Modified Urethral Graciloplasty Cross-Innervated by the Pudendal Nerve for Postprostatectomy Urinary Incontinence: Cadaveric Simulation Surgery and a Clinical Case Report.

An artificial sphincter implanted in the bulbous urethra to treat severe postprostatectomy urinary incontinence is effective, but embedding-associated complications can occur. We assessed the feasibility, efficacy, and safety of urethral graciloplasty cross-innervated by the pudendal nerve. A simulation surgery on three male fresh cadavers was performed. Both ends of the gracilis muscle were isolated only on its vascular pedicle with proximal end of the obturator nerve severed and transferred to the perineum. We examined whether the gracilis muscle could be wrapped around the bulbous urethra and whether the obturator nerve was long enough to suture with the pudendal nerve. In addition, surgery was performed on a 71-year-old male patient with severe urinary incontinence. The postoperative 12-month outcomes were assessed using a 24-hour pad test and urodynamic study. In all cadaveric simulations, the gracilis muscles could be wrapped around the bulbous urethra in a γ-loop configuration. The length of the obturator nerve was sufficient for neurorrhaphy with the pudendal nerve. In the clinical case, the postoperative course was uneventful. The mean maximum urethral closure pressure and functional profile length increased from 40.7 to 70 cm H 2 O and from 40.1 to 45.3 mm, respectively. Although urinary incontinence was not completely cured, the patient was able to maintain urinary continence at night. Urethral graciloplasty cross-innervated by the pudendal nerve is effective in raising the urethral pressure and reducing urinary incontinence.

Long-term effects of natalizumab on MRI activity and clinical outcomes in Japanese patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is the most common phenotype of multiple sclerosis (MS), and its active stage is characterized by active T2 lesions with or without gadolinium (Gd) enhancement on magnetic resonance imaging (MRI). Natalizumab is indicated as monotherapy in adults with active RRMS in Japan. The main objective of this study was to investigate the long-term effect of natalizumab on disease progression in Japanese patients with RRMS using MRI data. METHODS: This retrospective, chart review study was conducted at a single center in Japan. The main study outcome was the yearly proportion of patients with active T2-weighted image lesions detected with or without Gd enhancement on brain MRI (incidence rate) after treatment initiation for up to 5 years. Additional endpoints included annual relapse rate (ARR) and expanded disability status scale (EDSS) score. RESULTS: This study included data from 85 patients with RRMS who had received natalizumab for ≥ 1 year; of these, 65 (76.5%) were female and the mean ± standard deviation (SD) age at baseline was 37.5 ± 10.0 years. The incidence rate of active T2 lesions was 52.9% (45/85) in the year prior to natalizumab treatment (Year - 1), which decreased to 2.4% and 1.6% in Year 0.5-1.5 and Year 1.5-2.5, respectively. No active T2 lesions were detected in Year 2.5-5.5 in patients who continued natalizumab treatment. EDSS score was stable, improved, and worsened in 61.8%, 26.3%, and 11.8% of patients, respectively. The median (range) EDSS score was 2.0 (0.0-7.0) at baseline (n = 85) and remained within a similar range (median score between 1.0 and 2.25 during Years 1-5). ARR decreased from 1.12 relapses per year at baseline to 0.12 relapses per year during Year 1 and remained below 0.15 relapses per year up to Year 5. CONCLUSION: The results of this first long-term study evaluating the effect of natalizumab on MRI activity and clinical outcomes in Japanese patients with RRMS suggest that natalizumab markedly reduced disease activity and maintained effectiveness over several years.

Breast reconstruction using delayed pedicled transverse rectus abdominis muscle flap with supercharging: reports of three cases.

