Periungual pyogenic granulomas after ravulizumab therapy in a child with acute myelomonocytic leukemia treated with hematopoietic stem cell transplant.

Development of periungual pyogenic granulomas (pPGs) has been associated with several systemic treatments, including retinoids, taxanes, epidermal growth factor receptor inhibitors, and vascular endothelial growth factor inhibitors. We present the case of an 8-year-old girl with a personal history of acute myelomonocytic leukemia treated with a haploidentical hematopoietic stem cell transplant who developed pPGs 2 months after starting ravulizumab. Ravulizumab is a monoclonal antibody directed against C5 protein. No previous reports of pPGs development have been described with ravulizumab.

Choosing the right biologic treatment for moderate-to-severe plaque psoriasis: the impact of comorbidities.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease often associated with several comorbidities, such as psoriatic arthritis, inflammatory bowel disease, obesity, diabetes mellitus or cardiovascular diseases, infections, or cancer, among others. With the progressive aging of the population, a growing number of patients with psoriasis can be expected to present multiple comorbidities. Currently, there is a wide range of biological treatments available for moderate to severe psoriasis, including tumor necrosis alpha (TNF) inhibitors, IL12/23 inhibitor, IL17 inhibitors, and IL23 inhibitors. AREAS COVERED: This review aims to describe the specific characteristics of these drugs in relation to psoriasis comorbidities, in order to facilitate decision-making in clinical practice. EXPERT OPINION: Some of the biological treatments can influence comorbidities, in some cases even improving them. Therefore, comorbidities are a key factor when deciding on one biological treatment over another. The development of new drugs is expanding the therapeutic arsenal for psoriasis. A high level of expertise in the field with a detailed knowledge of the characteristics of every drug is imperative to provide personalized medicine.

Genetic and Epigenetic Mechanisms of Psoriasis.

Psoriasis is a disease involving the innate and adaptative components of the immune system, and it is triggered by environmental factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, especially in genome and epigenome-wide studies, have provided a better understanding of the genetic and epigenetic mechanisms to determine the physiopathology of psoriasis and facilitate the development of new drugs. This review intends to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.

Bimekizumab in the Treatment of Plaque Psoriasis: Focus on Patient Selection and Perspectives.

Psoriasis is a chronic systemic inflammatory disease that significatively impairs patients' quality of life. Biological treatments are highly effective and safe and have led to breakthroughs in the management of patients with moderate-to-severe psoriasis. However, therapeutic response can be unsatisfactory or lost with time, leading to discontinuation of treatment. Bimekizumab is a humanized monoclonal antibody that specifically inhibits both interleukin (IL)-17A and IL-17F. The efficacy and safety of bimekizumab in moderate-to-severe plaque psoriasis has been demonstrated in Phase 2 and Phase 3 clinical trials. Bimekizumab may offer some advantages over other biological treatments, making it especially indicated for certain patients. This narrative review aims to summarize the latest published evidence on the use of bimekizumab for the treatment of moderate-severe plaque psoriasis, focusing on patient selection and therapeutic perspectives. Bimekizumab has been shown to be more efficacious than adalimumab, secukinumab and ustekinumab in clinical trials, with high estimated probabilities of achieving complete (approximately 60%) or almost complete clearance (approximately 85%) of psoriasis at weeks 10-16, and a good safety profile. Response to bimekizumab is usually fast and maintained in the long term for both biologic-naive patients and those resistant to previous biologic treatments. The usual maintenance dose of 320 mg every 8 weeks makes bimekizumab especially convenient for non-compliant patients. Moreover, the efficacy and safety of bimekizumab have also been demonstrated in psoriasis affecting challenging-to-treat areas, psoriatic arthritis and hidradenitis suppurativa. In conclusion, dual inhibition of IL-17A and IL-17F with bimekizumab is a good therapeutic option for moderate-to-severe psoriasis.

