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Study design Multicentre cross-sectional study. Objective The objective of this study is to evaluate prevalence, location and characteristics of pain in hospital inpatients people with spinal cord injury (SCI). Setting Ten Italian rehabilitation centres specialized in spinal injury care, where inpatients are admitted both after the acute lesion and for late complications (time since injury, median [IQR]: 0.8 [0.2-8.2] years). Methods All the persons were submitted to AIS scale assessment [1] and modified Ashworth scale [2]; personal data and anamnesis were recorded; any pain within 1 week was investigated and the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) Italian version [3] was administered by physicians expert in type of pain definition. Results Of 385 included persons, 275 (72%) suffered pain, with the score value median [IQR]: 6 [4-8]. The worst pain of the person was nociceptive in 52% and neuropathic in 48% of the cases; 46% of nociceptive pain was located in the neck-shoulder region, whereas 67% of neuropathic pain was located in the sublesional part of the body. In 48% of the whole population, spasticity was observed but only 74% of them had pain. Being old and female are associated with high pain development, OR (95% CI): 1.24 (1.01-1.04) and 1.83 (1.05-3.20), respectively. Conclusions A high prevalence of pain is confirmed in persons with SCI, with both nociceptive and neuropathic pain characteristics. Only old age and female sex resulted as variables highly associated with pain.

Diagnosis of early invasive breast cancer relies on radiology and clinical evaluation, supplemented by biopsy confirmation. At least three issues burden this approach: a) suboptimal sensitivity and suboptimal positive predictive power of radiology screening and diagnostic approaches, respectively; b) invasiveness of biopsy with discomfort for women undergoing diagnostic tests; c) long turnaround time for recall tests. In the screening setting, radiology sensitivity is suboptimal, and when a suspicious lesion is detected and a biopsy is recommended, the positive predictive value of radiology is modest. Recent technological advances in medical imaging, especially in the field of artificial intelligence applied to image analysis, hold promise in addressing clinical challenges in cancer detection, assessment of treatment response, and monitoring disease progression. Radiomics include feature extraction from clinical images; these features are related to tumor size, shape, intensity, and texture, collectively providing comprehensive tumor characterization, the so-called radiomics signature of the tumor. Radiomics is based on the hypothesis that extracted quantitative data derives from mechanisms occurring at genetic and molecular levels. In this article we focus on the role and potential of radiomics in breast cancer diagnosis and prognostication., Highlights • In the screening setting, radiology sensitivity is suboptimal. • Artificial intelligence hold promise in cancer diagnosis and prognostication. • Radiomics include feature extraction from clinical images.

Mycosis fungoides (MF) is a rare neoplasm representing the most frequent form of primary cutaneous T-cell lymphoma (CTCL). Diagnosis of MF is generally complex, often requiring integration of clinical, histological, immunophenotypic and molecular data. Currently, there are no epidemiological data supported by registries or local studies on MF in Italy. Moreover, the clinical management of MF in Italy is heterogeneous, and differs according to the geographical area and experience of the physician who manages the disease. Considering the uncertainties in the current scenario for MF in Italy, a consensus project involving experts on CTCL was initiated to define the epidemiological impact of MF and obtain information about the current diagnostic and therapeutic pathway of this disease in Italy. The prevalence of MF in Italy was estimated to be 6,800 patients, 4,900 of whom with early stage of disease; the estimated incidence ranged between 270 and 330 new cases per year. Among the clinical figures involved in the multidisciplinary management of MF, dermatologists were recognised as a reference point for both diagnosis and therapeutic decisions. These findings suggest the importance of monitoring both the disease and its management; it is, therefore, interesting to set up regional registries for monitoring and recognition of rare tumor status for MF. The results further indicate the need to train physicians to favour more rapid diagnosis and simplify the pathway for referring patients to reference centres with adequate diagnostic and treatment standards. In light of the forthcoming introduction of new therapies, the development of a nationwide PDTA (Path of Diagnostic Therapeutic Care, in Italian defined as Percorso Diagnostico-Terapeutico Assistenziale) is also of substantial importance.

After spinal cord injury (SCI), patients face many physical and psychological issues including intestinal dysfunction and comorbidities, strongly affecting quality of life. The gut microbiota has recently been suggested to influence the course of the disease in these patients. However, to date only two studies have profiled the gut microbiota in SCI patients, months after a traumatic injury. Here we characterized the gut microbiota in a large Italian SCI population, within a short time from a not only traumatic injury. Feces were collected within the first week at the rehabilitation center (no later than 60 days after SCI), and profiled by 16S rRNA gene-based next-generation sequencing. Microbial profiles were compared to those publicly available of healthy age- and gender-matched Italians, and correlated to patient metadata, including type of SCI, spinal unit location, nutrition and concomitant antibiotic therapies. The gut microbiota of SCI patients shows distinct dysbiotic signatures, i.e. increase in potentially pathogenic, pro-inflammatory and mucus-degrading bacteria, and depletion of short-chain fatty acid producers. While robust to most host variables, such dysbiosis varies by lesion level and completeness, with the most neurologically impaired patients showing an even more unbalanced microbial profile. The SCI-related gut microbiome dysbiosis is very likely secondary to injury and closely related to the degree of completeness and severity of the lesion, regardless of etiology and time interval. This microbial layout could variously contribute to increased gut permeability and inflammation, potentially predisposing patients to the onset of severe comorbidities.

Syphilis is one of the greatest masqueraders in dermatology, like mycosis fungoides or sarcoidosis. In fact, secondary syphilis can simulate different dermatological conditions, not only clinically but also histopathologically. A 34-year old Brazilian man from Manaus (Amazonas) attended our Department complaining for 2 weeks of asthenia, weight loss and multiple asymptomatic disseminated erythematous papules and scaly plaques with well-defined borders and a tendency to confluence were observed on the trunk, neck and extremities, clinically similar to psoriasis guttata. The skin biopsy and laboratory tests disclosed secondary syphilis and the patient was treated with intramuscular benzathine penicillin with prednisolone, with a complete resolution. Psoriasiform syphilis, which imitates psoriasis, was well known by old dermatologists and was called syphilide psoriasiforme or psoriasis syphilitique. Psoriasiform syphilis is one of the atypical presentations of secondary syphilis and dermatologists should be aware of psoriasiform syphilis in order not to improperly treat syphilis patients with immunosuppressive drugs; also, pathologists should be aware of secondary syphilis histopathological features.

