Host-Microbiome Crosstalk in Chronic Wound Healing.

The pathogenesis of chronic wounds (CW) involves a multifaceted interplay of biochemical, immunological, hematological, and microbiological interactions. Biofilm development is a significant virulence trait which enhances microbial survival and pathogenicity and has various implications on the development and management of CW. Biofilms induce a prolonged suboptimal inflammation in the wound microenvironment, associated with delayed healing. The composition of wound fluid (WF) adds more complexity to the subject, with proven pro-inflammatory properties and an intricate crosstalk among cytokines, chemokines, microRNAs, proteases, growth factors, and ECM components. One approach to achieve information on the mechanisms of disease progression and therapeutic response is the use of multiple high-throughput 'OMIC' modalities (genomic, proteomic, lipidomic, metabolomic assays), facilitating the discovery of potential biomarkers for wound healing, which may represent a breakthrough in this field and a major help in addressing delayed wound healing. In this review article, we aim to summarize the current progress achieved in host-microbiome crosstalk in the spectrum of CW healing and highlight future innovative strategies to boost the host immune response against infections, focusing on the interaction between pathogens and their hosts (for instance, by harnessing microorganisms like probiotics), which may serve as the prospective advancement of vaccines and treatments against infections.

Perspectives on Psoriasiform Adverse Events from Immune Checkpoint Inhibitors: Lessons Learned from Our Practice.

Background: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality of life and potentially limit their use. Among these adverse events are psoriasis and psoriatic arthritis that may develop de novo or flare under treatment with ICIs. Given the exceptional immune status of patients receiving ICIs, managing these conditions without interfering with the effect of the oncologic treatment may prove very challenging. Aim: To review the literature data on ICI-induced psoriasis exacerbation or development, to present our own experience, and to discuss the pathogenic mechanisms underlying this association and the optimal therapeutic approach for these patients. Case Reports: We report three cases of ICI-induced de novo psoriasis and two cases of ICI-induced psoriasis exacerbation that required systemic treatment. Oral acitretin treatment successfully controlled psoriasis lesions in three cases and allowed for the continuation of immunotherapy. Literature Review: We performed a medical literature search across several databases (PubMed, Medline, Google Scholar) using the search terms "immune checkpoint inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis". We identified and revised 80 relevant publications that reported 1102 patients with psoriasis and/or psoriasis arthritis induced or exacerbated by ICIs. We assessed the type of cancer, the therapeutic agent involved, the clinical form of psoriasis, the presence or absence of psoriatic arthritis, the personal and family history of psoriasis, the age, the gender, the time until onset or exacerbation of skin lesions, the specific treatment recommended, the need for ICI discontinuation, and the patient's outcome. Conclusions: As ICIs represent a fairly novel therapy, the association with several adverse effects is only now unraveling. Psoriasis exacerbation or onset following the initiation of immunotherapy is one such example, as more and more reports and case series are being published. Awareness of the relationship between psoriasis and treatment with ICIs, prompt recognition, and initiation of adequate skin-directed therapies are essential for the avoidance of skin lesions worsening, the need for systemic treatments that may interfere with ICIs' effects, or the discontinuation of the latter. In the absence of generally accepted guidelines, it is advisable to treat patients with severe, widespread psoriasis with drugs that do not impair the effects of immunotherapy and thus do not alter the patient's prognosis.

Pyoderma Gangrenosum: The Impact of Treatment Non-adherence on Disease Progression.

Pyoderma gangrenosum (PG) is a rare, ulcerative, rapidly progressing, destructive, inflammatory cutaneous disease that is both diagnostically and therapeutically challenging. Due to the lack of standardized diagnostic criteria or conclusive guidelines for patient management, clinicians often find themselves without reliable tools for the daily management of PG patients. Additionally, the lack of strict therapeutic compliance in patients with this diagnosis might contribute to a catastrophic evolution of the condition. We report a case of ulcerative PG that is illustrative of the inherent challenges posed by patients frequently changing healthcare providers and treatment regimens, displaying inconsistency and non-adherence. Such behaviors can lead to the loss of disease control, particularly in the context of extensive or rapidly progressing PG, ultimately culminating in the development of mutilating forms of this disease.

Cutaneous Adverse Reactions Associated with Tattoos and Permanent Makeup Pigments.

