Exploring the Potential of IL-4 and IL-13 Plasma Levels as Biomarkers in Atopic Dermatitis.

Atopic dermatitis (AD) is a persistent inflammatory skin condition that impacts individuals of various age groups, including both children and adults. Its pathophysiology involves allergens penetrating a disrupted epidermal barrier, triggering the dermal cells to produce pro-inflammatory cytokines and eliciting a T-cell-mediated immune response. Notably, interleukins (ILs), particularly interleukin 4 (IL-4) and interleukin 13 (IL-13), play a key role in AD pathogenesis. Therapies directed at inflammatory mechanisms, including Dupilumab, have demonstrated notable effectiveness in enhancing skin lesions, alleviating subjective symptoms, and improving the overall quality of life for individuals with AD. Despite therapeutic advances, assessing AD severity remains challenging. The commonly used tools, such as the SCORAD and DLQI scores, rely on subjective patient responses. Paraclinically, the search for universal biomarkers continues, with efforts to identify reliable indicators reflecting disease severity and treatment response. Various biomarkers, including Th2-related chemokines and cytokines, have been explored, but none have gained universal recognition for routine clinical use. This study aims to investigate the dynamics of the plasma levels of IL-4 and IL-13 during Dupilumab treatment and establish correlations between these ILs and disease severity, as measured using the SCORAD and DLQI scores. The ultimate endpoint is to determine whether IL-4 and IL-13 can serve as reliable biomarkers, assessing their correlation with patient-reported feelings and disease activity and potentially influencing their inclusion or exclusion as diagnostic elements in routine clinical practice.

The Reduction of After-Hours and Weekend Effects in Upper Gastro-intestinal Bleeding Mortality During the COVID-19 Pandemic Compared to the Pre-Pandemic Period.

Background: In upper gastrointestinal bleeding (UGIB), admissions after normal working hours and during weekends may be associated with increased mortality. Aim: To assess the evolution of the after-hours and weekend effects during the COVID-19 pandemic as a result of progressive improved management despite management challenges during the pandemic. Methods: We performed an observational study of patients admitted for UGIB at a tertiary academic center between March 2020 and December 2021, compared to the corresponding timeframe before the pandemic. Admissions were assessed based on regular hours versus after-hours and weekdays versus weekends. We stratified patients based on demographic data, etiology, prognostic scores, the time between symptom onset and admission, as and between admission and endoscopy. The outcomes included mortality, rebleeding rate, the requirement for surgery and transfusion, and hospitalization days. Results: 802 cases were recorded during the pandemic, and 1006 cases before the pandemic. The overall mortality rate was 12.33%. Patients admitted after hours and during weekends had a higher mortality rate compared to those admitted during regular hours and weekdays (15.18% versus 10.22%, and 15.25% versus 11.16%), especially in cases of non-variceal bleeding. However, the difference in mortality rates was reduced by 2/3 during the pandemic, despite the challenges posed by COVID-19 infection. This suggests that there was an equalization effect of care in UGIB, regardless of the admission time. The differences observed in mortality rates for after-hours and weekend admissions seem to be primarily related to a higher proportion of patients who did not undergo endoscopy, while the proportion of severe cases remained similar. Blood requirements, hospital days, and rebleeding rate were similar between the two groups. Conclusion: Admissions during weekends and after-hours have been associated with increased mortality, particularly in cases of non-variceal bleeding. However, the impact of this association was significantly reduced during the pandemic.

Defining the short-term and long-term skin manifestations of COVID-19: insights after more than three years of the pandemic.