Economic Impact Associated with Patients with Overactive Bladder on Drug Treatment with Mirabegron or Antimuscarinics in Spain

Objective: To assess the economic impact associated with overactive bladder (OAB) patients, treated with mirabegron or antimuscarinics (AM) in Spain, over a 12-month period. Methods: A probabilistic model (second-order Monte Carlo simulation) was used in a hypothetical cohort of 1000 patients with OAB and a time horizon of 12 months. The use of resources was obtained from the retrospective observational study MIRACAT that included 3330 patients with OAB. The analysis was carried out from the perspective of the National Health System (NHS) including that of society with the indirect cost of abseenteism in a sensitivity analysis. Unit costs were obtained from Spanish public healthcare prices (€ 2021) and from previously published Spanish studies. Results: The annual average savings for the NHS for each patient with OAB treated with mirabegron would be € 1135 (95%confidence interval (CI) € 390; 2421) compared with a patient treated with AM. Annual average savings were maintained in all the sensitivity analyses carried out, ranging from a minimum of € 299 to a maximum of € 3381 per patient. The substitution of 25% of the AM treatments (for 81534 patients) to mirabegron would generate, within 1 year, savings for the NHS of € 92 million (95% CI € 31; 197 million). Conclusions: According to the present model, the treatment of OAB with mirabegron would generate savings compared with treatment with AM in all scenarios and sensitivity analysis performed, and for the NHS and for society perspectives (AU)

Is bladder outlet obstruction responsible for a successful surgical outcome in women with complicated stress urinary incontinence? Urodynamic results before and after a Remeex® readjustable sling.

AIMS: To describe the changes in urodynamic parameters after Remeex® placement in women with recurrent stress urinary incontinence (rSUI) or intrinsic sphincteric deficiency (ISD) and to analyze a potential relationship between postoperative bladder outlet obstruction and a successful surgical outcome. METHODS: Retrospective analysis of those women who had undergone Remeex® placement due to rSUI or ISD in our department between 2000 and 2017. All patients underwent urodynamic evaluation before and after the surgery. If tension readjustment was required, postoperative urodynamics was performed after the last regulation, once the final continence status had been achieved. The female Bladder Outlet Obstruction Index (BOOIf) was calculated for all patients postoperatively. Obstruction was considered present if BOOIf was >18. Pre- and postoperative urodynamic variables were compared. Postoperative urodynamic changes were also compared between cured and noncured patients. RESULTS: A total of 205 women were included. After a follow-up of 89 ± 36 months, 165 women (80.5%) were continent. A significant impairment in the majority of the urodynamic parameters was observed. Mean postoperative BOOIf was -11.8 ± 21.5 in cured patients and -15.3 ± 23.1 in noncured patients (p = 0.365); 15 (9.1%) patients in the cured group had a postoperative BOOIf >18, whereas all (100%) patients in the noncured group had a postoperative BOOIf <18. CONCLUSIONS: Most urodynamic parameters may worsen after the Remeex® system placement. Postoperative urodynamic parameters may not differ substantially between cured and noncured patients, although a certain grade of bladder outlet obstruction could be related to postoperative continence status in some patients.

Development and validation of a short version of the Female Sexual Function Index in the Spanish population.

BACKGROUND: The Female Sexual Function Index (FSFI) is a commonly used scale for the assessment of female sexual function. Our aim was to develop and validate a Spanish short version of the FSFI. METHODS: A parallel exploratory, sequential mixed-methods approach was used, involving 2 sites. The process consisted of 2 steps: (1) cognitive and content validation of the previously translated FSFI in the Spanish population, both through a focus group; and item selection based on the difficulty and discrimination parameters using item response theory (IRT), thereby obtaining a short version of the scale (sFSFI-sv); (2) assessment of test-retest reliability (intraclass correlation coefficient, ICC) of the sFSFI-sv. The presence or absence of a sexual disorder variable based on clinical interview was used on the Receiver Operating Characteristic (ROC) to establish the cut off point whose Area Under the Curve (AUC) based on sensibility and specificity was maximum. RESULTS: Specific modifications of the FSFI were made according to the focus group results. 114 women were included for IRT analysis. The initial IRT model pointed to the exclusion of items 1, 2, 5, 11, 18, and 19 (S-χ2 p < 0.001). Items 3, 9, 11, and 14 showed the best discrimination and difficulty parameters. On the basis of the IRT and focus group results, items 1, 3, 9, 12, 16, and 17 were included in the final sFSFI-sv. sFSFI-sv showed good reliability (ICC 0.91) in a group of 93 women. A total score ≤ 18 could indicate a higher risk of sexual disorder (sensitivity: 81.0%, specificity: 73.3%). CONCLUSION: A focus group and the IRT analysis allowed the development of a 6-item Spanish version of the FSFI, which showed good reliability in a group of Spanish women.