Tattooing is the procedure of implanting permanent pigment granules and additives into the dermal layer of the skin, serving various purposes such as decoration, medical identification, or accidental markings. There has been a significant rise in the popularity of decorative tattooing as a form of body art among both teenagers and young adults. Thus, the incidence of tattoos is increasing, with expanding applications such as permanent makeup, scar camouflage, nipple-areola, lips, and eyebrows tattooing, and utilization in oncological radiotherapy such as colon marking. However, there have been reported a broad range of adverse reactions linked to tattooing, encompassing allergic reactions, superficial and deep cutaneous infections, autoimmune disorders induced by the Koebner phenomenon, cutaneous tumors, and others. These reactions exhibit different onset times for symptoms, ranging from immediate manifestations after tattoo application to symptoms emerging several years later. Given the limited information on a tattoo's side effects, this review aims to elucidate the clinical spectrum of cutaneous complications of tattoos in different patients. The analysis will investigate both allergic and nonallergic clinical presentations of tattoo-related side effects, microscopic findings from skin biopsies, and therapeutic outcomes. This exploration is essential to improve our understanding of tattoo-related cutaneous complications and associated differential diagnoses and highlight the significance of patient awareness regarding potential risks before getting a tattoo.

Personalization of Minimally-Invasive Aesthetic Procedures with the Use of Ultrasound Compared to Alternative Imaging Modalities.

Ultrasonography is a well-tolerated procedure that aids in the targeted esthetic therapies of special cutaneous regions, as well as in the prevention (vascular mapping, identification of previous filler, and others) and management of potential complications (vascular occlusion, external vascular compression, product misplacement or migration, inflammatory reactions, and others). It has lately been promoted as the first-line imaging tool to address injectables. In this article, we aim to review the evolving role of ultrasonography in cosmetic filler procedures, from the fundamental ultrasound characterization of cosmetic fillers to the ultrasound-enhanced detection and management of cosmetic filler complications, including ultrasound's role in hyaluronidase-guided injections for cosmetic filler dissolution. Furthermore, the paper explores the integral role played by ultrasound in enhancing the precision, efficacy, and safety of additional minimally invasive aesthetic techniques such as mesotherapy, radiofrequency, cryolipolysis, and polydioxanone procedures.

An Insight on the Possible Association between Inflammatory Bowel Disease and Biologic Therapy with IL-17 Inhibitors in Psoriasis Patients.

Psoriasis is a chronic, inflammatory, multisystemic disease which affects approximately 2-3% of the population globally, whose onset is triggered by genetic and environmental factors which activate both dendritic cells and keratinocytes, resulting in the production of proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 17, interleukin 23, interleukin 22, and interleukin 1ß. An in-depth understanding of the pathophysiology of psoriasis led to significant advances in the development of safe and efficient novel therapeutic options, with four classes of biologic therapy being approved for the management of moderate to severe psoriasis: tumor necrosis factor alpha inhibitors, interleukin 23 inhibitors, anti-interleukin 12/23 agents, anti-interleukin 17 agents, as well as small-molecule inhibitors, such as apremilast. Psoriasis is associated with comorbid conditions, namely psoriatic arthritis, cardiovascular disease, metabolic syndrome, psychiatric disorders, malignancy, as well as inflammatory bowel disease. For patients affected by both psoriasis and inflammatory bowel disease, there is a strong recommendation to avoid IL-17 inhibitors since they may play a part in the exacerbation of the gastrointestinal disease. Our aim was to perform a thorough literature review regarding the development of inflammatory bowel disease lesions in psoriasis patients treated with IL-17 inhibitors, along with a case presentation to emphasize the need for close follow-up of these patients.

Antimicrobial Biomaterials for Chronic Wound Care.

Chronic wounds encompass a myriad of lesions, including venous and arterial leg ulcers, diabetic foot ulcers (DFUs), pressure ulcers, non-healing surgical wounds and others. Despite the etiological differences, chronic wounds share several features at a molecular level. The wound bed is a convenient environment for microbial adherence, colonization and infection, with the initiation of a complex host-microbiome interplay. Chronic wound infections with mono- or poly-microbial biofilms are frequent and their management is challenging due to tolerance and resistance to antimicrobial therapy (systemic antibiotic or antifungal therapy or antiseptic topicals) and to the host's immune defense mechanisms. The ideal dressing should maintain moisture, allow water and gas permeability, absorb wound exudates, protect against bacteria and other infectious agents, be biocompatible, be non-allergenic, be non-toxic and biodegradable, be easy to use and remove and, last but not least, it should be cost-efficient. Although many wound dressings possess intrinsic antimicrobial properties acting as a barrier to pathogen invasion, adding anti-infectious targeted agents to the wound dressing may increase their efficiency. Antimicrobial biomaterials may represent a potential substitute for systemic treatment of chronic wound infections. In this review, we aim to describe the available types of antimicrobial biomaterials for chronic wound care and discuss the host response and the spectrum of pathophysiologic changes resulting from the contact between biomaterials and host tissues.

