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Carmen Bobeica,1,* Elena Niculet,2,3,* Carmina Liana Musat,2,* Lina Iancu,4 Mihaela Craescu,2,3 Andreea Mioara Luca,5 Bogdan Ioan Stefanescu,6 Emma Gheorghe,7 Mihaela Debita,8 Claudiu-Ionut Vasile,8 Gabriela Balan,8– 10 Camelia Busila,8 Alin Laurentiu Tatu3,8,11 1Medical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, 800008, Romania; 2Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, 800008, Romania; 3Multidisciplinary Integrated Center of Dermatological Interface Research MIC-DIR (Centrul Integrat Multidisciplinar de Cercetare de Interfata Dermatologica - CIM-CID), “Dunărea de Jos” University, Galați, Romania; 4Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, 800008, Romania; 5Department of Plastic Surgery, “Sf. Ioan” Clinical Emergency Hospital for Children, Galați, 800487, Romania; 6Clinical Surgical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 7Department No. 1 (Preclinical), Faculty of Medicine and Pharmacy, “Ovidius” University, Constanța, 900527, Romania; 8Clinical Medical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, 800008, Romania; 9Department of Gastroenterology, “Sf. Apostol Andrei” County Emergency Clinical Hospital, Galaţi, 800578, Romania; 10Research Center in the Field of Medical and Pharmaceutical Sciences, “Dunărea de Jos” University, Galaţi, 800008, Romania; 11Dermatology Department, “Sf. Cuvioasa Parascheva” Clinical Hospital of Infectious Diseases, Galați, 800179, Romania*These authors contributed equally to this workCorrespondence: Elena Niculet; Carmina Liana Musat, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, 35 Alexandru Ioan Cuza Street, Galați, 800216, Romania, Tel +40741398895 ; +40723338438, Email helena_badiu@yahoo.com; carmina.musat@ugal.roPurpose: Systemic sclerosis (SSc) is a relatively rare collagenosis manifested as microvasculopathy, excessive cutaneous and visceral fibrosis in a background of autoimmune alteration. Autoimmune vasculopathy in SSc occurs early and begins with endothelial cell activation followed by blood vessel intimal proliferation in a context of defective angiogenesis. The alteration of peripheral micro and macrocirculation in SSc is evident through vascular lesions, such as Raynaud’s phenomenon, telangiectasias, acrocyanosis, digital ulcers, gangrene, peripheral pulse deficiency. Our paper details the results of the study on the association between telangiectasias and other types of immune-mediated peripheral vascular lesions that can be identified in SSc. The presence of these peripheral vascular lesions can provide information about the magnitude of the peripheral vasculopathy.Patients and Methods: A total of 37 patients diagnosed with SSc, recruited from a university clinic in Bucharest between February 2019 and March 2020, were enrolled in an observational study. We evaluated the presence of telangiectasias, as a stigma of autoimmune microvasculopathy, and their association with other immune-mediated peripheral vascular lesions that may be present in SSc.Results: The presence of telangiectasias was identified in the absence, but especially in the presence of acrocyanosis and digital ulcerations, and patients with peripheral pulse deficiency almost always had telangiectasias. Less than a quarter of the patients with digital ulcers progressed unfavorably to gangrene, and only one required amputation, telangiectasias being present not only in the patient with amputation but in all patients with gangrene.Conclusion: We appreciate that telangiectasias may be the clinical expression of peripheral vasculopathy characteristic of SSc, they can often be present in association with other peripheral vascular lesions and may represent a valuable indicator for the gangrene risk of digital ulcerations in SSc.Keywords: systemic sclerosis, vascular lesions, phenomenon Raynaud’s, telangiectasias, acrocianosis, digital ulcers