AIM: This review aimed to assess the impact of coronavirus disease 2019 (COVID-19) on skin health to establish a classification of the skin lesions that occur most frequently during the disease and whether a particular category of skin damage is more likely to occur both in the short term and in the long term. METHODS: We conducted a literature search of the PubMed database. Ultimately, 109 articles were included in this review. The exact phrases∕syntax and connectors used for the database search∕query were as follows: "Coronavirus and skin", "COVID-19 and skin", "SARS-CoV-2 and skin", "Coronavirus cutaneous manifestations", "COVID-19 cutaneous manifestations", "SARS-CoV-2 cutaneous manifestations", "Coronavirus dermatology", "SARS-CoV-2 and dermatology", "COVID-19 and dermatology", "COVID-19 and skin eruption", "Coronavirus and skin rash", "COVID-19 and hair", "Coronavirus and hair", "Coronavirus and nails", "SARS-CoV-2 and hair", and "SARS-CoV-2 and nails". Only articles with abstracts referring strictly to cutaneous manifestations of COVID-19 were chosen. Articles without abstracts were not considered. RESULTS: We established six of the most frequently reported clinical patterns associated with COVID-19 and their probability of occurring during COVID-19 disease evolution based on the current literature reports. We did not identify the particular types of skin lesions that are most prone to long-term persistence; most such cases are rare, and no conclusion can be drawn based on them. CONCLUSIONS: Apart from classified COVID-19-related skin disorders, this pandemic has been a challenge for dermatologists and a wide range of cutaneous side effects related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) treatments have been reported. We are aware of other polymorphic clinical presentations, with novel data being reported periodically, but the pathophysiological mechanisms and evolution are largely unknown.

Multimodality Cardiac Imaging in COVID-19 Infection.

COVID-19 infection often produces cardiovascular complications, which can range from mild to severe and influence the overall prognosis. Imaging is the cornerstone for diagnosing initial COVID-19 cardiovascular involvement as well as treatment guidance. In this review, we present the current state of the literature on this subject while also emphasizing possible algorithms for indicating and executing these investigations.

The Accuracy of Pre-Endoscopic Scores for Mortality Prediction in Patients with Upper GI Bleeding and No Endoscopy Performed.

(1) Background: The assessment of mortality and rebleeding rate in upper gastrointestinal bleeding (UGIB) is essential, and several prognostic scores have been proposed. Some patients with UGIB did not undergo endoscopy, either because they refused the procedure, suffered from alcohol withdrawal symptoms or altered general status, or because the bleeding was severe enough to cause death before the endoscopy. The mortality risk in the subgroup of patients without endoscopy is poorly evaluated in the literature. (2) Methods: The purpose of the study was to identify the most useful scores for the assessment of in-hospital mortality in patients with UGIB with no endoscopy performed and no known etiology. A total of 198 patients with UGIB and no endoscopy performed were admitted between January 2017 and December 2021 and the accuracy of 12 prognostic scores and the Charlson comorbidity index for in-hospital mortality prediction were analyzed, as well as Child-Pugh Turcotte (CPT) and Meld scores in patients with cirrhosis. (3) Results: The mortality rate was 37.9%, higher than in variceal (21.9%, p < 0.0001) and non-variceal bleeding (7.4%, p < 0.0001). The most accurate scores by AUC were the International Bleeding score (INBS, 0.844), Glasgow Blatchford (0.783), MAP score (0.78), Iino (0.766), AIM65 and modified N-score (0.745 each), modified Glasgow-Blatchford (0.73), H3B2 and N-score (0.701); Rockall, Baylor, and T-score had an AUC below 0.7. MELD score was superior to CPT in patients with cirrhosis (AUC 0.811 versus 0.670). (4) Conclusions: The mortality rate in UGIB with no endoscopy was higher than in both variceal and non-variceal bleeding and was higher in the pandemic period but with no statistical significance (45.3% versus 32.14%, p = 0.0586), mainly because of positive cases. Only one case of rebleeding was noted; the hospitalization period was significantly shorter. The most accurate score was International Bleeding Score; the MELD score had a higher but moderate accuracy compared with CPT in patients with cirrhosis.

Follow-Up of a Rare Case of Eosinophilic Gastroenteritis Associated with Persistent Blood Eosinophilia and Multiple Food Allergies.