The term non-melanoma skin cancer (NMSC) refers to skin cancer different from melanoma, and it is usually restricted to basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and their pre-cancerous lesions, e.g., actinic keratosis. These conditions represent the most frequent tumors in Caucasians and are characterized by an increasing incidence worldwide and a high socio-economic impact. The term Integrated Care Pathway (ICP) refers to “a complex intervention for the mutual decision making and organization of care processes for a well-defined group of patients during a well-defined period”. The purpose of this paper is to present a proposal from the Italian Association of Hospital Dermatologists (ADOI) for an ICP organization of care of NMSC, considering the hub-and-spoke model in the different geographical areas.This proposal is based on the most recent literature and on documents from the Italian Association of Medical Oncology (AIOM), the European consensus-based interdisciplinary guidelines from the European Association of Dermato- Oncology (EADO), and the National Comprehensive Cancer Network (NCCN). We initially discuss the NMSC outpatient clinic, the role of the multidisciplinary working groups, and the hub-and-spoke model regarding this topic. Then, we define the ICP processes specific for BCC and SCC. The ICP for NMSC is an innovative strategy to guarantee the highest possible quality of health care while the hub-andspoke model is crucial for the organization of different health care structures. Considering the importance on this topic, it is essential to create a valid ICP together with an efficient organization within the different geographical areas.

Background The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined. The purpose of our study was to assess the association between the p.E318K germline variant and clinic-phenotypical features of MITF+ compared to non-carriers (MITF−), including dermoscopic findings of melanomas and dysplastic nevi. Methods we retrospectively analyzed a consecutive series of 1386 patients recruited between 2000 and 2017 who underwent genetic testing for CDKN2A, CDK4, MC1R and MITF germline variants in our laboratory for diagnostic/research purposes. The patients were probands of melanoma-prone families and apparently sporadic single or multiple primary melanoma patients. For all, we collected clinical, pathological information and dermoscopic images of the histopathologically diagnosed melanomas and dysplastic nevi, when available. Results After excluding patients positive for CDKN2A/CDK4 pathogenic variants and those affected by non-cutaneous melanomas, our study cohort comprised 984 cutaneous melanoma patients, 22 MITF+ and 962 MITF−. MITF+ were more likely to develop dysplastic nevi and multiple primary melanomas. Nodular melanoma was more common in MITF+ patients (32% compared to 19% in MITF−). MITF+ patients showed more frequently dysplastic nevi and melanomas with uncommon dermoscopic patterns (unspecific), as opposed to MITF− patients, whose most prevalent pattern was the multicomponent. Conclusions MITF+ patients tend to develop melanomas and dysplastic nevi with histopathological features, frequency and dermoscopic patterns often different from those prevalent in MITF− patients. Our results emphasize the importance of melanoma prevention programs for MITF+ patients, including dermatologic surveillance with digital follow-up.

Palmoplantar pustulosis (PPP) is a chronic inflammatory condition where crops of sterile pustules with erythematous keratotic lesions causing bleeding and pain appear on the palms and soles. Recently, the European Rare and Severe Expert Network considered PPP as a variant of pustular psoriasis with or without psoriasis vulgaris. The prevalence of PPP varies from 0.050 to 0.12%. PPP occurs more frequently in women and the highest prevalence occurred between the ages of 50 and 69 years. Nail psoriasis seems to be frequent in PPP, ranging from 30 to 76%, and psoriatic arthritis in 8.6 to 26% of PPP patients. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and pustulotic arthro-osteitis are considered PPP-associated disorders. PPP has been reported with other co-morbidities such as psychiatric disorders, thyroid-associated disease, altered calcium homeostasis, gluten sensitivity diabetes, obesity, and dyslipidemia, but larger studies are required to prove such associations. Environmental exacerbating factors might contribute to the onset or worsening of PPP such as cigarette smoking, stress, focal infections, metal allergies, and drug intake. Genetic predisposition plays an important role in PPP. In PPP, both the innate and the adaptive immune systems are activated. The acrosyringeal expression of IL-17 has been demonstrated, indicating that the eccrine sweat gland is an active component of the skin barrier and an immune-competent structure. Increased levels of several inflammatory molecules, including IL-8, IL-1α, IL-1β, IL-17A, IL-17C, IL-17D, IL-17F, IL-22, IL-23A, and IL-23 receptor, have been detected in PPP biopsies. Increased serum levels of TNF-α, IL-17, IL-22, and IFN-γ have been detected in patients with PPP in comparison to healthy subjects, suggesting a similar inflammatory pattern to psoriasis vulgaris. Oral and tonsillar infections serve as trigger factors for PPP. Long-term therapy is required for many patients, but high-quality data are limited, contributing to uncertainty about the ideal approach to treatment.

Papular mycosis fungoides (PMF) is a rare variant of mycosis fungoides (MF). The exact nosology and prognosis of PMF are still unclear. We retrospectively identified cases of PMF from the files of the Department of Dermatology of the Medical University of Graz, Austria, and checked the follow-up data. The patients comprised 13 men and 5 women (median age: 57.5 y; range 13 to 77 y). In 4 patients, an initial clinicopathologic diagnosis of atypical pityriasis lichenoides was made; these cases were subsequently reclassified as PMF due to the onset of conventional patches of MF during follow-up. Follow-up data of our cases showed that 2 patients died of disease progression 50 and 199 months after the first presentation, respectively. Two patients are alive with progressive disease after 215 and 300 months, respectively. Ten patients are alive with stable disease (median: 70 mo). Four patients were in complete remission at last follow-up visit (median: 215 mo; 2 of them died of unrelated causes). Our data confirm that PMF represents a clinicopathologic variant of early MF with prognosis similar to conventional presentations of the disease. Familiarity with PMF and distinction from other cutaneous papular lymphoid proliferations is necessary for a precise diagnosis and management of these patients.