Carmina Liana Musat,1,* Elena Niculet,1,2,* Mihaela Craescu,1,2,* Luiza Nechita,3 Lina Iancu,4 Aurel Nechita,3 Doina-Carina Voinescu,3 Carmen Bobeica5,* 1Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, 800008, Romania; 2Multidisciplinary Integrated Center of Dermatological Interface Research MIC-DIR (Centrul Integrat Multidisciplinar de Cercetare de Interfata Dermatologica - CIM-CID), “Dunărea de Jos” University, Galați, Romania; 3Clinical Medical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, 800008, Romania; 4Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, 800008, Romania; 5Medical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, 800008, Romania*These authors contributed equally to this workCorrespondence: Elena Niculet; Mihaela Craescu, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, 35 Alexandru Ioan Cuza Street, Galati, 800216, Romania, Tel +40741398895 ; +40751869864, Email helena_badiu@yahoo.com; mihaela.craescu@ugal.roPurpose: The identification of sports and physical exercises with injury risk is necessary to preserve the capacity of athletes and people who perform physical education and also to prevent the installation of functional deficiencies.Methods: We have selected the articles related to the pathogenic mechanisms involved in musculotendinous and fascial injuries produced as a result of physical exercise.Results and Discussions: The lesional pathogenesis is complex and incompletely clarified. Recent theories put in a new light the mechanisms of muscle pain and tendinopathy production. The accumulation of lactate anion, known to be a residue that induces fatigue and muscle pain, has been reconsidered by some authors. It appears that lactate anion is an excellent fuel for the myocardial fiber. Moreover, the accumulation of lactic acid after intense physical exercise could prevent the inexcitability of the sarcolemma induced by the increased concentration of interstitial K+. Most of the time, overuse injuries are not limited to muscles. They can cause myofascial, myotendinous or purely muscular injuries. The muscular fascia is more susceptible to injuries produced under the action of large external forces. Also, fascia is more sensitive to pain compared to muscle when external forces act eccentrically. Overloading the tendon and putting it under tension repeatedly is followed by ruptures of the tendon fibers. The regeneration of the degenerated tendon is defective in the context of the inflammation produced by the injury. Tendon fibers undergo a process of fibrosis, scarring, adhesion and heterogeneous calcification. Oxidative stress is responsible for inflammation, degeneration and apoptosis of tenocytes.Conclusion: The benefits brought by physical education and sports are indisputable, but their practice requires a coordinated program to prevent possible traumatic and overuse injuries.Keywords: sport muscle injury, musculofascial injury, pathogenesis, stress tendinopathy, delayed onset muscle soreness

Elena Niculet1,2 *, Carmen Bobeica1 *, Mihaela Craescu,1,2 Alin Codrut Nicolescu3 *, George Tocu,4 Cristian Onisor1 *, Manuela Arbune5 *, Alin Laurentiu Tatu2,5,6 1Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 2Multidisciplinary Integrated Center of Dermatological Interface Research MIC-DIR (Centrul Integrat Multidisciplinar de Cercetare de Interfata Dermatologica - CIM-CID), “Dunărea de Jos” University, Galați, Romania; 3Roma Medical Center for Diagnosis and Treatment, Bucharest, Romania; 4Department of Pharmaceutical Sciences, “Dunărea de Jos” University, Galati, Romania; 5Clinical Medical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 6Dermatology Department, “Sf. Cuvioasa Parascheva” Clinical Hospital of Infectious Diseases, Galați, Romania*These authors contributed equally to this workCorrespondence: Mihaela Craescu, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, 35 Alexandru Ioan Cuza Street, Galați, 800008, Romania, Tel +40751869864, Email dr.craescumihaela@yahoo.ro George Tocu, Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, 35 Alexandru Ioan Cuza Street, Galați, 800008, Romania, Tel +40773819438, Email george_tocu@yahoo.comAbstract: Although basal cell carcinoma is a well-known tumor with confirmed clinical and histopathology traits, prognosis factors and treatment options, new facets of this tumor emerge as innovative approach methods develop. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) allow a basal cell carcinoma’s in vivo analysis of its depth of invasion, tumor margins prior to surgical approach and the tumor’s response to a non-invasive treatment, evaluating simultaneously the tumor’s vasculature. By RCM and OCT analysis, basal cell carcinoma has registered a groundbreaking discovery regarding a small (but with predictive factor potential) trait – the cleft, developing in between the tumor islands/nodules/chords and the surrounding tumor stroma; it was considered to date as a consequence of the tissue’s histopathology processing. RCM and OCT revealed that the “clefting artifact”, as it is frequently found in the medical literature, is not actually an artifact of laboratory processing, but a tumor trait found in vivo, with apparent mucin deposits. This review aims at merging the methods of evaluating basal cell carcinoma, both non-invasive (dermoscopy, RCM, OCT) and invasive ones (histopathology – with newly proposed classification), with special emphasis on the cleft issue – its assessment with the aforementioned techniques, with potential implications in the patient’s prognosis.Keywords: basal cell carcinoma, cleft, structural aggressive traits, reflectance confocal microscopy, optical coherence tomography, pathology