Eosinophilic gastroenteritis (EGE) is a subgroup of the eosinophilic gastro-intestinal disorders (EGIDs), characterized by eosinophilic infiltration and chronic inflammation of the gastrointestinal tract. These are rare diseases with still incompletely elucidated causes and mechanisms, with frequently delayed diagnosis and variable outcome. Despite increased interest in eosinophilic diseases in recent years, fewer data have been published on EGE and no standardized diagnostic and therapeutic approach exists. This paper reports the case of a young male patient diagnosed with EGE in 2017 based on clinical and histopathological criteria and constantly monitored during five years. Besides gastrointestinal eosinophilic infiltration, biopsies also revealed eosinophilic infiltration of the oesophagus, despite no declared characteristic oesophageal symptoms. We found increased specific IgE to multiple foods and progressive blood hypereosinophilia which preceded EGE diagnosis by three years. The EGE management included selective dietary restrictions and pharmacologic therapy based on daily budesonide non-enteric coated tablets, proton pumps inhibitors, antihistamines, cromoglycate, correction of iron, calcium and vitamin D deficiencies. The clinical outcome was good, while blood eosinophilia and endoscopic appearance remained almost unchanged. After one year the patient complained of respiratory symptoms suggesting asthma, needing continuous combined inhaled therapy. The reported case is illustrative for complex presentation, diagnosis and outcome of a rare case of mucosal chronic EGE associated with oesophageal involvement, peripheral eosinophilia, multiple food allergies and asthma.

Clinicopathological correlation of transient acantholytic dermatosis: A case report.

Transient acantholytic dermatosis (TAD) is a benign, non-familial, non-immune mediated acantholytic disorder of unknown etiology. The presence of polymorphous, unorganized, pruritic lesions on the trunk, associated with focal acantholysis and dyskeratosis, resembles a wide variety of dermatoses. The etiology of TAD (also known as Grover's disease) is unknown, and the success of treatment relies on the correct identification of the disease; however, some cases are refractory to all forms of therapy. For accurate diagnosis, a comprehensive literature review is required. Here, the case of a 55-year-old male with TAD displaying a Darier-like histopathological pattern was reported. The patient was successfully treated with retinoids and acitretin (Neotigason), as well as dapsone, an anti-inflammatory agent, as maintenance therapy. The presence of more than two histological findings, limited to small foci and clinical information, can diagnose Darier disease. The exact pathogenesis has not been elucidated, thus further studies of the pathogenesis of TAD are required.

Factors predicting occurrence and therapeutic choice in malignant colorectal polyps: a study of 13 years of colonoscopic polypectomy.

Colorectal carcinoma represents a major cause of mortality and 0.2-12% of resected colonic polyps have malignant cells inside. We performed a retrospective study of patients with resected polyps during a period of 13 years. A total of 905 patients had 2033 polyps removed; 122 polyps (109 patients) had malignant cells. Prevalence of malignant polyps with submucosal invasion was 1.23% and for all polyps with malignant cells was 6%; malignant polyps had a larger size (23.44 mm mean diameter) vs benign polyps (9.63 mm); the risk of malignancy was increased in polyps larger than 10 mm, in lateral spreading lesions and in Paris types 0-Ip, 0-Isp, in sigmoid, descending colon and rectum, in sessile serrated adenoma and traditional serrate adenoma subtypes of serrated lesions and in tubulovillous and villous adenoma. In 18 cases surgery was performed, in 62 patients only colonoscopic follow-up was made and in 35 patients no colonoscopic follow-up was recorded. From initially endoscopic resected polyps, recurrence was noted in seven (11.3%) cases; there was a trend toward association with depth of invasion, piecemeal resection, right and rectum location, sessile and lateral spreading type and pathological subtype. In surgical group, post-therapeutic staging was available in 11 cases; nodal involvement was noted in three (27.27%) cases; none had lymphatic or vascular invasion in endoscopically resected polyps. Four patients with no macroscopic local recurrence underwent surgery with no residual tumor. The rate of metastasis was 16.67% in surgical group and 1.61% in endoscopic group. Evaluation of lymph node (LN) invasion was available for 11 operated patients, with LN invasion (N1) in three patients, local residual tumoral tissue in one patient with incomplete resection and no residual tumor (R0 resection) in four patients with endoscopic resection before surgery.

Single Blind, Randomised Study Regarding the Treatment of the Telangiectasia of the Lower Limbs (C1EAP) Using Polidocanol 0,5%, 1%, and Nd:YAG Laser.