Challenging Patterns of Atypical Dermatofibromas and Promising Diagnostic Tools for Differential Diagnosis of Malignant Lesions.

Dermatofibroma (DF) or fibrous histiocytoma is one of the most frequent benign cutaneous soft-tissue lesions, characterized by a post-inflammatory tissue reaction associated with fibrosis of the dermis. Clinically DFs have a polymorphous clinical aspect from the solitary, firm, single nodules to multiple papules with a relatively smooth surface. However, multiple atypical clinicopathological variants of DFs have been reported and, therefore, clinical recognition may become challenging, leading to a more burdensome identification and sometimes to misdiagnosis. Dermoscopy is considered an important tool in DFs diagnosis, as it improves diagnostic accuracy for clinically amelanotic nodules. Although typical dermoscopic patterns are most frequently seen in clinical practice, there have also been some atypical variants described, mimicking some underlying recurrent and sometimes harmful skin afflictions. Usually, no treatment is required, although an appropriate work-up may be necessary in specific cases, such as in the presence of atypical variants or a history of recent changes. This narrative review's aim is to summarize current evidence regarding clinical presentation, positive and differential diagnosis of atypical dermatofibromas and also to raise awareness about the importance of specific characteristics of atypical variants to better differentiate them from malignant conditions.

Clinical and microbiological features of host-bacterial interplay in chronic venous ulcers versus other types of chronic skin ulcers.

Introduction: Chronic venous ulcers of the lower limbs develop in the context of advanced venous disease and have a significant impact on the patient's quality of life, being associated with depression and worrisome suicide rates, as well as with an economic burden caused by increased medical care costs and high epidemiological risks of healthcare associated infections and emergence of strains resistant to multiple classes of antibiotics and/ or antiseptics. Although numerous studies have investigated the composition of the chronic wounds microbiome, either by culture-dependent or independent methods, there are no data on the association between virulence and resistance profiles of strains isolated from venous ulcers and the clinical picture of this pathology. The elucidation of pathogenic mechanisms, at both phenotypic and molecular level, is crucial in the fight against these important human microbial agents, in order to develop novel biomarkers and discover new therapeutic targets. Methods: In this study we aimed to characterize the phenotypic virulence profiles (including the ability to develop biofilms) of microorganisms isolated from chronic skin wounds and to correlate them with the clinical symptomatology. Considering the high incidence of Staphylococcus aureus infections in chronic ulcers, but also the ability of this species to develop multi-drug resistance, we performed an more in-depth study of the phenotypic and genotypic virulence profiles of methicillin-resistant Staphylococcus. Results: The study revealed important differences regarding the clinical evolution and virulence profiles of microorganisms isolated from lower limb wounds, as well as between patients diagnosed with chronic venous ulcers and those with lesions of different etiology.

Pediatric inflammatory multisystem syndrome induced Panuveitis associated with SARS-CoV- 2 infection: What the Ophthalmologists need to know.