Carmen Bobeica,1,* Elena Niculet,1,2 Mihaela Craescu,1 Elena-Laura Parapiru,3,* Carmina Liana Musat,1,* Ciprian Dinu,4,* Iulia Chiscop,5,* Luiza Nechita,3,* Mihaela Debita,6,* Victorita Stefanescu,6,* Ioana Anca Stefanopol,1,7,* Alexandru Nechifor,3,* Ana Maria Pelin,8,* Gabriela Balan,3,9,10,* Silvia Chirobocea,11,* Claudiu Ionut Vasile,3,* Alin Laurentiu Tatu2,3,12 1Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 2Multidisciplinary Integrated Center of Dermatological Interface Research MIC-DIR (Centrul Integrat Multidisciplinar de Cercetare de Interfata Dermatologica - CIM-CID), ‘Dunărea de Jos’ University, Galați, Romania; 3Clinical Medical Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 4Dental Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 5Clinical Surgical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 6Medical Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 7Department of Pediatrics, Clinical Emergency Hospital for Children “Sf. Ioan”, Galati, Romania; 8Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 9Department of Gastroenterology, “Sf. Apostol Andrei” County Emergency Clinical Hospital, Galați, Romania; 10Research Center in the Field of Medical and Pharmaceutical Sciences, “Dunărea de Jos” University, Galați, Romania; 11Department of Neurology, Municipal Emergency Hospital, Moinești, Romania; 12Dermatology Department, “Sf. Cuvioasa Parascheva” Clinical Hospital of Infectious Diseases, Galați, Romania*These authors contributed equally to this workCorrespondence: Elena Niculet; Mihaela Craescu, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, 35 Alexandru Ioan Cuza Street, Galați, 800008, Romania, Tel +40741398895 ; +40751869864, Email helena_badiu@yahoo.com; dr.craescumihaela@yahoo.roIntroduction: CREST syndrome is a clinical entity associated with systemic sclerosis, which meets at least three of the five clinical features: calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. Three of these clinical features (Raynaud’s phenomenon, sclerodactyly and esophageal dysmotility) are often present in classical subsets of SSc: limited and diffuse, and their presence in association does not define CREST syndrome. Calcinosis seems to be less common in SSc and its association with other clinical features is characteristic of CREST syndrome. Therefore, it can be appreciated that calcinosis is the key element of CREST syndrome.Methods: This study included a number of 37 candidates with SSc, diagnosed with the help of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 criteria.Results and Discussions: These three elements (calcinosis, Raynaud’s phenomenon, esophageal dysmotility) were recorded both in the limited subset of SSc, but especially in the subset of diffuse SSc, contrary to the data in the literature.Conclusion: We appreciate that CREST syndrome is a clinical entity that can overlap with both subsets of SSc. Given the divergent views of the authors on the classification of CREST syndrome, future studies may contribute to a reassessment of SSc classification.Keywords: systemic sclerosis, dystrophic calcinosis, CREST syndrome, telangiectasia, Raynaud’s phenomenon, sclerodactyly