The treatment of leg telangiectasias could be done with liquid sclerotherapy or Nd:YAG laser. We evaluated randomly, in a simple blind, the efficacy of the treatment with 0,5% polidocanol (POL-0,5), 1% polidocanol (POL-1) and Nd:YAG laser (LAS) on 132 patient (264 limbs) with telangiectasia of the lower limbs with less than 2mm diameter (C1EAP). The main objective was to evaluate the efficacy of the sclerotherapy (chemical compared with Nd:YAG-LAS). Secondary objectives were: possible major complications (deep thrombosis, severe burns, ischemic complications, etc.), the percentage of the local complications, the cosmetic aspect-evaluated by both the patient and the doctor and the grade of discomfort of the patient during and after the procedure. Comparing the treatment with Nd:YAG laser (LAS), polidecanol-0.5% (POL-0.5), polidecanol 1% (POL-1), it was noticed that telangiectasias smaller than 1mm led to good and very good results in all the cases treated with Nd:YAG laser and the same outcome was obtained in one third of the subjects treated with POL-0.5, vs. 47.81% of patients treated with POL-1. When telangiectasias were larger than 1mm diameter, good and very good results occurred in 86.36% of patients treated with LAS and 100% of the cases treated with POL-0.5 and POL-1. In conclusion, we consider that leg telangiectasias can be treated with good results using Nd:YAG laser or sclerotherapy with polidocanol, Nd:YAG laser being reccomended for telangiectasia under than 1 mm diameter while sclerotherapy in larger vessels.

Mast cell activation syndromes - evaluation of current diagnostic criteria and laboratory tools in clinical practice (Review).

Mast cell activation syndromes (MCAS) represent a heterogeneous clinical entity caused by episodic and severe mast cell activation, including primary and secondary mast cell disorders (MCDs). The group of primary or clonal MCDs refers to systemic mastocytosis, other clonal MCAS and hereditary hypertryptasemia, while the secondary MCAS is characterized by normal mast cells (MCs) which are activated by external triggers, such as allergens or physical stimuli. Another category of MCAS is the idiopathic form, when no trigger or genetic mutation can be identified. Symptoms of mast cell activation are due to release of specific mediators and can be seen in many diseases, such as allergies, with localized or systemic clinical manifestations. Confirmation of MCAS is based on diagnostic criteria proposed by an international group of experts and the best available evidence in this field. It is generally accepted that the clinical picture of MCAS is non-specific and there are few available laboratory tools, making it difficult for clinicians to identify and confirm this entity. The diagnosis is established after exclusion of other possible clinical entities in most of the cases. Therefore, the actual diagnostic criteria of MCASs, some relevant clinical aspects and laboratory tools used in clinical practice were reviewed.

Gastric cancer - histopathological correlations between tumor and non-tumor gastric mucosa changes.

Gastric cancer is a widely geographically distributed malignancy with high prevalence, therefore being a serious health problem that needs standardized methods for early diagnosis and treatment. The aim of the study was to evaluate the correlation of some epidemiological and clinical data with the histological features. The study group was made up of 66 patients that underwent surgical removal of the gastric neoplasm, and the pathological exam showed the morphological features of the tumor, as well as the ones of the unaffected mucosal tissue. Topographically, the highest incidence of the tumor was registered in the gastric antrum, but in recent years, an increased incidence of the superior gastric pole localization was recorded. The macroscopic aspects reveal that the ulcerated type 2 Borrmann is the most frequent, and alongside type 3 Borrmann, the ulcer-infiltrative type represents most of the gastric antrum cancers. The analysis of the tumor invasion showed that most carcinomas underwent surgery when the tumor invaded the serosa (pT3) or even the perigastric tissues (pT4). In our research, we chose Goseki's microscopic classification because of its best coverage of the histological heterogeneity of the gastric carcinomas, providing information about the percentage of the cellular and secretory differentiation with direct impact on the invasion of the tumor. In more than 70% of the cases, the patients showed lesions of severe chronic atrophic gastritis of the non-tumor mucosa. Lately, the incidence of Helicobacter pylori has been 5.5%, lower than indicated by mainstream literature. We observed that the incidence of type 3 incomplete intestinal metaplasia, as the most commonly involved factor in the etiopathogenesis of gastric neoplasms, was encountered in 36.3% of the cases, this percentage rising proportionally with age and being frequently associated with antrum tumors. In conclusion, the permanent analysis of the relation between epidemiological data and some histological features might be relevant for the characterization of the tumoral process or the non-tumor gastric mucosa, leading to an evaluation of the prognosis.

