Secukinumab shows high and sustained efficacy in nail psoriasis: 2.5-year results from the randomized placebo-controlled TRANSFIGURE study.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, a cornerstone cytokine in psoriasis, has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. OBJECTIVES: To report the long-term (2·5-year) efficacy and safety of secukinumab in nail psoriasis. METHODS: TRANSFIGURE, a double-blind, randomized, placebo-controlled, parallel-group, multicentre phase IIIb study in 198 patients, investigated secukinumab 150 mg and 300 mg in patients with moderate-to-severe nail psoriasis. RESULTS: At week 16, the primary endpoint Nail Psoriasis Severity Index (NAPSI) was met, demonstrating superiority of secukinumab to placebo. The effect was sustained over 2·5 years with a large benefit for nail clearance, with mean NAPSI improvement of -73·3% and -63·6% with secukinumab 300 mg and 150 mg, respectively. At 2·5 years, secukinumab demonstrated sustained clinically significant reductions in total mean Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) quality-of-life (QoL) scores of -52·4% and -18·1%, and 70% and 71% of patients achieved a weighted NAPPA Patient Benefit Index global score of ≥ 2 with secukinumab 300 mg and 150 mg, respectively. Patients showed considerable improvements in the EuroQol 5-Dimension health status questionnaire at 2·5 years, reporting a decrease in pain and discomfort. No new safety findings were observed. CONCLUSIONS: Secukinumab demonstrated strong and clinically meaningful efficacy for up to 2·5 years in nail psoriasis, with significant sustained QoL improvements and a favourable safety profile.

Sustained efficacy of secukinumab in patients with moderate-to-severe palmoplantar psoriasis: 2·5-year results from GESTURE, a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Secukinumab has shown sustained efficacy and safety in several manifestations of psoriasis. OBJECTIVES: GESTURE investigated the long-term (2·5-year) safety and efficacy of 150 mg and 300 mg subcutaneous secukinumab in 205 patients with moderate-to-severe palmoplantar psoriasis. METHODS: GESTURE was a randomized, double-blind, placebo-controlled, multicentre, phase IIIb trial conducted across 15 countries. The study was 140 weeks long and consisted of four periods: screening (up to 4 weeks), treatment period 1 (16 weeks), treatment period 2 (116 weeks) and post-treatment follow-up (8 weeks). Eligible patients were aged ≥ 18 years with moderate-to-severe palmoplantar psoriasis and at least one plaque outside of the palms and soles. Efficacy was assessed via a palmoplantar Investigator's Global Assessment (ppIGA) and the palmoplantar Psoriasis Area and Severity Index (PASI). RESULTS: The primary end point, a ppIGA score of 0 or 1, was met at week 16. The effect was sustained over 2·5 years with 59% [95% confidence interval (CI) 43·5-74·1] and 53% (95% CI 35·1-69·6) of patients in the secukinumab 300 mg and 150 mg groups, respectively, achieving clear or almost clear palms and soles (ppIGA 0 or 1). At 2·5 years, the mean palmoplantar PASI percentage was reduced in both the secukinumab 300 mg group (-74·7%) and the secukinumab 150 mg group (-61·6%). A total of 17% (secukinumab 300 mg group) and 18% (secukinumab 150 mg group) of patients experienced no difficulty in hands and feet functionality, as indicated by the palmoplantar quality of life instrument overall scores. The safety profile was favourable. CONCLUSIONS: GESTURE revealed that secukinumab provides a strong and sustained response over 2·5 years in challenging-to-treat palmoplantar psoriasis.

Effect of secukinumab on the clinical activity and disease burden of nail psoriasis: 32-week results from the randomized placebo-controlled TRANSFIGURE trial.

