Rejected

Atopic dermatitis (AD) is characterized by dominance of T helper type 2 (Th2) cytokines associated with infiltration of inflammatory cells. Th2 cytokines, especially IL-13, also contribute to fibrotic remodeling of the skin, as shown in murine AD models. Dupilumab is an interleukin (IL)-4 receptor-α antagonist, which blocks both IL-4 and IL-13 signaling, and is approved for the treatment of moderate to severe AD. Dupilumab is effective for treating AD symptoms such as eczema and pruritus; however, its efficacy for skin fibrosis remains unknown. We herein report that dupilumab successfully treated atypical AD-associated plaques with marked fibrosis on histology. This article is protected by copyright. All rights reserved.

Netrin-1 has been shown to play a role in the initiation of atherosclerosis in mice models. However, little is known about the role of Netrin-1 in humans. We set out to study whether Netrin-1 is associated with different stages of atherosclerosis. Approach and Results: Plasma Netrin-1 levels were measured in different patient cohorts: (1) 22 patients with high cardiovascular risk who underwent arterial wall inflammation assessment using positron-emission tomography / computed tomography, (2) 168 patients with a positive family history of premature atherosclerosis in whom coronary artery calcium scores were obtained, and (3) 104 patients with chest pain who underwent coronary computed tomography angiography imaging to evaluate plaque vulnerability and burden. Netrin-1 plasma levels were negatively correlated with arterial wall inflammation (β, -0.01 [95% CI, 0.02 to -0.01] , 0.61; <0.0001), and concentrations of Netrin-1 were significantly lower when atherosclerosis was present compared with individuals without atherosclerosis (28.01 versus 10.51 ng/mL, <0.001). There was no difference in Netrin-1 plasma concentrations between patients with stable versus unstable plaques (11.17 versus 11.74 ng/mL, =0.511). However, Netrin-1 plasma levels were negatively correlated to total plaque volume (β, -0.09 [95% CI, -0.11 to -0.08] , 0.57, <0.0001), calcified plaque volumes (β, -0.10 [95% CI, -0.12 to -0.08] , 0.53; <0.0001), and noncalcified plaque volumes (β, -0.08 [95% CI, -0.10 to -0.06] , 0.41; <0.0001). Treatment of inflammatory stimulated endothelial cells with plasma with high Netrin-1 level resulted in reduced endothelial inflammation and consequently, less monocyte adhesion.

Stress-induced hyperalgesia is a problematic condition that lacks an effective therapeutic measure, and hence impairs health-related quality of life. The regulation of stress by oxytocin (OT) has overlapping effects on pain. OT can alleviate pain directly mainly at the spinal level and the peripheral tissues. Additionally, OT plays an analgesic role by dealing with stress and fear learning. When OT relieves stress by targeting the prefrontal brain regions and the hypothalamic-pituitary-adrenal axis, the body's sensitivity to pain is attenuated. Meanwhile, OT facilitates fear learning and may, in turn, enhance the anticipatory actions to painful stimulation. The unique therapeutic value of OT in patients suffering from stress and stress-related hyperalgesia conditions is worth considering. We reviewed recent advances in animal and human studies involving the effects of OT on stress and pain, and discussed the possible targets of OT within the descending and ascending pathways in the central nervous system. This review provides an overview of the evidence on the role of OT in alleviating stress-induced hyperalgesia.

To compare the efficacy of low dose fentanyl infusion and 24% oral sucrose in providing optimal pain relief during laser for retinopathy of prematurity (ROP), we enrolled fifty-eight spontaneously breathing preterm infants undergoing laser. The preterm infants were randomized to either fentanyl infusion (1 mcg/kg/hr) or 24% oral sucrose (2 ml). We evaluated and compared the proportion of time spent crying during the procedure, salivary cortisol before and after the procedure, premature infant pain profile- revised (PIPP-R) scores during the procedure, apnoea during and after the procedure, need for mechanical ventilation, and feed intolerance and urinary retention 24 h after the procedure between the two groups. We found that the proportion of time spent crying during the procedure was significantly less in the fentanyl group [62.5% (50.7-74.2) vs 73.8% (55.6-83.4); P = 0.02]. Average PIPP-R score during the procedure was significantly less in the fentanyl group [7.2 vs 9.0; (mean difference of – 1.8; P = 0.01)]. There was no difference in other outcomes between the two groups.Conclusion: During laser for ROP, low dose fentanyl infusion was found to be efficacious in reducing pain as compared with 24% sucrose.What is Known:• Preterm infants undergoing laser photocoagulation for ROP suffer significant amount of pain.• Standard of care for pain relief in infants undergoing laser therapy in developed countries is general anesthesia (GA) or combination of sedation, analgesia, and paralysis (SAP).What is New:• During laser photocoagulation for ROP, fentanyl infusion at low dose (1 mcg/kg/hr) is efficacious in reducing pain as compared to 24% oral sucrose.