Breast reconstruction using a pedicled transverse rectus abdominis muscle (TRAM) flap is a well-established surgical procedure. Although studies suggest that transplanting this flap using a delayed method reduces the risk of partial flap necrosis, challenges persist. Hence, we present three cases of breast reconstruction using a pedicled TRAM flap with both delaying and supercharging. Patient age, excised tissue volume for mastectomy, and follow-up period were as follows: Case 1, 58 years, 429 cm3, 5 months; Case 2, 35 years, 910 cm3, 6 months; and Case 3, 56 years, 489 cm3, 4 months. One patient (Case 2) required a large flap tissue volume to achieve breast symmetry, whereas the other two (Cases 1 and 3) had long, longitudinal scars from previous cesareans sections. In a delayed surgery, the flap was partially elevated with partial dissection and no ligation of the deep inferior epigastric artery and vein (DIEAV). An artificial dermis with a silicone membrane (Teldermis®) was used to prevent adhesion of the rectus abdominal muscles and DIEAV to the surrounding tissue. Supercharging was performed by anastomosis between the ipsilateral DIEAV and internal thoracic AV. Flaps in zones I-III and in half of zone IV for Case 2, and zones I-III for Cases 1 and 3, were transferred; all survived without infection. This method allowed the transferring of a larger tissue volume compared with the conventional pedicled TRAM flap-transfer method. Thus, it may be useful for patients who require larger tissue volume or high-risk patients.

Safety and effectiveness of secukinumab in psoriasis vulgaris and psoriatic arthritis: Real-world evidence in Japan.

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, has been available for the treatment of moderate to severe psoriasis and psoriatic arthritis since February 2015 in Japan. Because there was a time gap after the previous approval of biologics for psoriatic disease indication, it was suggested that patients to be treated with secukinumab at its launch might have refractory disease symptoms. In order to assess the safety and effectiveness of secukinumab in those patients, a 52-week, open-label, multicenter, observational cohort study was conducted. In total, 306 and 250 patients were included in the safety and effectiveness analysis sets, respectively. Over half of patients had previously received biologics (56.9%). Adverse events, serious adverse events and adverse reactions were reported in 41.2%, 7.2% and 24.2% of patients, respectively. The most commonly reported adverse reactions were oral candidiasis (2.9%), consistent with those reported in clinical studies. In addition, none of the patient characteristics assessed for the effect on safety of secukinumab increased the occurrence of adverse reactions. Psoriasis Area and Severity Index score (mean ± standard deviation) improved from baseline (14.7 ± 12.3) to week 12 (1.78 ± 3.3), which was maintained up to week 24 (1.59 ± 3.0). The proportion of patients with a Dermatology Life Quality Index score of 0/1 improved from baseline (2.2%) to week 12 (64.7%) and sustained up to week 24 (71.4%). In addition to the skin symptoms, improvement was observed in all psoriatic arthritis disease-related assessments. The current study reaffirmed the safety and effectiveness of secukinumab with broader patients than those in the clinical studies.

Assessment of serum biomarkers in patients with plaque psoriasis on secukinumab.

The molecular basis of interleukin (IL)-17A in driving psoriasis pathogenesis is not fully elucidated yet. To investigate the underlying mechanisms and biomarkers associated with IL-17A and the role in psoriasis pathogenesis, over 30 serum proteins were evaluated in a study assessing the effectiveness and safety of secukinumab, where treatment was directly switched from cyclosporin A to secukinumab. Serum ß-defensin 2 (BD-2) levels rapidly and robustly reduced following secukinumab treatment. BD-2 levels were well-correlated with Psoriasis Area and Severity Index (PASI) score; changes in BD-2 levels preceded change in PASI score. Serum BD-2, an easily measurable protein, can possibly be used as a suitable surrogate biomarker to monitor responses to IL-17A-targeted therapies for psoriasis in clinical practice.

Optimal intraoperative selection of the projection of silicone breast implant using simplified cotton sizers.

BACKGROUND: It is occasionally difficult to accurately measure the projection of the unaffected breast in unilateral breast reconstruction and decide the optimal projection of a silicone breast implant (SBI). SBI ready-made sizers are useful for selecting the optimal SBI; however, the cost of procuring multiple types of this ready-made sizers is high. Therefore, we aimed to develop a novel technique for selecting SBIs using simplified cotton sizers, intraoperatively. METHODS: We applied the novel technique on 15 patients who underwent SBI-based breast reconstruction after simple mastectomy, among whom two or three SBI candidates had similar height and width but different projection. The breast reconstructed using a cotton SBI sizer was compared with the unaffected breast in the sitting position. We then selected the optimal SBI with a little higher projection than that of the unaffected breast. At the postoperative 1 year, we confirmed whether we could select better SBI among the prepared SBIs. RESULTS: Creating and applying the cotton SBI sizer required approximately 10 min in all cases. Optimal SBI selection among the prepared SBIs was seen in 14 cases; capsule contracture occurred in 1 case. CONCLUSIONS: A simplified cotton SBI sizer is recommended because it is easy and inexpensive to develop and provides reliable assistance in identifying the optimal SBI projection.