Onabotulinumtoxin a injection with or without hydrodistension for treatment of bladder pain syndrome.

INTRODUCTION: Onabotulinumtoxin A (BoNT-A) injection has been used for bladder pain syndrome (BPS) treatment with good results. Our aim was to assess the efficacy and safety of BoNT-A injection with or without hydrodistension (HD). METHODS: Retrospective analysis of patients treated with BoNT-A injection with or without HD because of BPS between 2008 and 2014 in our department. One hundred U of Botox® was injected in the trigone and 100 U in the bladder wall. Follow-up included a VAS of pain (0-10), a patient satisfaction scale (0-10) and a treatment benefit scale (1-2: response to treatment; 3-4: non-response to treatment). Complications were classified according to the Clavien-Dindo (CD) classification. BoNT-A retreatment was offered at the patient's request. Reasons for non-retreatment request were collected. Postoperative outcomes were compared between BoNT-A and BoNT-A + HD. RESULTS: Forty-one patients were included (39 females, 2 males), median age: 73 years (69-78.5). Reduction in VAS, postoperative VAS = 0, satisfaction with surgery and responders to treatment were significantly higher after BoNT-A + HD (n = 26) than after BoNT-A (n = 15). Eleven (26.8%) complications (CD ≤ 2) were detected, with no differences between treatment groups. Mean follow-up was 153 (± 83) months. Twelve (46.2%) patients in the BoNT-A + HD group and seven (46.7%) patients in the BoNT-A group requested retreatment. Lack of severe pain was a common reason for treatment discontinuation. CONCLUSION: BoNT-A injection could represent a safe and effective BPS treatment. BoNT-A + HD seems to be better than BoNT-A alone for pain relief, with no significant additional morbidity.

Pelvic Organ Prolapse Repair with Mesh: Description of Surgical Technique Using the Surelift® Anterior Repair System.

INTRODUCTION: Although the use of transvaginal mesh (TVM) in the repair of pelvic organ prolapse (POP) has been restricted, there are still some cases in which TVM may be the most appropriate approach. The TVM Surelift® anterior repair surgical technique has not been described previously. OBJECTIVE: The aim of this study was to describe the surgical technique and to report our preliminary results regarding efficacy and complications. METHODS: A step-by-step description of surgical technique is presented. A descriptive retrospective analysis was performed to evaluate our preliminary results in 17 women who underwent POP repair using the Surelift® anterior repair system in our department between 2014 and 2017. TVM was offered to patients with symptomatic apical (primary or recurrent) or recurrent anterior POP stage ≥2. POP recurrence was classified as asymptomatic anatomic or symptomatic. Patients rated satisfaction with surgery on a scale from 0 to 10. Complications during follow-up were classified according to the International Urogynecological Association/International Continence Society recommendations. RESULTS: Median (IQR) follow-up was 19.9 months (24.8). Two (11.8%) anatomic recurrences were identified, both symptomatic, but neither required further surgery. No cases of pelvic pain, dyspareunia, voiding, or defecatory dysfunction were detected. Two (11.8%) patients presented a <1-cm vaginal mesh exposure (2AaT3S2) requiring partial mesh removal through a vaginal approach. At the end of follow-up, median satisfaction (IQR) with the surgery was 9 (3.1). CONCLUSION: The Surelift® anterior repair system is effective in correcting apical or recurrent anterior POP, with a high patient satisfaction rate. Complications after this surgery are infrequent and are mostly related to vaginal mesh exposure.

