Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials.

BACKGROUND: Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144). OBJECTIVES: The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials. METHODS: The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to < 12 and 12 to < 18 years) and bodyweight (< 25 kg, 25 to < 50 kg, and ≥ 50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125). RESULTS: A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to < 12 years subgroup and 12 to < 18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the < 25 kg, 25 kg to < 50 kg, and ≥ 50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (< 12 years: 11.8/100 PY; ≥ 12 years: 42.4/100 PY) and bodyweight (< 25 kg: 22.8/100 PY; 25 kg to < 50 kg: 19.0/100 PY; ≥ 50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab. CONCLUSIONS: Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients. GOV IDENTIFIER: NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023.

Primary Synovial Sarcoma of the Thyroid Gland: A Case Report and Review of Literature.

Synovial cell sarcoma (SS) is a rare soft tissue sarcoma which can occur at any site in the body. SS arise from pluripotent mesenchymal cells and can occur in the head and neck region. We present a case of primary SS of the thyroid gland in a 47- year- old male and discuss the diagnostic and management challenge. A literature review of this rare entity was done.

IFN-α and TNF-α serum levels and their association with disease severity in Egyptian children and adults with alopecia areata.

BACKGROUND: Alopecia areata (AA) is an autoimmune skin disease characterized by abnormal levels of several cytokines, such as interferon alpha (IFN-α) and tumor necrosis factor-alpha (TNF-α), which are T-helper type 1 cytokines that have important roles in the pathogenesis of AA. The aim of our study was to correlate circulating IFN-α and TNF-α levels with disease severity, activity, and clinical type in patients with AA and to evaluate the relationship between the two cytokines. METHODS: We investigated serum IFN-α and TNF-α levels in 72 patients with AA (35 children and 35 adults) and 75 healthy control individuals (34 children and 41 adults) using the enzyme-linked immunosorbent assay (ELISA) technique. We evaluated AA severity using the Severity of Alopecia Tool (SALT) and determined the activity based on dermoscopic criteria of disease activity. RESULTS: Serum IFN-α and TNF-α concentrations were significantly higher in the patients than in the controls. There was a significant positive correlation between serum IFN-α and TNF-α levels in all patients with alopecia areata, as well as between serum TNF-α levels and disease severity in all patients and in children. CONCLUSIONS: Our results support the association between IFN-α and TNF-α levels and AA and suggest that TNF-α might be related to disease severity.

Second branchial cleft fistula/sinus tract endoscopy: a novel intraoperative technique assisting complete surgical resection.

PURPOSE: Second branchial cleft (BC) sinus/fistula anomalies usually present in children. Their definitive management requires complete tract surgical excision, which necessities accurate extension assessment. Our aim is to propose and describe a novel intraoperative endoscopic technique that can help in evaluating the exact BC anomaly tract extension and overcome disadvantages of currently used methods including imaging and intraoperative methylene blue tract injection. METHODS: The innovative intraoperative endoscopic technique involves performing BC sinus/fistula tract intraluminal endoscopy utilizing miniature 1.3 or 1.6 mm all-in-one semi-rigid endoscopes as well as other accessory equipment currently available and used for sialendoscopy for delineation of exact tract extension followed by a complete standard surgical excision tailored to and assisted by the endoscopic procedure. RESULTS: This novel endoscopic technique was used successfully in five children (age range 8-16 years) presenting with unilateral or bilateral congenital second BC discharging fistula/sinus tracts in the neck. Intraoperative endoscopic assessment took 10-15 min and confirmed the exact tract extension and nature in all patients without complications. Five fistulas and two sinuses were identified and completely surgically resected. No recurrence has been observed after a median follow-up of 29 (range 13-45) months. CONCLUSION: Intraoperative second BC fistula/sinus tract endoscopy could help in accurately assessing anomaly extension, thereby assisting in complete surgical excision. This innovative novel endoscopic technique could avoid disadvantages of currently used methods, especially regarding radiation exposure required for imaging children in whom this anomaly usually presents.