Long-term efficacy and safety of secukinumab in Japanese patients with moderate to severe plaque psoriasis: 3-year results of a double-blind extension study.

Secukinumab, a fully human monoclonal antibody neutralizing interleukin-17A, has been shown to have significant efficacy in the treatment of moderate to severe psoriasis. Long-term (3-year) efficacy and safety of secukinumab in Japanese patients with moderate to severe psoriasis were evaluated in an extension study of a large phase 3 global study (SCULPTURE). In the core study, 52 Japanese patients with 75% improvement of Psoriasis Area and Severity Index (PASI-75) response at week 12 were re-randomized to a fixed interval (FI; every 4 weeks) schedule and retreatment as needed (RAN), in which patients received placebo until start of relapse, at which time secukinumab was reinitiated. Fifty Japanese patients completed the 52-week core study, and 47 patients entered the extension study with the same double-blind regimens up to week 152. All patients in the secukinumab 300 mg FI and seven patients in 150 mg FI groups completed 3 years of treatment. PASI-90 and -100 at the end of year 3 were achieved in 69.2% and 53.8%, respectively, in 300 mg FI and 42.9% and 42.9%, respectively, in 150 mg FI, indicating high sustained response in 300 mg FI. Mean absolute PASI was continually low in 300 mg FI and numerically higher in 150 mg FI. Dermatology Life Quality Index of 0/1 was maintained by approximately two-thirds of 300 mg FI patients, and all EuroQoL 5-Dimension Health Questionnaire domain measures were also improved. FI dosing was consistently more efficacious than RAN. The safety profile of secukinumab remained favorable, with no new safety concerns identified.

Evaluating the cost-effectiveness of secukinumab in moderate-to-severe psoriasis: a Japanese perspective.

AIM: To evaluate the cost-effectiveness of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, compared to other clinically used biologics (adalimumab, infliximab, and ustekinumab) in Japan for the treatment of moderate-to-severe psoriasis from the healthcare system (total costs) and patient co-payment (using different frequencies of drug purchase) perspectives. METHODS: A decision-tree (first year)/Markov model (subsequent years), with an annual cycle, was developed. The model adopted a 5-year time horizon. Efficacy inputs were obtained from a mixed-treatment comparison analysis, and other model inputs were collected from published literature and local Japanese sources. Model outcomes included quality-adjusted life years (QALYs) and an incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained. The annual discounting rate of 2% was applied to both costs and outcomes. RESULTS: Results for the healthcare system perspective showed that secukinumab had the highest number of quality-adjusted life years (QALYs) (4.07) vs other biologics, dominated ustekinumab and infliximab, and the ICER of secukinumab compared to adalimumab was ¥8,418,222/QALY gained. In the patient co-payment perspective with the monthly purchase of drugs, ustekinumab had the lowest co-payment cost, followed by infliximab, adalimumab, and secukinumab. In the patient co-payment perspective with a once every 3 months purchase of secukinumab and adalimumab, the co-payment costs of secukinumab, adalimumab, and ustekinumab became comparable, and infliximab had the highest co-payment cost. LIMITATIONS: Only short-term efficacy data was modeled, as there was a lack of data on long-term outcomes. Treatment sequencing was restricted to first-line biologic treatment. Drop-out rates for comparators were assumed to be equivalent to secukinumab in the absence of available data. CONCLUSIONS: Secukinumab is a cost-efficient treatment for moderate-to-severe psoriasis, providing greater health outcomes to patients at lower total costs compared to infliximab and ustekinumab, as well as comparable patient co-payment relative to other biologic treatments.

Impact of chronic urticaria on quality of life and work in Japan: Results of a real-world study.