Treatment Response and Complications after Intradetrusor OnabotulinumtoxinA Injection in Male Patients with Idiopathic Overactive Bladder Syndrome.

PURPOSE: We sought to assess the treatment response, complications and treatment continuation after onabotulinumtoxinA injection in male patients. MATERIALS AND METHODS: We performed a retrospective study of men with refractory idiopathic overactive bladder treated with intradetrusor injection of 100 IU onabotulinumtoxinA since 2007 in our department. Patients with previous radical prostatectomy were excluded from analysis. The treatment response was assessed using a treatment benefit scale of 1-greatly improved, 2-improved, 3-not changed and 4-worse after treatment. A treatment benefit scale score of 1 or 2 was considered a treatment response. Complications were classified according to the CD (Clavien-Dindo) classification. Treatment was considered to have continued if at the last visit patients had received an onabotulinumtoxinA injection within the preceding 12 months. We performed univariate and multivariate analyses to assess factors predictive of the treatment response, complications and continuation on treatment. RESULTS: Of the 146 men with a mean ± SD age of 70.1 ± 13.3 years who were included in study 91 (62.3%) reported a response to treatment. A total of 24 complications (16.4%) were detected, including 19 cases (13%) of urinary retention (CD 2), 2 (1.3%) of hematuria (CD 1) and 3 (2%) of urinary infection (CD 2). Followup was more than 12 months in 128 patients, of whom 88 (68.8%) had discontinued treatment by the end of followup. A higher bladder outlet obstruction index was the only factor predicting a lower treatment response rate and a higher complication rate. CONCLUSIONS: Most male patients with idiopathic overactive bladder showed a treatment response after intradetrusor onabotulinumtoxinA injection. However, the majority discontinued treatment. A higher bladder outlet obstruction index was related to a lower treatment response and a higher complication rate.

Validation of a 3 day electronic bladder diary as an app for smart-phone.

AIM: To validate an electronic 3-day bladder diary (BD) as an easy-to-use app for smart-phone (eDM3d). METHODS: Descriptive and cross-sectional prospective study. One hundred and thirty-six patients with overactive bladder syndrome (OABs) or nocturia who had a smart-phone and attended the urology clinics of a tertiary hospital from June to November 2017 were included. Patients filled the eDM3d (test) and the Spanish validated paper BD (DM3d) and questionnaires ICIQ-UISF and BASQ during the first week. Two weeks later, they repeated the eDM3d (retest). We assessed feasibility of the eDM3d (percentage of variables completed), test-retest reliability (qualitative variables: McNemar test; quantitative variables: ICC), paper-app correlation (qualitative variables: Kappa index; quantitative variables: ICC) and convergent validity (correlation between eDM3d and questionnaires, Spearman's rank test). Patients answered a question about satisfaction: "If you had to repeat a BD again, would you choose paper or the app version?" RESULTS: One hundred and twenty-three (90.4%) participants completed all the variables of the first eDM3d. There were no significant differences in the proportion of patients classified as positive for each symptom between test and retest. ICC ranged from 0.73 to 0.94 for all variables (P < 0.001) in the test-retest assessment. Paper-app correlation was good to excellent for all variables (ICC 0.76-0.95, P < 0.001; Kappa index 0.56-0.84, P < 0.001). Correlation between the eDM3d and the questionnaires ranged from 0.23 to 0.6 (P < 0.01). 120 (88.2%) patients would choose the eDM3d if they had to repeat a BD. CONCLUSION: The eDM3d presents suitable feasibility, reliability, and validity to assess patients with OABs or nocturia who have a smart-phone.

Long-term follow-up after cystectomy for bladder pain syndrome: pain status, sexual function and quality of life.