The diagnosis of bilateral panuveitis was made in a 9-year-old girl who was referred to our hospital for blurred vision accompanied by periorbital and abdominal pain. Endothelial dusting, vitreous haze and optic nerve edema were deemed as signs of involvement of all segments of the eye. The bloodwork results were suggestive of infectious uveitis, with elevated inflammatory markers and the patient was treated with IV antibiotics. Cerebral-CT was normal, screening for common infectious causes of uveitis and cultures were negative. There was no history of autoimmune disease, and autoimmune antibody tests were negative. Pediatric inflammatory multisystem syndrome induced panuveitis, secondary to SARS-CoV-2 (PIMS), was suspected by the infectious disease consultant. The syndrome commonly affects school-age children and represents a generalized inflammatory response in the body that appears about one month after the initial infection with the SARS-CoV-2 virus. Initial symptoms include fever, abdominal pain, eye redness, rashes, dizziness, accompanied by laboratory evidence of inflammation unexplained by any other plausible cause. The patient's coronavirus IgG titer was positive, while the RT-PCR for SARS-CoV-2 virus, taken from the nasopharyngeal swab, was negative. As all the other investigations turned out negative, COVID-19 was the only presumptive cause for the pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS). A diagnosis of probable COVID-19 induced uveitis was made and the patient started IV Dexamethasone, followed by oral steroids that were gradually tapered and made a full recovery. The aim of this report was to shed light and enrich the scarce literature available on Uveitis as a sign of pediatric inflammatory syndrome following COVID-19 infection. Abbreviations: ACE2 = Angiotensin converting enzyme 2, ANA = Antinuclear antibodies, c-ANCA, p-ANCA = Cytoplasmic and perinuclear anti-neutrophil cytoplasm antibodies, BCVA = Best corrected visual acuity, CMV = Cytomegalovirus, COVID-19 = coronavirus disease 2019, CRE = Carbapenem-resistant Enterobacteriaceae, CRP = C-Reactive Protein, EBV = Epstein Barr virus, ESBL = Extended spectrum beta-lactamase, ESR = Erythrocyte Sedimentation Rate, FCoV = Feline coronavirus, MDR = Multidrug resistant, MRSA = methicillin-resistant Staphylococcus aureus, MHV = mouse hepatitis virus, MIS-C = multisystem inflammatory syndrome in children, NSAID = Nonsteroidal anti-inflammatory drug, NT pro BNP = precursor natriuretic brain peptide, PIMS-TS = Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, RNFL = Retinal nerve fiber layer, SARS CoV-2 = severe acute respiratory syndrome coronavirus 2, SD-OCT = Spectral domain optical coherence tomography, VRE = Vancomycin-resistant Enterococci.

Botulinum Toxin Use for Modulating Neuroimmune Cutaneous Activity in Psoriasis.

Psoriasis is a complex immune-mediated inflammatory disorder that generates enormous interest within the scientific communities worldwide, with new therapeutic targets being constantly identified and tested. Despite the numerous topical and systemic medications available for the treatment of psoriasis, alternative therapies are still needed for the optimal management of some patients who present with localized, resistant lesions. Novel insights into the contribution of cutaneous neurogenic inflammation in the pathogenesis of psoriasis have yielded exciting new potential roles of nerve-targeting treatments, namely botulinum toxin type A (BoNT-A), for the management of this disease. This paper aims to review the existing literature on knowledge regarding the potential role of BoNT-A in psoriasis treatment, with a focus on its ability to interfere with the immunopathogenetic aspects of psoriatic disease. Furthermore, in our paper, we are also including the first report of psoriatic lesions remission following local BoNT-A injections that were administered for treating upper limb spasticity, in a patient that concomitantly suffered from psoriasis and post-stroke spasticity.

Current and Future Approaches in Management of Chronic Spontaneous Urticaria Using Anti-IgE Antibodies.

Chronic spontaneous urticaria (CSU) considerably alters patients' quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep, unexpected development of angioedema, and failure of conventional treatments in properly controlling signs and symptoms. Recent research focused on the development of new therapeutic agents with higher efficacy. Although the production of specific immunoglobulin E (IgE) antibodies against certain allergens is not a characteristic of the disease, treatment with omalizumab, a monoclonal anti-IgE antibody, proved efficient and safe in patients with moderate to severe chronic spontaneous urticaria uncontrolled by H1-antihistamines. Ligelizumab, a high-affinity monoclonal anti-IgE antibody, may also efficiently relieve symptoms of unresponsive chronic urticaria to standard therapies. This comprehensive review aims to present recently acquired knowledge on managing chronic spontaneous urticaria with new anti-IgE antibodies. We conducted extensive research on the main databases (PubMed, Google Scholar, and Web of Science) with no restrictions on the years covered, using the search terms "anti-IgE antibodies", "omalizumab", "ligelizumab", and "chronic spontaneous urticaria". The inclusion criteria were English written articles, and the exclusion criteria were animal-related studies. ClinicalTrials.gov was also reviewed for recent relevant clinical trials related to CSU treatment. CSU is a challenging disease with a significant effect on patients' quality of life. Current therapies often fail to control signs and symptoms, and additional treatment is needed. New biologic therapies against IgE antibodies and FcεRIα receptors are currently under investigation in advanced clinical trials. We reviewed recently published data on CSU management using these novel treatments. The development of new and improved treatments for CSU will lead to a more personalized therapeutical approach for patients and provide guidance for physicians in better understanding disease mechanisms. However, some agents are still in clinical trials, and more research is needed to establish the safety and efficacy of these treatments.