47 year-old man who suffered for plaque psoriasis since 2013 was previously treated with topicals, UVB photherapy, acitretin, methotrexate and adalimumab (Imraldi®) with scarce response. Brodalumab (IL-17 receptor chain A blocking antibody) at 210 mg sc day 0, week-1, week-2 and every 2 weeks was initiated (baseline PASI of 16) with fast improvement of psoriasis (PASI-90 at week 4) and new onset of erythema, pustules and pain in the palmoplantar area after each subcutaneous Brodalumab administration and progressive improvement after 5-8 days.

Background: The recovery of upper limb mobility and functions is essential for people with cervical spinal cord injuries (cSCI) to maximize independence in daily activities and ensure a successful return to normality. The rehabilitative path should include a thorough neuromotor evaluation and personalized treatments aimed at recovering motor functions. Body-machine interfaces (BoMI) have been proven to be capable of harnessing residual joint motions to control objects like computer cursors and virtual or physical wheelchairs and to promote motor recovery. However, their therapeutic application has still been limited to shoulder movements. Here, we expanded the use of BoMI to promote the whole arm’s mobility, with a special focus on elbow movements. We also developed an instrumented evaluation test and a set of kinematic indicators for assessing residual abilities and recovery. Methods: Five inpatient cSCI subjects (four acute, one chronic) participated in a BoMI treatment complementary to their standard rehabilitative routine. The subjects wore a BoMI with sensors placed on both proximal and distal arm districts and practiced for 5 weeks. The BoMI was programmed to promote symmetry between right and left arms use and the forearms’ mobility while playing games. To evaluate the effectiveness of the treatment, the subjects’ kinematics were recorded while performing an evaluation test that involved functional bilateral arms movements, before, at the end, and three months after training. Results: At the end of the training, all subjects learned to efficiently use the interface despite being compelled by it to engage their most impaired movements. The subjects completed the training with bilateral symmetry in body recruitment, already present at the end of the familiarization, and they increased the forearm activity. The instrumental evaluation confirmed this. The elbow motion’s angular amplitude improved for all subjects, and other kinematic parameters showed a trend towards the normality range. Conclusion: The outcomes are preliminary evidence supporting the efficacy of the proposed BoMI as a rehabilitation tool to be considered for clinical practice. It also suggests an instrumental evaluation protocol and a set of indicators to assess and evaluate motor impairment and recovery in cSCI.

Background: Psoriasis (Ps) is a chronic systemic autoimmune disease associated with pruritus in 64–98% of patients. However, few modestly sized studies assess factors associated with psoriatic pruritus. Objective: To investigate factors associated with Ps pruritus intensity. Methods: Psoriasis patients 18years or older seen in one of 155 centres in Italy between September 2005 and 2009 were identified from the Italian PsoCare registry. Patients without cutaneous psoriasis and those with missed information on pruritus were excluded. Results: We identified 10802 patients, with a mean age 48.8±14.3years. Mild itch was present in 33.2% of patients, moderate in 34.4%, severe in 18.7% and very severe in 13.7%. Higher itch intensity was associated with female gender, lower educational attainment compared to university degree, pustular psoriasis, psoriasis on the head, face, palmoplantar areas, folds and genitalia, more severe disease, disease duration

Because of the COVID‐19 emergency, on March 9, 2020 Italy went in lock‐down imposing the closure of non‐urgent outpatient clinics devoted to care of chronic, severe, inflammatory skin diseases that require periodic follow‐up. In this emergency situation, due to the lack of a teledermatology platform and in order not to leave our vulnerable high‐need patients without proper follow‐up, we started a teledermatologic service in smartworking using phone calls and emails. The total number of patients scheduled was 195; in 12 cases we were not able to talk to the patients. Remote monitoring was performed in 183 patients (126 moderate to severe psoriasis, 10 severe acne, 11 severe atopic dermatitis, 11 hidradenitis suppurativa, 9 blistering autoimmune diseases, 16 other autoimmune skin diseases). During remote‐visits several interventions were conducted: triage for COVID‐19 suspected symptoms, email check of clinical pictures and of laboratory examinations, advices for topical and systemic therapy continuation or discontinuation/switch and re‐schedule of next appointment. Only 5 patients required personal office visit (2.6%), reducing consistently the number of face‐to face visits. Our real‐life experience shows that remote monitoring was effective in preventing unnecessary worsening of severe chronic skin diseases and poor outcomes due to withdrawal of current therapy. This article is protected by copyright. All rights reserved.

Multiple Myeloma (MM) is a blood cancer implying bone marrow involvement, renal damages and osteolytic lesions. The skeleton involvement of MM is at the core of the present paper, exploiting radiomics and artificial intelligence to identify image-based biomarkers for MM. Preliminary results show that MM is associated to an extension of the intrabone volume for the whole body and that machine learning can identify CT image features mostly correlating with the disease evolution. This computational approach allows an automatic stratification of MM patients relying of these biomarkers and the formulation of a prognostic procedure for determining the disease follow-up.

Hemoptysis is the presence of blood in sputum, coming from the lower airway, under the glottis. It is an infrequent sign in children and rarely life threatening. Hemoptysis in children is hard to quantify and is generally mild, being associated with upper airway infections, but it is frequently confused with gastrointestinal hemorrhage. Hemoptysis may be easily attributable in a patient with a chronic condition such as advanced cystic fibrosis or congenital heart disease associated with increased pulmonary vein pressures, but it poses a challenge when it is the first sign of an autoimmune disease. In these circumstances, the differential diagnoses may include a long list of infrequent but serious diseases, which are a part of diffuse alveolar hemorrhage syndrome (DAHS) and must be considered, with use of a complete check list. The treatment will depend on the underlying cause, but as a first approach, hemoptysis must be considered a life-threatening event until the patient is stable.

