First‐in‐human phase I study of E7090, a novel selective fibroblast growth factor receptor inhibitor,in patients with advanced solid tumors

Fibroblast growth factor receptors (FGFR) are a family of transmembrane receptor tyrosine kinases involved in regulating cellular processes. FGFR mutations are implicated in oncogenesis, representing therapeutic potential in the form of FGFR inhibitors. This phase I, first‐in‐human study in Japan evaluated safety and tolerability of E7090, a potent selective FGFR1‐3 inhibitor, in patients with advanced solid tumors. Dose escalation (daily oral dose of 1‐180 mg) was carried out to assess dose‐limiting toxicity (DLT), maximum tolerated dose, and pharmacokinetics. Pharmacodynamic markers (serum phosphate, fibroblast growth factor 23, and 1,25‐(OH)₂‐vitamin D) were also evaluated. A total of 24 patients refractory to standard therapy or for whom no appropriate treatment was available were enrolled. No DLT were observed up to the 140‐mg dose; one patient in the 180‐mg cohort experienced a DLT (increased aspartate aminotransferase/alanine aminotransferase, grade 3). The maximum tolerated dose was not reached. Dose‐dependent increases in the maximum concentration and area under the curve from time 0 to the last measurable concentration were observed up to 180 mg. Dose‐dependent increases were observed in all pharmacodynamic markers and plateaued at 100‐140 mg, indicating sufficient FGFR pathway inhibition at doses ≥100 mg. In conclusion, E7090 showed a manageable safety profile with no DLT at doses ≤140 mg. Maximum tolerated dose was not determined. The recommended dose for the follow‐up expansion part, restricted to patients with tumors harboring FGFR alterations, was determined as 140 mg, once daily.     

Atopic dermatitis disease registry in Japanese adult patients with moderate to severe atopic dermatitis (ADDRESS‐J): Baseline characteristics,treatment history and disease burden

Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and long‐term disease control in the Japanese population. ADDRESS‐J is a non‐interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS‐J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0–4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient‐reported outcomes and current AD treatments. The registry patients’ median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0–72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0–10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments.     

Clinical features of 22q11.2 deletion syndrome related to hearing and communication

Abstract

Background: Individuals with 22q11.2 deletion syndrome (22q11.2DS) exhibit various phenotypes.

Objective: To compare the clinical and otorhinolaryngological features of Japanese patients with 22q11.2DS with those of patients reported in Western literature.

Materials and methods: We retrospectively assessed the medical records of 17 Japanese patients with 22q11.2DS and compared our findings with previously reported findings in Western literature.

Results: Hearing loss was the most frequent complaint (n?=?8, 47%), followed by articulation disorders and/or nasopharyngeal closure failure (n?=?4, 24%) and language development delay (n?=?2, 12%). Ten patients (59%) had hearing loss regardless of the chief complaint (total 15 ears – mild, 9; moderate, 6). Four patients had bilateral hearing loss. One patient (6%) underwent tympanostomy tube placement for refractory exudative otitis media, another (6%) underwent myringoplasty, and three patients (18%) underwent tympanoplasties for chronic otitis media or middle ear malformation. Previous studies in Western countries reported similar results in terms of frequency of hearing loss, severity of hearing loss, and the percentage of middle ear malformations.

Conclusions: The otorhinolaryngological characteristics of Japanese patients with 22q11.2DS were similar to those in Western countries. Hearing loss was primarily caused by disorders like otitis media and middle ear malformation.

Significance: Our findings may aid treatment planning for Asian patients with 22q11.2DS.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

iPhone charger-induced chemical burn from overnight contact with sweat: Two cases

Smartphones have become essential devices in modern society. The coverage rate of smartphones in 2017 in Japan was 75% according to the Ministry of Internal Affairs and Communications. The iPhone is one of the most well-known smartphone brands. According to the manufacturer of iPhones (Apple), more than 200 million iPhones had been sold worldwide by 2017. These devices are often charged at night-time, especially while being used in bed. There are only three reports of smartphone charger-induced skin damage. We present two new cases of skin ulcers induced by an iPhone charger. The iPhone’s “lightning cable” has electrodes outside, and we found that this can present a higher risk of causing a skin injury compared with other types of phone chargers. We also investigated the mechanism of the skin ulcers caused by the iPhone charger. The results indicated that these ulcers were chemical burns rather than an electrical injury or heat-induced burn.     

Cecal Volvulus Resolved Spontaneously

Cecal volvulus is an uncommon cause of colonic obstruction. First-line treatment for cecal volvulus is surgery, as nonoperative management is rarely achievable. We herein report an extremely rare case of a patient with spontaneously resolved cecal volvulus; no recurrence occurred without elective surgery. A 47-year-old woman presented with acute lower abdominal pain. She was misdiagnosed with small bowel obstruction and treated conservatively. A few hours later, she was correctly diagnosed with cecal volvulus. Subsequently, her symptoms and computed tomography findings of cecal volvulus completely disappeared. She refused elective surgery, but no recurrence occurred during five months of follow-up.     

MAGI-2 orchestrates the localization of backbone proteins in the slit diaphragm of podocytes

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Silencing of the foot-and-mouth disease virus internal ribosomal entry site by targeting relatively conserved region among serotypes

Virus Genes - Foot-and-mouth disease (FMD) is a host-restricted disease of cloven-hoofed animals, such as cattle and pigs. There are seven major serotypes of FMD virus that exhibit high antigenic...     

3D Printing of Tough Gels Having Tunable Elastic Modulus from the Same Pre‐Gel Solution

A gel forming method with sections with different elastic modulus is developed. Gels with hardness distribution are formed from one base gel material by adjusting the crosslinking density of the polymer network using a 3D gel printer. It is confirmed that hardness is arranged as designed by using mixing rules of composite materials. Furthermore, as a prototype of a practical gel application, a gel finger model having a soft‐fleshy part and a hard‐bony part is printed. 3D printing of an organ model that reproduces a realistic feel that takes not only the shape of the organ but also the distribution of hardness into consideration may become possible.