BACKGROUND: Nail psoriasis is associated with functional impairment, pain and reduced quality of life. OBJECTIVES: To demonstrate the superiority of secukinumab over placebo in clearing nail psoriasis as assessed by the Nail Psoriasis Severity Index (NAPSI) at week 16 and over time up to week 132. Presented here is the week 32 interim analysis. Impact on quality of life was assessed by Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) patient questionnaires. METHODS: TRANSFIGURE is a double-blind, randomized, placebo-controlled study in patients with moderate-to-severe plaque and nail psoriasis. RESULTS: The primary objective of this study was met: both doses of secukinumab were superior to placebo at week 16 (NAPSI improvements of -45·3%, -37·9% and -10·8% for secukinumab 300 mg and 150 mg and placebo, respectively, P < 0·001). Significant improvements were seen in patients' quality of life: the NAPPA-Quality of Life total score median decreases at week 16 were 60·9%, 49·9% and 15·8% for secukinumab 300 mg and 150 mg and placebo, respectively (P < 0·001). Improvement in nail psoriasis continued to week 32: NAPSI percentage change reached -63·2% and -52·6% for secukinumab 300 mg and 150 mg, respectively. Skin clearance measured by ≥ 90% improvement in Psoriasis Area and Severity Index was significant (rates of 72·5%, 54·0% and 1·7% for secukinumab 300 mg and 150 mg and placebo at week 16, respectively, P < 0·001) and was sustained to week 32. The most common adverse events were nasopharyngitis, headache and upper respiratory tract infections. CONCLUSIONS: Secukinumab demonstrated significant and clinically meaningful efficacy and quality-of-life improvements for patients with nail psoriasis up to week 32. What's already known about this topic? Nail psoriasis is understudied and there is a lack of effective treatment options. Nail psoriasis is correlated with more severe psoriatic disease and the development of psoriatic arthritis. What does this study add? TRANSFIGURE is one of the few prospective placebo-controlled trials specifically in nail psoriasis and includes nail-specific quality-of-life measures such as Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA)-Quality of Life and NAPPA-Patient Benefit Index. In this trial, secukinumab demonstrates significant efficacy and quality-of-life improvements in this difficult-to-treat population.

Different brain mechanisms mediate sensitivity to sensory consonance and harmonic context: evidence from auditory event-related brain potentials.

The goal of this study was to analyze the time-course of sensory (bottom-up) and cognitive (top-down) processes that govern musical harmonic expectancy. Eight-chord sequences were presented to 12 musicians and 12 nonmusicians. Expectations for the last chord were manipulated both at the sensory level (i.e., the last chord was sensory consonant or dissonant) and at the cognitive level (the harmonic function of the target was varied by manipulating the harmonic context built up by the first six chords of the sequence). Changes in the harmonic function of the target chord mainly modulate the amplitude of a positive component peaking around 300 msec (P3) after target onset, reflecting top-down influences on the perceptual stages of processing. In contrast, changes in the acoustic structure of the target chord (sensory consonance) mainly modulate the amplitude of a late positive component that develops between 300 and 800 msec after target onset. Most importantly, the effects of sensory consonance and harmonic context on the event-related brain potentials associated with the target chords were found to be independent, thus suggesting that two separate processors contribute to the building up of musical expectancy.

Breast reduction and mastopexy, an old love story: B technique update.

In summary, the recent findings of my personal experience with the B technique have been quite helpful and rewarding. I found that drawing a lateral angle when planning the procedure obtains a more circular areola contour and avoids last moment modifications. Also, upper pole undermining allows for an upper pole horizontal plication in the cases of a simple mastopexy. Figures 4 and 5 show results of the B technique. These modifications have been used over the last four years with no special complications and very satisfactory results.

The Regnault "B" technique in mastopexy and breast reduction: a 12-year review.

The "B" technique for mastopexy and reduction with and without prosthesis has been used by the author over the last 12 years for all forms of breast ptosis and hypertrophy. It has been used consistently and uniquely in over 1000 cases. Its cosmetic advantages are the short length of the scar, avoidance of a median projection of the scar, and a beautiful roundness in the best cases. The technique proved to be very adaptable to various deformities and is easy to use. The percent of complications is thought to be no greater than that of other techniques.

The minus-plus mastopexy.

The minus-plus mastopexy technique is designed for correction of moderate or major breast ptosis where breast volume is adequate but located in the lower quadrants and increased fullness in the upper quadrants is desired. The advantages of this procedure are absence of a medial scar, excellent projection, ensured nipple viability, speed, and flexibility.