Carmen Bobeica,1,* Elena Niculet,1,2 Mihaela Craescu,1 Elena-Laura Parapiru,3,* Carmina Liana Musat,1,* Ciprian Dinu,4,* Iulia Chiscop,5,* Luiza Nechita,3,* Victorita Stefanescu,6,* Ioana Anca Stefanopol,1,7,* Ana Maria Pelin,8,* Alexandru Nechifor,3,* Gabriela Balan,3,9,10,* Alin Laurentiu Tatu2,3,11 1Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 2Multidisciplinary Integrated Center of Dermatological Interface Research MIC-DIR (Centrul Integrat Multidisciplinar de Cercetare de Interfata Dermatologica - CIM-CID), ‘Dunărea de Jos’ University, Galați, Romania; 3Clinical Medical Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 4Dental Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 5Clinical Surgical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 6Medical Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 7Department of Pediatrics, Clinical Emergency Hospital for Children “Sf. Ioan”, Galati, Romania; 8Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 9Department of Gastroenterology, “Sf. Apostol Andrei” County Emergency Clinical Hospital, Galați, Romania; 10Research Center in the Field of Medical and Pharmaceutical Sciences, “Dunărea de Jos” University, Galați, Romania; 11Dermatology Department, “Sf. Cuvioasa Parascheva” Clinical Hospital of Infectious Diseases, Galați, Romania*These authors contributed equally to this workCorrespondence: Elena Niculet; Mihaela Craescu, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, 35 Alexandru Ioan Cuza Street, Galați, 800008, Romania, Tel +40741398895 ; +40751869864, Email helena_badiu@yahoo.com; dr.craescumihaela@yahoo.roAbstract: Systemic sclerosis (SSc) is a collagenosis with a substrate of chronic inflammation, which is determined by autoimmunity. The pathogenesis of this disease involves microvasculopathy (small vessel pathology) followed by excessive cutaneous and visceral fibrosis. Although acoustic and vestibular impairment is not classified as being a secondary pathology of SSc, several studies have identified cases of SSc that associate hearing loss and especially vertigo and tinnitus. This paper presents data from the medical literature that have identified vestibular and auditory symptoms among patients with SSc, associating the clinical case presentation of a patient suffering from SSc, which is associated with hearing loss. The need for additional studies on larger groups of patients is underlined, in order to clarify the impact of vasculopathy and fibrosis on the acoustic and vestibular analyzer in patients with SSc.Keywords: systemic sclerosis, hearing loss, vasculopathy, fibrosis, capillaroscopy

Carmen Bobeica,1,* Elena Niculet,1,2 Carmina Liana Musat,1 Mihaela Craescu,1,* Bogdan Ioan Stefanescu,3,* Ciprian Dinu,4,* Iulia Chiscop,3,* Silvia Chirobocea,5,* Luiza Nechita,6,* Alina Viorica Iancu,1,* Victorita Stefanescu,7,* Gabriela Balan,6,8,9,* Ioana Anca Stefanopol,1,10,* Ana Maria Pelin,11,* Alin Laurentiu Tatu2,6,12 1Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, Galati, 800008, Romania; 2Multidisciplinary Integrated Center of Dermatological Interface Research MIC-DIR (Centrul Integrat Multidisciplinar de Cercetare de Interfata Dermatologica - CIM-CID), “Dunărea de Jos” University, Galați, 800008, Romania; 3Clinical Surgical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 4Dental Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 5Department of Neurology, Municipal Emergency Hospital, Moinești, Romania; 6Clinical Medical Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 7Medical Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University, Galați, Romania; 8Department of Gastroenterology, “Sf. Apostol Andrei” County Emergency Clinical Hospital, Galați, Romania; 9Research Center in the Field of Medical and Pharmaceutical Sciences, “Dunărea de Jos” University, Galați, Romania; 10Department of Pediatrics, Clinical Emergency Hospital for Children “Sf. Ioan”, Galati, Romania; 11Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, Romania; 12Dermatology Department, “Sf. Cuvioasa Parascheva” Clinical Hospital of Infectious Diseases, Galați, Romania*These authors contributed equally to this workCorrespondence: Elena Niculet; Carmina Liana Musat, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, 35 Alexandru Ioan Cuza Street, Galați, 800008, Romania, Tel +40741398895 ; +40723338438, Email helena_badiu@yahoo.com; carmina.musat@ugal.roAbstract: Systemic sclerosis (SSc) is a chronic inflammatory disease with an autoimmune substrate that affects the skin and a large number of internal organs. The chronic inflammatory process is sustained by a wide range of cytokines and chemokines, which are discharged by inflammatory cells, with fibrosis and nail bed vascular changes (disorganized vasculature architecture with microhemorrhages, megacapillaries and areas without capillaries). Confocal microscopy contributes to the understanding of the molecular mechanism involved in chronic inflammation and mainly targets the field of research. Coherent optical tomography, capillaroscopy, and skin biopsy are useful for the differential diagnosis of SSc with other sclerodermoid syndromes. The immunological profile is a classification criterion for SSc and directs the diagnosis to the two subsets of the disease. Multisystemic damage requires evaluation with the help of a set of investigations specific to each affected organ, such as: diffusing capacity for carbon monoxide, forced vital capacity, 6-minute walk test, high-resolution computed tomography standard and reduced sequential, cardiac ultrasound and right cardiac catheterization. The current possibilities of diagnosis, treatment and monitoring are permanently adapting to new medical discoveries.Keywords: systemic sclerosis, antinuclear antibodies, capillaroscopy, confocal microscopy, coherent optical tomography