Spinal Cord Injury (SCI) affects trunk control and determines altered or absent neuromuscular activity and sensory feedback below the lesioned spinal segment. The practice of sport or of any physical activity are key elements for improving the health and quality of life of people with SCI. Paralympic athletes overcome limits related to their injuries, achieving high neuromuscular control and coordination. Among the sports that have been adapted for people with disabilities, sit-skiing is a sport that requires good trunk control. However, there is a lack of instruments and protocols for its quantitative assessment. In this work we describe a robot-based protocol designed to assess trunk control and tested with two expert sit-skiers and eight unimpaired subjects. We used the robotic platform hunova® to evaluate both the active and the reactive component of trunk control through two different exercises. We investigated the strategy adopted by subjects to perform these exercises and the changes due to their repetition. All unimpaired subjects successfully completed the proposed protocol. The repetition of both exercises induced a learning process leading to differences in motor performance. Similar results could be observed also in the two athletes, whose performance was characterized by differences due to the severity of their lesion and their skiing skills.

Purpose Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to neuromuscular palsy and death. We propose a computational approach to [18F]-fluorodeoxyglucose (FDG) PET/CT images to analyze the structure and metabolic pattern of skeletal muscle in ALS and its relationship with disease aggressiveness. Materials and methods A computational 3D method was used to extract whole psoas muscle’s volumes and average attenuation coefficient (AAC) from CT images obtained by FDG PET/CT performed in 62 ALS patients and healthy controls. Psoas average standardized uptake value (normalized on the liver, N-SUV) and its distribution heterogeneity (defined as N-SUV variation coefficient, VC-SUV) were also extracted. Spinal cord and brain motor cortex FDG uptake were also estimated. Results As previously described, FDG uptake was significantly higher in the spinal cord and lower in the brain motor cortex, in ALS compared to controls. While psoas AAC was similar in patients and controls, in ALS a significant reduction in psoas volume (3.6 ± 1.02 vs 4.12 ± 1.33 mL/kg; p < 0.01) and increase in psoas N-SUV (0.45 ± 0.19 vs 0.29 ± 0.09; p < 0.001) were observed. Higher heterogeneity of psoas FDG uptake was also documented in ALS (VC-SUV 8 ± 4%, vs 5 ± 2%, respectively, p < 0.001) and significantly predicted overall survival at Kaplan–Meier analysis. VC-SUV prognostic power was confirmed by univariate analysis, while the multivariate Cox regression model identified the spinal cord metabolic activation as the only independent prognostic biomarker. Conclusion The present data suggest the existence of a common mechanism contributing to disease progression through the metabolic impairment of both second motor neuron and its effector.

In recent years, an increasing number of clinical centres have started including powered exoskeleton-assisted gait training to SCI patients’ conventional therapy, but more evidence about the effects of this kind of therapy on gait patterns is needed. The goal of this study was to investigate: (1) the changes in muscle activations due to the use of the exoskeleton, (2) the changes in muscle activations and spatio temporal parameters after an exoskeleton-assisted gait training, both during unassisted and assisted gait. In the study, 3 incomplete SCI subjects underwent an exoskeleton assisted gait training and were assessed before and after the therapy. Changes in gait speed and endurance were evaluated using clinical metrics (10-MWT and 6-MWT), while spatio temporal and muscles activations changes were assessed using an electromyography (EMG) and a motion capture system. Clinical results showed an increase after training of endurance and gait speed as confirmed by the spatio temporal parameters (increment of the swing phase and reduction of the stride duration). As for the EMG data, small positive changes were observed in post training unassisted walking muscles activations of the three patients. As expected, changes due to training or to assistance were subject-dependent and varied in function of the initial residual abilities of the single individual.

In Argentina there is little information about diseases that affect exotic ungulates and the health risks that they pose to native wildlife, livestock, and humans. The aim of this study was to evaluate the health status of red deer ( Cervus elaphus) in the Nahuel Huapi National Park and surrounding areas in Patagonia, Argentina. During three consecutive hunting seasons, necropsies were performed on 101 red deer, and tissues were examined histologically. The most common lesions were those associated with hepatic and pulmonary parasites. Fasciola hepatica was observed in 15 red deer and was associated with cholangiohepatitis (8%) and/or cholangitis (10%). Dictyocaulus sp. (likely Dictyocaulus eckerti) was associated with interstitial pneumonia (5%), bronchitis (5%), pulmonary emphysema (13%), and bronchus-associated lymphoid tissue hyperplasia (13%). Other findings included Sarcocystis spp. cysts in the myocardium (89%) associated with interstitial, focal, lymphoplasmacytic myocarditis (8%); periportal lymphoplasmacytic hepatitis (8%); hepatic centrilobular necrosis (6%); lymphoplasmacytic interstitial nephritis (25%); and follicular hyperplasia in mediastinal, prescapular, and prefemoral lymph nodes (86%). Our report of lesions caused by endemic parasites of livestock in free-ranging exotic red deer in Patagonia sets the foundation for a health-monitoring and -surveillance system of wildlife in this region, which is essential for the sustainable management of threatened Argentinean native fauna.