Noncultured Extracted Hair Follicle Outer Root Sheath Cell Suspension versus Noncultured Epidermal Cell Suspension in the Treatment of Stable Vitiligo.

BACKGROUND: Various treatment modalities exist for vitiligo, yet none of them are curative. Vitiligo is still considered a challenging disease to manage. Surgical treatment offers an excellent option for patients with stable vitiligo, especially those who fail to respond to medical treatment. Cell suspension techniques carry the advantage of covering large surface areas. OBJECTIVE: To compare noncultured extracted hair follicle outer root sheath cell suspension (NCORSHFS) and noncultured epidermal cell suspension (NCES) in producing repigmentation. SUBJECTS AND METHODS: Twenty patients were randomly allocated into two groups. They were objectively evaluated for the extent of repigmentation (after 1, 2, and 3 months), complications, cosmetic outcome, and satisfaction. RESULTS: In NCORSHFS group, 10% showed excellent pigmentation, 20% showed good pigmentation, 50% fair, and 20% poor pigmentation. In NCES group, 10% showed excellent pigmentation, 10% good pigmentation, 40% fair, and 40% poor pigmentation. This difference was not statistically significant. Excellent color match was observed in 80% of NCORSHFS and in 70% of NCES. Donor area complications were absent in NCORSHFS group, whereas in NCES, mild scarring in 20% and hyperpigmentation in 40% of patients was observed. The difference in patients' satisfaction between the two groups was not statistically significant. CONCLUSION: Both NCORSHFS and NCES are effective in producing good repigmentation with perfect color match and patients' satisfaction. NCORSHFS has no donor area complications because it is a scarless procedure.

Expression levels of transcription factor PU.1 and interleukin-9 in atopic dermatitis and their relation to disease severity and eruption types.

BACKGROUND: The role of immunological factors in atopic dermatitis (AD) pathogenesis is well established. T-helper (TH) cells are central in AD pathogenesis. A relatively new subset of T cells, Th9 cells, was shown to be involved in the development of allergic asthma and allergic rhinitis, while its role in AD is still to be investigated. This study aimed to measure gene expression levels of interleukin-9 (IL-9) and PU.1, and to examine relationships with disease severity, serum IgE, and eruption types in AD patients. METHODS: The study enrolled 30 AD patients, 30 psoriasis patients, and 30 healthy subjects. The severity of AD was assessed using the SCORAD index. IL-9 and PU.1 expressions were measured by using real-time quantitative polymerase chain reaction (RQ-PCR). Serum IgE was measured by IgE (human) enzyme-linked immunosorbent assay (ELISA) Kit. RESULTS: IL-9 and PU.1 gene expressions were significantly higher in AD patients than in controls (P1 = 0.007, P2 < 0.001, respectively). In the atopic dermatitis patients, expression of IL-9 and PU.1 were significantly positively correlated with SCORAD index (P1 = 0.004, P2 = 0.002) and clinically with erythema and edema scores. IL-9 and PU.1 expressions were positively significantly correlated (P = 0.005) and positively correlated with serum IgE in the AD group (P1 = 0.017, P2 = 0.023). No significant difference was noted between AD patients with or without histories of other atopies regarding expression levels of IL-9 and PU.1 (P1 = 0.677, P2 = 0.135). CONCLUSIONS: PU.1 and IL-9 may play a role in AD pathogenesis and relate to disease severity and clinical eruption types.

Partial laser arytenoidectomy in the management of bilateral vocal fold immobility: a modification based on functional anatomical study of the cricoarytenoid joint.