Oxycodone tamper resistant (OTR) is a new extended-release abuse-deterrent formulation providing improvements in the tamper resistant characteristics. This study aimed to investigate the pharmacokinetic properties of the new OTR tablets and evaluate the bioequivalence of oxycodone from OTR and the original extended release (ER) formulation tablets administered with an opioid antagonist in patients with chronic pain.

The os subfibulare is usually asymptomatic and found incidentally on radiographs. However, sometimes it may cause subfibular pain and may be associated with chronic lateral ankle instability (CLAI). We hypothesized that os subfibulare could interrupt the talofibular space causing impingement, resulting in chronic pain and functional instability around the lateral malleolus. The purposes of this study were to analyze morphologic characteristics of os subfibulare, and to evaluate the clinical significance of the os subfibulare in patients with CLAI.

Research using a categorical-polythetic classification system for mental illness has raised concern regarding the validity of categorical classification systems. Recent efforts suggest psychopathology is better understood from a dimensional framework, though there has been varying evidence of a somatization factor. The current investigation seeks to produce and validate a dimensional model of psychopathology, with a particular emphasis on the placement of somatization, across three nonoverlapping medical samples. Using a bariatric surgery seeking sample (n = 1,268), a spine surgery/spinal cord stimulator seeking sample (n = 1,711), and a chronic pain treatment seeking sample (n = 1,388), a dimensional model of psychopathology was replicated across all three samples using a dimensional measure of psychopathology (the Minnesota Multiphasic Personality Inventory-2-Restructured Form [MMPI-2-RF]). Clear evidence of a separate somatization factor was found in addition to broad internalizing, externalizing, and social detachment factors. Constructs assessable with the model yielded good convergent and discriminant validity coefficients with external criteria, and further supported the presence of a higher-order somatization construct. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

We treated an extremely rare case of osteoid osteoma of the pisiform. Pisiform hypertrophy caused persistent pain and ulnar nerve irritation at Guyon's canal after the initial trauma. The re-enlargement of the pisiform attracted our attention allowing us to ultimately diagnose the condition as osteoid osteoma and treat the patient with a successful clinical result.

: Pituitary apoplexy (PA) is a rare but potentially life-threatening condition that may require urgent surgical intervention. : We report a case of a patient who was initially diagnosed with meningoencephalitis (ME) based on clinical presentation and cerebrospinal fluid (CSF) analysis, but was eventually diagnosed with PA. We present a summary of other cases reported in the literature of PA mimicking ME and analyze their clinical features and CSF findings. : Among all 22 PA cases reviewed, headache was the most commonly reported symptom. Hypopituitarism was seen in 94.4% of the cases; of these, panhypopituitarism was noted in 38.9%. The sensitivity of magnetic resonance image (MRI) for detecting PA was 94.7%, much higher than that of computed tomography (CT), which was only 31.6%. Neutrophil predominant pleocytosis was present in all cases with a neutrophil percentage ranging from 73% to 98%. CSF leukocyte count was less than 1000/ul in 86% of the cases. CSF erythrocytosis was seen in 92.9% of the cases with a count ranging from 15 to 2030/ul. Elevated CSF protein was present in all cases with a range of 69.8 to 239 mg/dl. CSF glucose level varied with a range between 12 and 136 mg/dl; the level was greater than 40 mg/dl in 73% of the cases. : PA tends to be misdiagnosed as ME due to the similarities of semiology and CSF findings. PA should be considered in refractory acute headache cases, especially those with visual and endocrine abnormalities. Early recognition and treatment may lead to significant reduction in morbidity and mortality.