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INTRODUCTION: Nowadays, chronic viral hepatitis represents one of the most common pathological entities with over 400 million cases worldwide, with high diagnosis and treatment cost, severe complications in late stages and an annual death-rate around 1 million. The purpose of this study was to identify noninvasive ultrasound markers in order to establish an early diagnosis in asymptomatic chronic hepatitis. METHODS: We enrolled in a prospective study 111 patients diagnosed with asymptomatic chronic hepatitis: 53 patients with hepatitis B (group A) and 58 patients with hepatitis C (group B). All patients underwent ultrasound exam; we evaluated the dimensions of the left hepatic lobe, right hepatic lobe, caudate lobe, portal vein, liver stiffness, presence of hepatic hilar lymph nodes, number and dimensions of the adenopathies. RESULTS: Increased liver size was found in over 16% of patients in group A and over 20% of patients in group B. We registered an enlarged portal vein in 3.77% of patients in group A and in 3.45% of patients in group B. Adenopathies were found in 64.16% of group A and 82.76% of group B. Using long adenopathic axis as marker, we obtained a NPV over 0.9, PPV of 0.5 in the detection of chronic hepatitis B and a PPV of 0.9 in the detection of chronic hepatitis C in asymptomatic patients, a specificity of 0.98 for both chronic hepatitis B and C, a sensitivity of 0.81 for group B and 0.64 for group A. CONCLUSIONS: The presence of hilar liver adenopathies represents an important marker in detecting asymptomatic chronic viral hepatitis.

Background: The severe manifestations of the coronavirus disease 2019 (COVID-19) are linked to viral hyper-inflammation, cytokine release syndrome and subsequent coagulation disturbances. The most common coagulation abnormality observed in COVID-19 patients is the elevation of the plasma levels of D-dimers. The aim of this study was to evaluate the characteristics of COVID-19-associated inflammatory syndrome and coagulopathy, in correlation with disease severity. Methods: We performed a cross-sectional study, enrolling all consecutive COVID-19 patients treated in the Adulti 3 Department of the Prof. Dr. Matei Bals National Institute of Infectious Diseases, Bucharest, Romania, between 1st march and 30th September 2020. We recorded clinical and epidemiological characteristics, inflammatory markers, coagulation abnormalities and lymphocyte count. The severity of lung involvement was assessed using native Computed Tomography examination. Results: We included 106 patients with SARS-COV2 infection, 50 males (47.2%) and 56 females (52.8%), age range 14-91 years. All markers of inflammation were increased in our study in patients with severe disease, as were lactate dehydrogenase, monocyte distribution width, and neutrophil-to-lymphocyte ratio. An elevated level of serum D-dimers was observed in approximately half of our subjects and was associated with disease severity. Our best linear regression model for predicting COVID-19 coagulopathy (manifested as abnormal D-dimer levels) included age, fibrinogen, and lymphocyte count. Conclusion: Our findings emphasize the association between COVID-19 coagulopathy and the presence of systemic inflammation. A significant proportion of patients with moderate and severe disease had coagulation abnormalities and these were linked with the presence of inflammation and older age..

The global prevalence of arterial hypertension is increasing. Due to its consequences, hypertension is a leading cause of morbidity /mortality. In this regard, awareness of the importance of diagnosis as well as proper treatment of hypertension is mandatory. Objectives: This study aims to analyze vascular compliance and different pressure characteristics depending on age, along with highlighting some clinical-paraclinical correlations in people diagnosed with hypertension. We used usual laboratory analyzes and the blood pressure values obtained using ABPM/24 hr, in addition to highlighting the impact of age on those parameters. Materials and methods: The sample comprises of 99 adults diagnosed with hypertension. We divided them into 2 groups, according to age: cases sample: 52 patients (age> 60 years old) and control sample: 47 patients (age< 60 years old). Results: In the control group, RDW was correlated with the general and diurnal systolic and diastolic hypertonicity indexes and the platelet count was positively correlated only with the morning surge. The dipping profile correlates negatively with RDW. In the elderly, all three systolic blood pressure parameters are influenced by ESR and also correlate negatively with HDL, with an inverse proportional relationship. Statistically significant correlations were found between blood glucose and diurnal systolic and diastolic hypertonicity indexes. Mean Pulse Pressure correlates in the elderly with HDL (negative correlations) and in the young with RDW (positive correlations). Conclusions: Vascular compliance can be estimated with the help of HDL in the elderly and RDW in young people, considering the influence of the two parameters on pulse pressure.