Background: This study aims to explore the tumor-stroma separation or the cleft characterizing basal cell carcinoma (BCC)., Methodology: In this retrospective cohort investigation, we enrolled 244 patients who received a confirmed diagnosis of BCC through histopathological examination in the period of 2019-2020 at the Pathology Laboratory of the "Sfântul Apostol Andrei" Emergency Clinical Hospital located in Galați, Romania. The identification of patients was accomplished by utilizing electronic health records, and relevant clinical, demographic, and histopathological data were retrieved from the physical database of the Pathology Laboratory. Key tumor characteristics were gathered, and an in-depth analysis of case slides was performed., Results: The average tumor-stroma cleft's width measurement was 48.136 µm, while its respective tumor island's width was on average 952.587 µm. The cleft's width and its respective tumor island's width are dependent on the BCC subtype, just like the ratio between the tumor island's measurement and its cleft's width are, being larger in basosquamous BCC, micronodular BCC, infiltrative BCC, and morpheaform BCC., Conclusion: The BCC tumor islands were found to have a minimal approximately equal measurement to the tumor-stroma separation cleft, but they were always larger than the latter. Large clefts and their respective tumor islands were found in specific tumor subtypes such as basosquamous BCC, micronodular BCC, infiltrative BCC, and morpheaform BCC, but in nodular BCC also., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. "Sfantul Apostol Andrei" Emergency Clinical Hospital Ethics Committee issued approval 23903/October 30, 2023. We communicate the ethical favorable decision for the current paper to be published, in concordance with the current legislation. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Niculet et al.)

Scleroderma-like cutaneous lesions have been found in many pathological conditions and they have the clinical appearance of sclerotic or scleroatrophic lesions. Affected skin biopsies described histopathological changes similar to those of scleroderma located strictly on the skin or those of systemic sclerosis. These skin lesions can be found in inflammatory diseases with autoimmune substrate (generalized morphea, chronic graft versus host disease, eosinophilic fasciitis), tissue storage diseases (scleredema, scleromyxedema, nephrogenyc systemic fibrosis, systemic amyloidosis), metabolic diseases (porphyrya cutanea tarda, phenylketonuria, hypothyroidism, scleredema diabeticorum), progeroid syndromes. Given the multiple etiologies of sclerodermal lesions, a correct differential diagnosis is necessary to establish the appropriate treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bobeica, Niculet, Craescu, Parapiru, Corduneanu-Luca, Debita, Pelin, Tiutiuca, Vasile, Nicolescu, Miulescu, Balan and Tatu.)

Systemic sclerosis (SSc) is a chronic inflammatory disease with autoimmune determinism having an incompletely known pathogenesis. Although not all links in the pathogenic chain are known, studies have shown that vasculopathy is the initial event and is followed by extensive fibrosis of the skin and internal organs. New therapeutic strategies have been developed in recent years, thanks to innovative research which has increased understanding of the disease mechanisms. No curative treatment for SSc is currently known. Therefore, the therapeutic target in SSc is its symptomatology. Peripheral vasculopathy can be improved by administering vasodilators. Endothelin receptor antagonists and 5-phosphodiesterase inhibitors have a double benefit, both on peripheral and on pulmonary vasculopathy. Several molecules with antifibrotic effects are currently available; however, further studies are needed to confirm their beneficial effects. Immunosuppressants manage to control the cutaneous and visceral fibrotic process, thereby remaining as first-line drugs in the treatment of SSc. Although biological therapy using rituximab and tocilizumab has shown promising results in pulmonary fibrosis, ongoing studies are needed to determine their exact impact. The authors have differing views on the triggering role of glucocorticoids and the benefits of angiotensin-converting enzyme inhibitors in renal scleroderma. Some aspects of this disease such as calcinosis and pruritus, asthenia, or joint and muscle damage, remain difficult to manage., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Bobeica et al.)