The role of non-invasive scores in determining the liver fibrosis in NAFLD and psoriatic patients.

According to recent data, psoriatic patients have an increased prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome, compared with the general population. In some published studies, the severity and presence of psoriasis disease were correlated with the severity of NAFLD. In the current study, we aimed to compare the sensibility and specificity of the non-invasive scores and liver biopsy in determining fibrosis in patients with NAFLD and moderate to severe psoriasis. We performed the scientific research from June 2014-December 2017 and we included 71 patients: 40 patients with NAFLD and 31 patients with moderate to severe psoriasis according to Psoriasis Area and Severity Index (PASI) score and NAFLD, who received Etanercept treatment for at least one year. Based on the clinical and laboratory data, we calculated the following scores for fibrosis: body mass index (BMI), aspartate aminotransferase (AST)∕alanine aminotransferase (ALT) ratio, diabetes (BARD) score, Fibrosis-4 (FIB-4) score, and NAFLD fibrosis score (NFS). For liver biopsy, we used the Menghini technique. By calculating Kendall's test, we also observed a strong direct correlation between the degree of fibrosis and FIB-4 (tau=0.558) and NFS (tau=0.490) scores, with a critical statistical impact, and the lack of a correlation with the BARD score (tau=0.095; p=0.332). The hepatic biopsy allowed the more accurate establishment of the role of the non-invasive tests in the diagnosis of the lesions of steatosis, steatohepatitis, and hepatic fibrosis. The non-invasive tests are most useful for the exclusion of the evolution lesions and for the confirmation of the advanced stages of the disease. Among these, the NFS score proved a high statistically significant correlation (p<0.0001) with the fibrosis histological lesions.

An unusual onset of Crohn's disease with oral aphthosis, giant esophageal ulcers and serological markers of cytomegalovirus and herpes virus infection: a case report and review of the literature.

Isolated esophageal ulcerations in Crohn's disease pose a great challenge in diagnosing and providing the correct treatment. We present the case of a 23-year-old woman with recurrent episodes of oral aphthosis, dysphagia, odynophagia and heartburn. Upper digestive endoscopy revealed an irregular mucosa with multiple ulcerations with irregular margins within the mid-esophagus. Immunoglobulin G (IgG) for cytomegalovirus and herpes virus were both positive. Four years after, she presented with the same symptoms and the involvement of ileo-colonic lesions, with pathological findings helped establish the Crohn's disease diagnosis. Crohn's disease represents an idiopathic chronic inflammatory gut disease, which can affect any part of the digestive tract. The onset by esophageal disease and no intestinal involvement is rare and challenging for a proper diagnosis.

In-hospital and short-term prognostic factors in acute pulmonary edema: clinical and morphological features.

INTRODUCTION: There are extensive records which have included patients with acute heart failure (AHF), but specific studies about prognosis in acute pulmonary edema (PE) are scarce and have enrolled a small number of patients. The objectives of this study were to evaluate the predictive factors of short-term evolution in patients with PE. PATIENTS, MATERIALS AND METHODS: This was a prospective, two-center survey of 70 consecutive patients admitted for acute cardiogenic PE. The follow-up was performed one month after discharge. The composite endpoint was in-hospital death, and death of any cause or readmission for heart failure (HF) at one month after discharge. Heart and lung tissue analysis was performed postmortem to identify morphological features of PE. RESULTS: In-hospital mortality was 4.2%, another 14.2% died in the first month, and an additional 10% required rehospitalization for HF. The characteristics significantly associated with end-point occurrence were: history of kidney disease, anemia, diabetes mellitus, lack of prior angiotensin-converting enzyme inhibitor÷angiotensin-receptor blocker treatment, lower systolic blood pressure (BP) at admission, lower diastolic BP at admission, creatinine at admission and at discharge, an increase in creatinine during stay, glomerular filtration rate at admission, serum sodium at admission, decrease in serum sodium during hospitalization, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at discharge, right ventricle fractional area change, left atrium volume index. We created a multiple logistic regression model and identified five prognostic factors: age, diabetes, creatinine, diastolic BP, serum sodium. This model correctly classified 48 (96%) patients without worsening and 13 (65%) patients with worsening, providing an overall accuracy of 87.1%. Necropsy was performed on five patients and fragments of left ventricle myocardium and lung were harvested for histopathological and immunohistochemical studies. The myocardium exhibited fibrosis areas where the myocytes were completely or partially replaced by collagen fibers. Lung tissue analysis revealed some case-to-case differences, but the common finding was alveoli size larger than normal, with the lumen completely or almost completely covered by an eosinophilic liquid. CONCLUSIONS: The factors that best predicted the short-term outcome in PE were age, diabetes, diastolic BP, creatinine, serum sodium.

