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Introduction/Objective: Phosphodiesterase-5 inhibitors (PDE5i) are traditionally employed for the management of erectile dysfunction and lower urinary tract symptoms. However, their role in the healing of complex penile wounds remains scarcely discussed. This study aims to describe the case of a 27-year-old man who suffered from penile strangulation, treated with sildenafil. Additionally, a literature review concerning the use of PDE5i for the treatment of complex penile injuries will be conducted. Methods: A 27-year-old man presented to the emergency room after a self-induced penile strangulation using a ring placed at the base of the penis. Extensive necrosis of the corpus cavernosum was identified through magnetic resonance imaging. Considering the psychosocial implications of penile amputation, organ preservation was chosen, and conservative treatment with sildenafil and daily local dressings was initiated. Thirty days after admission, Doppler ultrasound revealed symmetrical corpus cavernosum with normal echogenicity and usual blood flow patterns. Subsequently, the patient underwent superficial necrotic tissue debridement followed by partial skin grafting in a second stage, leading to hospital discharge after 55 days of hospitalization. Results: PDE5 inhibitors enhance nitric oxide bioavailability, promoting vasodilation and improved tissue oxygenation, thereby facilitating various phases of the healing process. Evidence indicates their benefit in microvascular perfusion in skin and soft tissues. Reports suggest satisfactory outcomes of topical PDE5i application in radiation-induced lesions, implying their role in epidermal cell expansion, reduction of inflammatory infiltrates, enhanced vascularization, and decreased collagen deposition. Conclusion: This study presents a successful case of sildenafil use in treatment of a complex penile wound, shedding light on an unconventional application of PDE5i. Financing: No conflict. [ABSTRACT FROM AUTHOR]

Basophilic granulocytes, containing and releasing histamine after a specific allergy stimulation, are directly involved in IgE-mediated allergic reactions. CD63 is a transmembrane protein of secretory lysosomes of basophils and its upregulation is related with the release of histamine to the extracellular space during IgE-mediated allergic reactions. Basophil activation test (BAT) measures the activation of circulating basophils upon the in vitro stimulation of living blood cells with specific allergens. Such a test is particularly safe and reproducible and has recently emerged as a new promising diagnostic tool for allergic diseases. BAT can be used to diagnose food allergy and represents a promising alternative to oral food challenge tests, especially in children as it is less invasive, safer, and cheaper than the gold standard tests. As a biomarker of tolerance and reactivity, it is also useful to monitor natural resolution and clinical response to immune-modulatory treatments. Regarding drug allergies, BAT is even the only possible applicable diagnostic tool for allergy reactions to some drugs, because of the lack of alternative test, or given that those commonly used are unreliable, or equivocal. Additionally, BAT allows to screen patients with more active urticarial and identify Hymenoptera-allergic patients with negative venom-specific immunoglobulin (Ig)E. In respiratory allergic diseases, BAT can facilitate the diagnosis of local allergic rhinitis and evaluate basophil allergen sensitivity in allergic asthma. Although IgE-sensitization in allergic asthma is usually demonstrated by skin prick test and specific IgE, those tests do not predict the clinical allergy contribution to asthma pathogenesis. To date, the potential of BAT in the diagnostic work-up of allergic diseases is well established, but a better standardization of its use is needed. This narrative review summarizes the state-of-the-art BAT technology and applications in pediatric allergic diseases, focusing on immune-related mechanisms and the BAT real clinical utility., Competing Interests: The authors have no conflicts of interest to declare that are relevant to the content of this article., (© 2024 Published by Elsevier Inc. on behalf of World Allergy Organization.)

The most important pollinator for agricultural crops is the Western honeybee ( Apis mellifera ). During the winter and summer seasons, diseases and stresses of various kinds endanger honeybee numbers and production, resulting in expenses for beekeepers and detrimental effects on agriculture and ecosystems. Researchers are continually in search of therapies for honeybees using the resources of microbiology, molecular biology, and chemistry to combat diseases and improve the overall health of these important pollinating insects. Among the most investigated and most promising solutions are medicinal plants and their derivatives. The health of animals and their ability to fight disease can be supported by natural products (NPs) derived from living organisms such as plants and microbes. NPs contain substances that can reduce the effects of diseases by promoting immunity or directly suppressing pathogens, and parasites. This literature review summarises the advances that the scientific community has achieved over the years regarding veterinary treatments in beekeeping through the use of NPs. Their impact on the prevention and control of honeybee diseases is investigated both in trials that have been conducted in the laboratory and field studies.