PURPOSE: To assess the long-term complications, pain status, sexual function and quality of life after cystectomy for bladder pain syndrome (BPS). METHODS: We retrospectively reviewed functional variables for 35 patients (34 women/1 man, 67 ± 9 years old) who underwent cystectomy due to BPS since 1993 in our department. Cystectomy was offered to patients with BPS refractory to conservative treatments. Six cystectomies with ileal conduit (17.1%) and 29 supratrigonal cystectomies with enterocystoplasty (82.9%) were performed. Prospectively, patients completed questionnaires on pain [BPIC-SS, visual analogue scale (VAS) for pain], health-related quality of life (EQ-5D) and sexual function (FSFI; 2-36), rated satisfaction with surgery (0-10) and reported whether they would undergo the same surgery again. RESULTS: Mean follow-up was 107 ± 83 months. In two (5.7%) patients, pain persisted and in one patient (2.8%) pain recurred after 20 months. Significant improvements in daytime and nighttime frequency and bladder capacity were observed postoperatively. 21 patients completed questionnaires. Mean BPIC-SS was 7.5 ± 8.4, mean VAS score 2.5 ± 2.8. 14 (66.7%) patients reported no problems related to pain on the EQ-5D, similar to our regional reference population. 13 (61.9%) patients had sexual intercourse after surgery, ten of them without pain. Mean FSFI score was 9.5 ± 9. Satisfaction with surgery was 8.8 ± 1.7 and 20 (95.2%) patients would undergo the same surgery again. CONCLUSION: Pain persistence or recurrence after cystectomy for BPS is infrequent. Quality of life related to pain is similar to that in the general population and patients can resume sexual activity without pain.

Pelvic Organ Prolapse Repair with Mesh: Mid-Term Efficacy and Complications.

INTRODUCTION: Our aim was to assess the efficacy and complications of pelvic organ prolapse (POP) correction with transvaginal mesh (TVM). MATERIALS AND METHODS: We retrospectively assessed patients who had undergone a repair of an apical (primary or recurrent) or recurrent POP using TVM in our department since 2007. Meshes used were Prolift®, Elevate®, and Surelift®. Satisfaction with surgery was assessed on a 0-10 scale. RESULTS: A total of 83 patients were included (33 Prolift®, 36 Elevate®, 14 Surelift®), with a mean age of 67.8 ± 9.7 years. Eighteen (21.6%) patients underwent a recurrent POP correction. Follow-up was 49 ± 34 months. Twelve (14.4%) symptomatic recurrences were identified, 3 of which required further surgery. Satisfaction was 8.7. Four (4.8%) vaginal exposures were detected, 2 of which required partial mesh removal. Three (3.6%) cases of dyspareunia and 1 (1.2%) case of mild pelvic pain were reported, which did not require further treatment. CONCLUSION: The use of TVM for apical or recurrent POP repair is effective and is associated with a high satisfaction rate while complications are infrequent.

Development and feasibility assessment of a 3 day electronic bladder diary as an app for smart-phone.

AIMS: To develop a 3 day bladder diary (BD) as an easy-to-use application for smart-phone (eDM3d). To test its feasibility and acceptance in a reduced number of patients. METHODS: An external agency developed the eDM3d following the structure of the Spanish validated 3 day BD (DM3d©), which includes a frequency-volume chart, the assessment of the grade of urgency, the incontinence events and fluid intake. The eDM3d consisted in a main interface of four buttons ("wake up," "go to bed," "urinate," "drink") which had to be clicked to create an event. Results were automatically transferred to an internet server to obtain an electronic report. We recruited 25 patients with overactive bladder syndrome or nocturia and previous experience on paper BD. They were asked to complete the eDM3d. Finally, a direct question about satisfaction was answered: "If you had to complete a BD again, would you choose the paper or the app version?" RESULTS: Three patients (12%) did not complete the eDM3d, 1 patient (4%) completed 2 days of the eDM3d and did not register volumes of micturition nor fluid intake, 1 patient (4%) completed all 2 days variables and 20 patients (80%) completed all 3 day variables. Regarding satisfaction, 19 patients (86.4%) would choose the app version, 2 patients (9.1%) would choose a paper version and 1 patient (4.5%) would choose either indistinctly. CONCLUSIONS: The eDM3d is a useful tool easily filled in by patients with a high satisfaction rate. Adequate validation of the eDM3d is required.