Correlations between endothelial cell markers CD31, CD34 and CD105 in colorectal carcinoma.

PURPOSE: Colorectal carcinoma is an important cause of mortality worldwide. The fact that tumor growth is dependent on angiogenesis has supported researches for new prognostic parameters and the development of novel therapeutic strategies. Accordingly, we sought to evaluate angiogenesis quantitatively by assessing microvessel density in colorectal cancer. MATERIALS AND METHODS: The blood vessels stained with CD31, CD34 and CD105 were counted, and we reported their number per square millimeter in order to obtain microvascular density (MVD). Then, we aimed at comparing the performance of three endothelial cell markers (CD31, CD34, and CD105) on formalin-fixed tissues from 58 patients diagnosed with colorectal cancer. RESULTS: Following the comparison of the average effective vessels marked with the three markers, Student's t-test showed that the mean number of blood vessels marked with CD34 is higher than the blood vessels marked with CD31 and CD105. A significant difference that has been registered between the three levels of the T stage was found in the patients in our study, in terms of value marker CD105, ANOVA p=0.049, which returns to a value <0.05. Quick time decreases the pT stage, the observed differences being close to statistical significance. However, the result of ANOVA test does not allow us to say that differences can be generalized and not just a particular result, valid only for the study group, p=0.061 >0.05. There is a significant difference between patients with stage T, in terms of value: hemoglobin (ANOVA p<0.001), hematocrit (ANOVA p<0.001), mean corpuscular volume (MCV) (ANOVA p<0.001), mean corpuscular hemoglobin (MCH) (ANOVA p=0.002 <0.01 - significant difference with 99% confidence). By calculating the Pearson's correlation coefficient for the relationship CD31-CD105, we obtained a value r=0.440, which corresponds to p=0.0013 <0.05, indicating a statistically noteworthy direct correlation between the two factors. CONCLUSIONS: CD31 marker increases simultaneously with the CD105, in the cases analyzed throughout the present study. The ability of tumors to maintain a high vascular blood density in their inner portions may represent a reliable parameter to evaluate tumor angiogenesis and a finding relevant for future development of therapeutic angiogenesis strategies.

Non-alcoholic fatty liver disease - clinical and histopathological aspects.

INTRODUCTION: We conducted a retrospective study on patients who were hospitalized in the Emergency County Hospital of Craiova, Romania, between 2009-2014. We selected 75 patients out of 248 cases of fatty liver disease who underwent liver biopsies performed during surgical procedures for various diagnoses. PATIENTS AND METHODS: We analyzed the patients' data recorded in examination charts: anthropometric parameters [height, weight, body mass index (BMI), abdominal circumference], metabolic lab tests (blood glucose, lipid profile), liver destruction enzymes, imaging examinations (abdominal ultrasound). The pathological study was performed on specimens directly after sampling as well as after staining. RESULTS: After analyzing the results of the histological examination, we grouped our studied patients according to the degree of the liver steatosis: 21 (28%) cases with mild steatosis, 46 (61.33%) cases with moderate disease and eight (10.66%) cases with severe steatosis. The necrotic-inflammatory activity was mild in 28 (37.33%) cases, moderate in 36 (48%) cases and severe in 11 (14.66%) cases. Most of the studied patients exhibited septal fibrosis (45 cases - 60%) and porto-portal and porto-central bridging fibrosis (21 cases - 28%). Septal fibrosis and cirrhosis were recorded in four (5.33%) and five (6.66%) cases, respectively. There was a significant correlation between the degree of the hepatic steatosis, the degree of obesity (as expressed by BMI) and the waist circumference (as a measure of central obesity) - p<0.001. CONCLUSIONS: The non-alcoholic fatty liver disease (NAFLD) was found to be significantly associated with waist circumference, BMI, triglycerides. The liver enzymes are not considered to be sensitive or specific for diagnosing NAFLD. Concerning the association between the steatosis and fibrosis, in our study the septal fibrosis was associate with mild steatosis in most of the cases. Moderate steatosis was mostly associated with septal fibrosis as well as porto-portal and porto-central fibrosis. Severe steatosis was correlated with both porto-portal and porto-central fibrosis and cirrhosis in the majority of cases.

