Rejected

The innate immune system has an emerging role as a mediator of neuro-immune communication and a therapeutic target for itch. Toll-like receptor 3 (TLR3) plays an important role in itch, as shown in TLR3 knock-out mice. In this study, to evaluate effects of TLR3 inhibitors on histamine-independent itch, we used two kinds of isothiocyanate (ITC). Both phenethyl isothiocyanate (PEITC) and sulforaphane (SFN) inhibited Poly I:C (PIC)-induced signaling in the RAW264.7 cell line. We then investigated the anti-pruritic effect of these compounds on PIC- and chloroquine (CQ)-induced scratching behavior. PEITC and SFN both suppressed PIC-evoked scratching behavior in mice, and PEITC also inhibited CQ-induced acute itch. Finally, we examined the oxazolone-induced chronic itch model in mice. Surprisingly, oral dosing of both compounds suppressed scratching behaviors that were observed in mice. Our findings demonstrate that TLR3 is a critical mediator in acute and chronic itch transduction in mice and may be a promising therapeutic target for pruritus in human skin disorders. It is noteworthy that SFN has potential for use as an antipruritic as it is a phytochemical that is used as a supplement.

Urticaria is a heterogeneous inflammatory disorder that can be acute or chronic and is defined by the appearance of wheals, angioedema, or both. Very recently, the newest update and revision of the international European Academy of Allergy and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum/Asia Pacific Association of Allergy Asthma Clinical Immunology guideline for the definition, classification, diagnosis, and management of urticaria was published. It aims to help primary care physicians and specialists in the management of their patients with urticaria. The guideline applied the Grading of Recommendations Assessment Development and Evaluations approach to developing consensus recommendations. These recommendations were then discussed in a Delphi conference that included more than 250 specialists in the field, and they are endorsed by more than 50 international societies. Here, we highlight changes from previous versions of the international urticaria guideline and their impact on clinical practice.

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome characterized by acute or subacute onset of neurological symptoms (e.g., headache, seizure, confusion, vomiting, and diminished eyesight) and impaired endothelial barrier function of the cerebral circulation that leads to bilateral subcortical vasogenic edema, while exhibiting a "reversible" feature in most cases. Clinically, various predisposing or precipitating conditions have been identified, such as hypertension, autoimmune diseases, renal dysfunction/failure, preeclampsia/eclampsia, post-transplantation conditions, and certain therapeutic agents. Among several putative mechanisms, the immune activation hypothesis prevails, as up to 50% of patients with PRES harbor abnormalities related to autoimmunity, such as concurrent systemic lupus erythematosus. In this Review, we summarize the clinical and laboratory evidence that places PRES in the context of autoimmunity.

To study the feasibility and safety of One-Shot Dilatation (OSD), versus serial sequential dilatation in tubeless Percutaneous Nephrolithotomy (PCNL). One Hundred and Fifty patients were randomised into two groups; Group A (One-Shot Dilatation), Group B (Serial Dilatation). Twenty-one patients were excluded from the study. Detailed history was taken and full physical examination was performed. Pre-operative routine laboratory investigations were done. Also, non-contrast Computed Tomography of the Urinary Tract (CTUT) and plain urinary tract x-ray were done. Intra-operative assessments of dilatation, total operative, total fluoroscopy and fluoroscopy during dilatation durations were recorded, as well as estimated blood loss. Post-operatively haemoglobin, creatinine levels and CTUT were performed for all patients. Complications, as urinary leakage time, analgesic requirements and hospitalization time were measured. There were statistically significant differences in the intraoperative durations, where Group A had shorter dilatation time, fluoroscopy time during dilatation and total operative time. Group B had a higher complications rate than Group A; 37.9%, 11.3%, respectively. Also, Group B showed haemoglobin drop by 0.44 mg/dl higher than Group A. More doses of analgesia were required for Group B. Hospitalization time and rate of urinary leakage were both in favour of Group A. For patients undergoing Tubeless PCNL, we have concluded that one-shot dilatation seems to be a safer and more feasible technique than Serial dilatation.