Basal cell carcinoma (BCC) is one of the most common malignant tumors worldwide, involving the skin. It is also part of keratinocyte carcinomas, alongside its squamous counterpart. It has low mortality and extremely low metastatic rates (although when present, it indicates a poor patient prognosis); it also has a high morbidity rate through local destruction and recurrence, particularly when perineural invasion is observed, clinically or histopathologically. BCC development is the result of environmental and patient factors, with genetics and ultraviolet radiation playing major roles. The clinical and histopathological aspects vary according to tumor subtype, being classified as high-risk tumors (nodular, superficial, pigmented and infundibulocystic BCC with adnexal differentiation) and fibroepithelial subtypes, or as high-risk tumors (micronodular, infiltrating, sclerosing/morphoeic and basosquamous subtype or the type with sarcomatoid differentiation). Dermoscopy is now complimented by novel in vivo diagnostic tools (optical coherence tomography, reflectance confocal microscopy, high-resolution ultrasonography, Raman spectroscopy or terahertz pulse imaging), improving the diagnostic accuracy and providing tumor depth and lateral margins without the use of invasive techniques. Novel treatment approaches for the treatment of BCC have recently been investigated with the use of hedgehog pathway inhibitors, such as Vismodegib. These approaches aim for complete resolution, minimal side-effects, high patient satisfaction with the optimal cosmetic results, particularly in key areas, such as the face. The present review article summarizes and discusses the comprehensive clinical and histopathological aspects of BCC, and presents novel imaging tools and therapeutic approaches that have been identified., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Niculet et al.)

Systemic sclerosis (SSc) is a collagenosis characterized by excessive deposition of collagen in the skin and viscera, in a background of immune disorder. The immunological profile of SSc often shows elevated levels of antinuclear antibodies (ANAs). However, many authors have identified cases of SSc having normal ANA levels, framed as paraneoplastic SSc. Among patients with negative ANAs in our group, we did not identify any neoplastic process that could support this hypothesis. The extended detection of autoantibodies is extremely useful in establishing the subset of SSc. Thus, anti-Scl70 antibodies are specific for the diffuse subset of SSc, while anticentromere antibodies (ACAs) have specificity for a limited subset. However, studies have shown the existence of cases of diffuse SSc having high titers of ACAs and cases of limited SSc with high titers of anti-Scl70 antibodies. This indicates an inconsistent association between the disease subset and the autoantibodies specific to each subset. Our study found a more balanced consistency between disease subsets and autoantibodies specific for each subset. Therefore, the percentages of patients having an immunological profile inconsistent with the subset of SSc, are lower than those found by other authors. This observation opens the perspective of larger studies on the immunological profile in SSc., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Bobeica et al.)

Interleukin 6 (IL-6), a cytokine produced by various cells of the human body (macrophages, lymphocytes, astrocytes, ischemic myocytes, endothelial cells) has both pro-inflammatory and anti-inflammatory properties, being a key component in regulating various physiologic and pathological processes. The structure of this molecule and the receptor system it possesses are important due to the different activities that IL-6 can exert; through trans-signaling pro-inflammatory activities are mediated, while through classic signaling, IL-6 is responsible for anti-inflammatory and regenerative activities. IL-6 signaling is involved in coronary artery disease and the global COVID-19 pandemic. This proatherogenic cytokine reaches elevated serum levels in the cytokine storm generated by SARS-CoV-2, and is also associated with smoking or obesity-classic cardiovascular risk factors which promote inflammatory states. IL-6 levels are proportionally correlated with dyslipidemia, hypertension and glucose dysregulation, and they are associated with poor outcomes in patients with unstable angina or acute myocardial infarction. IL-6 targeting for treatment development (not only) in cardiovascular disease and COVID-19 is still a matter of ongoing research, although tocilizumab has proven to be effective in reducing the proatherogenic effects of IL-6 and is suggested to improve COVID-19 patient survival., (Copyright: © Niculet et al.)