Background: Reliable evidence to guide the management of melanoma in situ (MIS) and minimize the risk of recurrence is lacking., Objective: To identify clinicopathological predictors of local recurrence (LR) in patients with MIS and evaluate long-term outcomes according to pathological excision margins., Methods: A case-control study of patients with MIS treated at a large Australian melanoma treatment center from January 2008 to December 2012 was undertaken. Clinicopathological characteristics of patients who developed LR and those who did not were compared., Results: LR developed in 34 of 1407 patients with MIS (2.5%). Median time to LR was 20 months. The primary lesion was removed with pathological margins <4 mm ( P  < .001) in 67.6 % of patients with LR. Four patients died of metastatic melanoma following LR. Comparing patients with pathological margins <4 mm and ≥4 mm, the former were older (>60y, P  < .001), more frequently had MIS on the head or neck ( P  < .001), had a greater LR rate ( P  < .001), and had a higher mortality from all causes ( P  < .001)., Limitations: Retrospective, single-institution study., Conclusions: Pathological margins of ≥4 mm should be considered for patients with MIS who are treated with standard surgical excision and assessed by examining serial slices taken from the formalin-fixed, paraffin-embedded specimen., Competing Interests: RAS has received fees for professional services from Evaxion, Provectus Inc, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, AMGEN Inc, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline. JFT has received honoraria for advisory board participation from BMS Australia, MSD Australia, GSK, and Provectus Inc and travel and conference support from GSK, Provectus Inc, and Novartis., (© 2022 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Oral cavity mucosal melanomas (OCMM) represent only 3% of all malignant melanomas. Surgery is the mainstay of treatments and it is often followed by adjuvant radiotherapy. The role of adjuvant immunotherapy and/or chemotherapy is still debated and to date neither treatment is routinely used. From January 1990 to January 2010, we have collected from our database data of 20 patients with a histologically proven diagnosis of OCMM. Upfront surgery, followed by adjuvant radiotherapy was performed in 16/20 (80%) patients. Immunohistochemical analysis was carried out on all tissue samples and the following markers were assessed: Ki-67, HMG-45, Melan-A, S-100, CD31, CD35, CD20, CD21, and CD3. Although Ki-67, HMG-45, Melan-A, and S-100 were assessed in tumor cells, the analysis of CD31, CD21, CD20, CD3, and CD35 was carried out on the tumor-infiltrating lymphocytes. Patient outcome was analyzed and associated with clinical and Immunohistochemical tumor characteristics. The median overall survival (OS) was 12 months, with a 2-year OS rate of 30%. The median progression-free survival (PFS) was 9 months, with a 2-year PFS rate of 25%. Grade of lymphocyte infiltration (CD20 and CD3 expression) correlated strongly with prognosis. Interestingly, overexpression of CD21 along with downregulation of CD31 was significantly associated with better OS and PFS, whereas the reversal features correlated with a poor prognosis. Our report shows that patients affected by OCMM have a poor prognosis despite the administration of multimodal treatments. Moreover, our analysis suggests that the evaluation of several biomarkers, especially in tumor-infiltrating lymphocytes, may identify categories of patients with distinct immune response against the tumor and possibly different treatment response and prognosis.

The aim of the study was to report three patients affected by interstitial lung disease associated with positive anti-SS-A/Ro autoantibody who showed a dramatic improvement after immunosuppressive treatment. Medical charts were reviewed to obtain clinical data, laboratory parameters, lung function tests, high-resolution computed tomography results and response to immunosuppressive treatment. The three patients showed a clinical picture of a lung-dominant connective tissue disease characterized by a sudden onset with dyspnea, cough and subtle extrathoracic features together with positive anti-SS-A/Ro antibody and weak titer antinuclear antibodies. All three patients responded favorably to immunosuppressive therapy: Two cases were treated with a combination of corticosteroid and cyclophosphamide followed by mycophenolate mofetil; in the third patient, clinical benefit was obtained after rituximab was added to corticosteroid and immunosuppressant drug. In spite of an abrupt onset with significant lung function impairment, all three patients had a favorable clinical response to immunosuppressive therapy. This report may be useful in making therapeutic decisions in case of interstitial lung disease associated with anti-SS-A antibody.

Septic shock, a severe form of sepsis, is characterized by cardiovascular collapse following microbial invasion of the body. The progressive hypotension, hyporeactivity to vasopressor agents and vascular leak leads to circulatory failure with multiple organ dysfunction and death. Many inflammatory mediators (e.g. TNF-alpha, IL-1 and IL-6) are involved in the pathogenesis of shock and, among them, nitric oxide (NO). The overproduction of NO during septic shock has been demonstrated to contribute to circulatory failure, myocardial dysfunction, organ injury and multiple organ failure. We have previously demonstrated with in vitro and in vivo studies that methylguanidine (MG), a guanidine compound deriving from protein catabolism, significantly inhibits iNOS activity, TNF-alpha release and carrageenan-induced acute inflammation in rats. The aim of the present study was to evaluate the possible anti-inflammatory activity of MG in a model of septic shock induced by lipopolysaccharide (LPS) in mice. MG was administered intraperitoneally (i.p.) at the dose of 30 mg/kg 1 h before and at 1 and 6 h after LPS-induced shock. LPS injection (10 mg/kg in 0.9% NaCl; 0.1 ml/mouse; i.p.) in mouse developed a shock syndrome with enhanced NO release and liver, kidney and pancreatic damage 18 h later. NOx levels, evaluated as nitrite/nitrate serum levels, was significantly reduced in MG-treated rats (78.6%, p < 0.0001; n = 10). Immunohistochemistry revealed, in the lung tissue of LPS-treated group, a positive staining for nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) synthase, both of which were reduced in MG-treated mice. Furthermore, enzymatic evaluation revealed a significant reduction in liver, renal and pancreatic tissue damage and MG treatment also improved significantly the survival rate. This study provides evidence that MG attenuates the degree of inflammation and tissue damage associated with endotoxic shock in mice. The mechanisms of the anti-inflammatory effect of MG is, at least in part, dependent on the inhibition of NO formation.