Little attention has been given to the burden of chronic urticaria (CU) in Japan compared with other skin diseases, such as atopic dermatitis (AD) and psoriasis. The primary objective of the RELEASE study was to evaluate the real-life quality-of-life impairment in CU patients in Japan. Data were collected from 1443 urticaria, 1668 AD and 435 psoriatic patients; 552 urticaria patients who presented urticaria symptoms for over 6 weeks were defined as CU. The mean Dermatology Life Quality Index (DLQI) total score was 4.8, 6.1 and 4.8 in CU, AD and psoriatic patients, respectively. Disease control of urticaria evaluated by the Urticaria Control Test (UCT) and DLQI exhibited a strong correlation with a Spearman's rank correlation coefficient of -0.7158. CU and AD patients had relatively higher scores in all Work Productivity and Activity Impairment - General Health subscales except for absenteeism. At the time of the survey, approximately 64% of CU patients reported UCT scores of <12 and demonstrated higher work productivity loss and activity impairment versus patients with UCT scores of ≥12. Patients with lower UCT scores also displayed a higher percentage of dissatisfaction with their health state and the treatment they received. Approximately 85% of patients with CU had visited dermatology clinics, and less than 20% had visited hospital, indicating existence of a highly burdened population outside specialized centers. These results highlight the unmet medical needs of CU patients, suggesting the need to increase awareness of CU burden among both physicians and patients and to pursue improved real-life patient care.

Secukinumab improves psoriasis symptoms in patients with inadequate response to cyclosporine A: A prospective study to evaluate direct switch.

There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate-to-severe psoriasis. In this multicenter, open-label, phase IV study, 34 patients with moderate-to-severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end-point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end-point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy.

Reconstruction of the Urethral Sphincter with Dynamic Graciloplasty in a Male Rabbit Model.

INTRODUCTION: The use of artificial urinary sphincters can improve urinary incontinence after radical prostatectomies; however, complications can arise. We hypothesized that dynamic graciloplasty improves urethral sphincter reconstruction. MATERIALS AND METHODS: Models of urethral sphincter muscle reconstruction were developed in 5 adult rabbits by wrapping the gracilis muscle flap around the urethra. Intra-urethral pressure was measured in each of the models before reconstruction (control), after reconstruction, and after electrical stimulation of the flap in reconstructed models (stimulated models). RESULTS: The mean maximum urethral closure pressure was significantly greater in the reconstruction model (69.7 (66.5-115.8) mm Hg) than in the control model (39.2 (33.7-49.6) mm Hg). The mean integral of the urethral pressure and urethral length was also significantly greater in the reconstruction model than in the control model. Furthermore, sphincter tightening was enhanced by the electrical stimulation of the flap. CONCLUSIONS: Our results support our hypothesis that the functional reconstruction of urethral sphincters using muscle flaps is promising for the treatment of urinary incontinence.

Effects of capsinoid on serum and liver lipids in hyperlipidemic rats.

We compared the effects of capsinoid, a non-pungent component, on serum and liver lipids, with that of synthetic capsaicin in hyperlipidemic rats. Male Wistar rats of 9 wk old were divided into 4 groups: a control group receiving a high-fat diet containing 1% cholesterol, and capsaicin, capsinoid-I and capsinoid-II groups supplemented with 0.1 mmol of N-pelargonylvanillylamide (synthetic capsaicin), and 0.1 mmol and 1.0 mmol of capsinoid (capsiate: dihydrocapsiate=63 : 37) per kg of control diet, respectively. All groups were pair-fed for 4 wk. Compared with the control group, serum lipid levels in both capsinoid groups and liver lipid contents in the capsinoid-II group showed the same reduction as that of the capsaicin group. In the capsaicin and capsinoid-I groups, fatty acid synthase (FAS) activities were lower and hepatic triacylglycerol lipase (HTGL) [EC 3.1.1.3] activities tended to be higher than those of control group. Lipoprotein lipase (LPL) [EC 3.1.1.34] activity in adipose tissue was higher in the capsaicin and capsinoid-II groups than in the control group. These results showed that capsinoid can improve serum and liver lipid metabolism comparable to synthetic capsaicin.