Systemic sclerosis (SSc) is a relatively rare autoimmune disease with skin and visceral involvement, having a yet unknown etiopathogenesis. Research has shown that professional exposure to various polluting chemicals such as dyes, aliphatic and aromatic organic solvents, inhalable silica dust or certain heavy metals, can be triggering factors for this disease when they overlap a predisposing genetic profile. Smoking is still a debated factor involved in the etiology of SSc, as authors have divergent opinions on this matter. The present study was designed to analyze the etiological factors identified in the group of 37 patients with diffuse and limited SSc from the southeast region of Romania and the results were compared to the literature data. In the group of patients included in this study, occupational exposure and smoking history were not present in all patients, and a hereditary factor was identified only in an isolated case. The majority of patients suffered from a major negative psychological event or from long-term stressful situations and these factors were associated with smoking history or occupational exposure; this suggests that SSc is initiated in a set of cumulative triggering factors., (Copyright: © Bobeica et al.)

Systemic sclerosis (SSc) is a collagenosis, in which the microvasculature of the skin and internal organs becomes affected, followed by excessive deposition of connective tissue. It has been included in the group of rare diseases, and it seems to have had an increasing incidence over the last two decades. Statistics show, not only an increase in the incidence of SSc, but that of autoimmune diseases as a whole. The present study aimed to outline the epidemiological profile of SSc in the southeast region of Romania and to identify similarities and differences concerning the epidemiology of this disease in other countries. The current observational study was carried out on a group of 22 patients who were diagnosed with SSc and who were hospitalized at a university clinic in Bucharest. Our research revealed a higher prevalence of women suffering from SSc, with higher numbers suffering from the diffuse subset of this disease. In addition, we found that the majority of patients came from urban areas. SSc has an important impact on the quality of life of patients, thus opening the opportunity for studies to be carried out on larger populations of patients in order to identify epidemiological similarities and differences in various countries, as well as finding new experimental models useful for future research., (Copyright: © Bobeica et al.)

The scope of the study was to identify the associated risk factors of lower limb lymphedema development in cervical and endometrial cancer patients. We retrospectively analysed 326 patients: 186 cases (57.06%) with cervical cancer and 140 cases (42.94%) with endometrial cancer were treated in Surgery, Radiotherapy, Oncology and Gynaecology Clinics of 'St. Apostle Andrew' Emergency Clinical Hospital Galati over 9 years. Adjuvant radiotherapy was performed in 83.57% of endometrial cancer cases. Adjuvant chemotherapy was performed in 45.16% of cervical cancer cases. Over 10 lymph nodes were removed in 74.73% of cervical cancer patients. Incidence of lymphedema was 15.05% in cervical cancer patients and 10% in endometrial cancer patients, P=0.06. Analysed risk factors for lower limb lymphedema occurrence were: Age, disease stage, radiotherapy, number of invaded lymph nodes (for cervical cancer patients), number of removed lymph nodes (for cervical cancer patients) and obesity. Multivariate analysis for associated risk factors of lower limb lymphedema development in cervical cancer showed that number of removed lymph nodes, OR=2.109 (0.907-4.903), P<0.0001, number of lymph nodes with metastasis, OR=1.903 (0.253-4.332), P=0.004 and obesity, OR=1.713 (0.226-2.967), P=0.006 were found as statistically significant risk factors for lower limb lymphedema onset. For endometrial cancer patients, obesity, OR=1.518 (0.721-2.75), P=0.0003, was the only associated risk factor with statistical significance for the lower limb lymphedema development. Lower limb lymphedema represents one of the adverse reactions of multimodal treatment in gynaecological cancers which affects patient's quality of life. Lower limb lymphedema occurrence is related with number of risk factors, the most important being removed lymph nodes, obesity and radiotherapy., (Copyright: © Rebegea et al.)