrophils in the bidirectional regulation between the nervous and immune systems. First, the role of neutrophils as a diffuse source of acetylcholine and catecholamines is controversial as well as the effects of these neurotransmitters in neutrophil's functions. Second, neutrophils contribute for the activation and sensitization of sensory neurons, and thereby, in events of nociception and pain. In addition, nociceptor activation promotes an axon reflex triggering a local release of neural mediators and provoking neutrophil activation. Third, the recruitment of neutrophils in inflammatory responses in the nervous system suggests these immune cells as innovative targets in the treatment of central infectious, neurological and neurodegenerative disorders. Multidisciplinary studies involving immunologists and neuroscientists are required to define the role of the neurons-neutrophils communication in the pathophysiology of infectious, inflammatory, and neurological disorders.

Postmenopausal osteoporosis is one of the most common types of osteoporosis resulting from estrogen deficiency in elderly women. Nonsteroidal anti-inflammatory drugs (NSAIDs) are important drugs for pain relief in patients with osteoporosis. In this study, we report for the first time that flufenamic acid, a clinically approved and widely used NSAID, not only has analgesic properties but also shows a significant effect in terms of preventing postmenopausal osteoporosis. Quantitative RT-PCR analysis showed that treatment with flufenamic acid significantly downregulated the genes associated with osteoclast differentiation. Meanwhile, RNA-sequencing and western blot analyses suggested that flufenamic acid could inhibit the bone resorption by suppressing the phosphorylation of MAPK pathways. Moreover, an ovariectomy (OVX)-induced bone-loss mouse model indicated that flufenamic acid might be a potent drug for preventing osteoporotic fractures, as verified by micro-CT scanning and histological analysis. Therefore, this study proposes an attractive and potent drug with analgesic properties for the prevention of postmenopausal osteoporosis.

Abdominal pain is a common cause for emergency department visits in the United States, and biliary tract disease is the fifth most common cause of hospital admission. Common causes of acute hepatobiliary include gallstones and its associated complications and multiple other hepatobiliary etiologies, including infectious, inflammatory, vascular, and neoplastic causes. Postoperative complications of the biliary tract can result in an acute abdomen. Imaging of the hepatobiliary tree is integral in the diagnostic evaluation of acute hepatobiliary dysfunction, and imaging of the biliary tree requires a multimodality approach utilizing ultrasound, computed tomography, nuclear medicine, and MR imaging.