The occurrence of pseudolymphomatous infiltrates in cutaneous lupus erythematosus (cLE) is described mainly in lupus panniculitis and lupus tumidus/lymphocytic infiltration of the skin (Jessner-Kanof). We collected 15 cases of pseudolymphomatous cLE other than lupus panniculitis and lupus tumidus (M:F = 4:11; age range: 23-79 years; mean age: 50.9 years; median age: 57 years). Of the 15 cases, 9 (60%) were characterized by dense nodular infiltrates. Three cases (20%) showed an angiocentric pattern with cytological atypia of lymphoid cells; 2 cases (13.3%) showed a band-like infiltrate mimicking mycosis fungoides, and 1 case had mixed features of the band-like and angiocentric patterns. Clues to the histopathological diagnosis of cLE were presence of interface dermatitis, clusters of plasmacytoid dendritic cells, and dermal mucin deposition. Our study shows that the spectrum of pseudolymphomatous presentations of cLE is broader than previously described, including band-like cases that may be misconstrued as mycosis fungoides, and angiocentric cases that may be misinterpreted as an aggressive lymphoma. Recognition of such cases is possible only on careful clinicopathologic correlation and requires a high level of histopathological suspicion to allow a correct diagnosis and the proper management of the patients.

Non-small cell lung cancer (NSCLC) accounts for most cases of lung cancer. The peel oil of Mandarin Citrus reticulata Blanco cv. Dancy (MPO) is a natural source of essential oils and carotenoids. Volatile and non-volatile lipid compounds were characterized by chromatographic methods. We demonstrate that MPO causes a dose-dependent growth inhibition of NSCLC model cells (A549) in culture and tumour growth in vivo of the same cells implanted in nude mice fed with MPO-supplemented diets. MPO induced cell cycle arrest mainly at the G0/G1 phase and reduced the amount of membrane-bound Ras protein along with apoptosis induction. No toxicological effect was found in liver parameters analysed in treated mice and histopathological analyses of their organs did not show any morphological changes. In conclusion, the data suggest that MPO possesses significant antitumor activity without causing systemic toxicity, proposing it as a dietary supplement that may be helpful in cancer prevention. Fil: Castro, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Rodenak Kladniew, Boris Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Massone, Adriana Raquel. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Departamento de Patología. Laboratorio de Patología Especial Veterinaria "Dr. Bernardo Epstein"; Argentina Fil: Polo, Monica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: García de Bravo, Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina

Cutaneous mucinoses are a complex and diverse group of connective tissue disorders characterized by the accumulation of mucin and/or glycosaminoglycan in the skin and adnexa. Cutaneous focal mucinosis appears as a solitary, asymptomatic, skin-colored to white papule, nodule, or plaque located anywhere on the body or in the oral cavity. It presents mainly in adults and is characterized on histopathology by mucin throughout the upper and mid dermis. We describe the dermoscopy of two cases of cutaneous focal mucinosis. Both lesions presented a nonspecific homogenous whitish pattern; the first case also exhibited a sharply demarcated yellow border.

Dermoscopy is a non-invasive, in vivo technique that allows the visualization of subsurface skin structures in the epidermis, at the dermoepidermal junction, and in the upper dermis. Dermoscopy brought a new dimension in evaluating melanocytic skin neoplasms (MSN) also representing a link between clinical and pathologic examination of any MSN. However, histopathology remains the gold standard in diagnosing MSN. Dermoscopic–pathologic correlation enhances the level of quality of MSN diagnosis and increases the level of confidence of pathologists. Melanoma is one of the most genetically predisposed among all cancers in humans. The genetic landscape of melanoma has been described in the last years but is still a field in continuous evolution. Melanoma genetic markers play a role not only in melanoma susceptibility, initiation, and progression but also in prognosis and therapeutic decisions. Several studies described the dermoscopic specific criteria and predictors for melanoma and their histopathologic correlates, but only a few studies investigated the correlation among dermoscopy, pathology, and genetic of MSN. The aim of this work is to review the published data about dermoscopic features of melanoma, their histopathological correlates with regards also to genetic alterations. Particularly, this review will focus on low-CSD (cumulative sun damage) melanoma or superficial spreading melanoma, high-CSD melanoma, and nevus-associated melanoma.

Dear Editor, Genital lesions are estimated to occur in 30–40% of patients with psoriasis, with a slight predominance in men. Less frequently they are the first and rarely the sole presentation of this common inflammatory disease in only 2–5% of affected patients.1 Therefore, its differential diagnosis can be wide, including mainly inflammatory diseases. As genital psoriasis is also a source of anxiety and sexual embarrassment, with other quality of life limitations, mostly in young patients, a fast and preferably noninvasive diagnosis is needed.2 Dermoscopy and reflectance confocal microscopy (RCM) have been developed in recent years, aiming for a higher accuracy in in vivo diagnosis. They can be of particular interest as complementary tools in the examination of sensitive areas like genital skin.3-6 The aim of our study was to describe RCM features of biopsy‐proven psoriatic balanitis in patients with no other skin or nail involvement from psoriasis, with dermoscopic and histopathological correlation. Seven male patients were consecutively recruited (mean 36 years of age, range 26–53). The genital lesions were first assessed using dermoscopy and RCM (Table 1). A punch biopsy from each suspicious glans lesion was also performed for histopathological examination. RCM imaging was obtained using a near infrared, reflectance mode, confocal laser scanning microscope (VivaScope1500®; Caliber I.D., Rochester, NY, U.S.A.).

Hypertrophic osteopathy is commonly associated with primary lung neoplasms. It may also be secondary to intrathoracic lesions such as pulmonary metastasis, granulomatous pleurisy and chronic pneumonia, among others. It is characterized by progressive proliferation of sub periosteal bone tissue in limb bones. Clinically, patient usually exhibits lameness. It is a rare disease most frequently observed in dogs among domestic animals. A case of a dog with pulmonary hypertrophic osteopathy associated with pulmonary metastases coming from an appendicular periosteal osteosarcoma is reported., Facultad de Ciencias Veterinarias