Hirschprung's disease in different settings - a series of three cases from a tertiary referral center.

Failure of neural crest cells to migrate from neural crests during intrauterine development result in partial or total aganglionosis of the colon in newborn. Hirschprung's disease (HD) represents the clinical manifestation of this pathogenic process, currently accounting for the majority of lower intestinal obstruction in the first period of life. Our aim was to present a series of three cases presenting to our tertiary care center with a range of symptoms, all benefiting from surgery and consequent pathology examination of biopsy or resection pieces. The first case was of a male newborn that presented several years ago with common symptoms for HD (abdominal distension, vomiting and the total lack of intestinal passage for feces). Coming from young healthy parents after normal labor, the newborn displayed signs of Down's disease after physical examination. After abdominal radiography, the patient underwent surgery and consecutive pathology revealed notable signs of Crohn's disease (CD): massive stasis in the serosa and submucosa, chronic inflammatory infiltrate and lack of nervous cells in both plexuses and mucosa. Immunohistochemistry revealed low intensity CD34 membrane staining for fibroblast-like ganglion cells while CD117 staining showed few nervous cells within the mucosa. The second case presented before one year of age with an infectious background, already being operated upon with colostoma. We performed corrective surgery of the colostoma and consecutive pathology showed low CD117 cytoplasmic staining and intensely positive NSE (neuron specific enolase) staining within myenteric plexuses. Finally, the third and most recent case was that of a 4-year-old boy with an early diagnosis of megacolon and no previous surgery, who we evaluated by laparoscopy with five biopsies and consecutive S100 staining revealed a small number of nervous cells within nervous plexuses. In conclusion, an early diagnosis of HD is essential for successful therapeutic measures. Histology and, more recently, immunohistochemistry, represent the gold-standard procedures needed to objectify the diagnosis.

Specific features of a rare form of disseminated necrobiosis lipoidica granuloma annulare type: a case report.

Necrobiosis lipoidica (NL) is a rare dermatosis that has been shown to precede the onset of diabetes mellitus in 15% of patients. It is more common in women; the average age of the onset is 30 years. Skin lesions of classic NL begin as a small papule, typically on the bilateral pretibial area. Progressively, these papules become indurated plaques with an atrophic, yellow center and multiple telangiectatic vessels, and brown-violaceous borders. We present the case of a 57-year-old male with type II diabetes mellitus from 2004, class II obesity, hepatosteatosis and metabolic disturbances who presents a disseminated eruption from 2010, formed by indurated plaques with flattened centers and a tendency of atrophy and raised, sharply demarcated, red-violaceous borders, having a variable diameter between 1.5 and 5 cm. The laboratory findings revealed elevated glucose levels between 250 and 300 mg%, high levels of transaminases and lipids. Diagnosis of disseminated necrobiosis lipoidica granuloma annulare-type was histopathologically confirmed. For the treatment, we have used topical corticosteroids and Tacrolimus 0.1% and systemic vasodilators. We consider this rare case interesting because has some peculiarities, as: disseminated lesions extend over the characteristic areas for necrobiosis lipoidica, the characteristic features of lesions similar to granuloma annulare, gender (male) and the onset of the disease over fifth decade.