Combining Reflectance Confocal Microscopy, Optical Coherence Tomography and Ex-Vivo Fluorescence Confocal Microscopy for Margin Assessment in Basal Cell Carcinoma Excision.

INTRODUCTION: Recent developments of noninvasive, high-resolution imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have enhanced skin cancer detection and precise tumor excision particularly in highly aggressive and poorly defined basal cell carcinomas (BCCs). OBJECTIVES: The aim of this pilot study is to assess the feasibility and reproducibility of a systematic clinical workflow combining noninvasive (RCM-OCT) and invasive fluorescence confocal microscopy (FCM) imaging modalities in pre- and intra-surgical evaluations of the lateral and deep margins of BCC. METHODS: Superficial incisions were made 2 mm beyond the clinical-dermoscopic BCC margins. Lateral margins were then explored with OCT and RCM. In positive margins, a further cut was made 2 mm distal from the previous. A final RCM/OCT-based double-negative margin was drawn around the entire perimeter of the lesion before referring to surgery. The freshly excised specimen was then examined with FCM (ex-vivo) for the evaluation of the deep margin. Histopathologic examination eventually confirmed margin involvement. RESULTS: The study included 22 lesions from 13 patients. At the end of the study, 146 margins-106 negative (73%) and 40 positive (27%) at RCM/OCT-were collected. The RCM/OCT margin evaluation showed an overall sensitivity of 100% and a specificity of 96.3%. The overall positive margins diagnostic accuracy was 98.2%. Reproducibility was evaluated on recorded images and the raters showed a substantial inter-observer agreement on both RCM (κ = 0.752) and OCT images (κ = 0.724). CONCLUSIONS: The combined RCM/OCT/FCM ex-vivo approach noninvasively facilitates the presurgical and intrasurgical lateral and deep margin assessment of poorly defined BCCs.

Therapeutic Potential of Spesolimab-Sbzo in the Management of Generalized Pustular Psoriasis Flares in Adults: Evidence to Date.

Generalized pustular psoriasis (GPP) is a rare, chronic, and severe skin disorder characterized by the eruption of non-infectious pustules on an erythematous background often associated with systemic symptoms. It may appear in association with plaque psoriasis or occur in previously healthy individuals. It differs from psoriasis vulgaris in clinical presentation, immunopathogenesis, histology, and therapeutic strategies. Overexpression of interleukin 36 (IL-36) or a loss-of-function mutation of IL-36 receptor antagonist (IL-36RA) are thought to play a pivotal role in the pathogenesis of this disease. There are currently no globally approved guidelines for the treatment of GPP, and the therapies used so far, with variable results, have given unsatisfactory results. Spesolimab, a selective humanized antibody against the IL-36 receptor that blocks its activation, is the first biologic drug approved in Europe in December 2022 for the treatment of GPP flares. It represents a promising therapy, demonstrating efficacy in reducing disease severity and improving patient outcomes. In our review, we have analyzed the latest advancements and findings regarding the efficacy and safety of spesolimab in the context of GPP management.

Supraorbital Basosquamous Carcinoma Treated with Cemiplimab Followed by Sonidegib: A Case Report and Review of the Literature.

Basal cell carcinoma (BCC) is a skin cancer with low local aggressiveness and a low tendency to metastasize. Basosquamous Carcinoma (BSC) represents an aggressive histological subtype of BCC with intermediate features between Squamous Cell Carcinoma (SCC) and BCC. Cemiplimab is currently approved as first-line therapy in SCC and second-line therapy in BCC patients who have progressed on or are intolerant of a Hedgehog pathway Inhibitor (HHI). Our study describes the case of a 59-year-old man with BSC who was successfully treated with 5 cycles of Cemiplimab as first-line therapy and Sonidegib as second-line therapy. Currently, the efficacy of Cemiplimab against BSC and other histopathological subtypes of BCC has not been fully elucidated, as has the role of sequential or combination therapy with Cemiplimab and HHI in the management of BSC. The aim of this case report is to highlight the need to outline the use of checkpoint inhibitors in BCCs and focus attention on the synergistic role of Cemiplimab and HHIs in such a controversial entity as BSC.

Supine mini percutaneous nephrolithotomy in horseshoe kidney.

OBJECTIVE: The percutaneous nephrolithotomy (PCNL) in Horseshoe kidneys (HSK) is usually performed in the prone position, allowing entry through the upper pole and providing good access to the collecting system. However, in patients with normal kidney anatomy, the supine position is reliable and safe in most cases, but it is unknown whether the supine position is adequate in patients with HSK. The purpose of this study was to describe the results of PCNL in HSK in three different surgical institutions and to evaluate the impact of supine position during surgery, comparing pre-operative and post-operative data, complications, and stone status after surgery. MATERIAL AND METHODS: Between 2017 and 2022, a total of 10 patients underwent percutaneous renal surgery for stone disease in HSK. All patients were evaluated pre- and post- operatively with non-contrast CT. we evaluated patients (age and gender), stones characteristics (size, number, side, site and density ), and outcomes. The change in haemoglobin, hematocrit, creatinine and eGFr were assessed between the most recent preoperative period and the first postoperative day. Procedure success was defined as stone-free or presence of ≤4 mm fragments (Clinically Insignificant residual Fragments - CIrF). Complications were registered and classified according to Clavien-dindo Grading System, during the 30 - day postoperative period and Clavien scores ≥ 3 were considered as major complications. Statistical analysis was performed using "r 4.2.1" software, with a 5% significance level. we also compared pre-operative and post-operative data using "wilcoxon signedrank test". RESULTS: No statistical difference was observed between preoperative and post-operative renal function data. At one post operative day CT scan, an overall success rate of 100% was registered. 9/10 patients were completely free from urolithiasis (stone-free rate: 90%), while 1/10 patients had ≤4 mm residual stone fragments (CIrF rate: 10%). No cases of intraoperative complications were registered. Post-operative complications were reported in 1/10 patients. A patient developed urosepsis (defined as SIrS with clinical signs of bacterial infections involving urogenital organs - Clavien-dindo Grade II) after procedure, and was treated with intravenous antibiotic therapy successfully.  Conclusions: This study shows that in patients with HSK mini- PCNL in supine position allows to achieve good stone free rate with a very low morbidity. According to our series, the described technique for PCNL in HSK should be an option. Nevertheless these results must be confirmed by further studies.

Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium).

PURPOSE: To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR - baseline eGFR; Δ2 = 6 months eGFR - POD-1 eGFR; Δ3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. RESULTS: A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up. CONCLUSION: Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

A Proposal of a New Nomogram to Predict the Need for Testosterone ReplACEment (TRACE): A Simple Tool for Everyday Clinical Practice.

International guidelines suggest to use testosterone therapy (TTh) in hypogonadal men presenting symptoms of testosterone deficiency (TD), even if there is no fixed threshold level of T at which TTh should be started. We aimed to develop and validate a nomogram named TRACE (Testosterone ReplACEment) for predicting the need of TTh in patients with "low-normal" total testosterone levels. The following nomogram variables were used: serum T level; serum LH level; BMI; state of nocturnal erections; metabolic comorbidities; and IPSS total score. The nomogram has been tested by calculating concordance probabilities, as well as assaying the calibration of predicted probability of clinical testosterone deficiency and need for TTh, together with the clinical outcome of the TTh. A cohort of 141 patients was used for the development of the nomogram, while a cohort of 123 patients attending another institution was used to externally validate and calibrate it. Sixty-four patients (45.3%) received TTh. Among them, sixty patients (93.7%) reported a significant clinical improvement after TTh. The nomogram had a concordance index of 0.83 [area under the ROC curve 0.81 (95% CI 0.71-0.83)]. In conclusion, the TRACE nomogram accurately predicted the probability of clinical impairment related to TD, and resulted in a simple and reliable method to use to select hypogonadal patients with not clearly pathological testosterone values who will benefit from TTh.

Effects of Vaccination against COVID-19 in Chronic Spontaneous and Inducible Urticaria (CSU/CIU) Patients: A Monocentric Study.

BACKGROUND: Patients affected by pre-existing chronic spontaneous/Inducible urticaria (CSU/CIU) still feel unsafe due to the potential risk of an Adverse Event Following Immunization (AEFI) and Cutaneous Adverse Reactions (CARs) of COVID-19 vaccines. The appropriate management in this field remains debated and evidence is still lacking. METHODS: We considered 160 CSU/CIU patients in Omalizumab/antihistamine therapy who received two doses of Comirnaty/Moderna mRNA vaccines; 20 of them also received a booster dose. Urticaria Activity Score-7 (UAS7) was used to assess the severity of the disease. Demographics, medical history, AEFI and CARs outcome after vaccination were collected by administering a web-based questionnaire completed by phone interview. RESULTS: In total, 147 patients did not show urticaria relapse (91.88%). Worsening cutaneous symptoms were experienced by 13 of our patients (8.12%). Exacerbation had a mean duration of 2 days and 11 h and mostly occurred after the first dose (69.23%). Systemic mild side effects were experienced by 9 patients (5.62%). No severe reactions were observed. CONCLUSIONS: Omalizumab can potentially prevent CARs and AEFI; however, major problems were registered during the 2-month stop period scheduled in the treatment. We suggest patients should not undergo vaccination during this period. CSU/CIU exacerbations appear to be transient and can be managed by antihistamines.

Effects of dutasteride on sex hormones and cerebrospinal steroids in patients treated for benign prostatic hyperplasia.

PURPOSE: Neuroactive steroids may have a role in regulating sexual function. This case-control study assessed whether dutasteride, a 5α-reductase inhibitor used for treatment of patients with benign prostate hyperplasia (BPH), impacts on the levels of neuroactive steroids, leading to erectile dysfunction (ED) and/or hypoactive sexual desire (HSD). METHODS: Forty patients with BPH and moderate-to-severe lower urinary tract symptoms (LUTS), pre-scheduled for prostate transurethral resection or open prostatectomy were enrolled. Twenty of these patients with prostate volume ≤40 mL were treated with α-blockers (Group A) and the remaining 20, with prostate volume >40 mL, with dutasteride plus α-blockers (Group B) for at least 6 months before surgery. Serum sex steroids and gonadotropin levels were measured the day before surgery, and the neuroactive steroid levels were assessed in the cerebrospinal fluid (CSF) collected during spinal anesthesia, at the day of surgery. RESULTS: Before surgery, the International Index of Erectile Function 5-item score was higher in Group A that Group B (18.8 ± 4.8 vs. 15.1 ± 5.4, p < 0.01). Group A showed lower total testosterone (TT) (4.5 vs.6.4 ng/ml, p < 0.01) and 17ß-estradiol (E2) (24.3 vs.30.7 pg/ml, p < 0.05) serum levels than Group B. CSF levels of TT (1446.6 vs. 19.9 pg/ml, p < 0.05) and dihydrotestosterone (7.9 vs. 1.4 pg/ml, p < 0.05) were higher and CSF E2 levels were lower (26.0 vs.36.0 pg/ml, p < 0.01) in Group A than Group B. CONCLUSIONS: A decrease of neuroactive steroids in the CSF of patients treated with dutasteride occurs. This may be one of the mechanisms by which dutasteride may cause ED and HSD.