Background Primary cutaneous follicle center lymphoma (pcFCL) usually presents with reddish nodules, plaques, and tumors on the head and neck or the back. Objective We sought to describe a peculiar clinical presentation of pcFCL and secondary cutaneous follicle center lymphoma (FCL). Methods We report a series of 13 patients (7 male and 6 female; median age 58 years, mean age 58.2 years, age range 26-83 years) with either pcFCL (11 patients) or secondary cutaneous FCL (2 patients) presenting with lesions on the head deviating from the classic clinical manifestations characterized by plaques and tumors. Results All patients presented clinically with diffuse, ill-defined, partly hypochromic, partly erythematous macules or with inconspicuous lesions located predominantly on the scalp and forehead. Dimension ranged between 4 to 5 cm 2 and greater than 30 cm 2 . The initial diagnosis was never cutaneous lymphoma, and all patients received various diagnoses including rosacea, alopecia, erysipelas, discoid lupus erythematosus, angiosarcoma, Borrelia infection, or sarcoidosis. Histologic examination confirmed the diagnosis of FCL in all patients. Limitations Small number of cases and retrospective study design are limitations. Conclusions This clinical presentation of both pcFCL and secondary cutaneous FCL is unusual and represents a pitfall in the clinical diagnosis. Dermatologists should be aware of this clinical variant of FCL to establish a timely diagnosis and treat patients properly.

Psoriasis has been controversially associated with risk of non-Hodgkin lymphoma (NHL) and mycosis fungoides (MF). Also patients who developed MF after systemic treatment for psoriasis have been reported, and some authors suggested that the association between MF and psoriasis is not infrequent. We performed an extensive literature review in order to examine the risk of developing MF in psoriatic patients with a systematic search of the English-language databases. An increased risk for lymphoma overall in psoriatic patients has been found only by three out of seven studies. The risk of developing MF in psoriatic patients has been investigated by different studies in different populations and with different methodologies presenting bias and limitations, and it seems reasonable that misclassification between psoriasis and MF may explain the association reported. In contrast to the large number of psoriatic patients treated with biologicals, only 27 case reports of MF after biological therapy for psoriasis have been reported, and in 10 cases, the initial psoriasis diagnoses were then revised as MF. A true association between MF and psoriasis is possible, but the real incidence and prevalence are still unknown. The reported higher risk of developing MF in psoriatic patients should be reconsidered in the light of the bias of misclassification and the low magnitude reported in previous studies. There is not enough evidence to support a causal relation among biological therapies and MF in psoriatic patients.

Background: In 2007 the International Psoriasis Council considered palmoplantar pustulosis (PPP) a condition separate from psoriasis, and several authors maintain that PPP is a reactive process to metal contact allergies independent from psoriasis. Objectives: To evaluate the frequency of allergies and psoriasis in patients with PPP and to determine the role of allergens in PPP. Methods: A systematic search of the English databases (PubMed and Web of Science) from January 1964 to August 2018 to identify all patients affected by PPP and allergies and/or psoriasis. Results: In total, 16 publications describing a total of 519 patients with PPP were evaluated and 122 cases of concomitant PPP and metal allergy were found. The frequency of allergies among patients with PPP was 22.7%; between the identified allergens, 84.3% of cases correspond to metal allergies. In 65.1% of metal allergies, an improvement in PPP was seen after withdrawal of contact. The concomitant presence of psoriasis was recorded in 18% of the cases. Conclusion: There is some evidence to support the association of PPP with metal allergies but also with psoriasis, suggesting the role of metal allergens as a trigger factor in patients with PPP.

El objetivo de la presente revisión fue realizar una actualización sobre los aspectos clínicos, histopatológicos y patogenia de las dermatosis autoinmunes que afectan a los caninos y que se caracterizan por pústulas, vesículas y ampollas como lesión primaria. Se consideran los aspectos clínicos y las características histopatológicas de las enfermedades que componen el complejo pénfigo y las enfermedades ampollares subepidérmicas autoinmunes. Además, se describen las técnicas inmunológicas utilizadas en el diagnóstico y la caracterización de este grupo de enfermedades., The aim of this revision was to update the clinical, histopathological and pathogenic aspects of autoimmune dermatoses that affect canines and that are characterized by pustules, vesicles and blisters as the primary lesion. The clinical aspects and the histopathological features of the diseases that are part of the pemphigus complex and the autoimmune subepidermal bullous diseases are considered. In addition, immunological techniques used in the diagnosis and characterization of this group of diseases are described., Facultad de Ciencias Veterinarias

Myoelectric Computer Interfaces (MCIs) are a viable option to promote the recovery of movements following spinal cord injury (SCI), stroke, or other neurological disorders that impair motor functions. We developed and tested a MCI interface with the goal of reducing abnormal muscular activations due to compensatory strategies or undesired co-contraction after SCI. The interface mapped surface electromyographic signals (sEMG) into the movement of a cursor on a computer monitor. First, we aimed to reduce the co-activation of muscles pairs: the activation of two muscles controlled orthogonal directions of the cursor movements. Furthermore, to decrease the undesired concurrent activation of a third muscle, we modulated the visual feedback related to the position of the cursor on the screen based on the activation of this muscle. We tested the interface with six unimpaired and two SCI participants. Participants were able to decrease the activity of the targeted muscle when it was associated with the visual feedback of the cursor, but, interestingly, after training, its activity increased again. As for the SCI participants, one successfully decreased the co-activation of arm muscles, while the other successfully improved the selective activation of leg muscles. This is a first proof of concept that people with SCI can acquire, through the proposed MCI, a greater awareness of their muscular activity, reducing abnormal muscle simultaneous activations.