In most dermatological pathologies, the phenomena observed on the skin are a reflection of internal disorders. In patients with associated acral involvement on the dorsal sides of the hands, this “vitiligo phenotype” may lead to the investigation of certain associated pathologies that sometimes have no obvious clinical impact. To assess the link between skin depigmentation and autoimmune pathologies, we conducted a systematic review involving article selection from the PubMed database. Patients with coexisting thyroid pathologies were found to have a predisposition for developing acral vitiligo and depigmentation of the wrists, and autoimmune thyroid pathologies appeared to be the only coexisting autoimmune or inflammatory diseases in vitiligo patients to show a pattern of distribution. The association of concomitant thyroid dysfunction with depigmentation of the hands was found to be so strong that the absence of depigmented macules on the hands may exclude the coexistence of an autoimmune thyroid pathology. Although the frequency of acral involvement in patients with vitiligo and autoimmune pathologies is higher, the mechanism by which thyroid dysfunction influences this distribution pattern remains incompletely elucidated and requires future studies.

The pathogenesis of vitiligo is still unclear. The complexity of the disease seems to be based on the intervention of environmental factors in the background of genetic predisposition which will determine the response of the immune system, the involvement of the nervous and endocrine systems, altered metabolisms and increased oxidative stress - all these elements leading to melanocytic dysfunction and their subsequent destruction. Melanocytic death has a clinical correspondent that embraces the form of white macules on the skin, associated or not with leucotrichia. A better understanding of vitiligo' s pathophysiology and mechanisms of cell death at the skin level can be a step to some appropriate treatment strategies.

Cutaneous melanoma is the most aggressive form of skin cancer and its incidence is unfortunately increasing. In the last decades, a progressive increase of new cases of diagnosed thin melanoma has been noted. This may be due to earlier detection, better surveillance, improved diagnostic criteria or increased exposure to sunlight. Despite the fact that Breslow tumor thickness has the strongest proven prognostic significance, there are still thin melanomas that metastasize and thick melanomas with favorable evolution. Therefore, the identification of strong predictive factors for survival is mandatory, particularly for patients with thin melanoma.

Spinal muscular atrophy (SMA) is a spectrum of genetically and clinically heterogeneous diseases leading to the progressive degeneration of peripheric motor neurons with subsequent muscle weakness and atrophy. More than 95% of the cases of SMA are represented by homozygous mutations of the SMN1 gene (5q-SMA). Because this disease represents the leading cause of death due to a genetic cause and due to the availability of genetic therapies which can now save the life of the patient and stop the progress of the disease, early diagnosis is crucial. This report presents the case of a 13-year-old patient admitted to our hospital in 2018 who presented a phenotype typical to 5q-SMA. Next-generation sequencing (NGS) and Sanger sequencing of the SMN1 gene were performed, and a negative result was obtained. Consequently, we continued testing using whole-exome sequencing and discovered three mutations in the ASAH1 gene (one pathogenic and two variants of uncertain significance). Pathogenic mutations in the ASAH1 gene are responsible for spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and Farber disease, which overlapped with our patient’s phenotype. Currently, there are 45 SMA cases caused by mutations in the ASAH1 gene reported worldwide; however, the present case is the first reported in Romania.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology, presenting with variable clinical picture. Having a high heterogeneity and lacking pathognomonic features, very often the diagnosis poses a great challenge for the clinician. Several unusual clinical manifestations such as nasal septal perforation and digital gangrene can occur in LES patients. Case report. We report the case of a 42-year-old woman, known with SLE, hospitalized in our department for a clinical presentation consisting of a recent major epistaxis, physical asthenia and acral necrosis of the upper limbs. Physical examination revealed an afebrile patient, with a cushingoid facies, facial telangiectasias, and necrotic scars localized on the distal phalanges, bilaterally. A diagnostic nasal endoscopy showed a large septal perforation with the absence of the cartilaginous nasal septum. CT highlighted an extended defect at the level of the cartilaginous part of the nasal septum. Conclusion. Nasal septal perforation remains an underdiagnosed invalidating complication of lupus and treated and discovered early could have an important impact on the general health of an already burdened by disease patient.

Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis of multiorgan failure and lead to a subsequently worsening prognosis. Alongside the global impact of the COVID-19 pandemic, a great number of research papers have focused on SARS-CoV-2 pathogenesis and treatment. Significant progress has been made in this regard and coagulation disturbances were once again found to underlie some of the most serious adverse outcomes of SARS-CoV-2 infection, such as acute lung injury and multiorgan dysfunction. In the attempt of untangling the mechanisms behind COVID-19-associated coagulopathy (CAC), a series of similarities with sepsis-induced coagulopathy (SIC) became apparent. Whether they are, in fact, the same disease has not been established yet. The clinical picture of CAC shows the unique feature of an initial phase of intravascular coagulation confined to the respiratory system. Only later on, patients can develop a clinically significant form of systemic coagulopathy, possibly with a consumptive pattern, but, unlike SIC, it is not a key feature. Deepening our understanding of CAC pathogenesis has to remain a major goal for the research community, in order to design and validate accurate definitions and classification criteria.

Epithelial-mesenchymal transition (EMT) is involved in physiologic processes such as embryogenesis and wound healing. A similar mechanism occurs in some tumors where cells leave the epithelial layer and gain mesenchymal particularities in order to easily migrate to other tissues. This process can explain the invasiveness and aggressiveness of these tumors which metastasize, by losing the epithelial phenotype (loss of E-cadherin, desmoplakin, and laminin-1) and acquiring mesenchymal markers (N-cadherin). Complex changes and interactions happen between the tumor cells and the microenvironment involving different pathways, transcription factors, altered expression of adhesion molecules, reorganization of cytoskeletal proteins, production of ECM-degrading enzymes, and changes in specific microRNAs. The purpose of this review is to determine particularities of the EMT process in the most common malignant cutaneous tumors (squamous cell carcinoma, basal cell carcinoma, and melanoma) which still have an increasingly high incidence. More studies are required on this topic in order to establish clear correlations. High costs related to skin cancer therapies in general as well as high impact on patients’ quality of life demand finding new, reliable prognostic and therapeutic markers with significant public health impact.

Halo nevi, known as leukoderma acquisitum centrifugum, Sutton nevus, leukopigmentary nevus, perinevoid vitiligo, or perinevoid leukoderma, together with vitiligo and melanoma-associated hypopigmentation, belong to the group of dermatoses designated as immunological leukodermas. The etiology and pathogenesis of halo nevi has not been fully elucidated. There are several mechanisms through which a lymphocytic infiltrate can induce tumoral regression. In this review, we aimed to update the knowledge about Sutton nevi starting with the clinical appearance and dermoscopic features, continuing with information regarding conventional microscopy, immunohistochemistry, and the immunological mechanisms responsible for the occurrence of halo nevi. We also included in the article original unpublished results when discussing dermoscopic, pathologic and immunohistochemical results in halo nevi. Sutton nevi are valuable models for studying antitumor reactions that the human body can generate. The slow and effective mechanism against a melanocytic skin tumor can teach us important lessons about both autoimmune diseases and anticancer defenses.