Nasal augmentation in the problem nose.

The author emphasizes that nasal implants made of pierced silicone material, or conchal cartilage, are extremely satisfactory in selected cases. Their use should be restricted to dorsal implants, and the type of implant individually adapted to each case. The implant used should be made of solid silicone with numerous large holes piercing its form to create a natural fixation. In addition, the author stresses that cartilage grafts are very satisfactory, especially for small depressions or tip augmentation.

Secondary thigh-buttock deformities after classical techniques. Prevention and treatment.

Secondary high-buttock corrections pose difficult problems because of the poor vascularization of certain areas, the limited mobilization of the soft tissue, and the tendency toward poor scar formation. These factors limit the surgical techniques available. The tendency for the deformity to recur may necessitate several corrective procedures. The authors discuss correction of supratrochanteric depressions, trochanteric bulges, scars, contour irregularities, perineal bands, and flat buttocks.

Depressed scars and soft tissues.

The authors describe a technique that brings great improvement to the treatment of depressed scars. It is simple and safe as long as enough superficial tissue is available. Unequal peripheral undermining allows closure under minimal tension, is less extensive than in previously described techniques, and separates the deep scar from the superficial one.

Brachioplasty, axilloplasty, and pre-axilloplasty.

Brachioplasty can be a satisfactory means of removing excess fat and skin from the upper extremity after moderate to massive weight loss. However, patients must be well informed preoperatively of the scars that are to be expected. The procedure itself is simple, easily performed under local anesthesia, requires minimal or no undermining, and rarely produces complications. Preaxillary fat deposits can also be satisfactorily corrected surgically.

Facial and submandibular lipectomy with upward rhytidectomy.

This paper describes the removal of fat from several areas of the face and neck. Defatting is recommended whenever an excess is unaesthetic. The areas to be treated are most frequently submental and submandibular, but also chin, lower check and Bichat fat pads may have to be removed. A special type of rhytidectomy with upward pulling and direct crow's foot excision is often performed in conjunction with the defatting.

The Skoog rhinoplasty: a modified technique.

This study is a 6-year experience with 305 cases in which the technique was used for large noses. The techniques described is based on the Skoog rhinoplasty principle: autografting the osteocartilagineous nasal dorsum after its reduction to the best suitable shape and size, so that the osseous part of the graft lies on the remaining nasal bones. The authors have conjointly used the intracartilaginous approach, which leaves a unique scar away from the graft, and the extramucosal dissection, which keeps the graft separated from the nasal cavity by an intact mucosal lining. They also used the internal lateral osteotomy, which reduces postoperative swelling. The technique is described with all details. The cases shown demonstrate that this type of rhinoplasty prevents the middle third retraction because of the osteocartilaginous graft and most of the common secondary deformities. The analysis of results obtained in this series show 89 percent excellent (patient and surgeon pleased). Secondary correction had to be done in eight cases, by reducing or removing the graft.

Breast reduction: B technique.

The B breast reduction remains an excellent technique. It gives a small scar, well located, and a natural looking breast with good projection (Figs. 5, 6, and 7). In comparison to most classical techniques, the breast has less tendency to become flat with time, and the nipple-areola complex does not migrate up while the breast tissue sags down, but follows, like a nonoperated breast. It certainly is the method of choice in all kinds of mastopexies where it is useless to make long scars when short ones give a more aesthetic result.

Reconstructive rhinoplasty with nasal implants.

A new method of immobilizing nasal implants is the creation of a strong fibrotic reaction with sewn polyester (Dacron) felt. It has been applied to saddle nose deformity, as well as maxillary retrusion of flat nasal tip. Over a period of 15 years in a large number of cases, the complications have been only a temporary inflammatory reaction in 5% of the cases.

Correction of lower limb lipodystrophy.

The authors study various types of thigh lipodystrophy. To each type is applied a special technique. The complications are studied and the limitations given.

Correction of the infrapalpebral depression.

According to the author, the infrapalpebral depression is often overlooked or refused for correction. Its anatomical relation is shown and a way of correction is proposed, which has been used successfully for several years.