Risks of Biologic Therapy and the Importance of Multidisciplinary Approach for an Accurate Management of Patients with Moderate-Severe Psoriasis and Concomitant Diseases.

Psoriasis is a chronic multisystem inflammatory disease associated with a plethora of comorbidities including metabolic syndrome, cardiovascular disease, hypertension, diabetes, hyperlipidemia, obesity, anxiety, depression, chronic kidney disease, and malignancy. Advancement in unveiling new key elements in the pathophysiology of psoriasis led to significant progress in the development of biologic agents which target different signaling pathways and cytokines involved in the inflammatory cascade responsible for the clinical manifestations found in psoriasis. Currently available novel therapeutic options for moderate-severe psoriasis include tumor necrosis factor alpha inhibitors, inhibitors of the interleukin 17, and inhibitors of the interleukin 23. Nevertheless, concerns have been raised with respect to the possible risks associated with the use of biologic therapy requiring close collaboration between dermatologists and physicians of different specialties. Our aim was to perform an in-depth literature review and discuss the potential risks associated with biologic therapy in patients with psoriasis and concurrent diseases with a focus on the influence of novel therapeutic agents on liver function in the context of hepatopathies, particularly viral hepatitis. A multidisciplinary teamwork and periodic evaluation of psoriasis patients under biologic therapy is highly encouraged to obtain an accurate management for each case.

Complementary Strategies to Promote Hair Regrowth in Post-COVID-19 Telogen Effluvium.

Post-COVID-19 telogen effluvium has been largely reported as a sequela in the post-acute phase of COVID-19, causing major emotional distress among the affected patients. The affected individuals are further exposed to a vast amount of misinformation from the internet and social media and it is important for physicians to be familiar with the phenomenon and provide appropriate counselling to their patients regarding this condition. This article aims to review the evidence-based complementary strategies that can help enhance hair regrowth after post-COVID-19 hair loss, from psychological support and patient education to the importance of optimal nutrition and potential indications and benefits of oral nutritional supplementation, as well as the role of both topical and injectable hair growth stimulators.

How Many Times Can One Go Back to the Drawing Board before the Accurate Diagnosis and Surgical Treatment of Glucagonoma?

Glucagonomas are neuroendocrine tumors (NETs) that arise from the alpha cells of the pancreatic islets. They are typically slow-growing tumors associated with abnormal glucagon secretion, resulting in one or more non-specific clinical features, such as necrolytic migratory erythema (NME), diabetes, diarrhea, deep vein thrombosis, weight loss, and depression. Here, we report the case of a 44-year-old male with a history of diabetes mellitus, presenting with a pruritic and painful disseminated cutaneous eruption of erythematous plaques, with scales and peripheral pustules, misdiagnosed as disseminated pustular psoriasis and treated for 2 years with oral retinoid and glucocorticoids. During this period, the patient complained of weight loss of 32 kg and diarrhea and developed deep vein thrombosis. These symptoms, together with an inadequate response to therapy of the skin lesions, led to the reassessment of the initial diagnosis. Laboratory tests confirmed elevated plasma glucagon levels (>1000 pg/mL) and computed tomography (CT) scans revealed a 35/44 mm tumor in the pancreatic tail. Due to considerable disease complications and the COVID-19 pandemic, the surgical removal of the tumor was delayed for nearly 2 years. During this time, somatostatin analogue therapy efficiently controlled the glucagonoma syndrome and likely prevented tumor progression. As in other functional pancreatic NETs, the early clinical recognition of hormonal hypersecretion syndrome and the multidisciplinary approach are the keys for best patient management.

Dysplastic nevus syndrome and pancreatic cancer: A case report.

Multiple primary cancers may occur in the same patient, with a prevalence that follows an ascendant trend. Their development is dictated by a complex interplay between a variety of factors, both patient-dependent and external. The case of a 38-year-old female patient diagnosed and treated for pancreatic cancer (PC) is presented in whom the digital dermoscopic monitoring of melanocytic nevi revealed a marked change of two nevi that acquired rapidly highly atypical features. They were surgically excised and the histopathological examination revealed two completely excised dysplastic compound nevi. Clinicians should be aware of the strong association between dysplastic nevus syndrome and PC, a malignancy associated with an extremely poor prognosis. Familial atypical multiple mole melanoma syndrome (FAMMM) predisposes to the development of melanoma, pancreatic cancer and other neoplasms. The common genetic background of PC and hereditary melanoma is discussed and the importance of regular skin checkup and screening for PC in these patients is underlined.