Atopic Dermatitis (AD) is a highly pruritic, chronic-recurrent inflammatory skin condition associated with erythematous lesions that affect a significant proportion of the population. Although AD is a non-communicable disease, it can cause pain, unbearable itchiness, sleep disturbance, loss of work productivity, and reduced quality of life. As a heterogeneous disease, AD is influenced by multiple genes and environmental triggers. As such, it is imperative to gain a deeper insight into the intricate gene-environment relationship that results in the manifestation of AD.

Hydatid cyst is an uncommon parasitic disease caused by larval stages of Echinococcus granulosus. The liver is the most frequently affected organ followed by the lungs and the spleen. Intracranial hydatid cysts are uncommon and occur mostly in supratentorial region. It can present with nonspecific symptoms and can be difficult to diagnose, thus regardless of unusual clinical presentation and unusual location of cystic lesion in brain, it is crucial to keep hydatid cyst as one of the differentials. We describe a case of a 28-year-old male who presented with headache, vomiting and cerebellar signs. MRI showed multiple cystic lesions in posterior fossa with asymmetrically dilated posterior horn of left lateral ventricle. Biopsy from one of the cystic lesions from posterior fossa was performed which confirmed the diagnosis of hydatid cyst. Patient was started on Albendazole and subsequently planned for surgery.

Epidermal Nevus Syndrome (ENS), also known as Cutaneous Skeletal Hypophosphatemia Syndrome or Linear Sebaceous Nevus Syndrome, is caused by a mosaic somatic mutation of (Rat Sarcoma genes) which leads to abnormally elevated levels of fibroblast growth factor 23 (FGF23). FGF23 is a major regulator in phosphate homeostasis. There are multiple disorders, along with Epidermal Nevus Syndrome (ENS), that result in unusually high circulating levels of FGF23. This increase ultimately leads to renal phosphate wasting and reduced levels of 1,25-dihydroxy vitamin D. Across these disorders, the clinical symptoms are similar and often include osteomalacia (hypophosphatemic rickets in children), muscle weakness, fatigue, joint deformities, bone pain, and fractures. Burosumab (KRN23), is an IgG1 monoclonal antibody that binds to the FGF23 receptor and inhibits the activity of FGF23. This leads to an increase in serum phosphate levels. Burosumab emerged as a potential therapy in FGF23 overactivity disorders. Burosumab was successful in the treatment of X-linked hypophosphatemia (XLH) and is now FDA-approved for its treatment. Studies have indicated that Burosumab therapy in subjects with XLH consistently increases and sustains serum phosphorus levels and tubular reabsorption of phosphate without a major impact on urine calcium levels or vitamin D metabolism. We studied the effect of Burosumab treatment in a single pediatric patient with Epidermal Nevus Syndrome. Serum phosphorus rose gradually as we titrated the dose of Burosumab upwards. During treatment, a persistent elevation of parathyroid hormone levels was noted along with a persistent elevation of serum calcium. We presumed the patient had tertiary hyperparathyroidism. However, after the removal of three parathyroid glands, the pathology came back with a single enlarged parathyroid adenoma. Subsequently, his calcium and PTH, and phosphorus levels stabilized while taking only Burosumab. ClinicalTrials.gov NCT04320316.

Variations of the foramina located at the skull base can have direct clinical implications. For example, transcutaneous approaches to the trigeminal nerve using long spinal needles for treatment of trigeminal neuralgia can inadvertently enter such variant foramina and potentially result in hemorrhage. Therefore, knowledge of such variant foramina is important to the clinician treating or diagnosing patients based on imaging of this region. We report an adult male skull found to have unusual foramina located at the skull base. The foramina were located approximately 3.1 cm lateral to the plane of the foramen rotundum and foramen ovale. The left foramen had a diameter of 0.82 mm and the right foramen had a diameter of 0.77 mm. Both foramina opened up just medial to the sphenotemporal suture into the roof of the infratemporal fossa. Additionally, each foramen was the most lateral of a larger collection of foramina found to exit the skull base but confluent with the diploic space of the greater wind of the sphenoid and not with the floor of the middle cranial fossa. This group of openings, including the most lateral which communicated with the middle cranial fossa, were lateral to the lateral plate of the pterygoid process. Knowledge of variant foramina of the skull base is important to clinicians treating patients with pathology of this region. To our knowledge, foramina as described herein have not been previously reported in the extant medical literature.