The pathogenesis of leprosy is still not fully understood. Several studies have been performed on the involvement of T cells in leprosy and more recently have focused on genetic factors and innate immune response. There are still only few reports about the role of B cells in active leprosy lesions in different spectral forms of the disease. The literature on tuberculosis suggests that B cells play an important role in the regulation of the granulomas, in cytokine production, T-cell response, and antigen presentation. Only few studies investigated the role of B cell in leprosy. We investigated the distribution of B cells in 85 leprosy biopsies covering all forms of the disease and compared results with 13 biopsies of tuberculosis and atypical mycobacteriosis, expanding the previous experiences. A statistically significant difference in the number of CD20 (P = 0.014) and CD138+ (P = 0.01) cells between the different forms of leprosy was observed. A remarkable amount of CD138+ cells could also be detected in borderline tuberculoid. The median of the CD20 cells decreased from the bacilloscopy-negative samples to the bacilloscopy-positive samples by 50% (P = 0.004). Contrarily, the median of CD138+ cells showed an increase from bacilloscopy-negative to bacilloscopy-positive samples of 966.67% (P = 0.001). In our experience, tuberculoid leprosy showed more B cells and less plasma cells than lepromatous leprosy. Our results show that B cells might be implicated in leprosy pathogenesis, not only in the lepromatous pole as previously postulated, but also in tuberculoid granuloma formation and type 1 reactions.

OBJECTIVE: The present study was conducted to identify possible dermoscopic patterns, associated with mitotic rate > 1/mm2, histological ulceration in melanoma and metastatic disease. METHODS: For this retrospective data analysis all clinical and dermoscopic digital images of primary malignant melanomas between 2008 and 2013 documented at the Department of Dermatology Graz were included, using the internal image data-base. 550 patients with 559 melanomas were included. RESULTS: While clinical or dermoscopic analysis considered ulceration to be present in 120 (21.5%) and 117 (20.9%) of all lesions, respectively, histopathology reported ulceration in only 96 cases (17.2%). The presence of milky-red areas, shiny-white streaks, a blue-white veil and blue-grey areas in dermoscopy is highly correlated with histological ulceration and a mitotic rate > 1/mm2. The dermoscopic patterns shiny-white streaks, milky-red areas and blue-white veil were also significantly associated with development of distant metastases. CONCLUSION: Our study proves a significant correlation between the dermoscopic patterns "blue white veil", "milky-red areas"and "shiny-white streaks"and the histological findings "ulceration"and "mitotic rate > 1/mm2". Furthermore these dermoscopic patterns are highly related to distant metastases. Thus, dermoscopy renders earlier prognostic statements possible. info:eu-repo/semantics/publishedVersion

Skeletal erosion has been found to represent an independent prognostic indicator in patients with advanced stages of chronic lymphocytic leukaemia (CLL). Whether this phenomenon also occurs in early CLL phases and its underlying mechanisms have yet to be fully elucidated. In this study, we prospectively enrolled 36 consecutive treatment-naïve patients to analyse skeletal structure and bone marrow distribution using a computational approach to PET/CT images. This evaluation was combined with the analysis of RANK/RANKL loop activation in the leukemic clone, given recent reports on its role in CLL progression. Bone erosion was particularly evident in long bone shafts, progressively increased from Binet stage A to Binet stage C, and was correlated with both local expansion of metabolically active bone marrow documented by FDG uptake and with the number of RANKL + cells present in the circulating blood. In immune-deficient NOD/Shi-scid, γcnull (NSG) mice, administration of CLL cells caused an appreciable compact bone erosion that was prevented by Denosumab. CLL cell proliferation in vitro correlated with RANK expression and was impaired by Denosumab-mediated disruption of the RANK/RANKL loop. This study suggests an interaction between CLL cells and stromal elements able to simultaneously impair bone structure and increase proliferating potential of leukemic clone.

Interstitial mycosis fungoides (IMF) is a rare histopathologic variant of mycosis fungoides (MF) that may mimic other inflammatory dermatoses, mainly interstitial granuloma annulare, inflammatory morphea, and interstitial granulomatous dermatitis. Only small series and sporadic case reports of IMF have been described in the literature. We reviewed 27 specimens from 21 patients with IMF (M:F=11:10, median age 60) to better characterize clinical, histopathologic, and immunohistochemical features of this disease. Most patients presented clinically with patches and/or plaques. Conventional MF was documented before, concomitant with, or after IMF in 12 patients, whereas only in 2 patients different biopsies showed exclusive features of IMF over a period of 4 and 191 months, respectively. Histology revealed in all cases variably long, linear aggregates of dermal lymphocytes splaying the collagen fibers, involving predominantly the superficial and mid-dermis (6 cases) or the entire dermis (21 cases). Immunohistochemical stainings revealed a cytotoxic phenotype in 9/18 tested cases. Variable amounts of histiocytes/macrophages were found interstitially in all tested biopsies but never represented a population larger than that of T lymphocytes. Our study shows that IMF is a peculiar variant of MF with frequent cytotoxic phenotype. This histopathologic variant in most cases represents a transient pattern in otherwise conventional MF. Accurate clinicopathologic correlation and phenotypic studies of atypical dermal interstitial lymphohistiocytic infiltrates allow to make a correct diagnosis.

Hydroa vacciniforme-like lymphoma is a recently recognized cutaneous T-cell lymphoma associated with Epstein-Barr virus. The disease is observed in children of Latin American or Asian ethnicity. The authors report the clinical, histopathological, and immunophenotypical features of 9 new Mexican patients (M:F = 2:1; mean age, 14.5 years; median age, 13.3 years; age range, 4-27 years), expanding on previous observations of this elusive disease. The most common clinical aspects were persistent facial edema with necroses and pitted scars. Histopathological analyses revealed variably dense lymphoid infiltrates with common angiodestructive features. Neoplastic cells expressed CD3 and cytotoxic markers in all cases and were constantly positive for Epstein-Barr virus (EBER-1). Expression of other markers was variable. Follow-up data revealed that all patients died within 6 months or less, thus showing a very aggressive course with poor prognosis.

Spark's nevus is a particular type of melanocytic nevus that on histology shows features of both Spitz's and Clark's nevus. Clinically, it is an asymmetric, irregular, multicolored, pigmented lesion that is not clearly distinguishable from melanoma or dysplastic (Clark's) nevus. Dermoscopic features have not been described yet, and one could speculate that they are similar to those of Clark's nevi because the histopathologic architecture of Spark's nevus is similar to that of a Clark's nevus, resembling Spitz's nevi in the epithelioid morphology of melanocytes. We present a 32-year-old woman with a Spark's nevus, who upon dermoscopy showed a pronounced atypical network with accentuation of the blue veil and mostly peripheral dots.