The immunoexpression of epidermal growth factor receptor in cutaneous squamous cell carcinoma.

Although cutaneous squamous cell carcinomas (cSCCs) account for only 20-25% of non-melanoma skin cancers (NMSCs), they are responsible for most deaths attributable to NMSCs. Apart from SCC seric level, which increases in late-stage disease, no other predictive biomarker for cSCC exists. Epidermal growth factor receptor (EGFR) serves as a predictive biomarker and therapeutic target in numerous malignancies. EGFR immunoexpression is highly elevated in head and neck mucosal SCC. However, its immunoexpression pattern, its relationship with prognosis and survival, and the effect of EGFR targeted therapy in advanced cSCC have not been clarified. We assessed EGFR immunoexpression in 18 cases of cSCC and correlated our findings with the clinicopathological features. Immunohistochemical stainings with anti-EGFR monoclonal antibodies were practiced and the membrane and cytoplasmic immunostaining intensity and quality in the tumors and the non-lesional epithelium were analyzed. Membrane EGFR immunoexpression within the tumors increased with the tumor grade. EGFR overexpression was more frequently found in head and neck cSCCs. We did not find a direct relationship between cytoplasmic EGFR immunoexpression and clinicopathological findings and prognosis. Our results confirm that increased EGFR immunoexpression correlates with aggressive cSCC phenotypes and underline the need for novel treatments for these patients.

Autologous Platelet-Rich Plasma Efficacy in the Field of Regenerative Medicine: Product and Quality Control.

Platelet-rich plasma (PRP) has emerged as a significant regenerative therapy used alone or combined mainly with stem cells, autologous fat grafts, hyaluronic acid, and biomaterials in a variety of medical fields, especially in hair regrowth, wound healing, and sports and rehabilitation medicine. However, the results obtained with this biologic therapy are heterogeneous and conflicting. The observed disparities in the effectiveness of PRP therapies may be due to a lack of standardization in blood processing and preparation. This article is aimed at reviewing the main biological parameters that need to be documented for a thorough reporting of quantitative and qualitative characteristics of the PRP injected, to allow a comparison between the quality of samples and the clinically obtained results and advance the efforts towards treatment standardization.

The Impact of Long-Term Antibiotic Therapy of Cutaneous Adverse Reactions to EGFR Inhibitors in Colorectal Cancer Patients.

Colorectal cancer (CRC) is an important public health issue, in terms of incidence and mortality, with approximately 1.8 million new cases reported worldwide in 2018. Advancements in understanding pathophysiological key steps in CRC tumorigenesis have led to the development of new targeted therapies such as those based on epidermal growth factor receptor inhibitors (EGFR inhibitors). The cutaneous adverse reactions induced by EGFR inhibitors, particularly papulopustular rash, often require long-term antibiotic treatment with tetracycline agents (mostly minocycline and doxycycline). However, this raises several issues of concern: possible occurrence of gut dysbiosis in already vulnerable CRC patients, selection of highly antibiotic resistant and/or virulent clones, development of adverse reactions related to tetracyclines, interference of antibiotics with the response to oncologic therapy, with a negative impact on disease prognosis etc. In the context of scarce information regarding these issues and controversial opinions regarding the role of tetracyclines in patients under EGFR inhibitors, our aim was to perform a thorough literature review and discuss the main challenges raised by long-term use of tetracyclines in advanced CRC patients receiving this targeted therapy.

Electrochemotherapy and Other Clinical Applications of Electroporation for the Targeted Therapy of Metastatic Melanoma.

Electrochemotherapy (ECT) is an effective bioelectrochemical procedure that uses controlled electrical pulses to facilitate the increase of intracellular concentration of certain substances (electropermeabilization/ reversible electroporation). ECT using antitumor drugs such as bleomycin and cisplatin is a minimally invasive targeted therapy that can be used as an alternative for oncologic patients not eligible for surgery or other standard therapies. Even though ECT is mainly applied as palliative care for metastases, it may also be used for primary tumors that are unresectable due to size and location. Skin neoplasms are the main clinical indication of ECT, the procedure reporting good curative results and high efficiency across all tumor types, including melanoma. In daily practice, there are many cases in which the patient's quality of life can be significantly improved by a safe procedure such as ECT. Its popularity must be increased because it has a safe profile and minor local adverse reactions. The method can be used by dermatologists, oncologists, and surgeons. The aim of this paper is to review recent literature concerning electrochemotherapy and other clinical applications of electroporation for the targeted therapy of metastatic melanoma.