Risankizumab as a Therapeutic Approach for Recalcitrant Pyoderma Gangrenosum.

ABSTRACT: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is challenging to diagnose and treat. Clinicians frequently use fast-acting corticosteroids, which are subsequently combined with slower-acting immunosuppressants to progressively taper the corticosteroid dosage. Current research is focused on the use of monoclonal antibodies (mAbs) directed against target molecules involved in the pathogenesis of PG. However, available data on their efficacy are based on sporadic case reports and clinical experiences, so the authors aimed to evaluate the efficacy of risankizumab, an anti-interleukin-23 mAb, in the management of two complex PG cases. The authors enrolled two patients with PG who were already treated with immunosuppressive therapies. Their management was based on the off-label use of an mAb directed against the p19 subunit of interleukin-23: risankizumab. Patients received subcutaneous injections of 150 mg at the start of treatment, at week 4, and then every 10 weeks thereafter. Systemic therapy was combined with local management of ulcers, based on the principles of TIME (tissue, infection, moisture balance, and epithelialization) applied to the inflammatory and noninflammatory phases of PG. Clinical resolution was obtained at week 24 for patient 1 and week 16 for patient 2 and was maintained until week 40, without adverse effects or disease recurrence. These clinical cases demonstrate that risankizumab is a valid tool in terms of efficacy and safety for complicated cases of multirefractory PG when provided in parallel with local personalized wound management.

Pd8(PDip)6: Cubic, Unsaturated, Zerovalent.

Atomically precise nanoclusters hold promise for supramolecular assembly and (opto)electronic- as well as magnetic materials. Herein, this work reports that treating palladium(0) precursors with a triphosphirane affords strongly colored Pd8(PDip)6 that is fully characterized by mass spectrometry, heteronuclear and Cross-Polarization Magic-Angle Spinning (CP-MAS) NMR-, infrared (IR), UV-vis, and X-ray photoelectron (XP) spectroscopies, single-crystal X-Ray diffraction (sc-XRD), mass spectrometry, and cyclovoltammetry (CV). This coordinatively unsaturated 104-electron Pd(0) cluster features a cubic Pd8-core, µ4-capping phosphinidene ligands, and is air-stable. Quantum chemical calculations provide insight to the cluster's electronic structure and suggest 5s/4d orbital mixing as well as minor Pd─P covalency. Trapping experiments reveal that cluster growth proceeds via insertion of Pd(0) into the triphosphirane. The unsaturated cluster senses ethylene and binds isocyanides, which triggers the rearrangement to a tetrahedral structure with a reduced frontier orbital energy gap. These experiments demonstrate facile cluster manipulation and highlight non-destructive cluster rearrangement as is required for supramolecular assembly.

Insights on the Anion Effect in N-heterocyclic Carbene Based Dinuclear Gold(I) Catalysts.

Dinuclear bisNHC (bis(N-heterocyclic carbene)) gold(I) complexes 3 a and 4 a of general formula [Au2 Br2 (bisNHC)] were tested as catalysts in the cycloisomerization of N-(prop-2-yn-1-yl)benzamide and in the hydromethoxylation of 3-hexyne in the presence of silver(I) activators bearing different counteranions. The catalytic performance of mononuclear NHC complexes (1 a, 2 a) in the same reactions was also studied. The results highlighted the fundamental role of both NHC ligand and counterion in the catalytic cycles and activation process: dinuclear catalysts exhibit higher initial activity even under milder conditions but suffer in terms of stability with respect to mono NHCs. Furthermore, a new dinuclear bisNHC gold(I) complex 4 b of general formula [Au2 (OTs)2 (bisNHC)] (OTs=p-toluenesulfonate) was successfully synthesized and characterized by means of NMR and ESI-MS analyses.

Melanoma Arising on a Nevus After Tattooing.

The pathogenetic relationship between tattooing and the development of malignant melanoma has not been demonstrated yet, but there are numerous instances documented in the literature where both benign and malignant lesions have developed on tattoos. We report the case of a 39-year-old man with a melanoma that arose on a nevus on the back after tattooing. Since the identification of melanocytes lesions can be heavily hindered by large tattoos, implementing a dedicated screening process with regular monitoring of the tattooed region could be necessary to prevent potential diagnostic delays.

Serum Amyloid A: A Potential New Marker of Severity in Hidradenitis Suppurativa.

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with systemic inflammation and high impact on quality of life. Treatment strategies are still inadequate with a lack of inflammation biomarkers. We conducted a prospective study to assess the correlation between serum amyloid A (SAA) levels and active lesion count; disease severity; Dermatology Life Quality Index (DLQI); smoking; BMI; and lesion sites. Methods: Forty-one patients (M/F: 22/19) were enrolled. Demographic, clinical, laboratory, and therapeutic data were assessed at baseline on patients not under treatment or in wash-out from systemic treatment for at least 2 weeks. Associations were investigated by univariate and multivariate analyses. Results: SAA levels were significantly associated with number of nodules (p = 0.005), abscesses (p < 0.001), fistulas (p = 0.016), and severe IHS4 (p = 0.088 and r = 0.514). Gluteal localization was correlated with high values of mSartorius and severe IHS4. Conclusions: We recommend assessment of SAA levels to monitor therapeutic response in patient with HS in order to prevent disease's flare and potential complications.

Mitotic rate as a predictive factor for positive sentinel lymph nodes in pT1 and pT2 melanomas.