Using a computational approach to extract the spinal canal from whole-body PET/CT images, Marini et al. reveal increased glucose consumption in the spinal cord in prospectively recruited patients with amyotrophic lateral sclerosis. Simultaneous measurement of brain 18F-Fluorodeoxyglucose uptake reveals a divergent metabolic response in the two structures., We recently reported the potential of Hough transform in delineating spinal cord metabolism by 18F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to 18F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Our results confirmed higher 18F-fluorodeoxyglucose uptake in both cervical and dorsal spinal cord in patients with amyotrophic lateral sclerosis with respect to controls. This finding was paralleled by the opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake. This hypometabolism was particularly evident in wide regions of the frontal-dorsolateral cortex while it did not involve the midbrain. Bulbar and spinal disease onset was associated with similar degree of metabolic activation in the spinal cord. However, among spinal onset patients, upper limb presentation was associated with a more pronounced metabolic activation of cervical segment. Obtained data suggest a differential neuro-pathological state or temporal sequence in disease progression.

Metastasized castration-resistant prostate cancer (mCRPC), is the most advanced form of prostate neoplasia, where massive spread to the skeletal tissue is frequent. Patients with this condition are benefiting from an increasing number of treatment options. However, assessing tumor response in patients with multiple localizations might be challenging. For this reason, many computational approaches have been developed in the last decades to quantify the skeletal tumor burden and treatment response. In this review, we analyzed the progressive development and diffusion of such approaches. A computerized literature search of the PubMed/Medline was conducted, including articles between January 2008 and March 2018. The search was expanded by manually reviewing the reference list of the chosen articles. Thirty-five studies were identified. The number of eligible studies greatly increased over time. Studies could be categorized in the following categories: automated analysis of 2D scans, SUV-based thresholding, hybrid CT- and SUV-based thresholding, and MRI-based thresholding. All methods are discussed in detail. Automated analysis of bone tumor burden in mCRPC is a growing field of research; when choosing the appropriate method of analysis, it is important to consider the possible advantages as well as the limitations thoroughly.

OBJECTIVE: Atypical ductal hyperplasia (ADH) is a proliferative lesion associated with a variable increased risk of breast malignancy, but the management of the patients is still not completely defined, with mandatory surgical excision in most cases. To report the results of the conservative management with mammographic checks of patients with ADH diagnosed by vacuum assisted breast biopsy (VAB), without residual calcifications. METHODS: The authors accessed the institutional database of radiological, surgical and pathological anatomy. Inclusion criteria were: ADH diagnosed by VAB on a single group of microcalcifications, without residual post-procedure; follow-up at least of 12 months. Exclusion criteria were the presence of personal history of breast cancer or other high-risk lesions; association with other synchronous lesions, both more and less advanced proliferative lesions. RESULTS: The 65 included patients were all females, with age range of 40–79 years (mean 54 years). The maximum diameter range of the groups of microcalcifications was 4–11 mm (mean 6.2 mm), all classified as BI-RADS 4b (Breast Imaging Reporting and Data System 4b) and defined as fine pleomorphic in 29 cases (45%) or amorphous in 36 cases (55%). The range of follow-up length was 12–156 months (mean 67 months). Only one patients developed new microcalcifications, in the same breast, 48 months after and 15 mm from the first VAB, interpreted as low-grade ductal carcinoma in situ (DCIS) at surgical excision. CONCLUSION: These results could justify the conservative management, in a selected group of patients, being the malignancy rate lower than 2%, considered in the literature as the “probably benign” definition. ADVANCES IN KNOWLEDGE: Increasing the length of follow-up of selected patients conservatively managed can improve the management of ADH cases.

Multicentric prospective psychometric study. To provide a translation of the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) for Italian persons and to evaluate the interrater reliability of the translated version. Ten Italian rehabilitation centres specialized in spinal injury care. The initial translation was performed by two medical doctors who had an in-depth knowledge of spinal cord injury (SCI), and then a back translation (from Italian to English) was given to an accredited agency. Sixty-six participants with SCI (53 men, 13 women; mean ± SD age: 53.4 ± 16.0 years) were evaluated by means of the Italian version of the ISCIPBDS by two different examiners. Intraclass correlation coefficient (ICC) or Cohen’s Kappa (ĸ) was calculated to test the interrater agreement for the test−retest cases. All 66 participants had at least one pain problem and 34% of them had only one type of pain. A good interrater agreement was obtained in terms of number of pain (ICC = 0.781), type of pain (ĸ = 0.683), pain intensity (ICC = 0.798), correspondence of pain localization (ĸ = 0.750), and the value of the pain interference in day-to-day activities, overall mood and night’s sleep (ICC = 0.827, ICC = 0.861 and ICC = 0.724, respectively). Eventually a prominent prevalence of neuropathic pain was recorded (64% from the first examiner and 62% from the second one). The authors propose the Italian version of ISCIPBDS that can be used for research and clinical evaluation of pain in SCI persons; it shows a significant interrater reliability.

The histopathology of lepromatous skin varies according to the cell-mediated immunity of the host against Mycobacterium leprae. In tuberculoid and borderline tuberculoid leprosy, epithelioid noncaseating granulomas predominate, and acid-fast bacilli (AFB) are absent or only rarely present. In borderline lepromatous and lepromatous leprosy, the infiltrate is composed of macrophages with a vacuolar cytoplasm, lymphocytes, and plasma cells. AFB are numerous. Edema inside and outside the epithelioid granulomas, together with the appearance of large giant cells, are the main features of type 1 reactions. A conspicuous neutrophilic infiltrate in the subcutis with or without vasculitis is found in erythema nodosum leprosum. The main histopathologic features of leprosy and its particular forms are discussed in this review.