OBJECTIVE: To establish the anatomical relationships between the arytenoid and cricoid cartilages and apply these findings to design an arytenoidectomy based on a sound anatomical basis. STUDY DESIGN: In 50 patients the length of the vocal process and the distance between vocal process tip and upper border of the cricoid cartilage were endoscopically measured. Twenty-five total laryngectomy specimens were sagittally and axially sectioned to verify the position of the arytenoids and their relation to the cricoid. The anatomical findings led to the design of laser partial arytenoidectomy and cordotomy (L-PAC), which was used in 45 patients with bilateral cord paralysis in adduction. RESULTS: The anatomical findings showed that the cricoarytenoid joint did not contribute to the airway in any of the measured specimens. Using L-PAC, 100% of the patients were decannulated and no patient needed a postoperative tracheostomy at any time. Only 3 patients experienced minimal postoperative aspiration to liquids (6.7%). Reasonable phonation was achieved as regarded by a speech analysis battery. Three patients (6.7%) needed a contralateral L-PAC. CONCLUSIONS: The shape of the cricoid and the location of its axis of maximum width ought to dictate the technique of glottic widening to be used in bilateral cord immobility in adduction. The present extra-articular technique, L-PAC, showed its versatility in providing an effective balance between the protective, the respiratory, and to lesser extent the phoniatory functions.

The use of mitomycin-C for respiratory papillomas: clinical, histologic and biochemical correlation.

OBJECTIVE: To assess the clinical effects of mitomycin-C (MMC) on human papilloma virus (HPV)-infected tissues of the airway. METHODS: We included 10 patients with previous histologic diagnosis of recurrent respiratory papillomas (RRP) in this prospective study, conducted at the Department of Otolaryngology-Head and Neck Surgery, University of Alexandria, Egypt, between January 2000 and December 2002. Under general anesthesia, each patient underwent laser excision of all visible papillomas, followed by topical application of 1 cc of 0.5 mg/ml MMC. The procedure was repeated weekly until no visible papillomas could be microscopically detected. We histopathologically studied the obtained specimens and tested for the presence of HPV DNA using polymerase chain reaction (PCR) technique. We collected blood samples from all patients and from another 10 healthy volunteers for determination of serum interleukin-2 (IL-2) level using enzyme-linked immunosorbent assay technique. RESULTS: We achieved clinical remission in 8 of the patients (80%), a fact that was confirmed histopathologically and by PCR data. The mean serum IL-2 levels+/- SD was significantly lower in papilloma patients (83.6+/- 28.83 pg/ml) than in control subjects (196.3+/- 42.46 pg/ml) (p<0.01). Among patients with RRP, serum IL-2 levels+/-SD was lower in initial samples (83.6+/- 28.83) than follow-up (95.7+/- 27.98 and 112.3+/- 33.8 and 129.4+/- 34.04) and remission samples (154+/- 37.84 pg/ml) CONCLUSION: Our result suggests that topical application of MMC may act adjunctively to laser surgery for RRP.

Partial laser arytenoidectomy in the management of bilateral vocal fold immobility. A modification based on functional anatomical study of the cricoarytenoid joint.

OBJECTIVES: To establish the anatomical relationships of the arytenoid and cricoid cartilages and apply these findings to design an arytenoidectomy based on a sound anatomical basis. METHODS: We prospectively conducted this study between 1996 and 2002 at the Main University Hospital of Alexandria, Egypt. In 50 patients, we endoscopically measured the length of the vocal process and the distance between the vocal process tip and upper border of the cricoid cartilage. We sagittally and axially sectioned 25 total laryngectomy specimens to verify the position of the arytenoids and their relation to the cricoid. The anatomical findings led to the design of a laser partial arytenoidectomy and cordotomy (L-PAC), which we used in 45 patients with bilateral cord paralysis in adduction. RESULTS: The anatomical findings showed that the cricoarytenoid joint did not contribute to the airway in any of the measured specimens. Using L-PAC, we decannulated 100% of the patients and no patient needed postoperative tracheostomy at any time. Only 3 patients experienced minimal postoperative aspiration to liquids (6.7%). We achieved reasonable phonation as assessed by a speech analysis battery. However, 3 patients (6.7%) needed contralateral L-PAC. CONCLUSION: The present extra-articular technique, L-PAC, showed its superiority to previous endoscopic or transcervical complete arytenoidectomy techniques in providing an effective balance between the protective, respiratory, and to a lesser extent the phonatory functions.