Sentinel lymph node biopsy is a crucial step in the management of patients affected by melanoma. The decision whether to perform it or not is based on different histological parameters, but the mitotic rate is no longer considered a prognostic variable after the release of the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines. Our objective was to investigate the risk factors that increase the chance for sentinel lymph node positivity in melanomas with a Breslow thickness of less than 2.00 mm, including the mitotic count. A retrospective single-center study was performed on a homogenous cohort of 408 patients treated for cutaneous melanoma. Histological and clinical features were gathered and correlated with the increased risk for sentinel lymph node positivity by means of univariate and multivariate analyses. A statistically significant correlation between a high mitotic index and a positive sentinel lymph node was found in pT1 and pT2 patients, suggesting that in the case of pT1a melanoma with a high number of mitoses, a discussion about whether a sentinel lymph node biopsy is required should be done.

Pyoderma gangrenosum in a patient with Dubowitz syndrome: a new comorbidity?

INTRODUCTION: Dubowitz syndrome is a rare genetic disease with only a few cases reported in the literature. It is characterized by growth retardation, microcephaly, facial dysmorphism and higher risk of developing cancer and cardiomyopathies. PG is an autoinflammatory disorder that causes painful ulcers to develop on the skin and has not been previously associated with Dubowitz syndrome. CASE PRESENTATION: The authors report the case of a 50-year-old female with Dubowitz syndrome who developed painful ulcerative lesions. An incisional biopsy was performed to rule out other diagnoses, and a subsequent clinical diagnosis of PG was made. The patient was treated with specialized wound dressings and oral glucocorticoids. The clinical picture improved consistently after 7 weeks of therapy. CONCLUSIONS: This case report, to the authors' knowledge, is the first to suggest a possible association between Dubowitz syndrome and PG and also to indicate an effective treatment.

An Integrated Systemic and Local Wound Management in Recalcitrant Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic inflammatory dermatosis, whose management still represents a clinical challenge due to frequent unresponsive cases. The aim of our study was to evaluate the efficacy of a novel, combined approach including local wound management, based on the principle of PG-TIME and a systemic therapy with an anti interleukin (IL)-17A monoclonal antibody (mAb). We presented a case of a 37-year-old female patient, affected by multi-refractory PG. The patient was treated with a combined approach of both local and systemic therapy. Wound clinical improvement was assessed by Wound Bed Score (WBS), wound size was evaluated through 3D camera laser scanner, and pain was evaluated with visual analog scale (VAS). After 52 weeks of therapy, the association of local wound management with ixekizumab 80 mg [160 mg at time (T) 0; 80 mg every 2 weeks until week 12; 80 mg every 4 weeks] allowed us to perform skin grafting and obtain complete wound healing. Our clinical case demonstrated the efficacy of a novel combination therapy for the treatment of recalcitrant PG based on IL-17 mAbs and local wound management built on the main features of PG-TIME.

From Au11 to Au13: Tailored Synthesis of Superatomic Di-NHC/PPh3-Stabilized Molecular Gold Nanoclusters.

Herein, we report a new method to synthesize molecular gold nanoclusters (AuNCs) stabilized by phosphine (PR3) and di-N-heterocyclic carbene (di-NHC) ligands. The interaction of di-NHC gold(I) complexes, with the general formula [(di-NHC)Au2Cl2] with well-known [Au11(PPh3)8Cl2]Cl clusters provides three new classes of AuNCs through a controllable reaction sequence. The synthesis involves an initial ligand metathesis reaction to produce [Au11(di-NHC)(PPh3)6Cl2]+ (type 1 clusters), followed by a thermally induced rearrangement/metal complex addition with the formation of Au13 clusters [Au13(di-NHC)2(PPh3)4Cl4]+ (type 2 clusters). Finally, an additional metathesis process yields [Au13(di-NHC)3(PPh3)3Cl3]2+ (type 3 clusters). The electronic and steric properties of the employed di-NHC ligand affect the product distribution, leading to the isolation and full characterization of different clusters as the main product. A type 3 cluster has been also structurally characterized and was preliminarily found to be strongly emissive in solution.

Sublingual AKBA Exerts Antidepressant Effects in the Aß-Treated Mouse Model.

The 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) is the most active compound of Boswellia serrata proposed for treating neurodegenerative disorders, including Alzheimer's disease (AD), characterized in its early phase by alteration in mood. Accordingly, we have previously demonstrated that an intracerebroventricular injection of soluble amyloid beta 1-42 (Aß) peptide evokes a depressive-like phenotype in rats. We tested the protective effects of AKBA in the mouse model of an Aß-induced depressive-like phenotype. We evaluated the depressive-like behavior by using the tail suspension test (TST) and the splash test (ST). Behavioral analyses were accompanied by neurochemical quantifications, such as glutamate (GLU), kynurenine (KYN) and monoamines, and by biochemical measurements, such as glial fibrillary acid protein (GFAP), CD11b and nuclear factor kappa B (NF-kB), in mice prefrontal cortex (PFC) and hippocampus (HIPP). AKBA prevented the depressive-like behaviors induced by Aß administration, since we recorded a reduction in latency to initiate self-care and total time spent to perform self-care in the ST and reduced time of immobility in the TST. Likewise, the increase in GLU and KYN levels in PFC and HIPP induced by the peptide injection were reverted by AKBA administration, as well as the displayed increase in levels of GFAP and NF-kB in both PFC and HIPP, but not in CD11b. Therefore, AKBA might represent a food supplement suitable as an adjuvant for therapy of depression in early-stage AD.