Arterial hypertension represents one of the most common pathologies in the adult population. Hypertensive patients have structurally altered arteries, with a higher rigidity that leads to a significant decrease in vascular compliance. At the base of the pathophysiological process stands the inflammation, as a reaction of the organism to injury. Objectives: This study aims to highlight clinical-paraclinical correlations in people diagnosed with arterial hypertension and inflammatory status. Thus, we would like to evaluate possible correlations between the usual inflammatory markers and blood pressure values. Materials and methods: The sample comprises 64 adults who were subsequently divided based on the diagnosis of arterial hypertension, by using Automatic Blood Pressure Monitoring, as following: Study group=26 patients (with arterial hypertension) and Control group: 38 patients (without arterial hypertension). Results: The study has revealed negative correlations between the neutrophil/lymphocyte ratio (NLR) and the general diastolic average (r=-0.248 and p=0.047), the diurnal diastolic average (r=-0.258 and p=0.038) and the diurnal mean arterial pressure (r=-0.249 and p=0.046) and a negative correlation between the red cell distribution width (RDW) and the dipping index (r=-0.402 and p=0.013), each of them accomplishing the level of statistical significance. Conclusions: NLR can be used as a predictor of diastolic blood pressure values and as a factor of prognosis for the evolution of arterial hypertension. RDW is higher in non-dipping patients.

Cutaneous melanoma is the most aggressive type of skin cancer, with high invasive potential. Lentigo maligna melanoma (LMM) is a relatively rare type, accounting for about 10% of all melanomas, while the most common subtype of melanoma on the face, typically on chronically sun-exposed skin of elderly people. Its in situ stage is lentigo maligna (LM). During the process of transformation from LM to LMM, tumor cells secrete or induce the release from neighboring cells of large amounts of matrix metalloproteinases (MMPs) that degrade the extracellular matrix. Some MMPs, as MMP3 and MMP9 expressed melanoma cells is associated with statistical significance in both in vitro and in vivo studies, with an invasive phenotype. Unfortunately, there is scarce data published about MMPs expression in LM∕LMM, as majority of research on melanoma refer to superficial spreading and nodular melanoma. Our personal, unpublished yet fully data is an attempt to complete a specific panel of immunohistochemical markers that could explain the slow growing rate of LMM.

E-cadherin is an adhesion molecule essential in maintaining cellular integrity and preserving normal epithelial tissue architecture in adult organisms. Loss of E-cadherin expression and epithelial characteristics has been described in the late stages of carcinogenesis in various human cancers. By loosing cell-cell adhesion mediated by E-cadherin and acquiring mesenchymal properties, a process reffered to as epithelial to mesenchymal transition (EMT), carcinoma cells become more motile and invasive, thus being able to penetrate the surrounding stroma. Our aim is to investigate E-cadherin expression, part of the EMT phenomenom, in cutaneous squamous cell carcinomas (cSCCs), knowing that it represents a valuable model for understanding cancer progression. We conducted a retrospective study, performing immunohistochemical staining of E-cadherin and analyzing its expression in 32 cases of primary cSCCs. E-cadherin membrane positivity was assessed in cells from the main tumor and cells from the invasion front and described in terms of percentage of positive tumoral cells and in terms of intensity. Statistycal analysis showed the proportion of E-Cadherin positive cells in the tumor central and superficial areas is lower in higher degrees of anaplasia (marginally significant p=0.07), confirming the higher potential of poor outcome in these tumors. Median intensity and proportion values of E-Cadherin positive cells were significantly higher in the tumor central and superficial areas than in the invasion front (p

Despite their commensal status, staphylococci can become problematic pathogens expressing multiple and redundant virulence factors. This study aimed to evaluate aggressiveness markers comparatively in staphylococcal strains isolated from severe infections versus asymptomatic carriage in order to identify clinically relevant bacterial traits that could easily be detected in clinical practice and could be suggestive for particular host-pathogen interactions such as cyto-adhesion or biofilm formation, ultimately orienting the clinical decision-making process. We have used in vitro phenotypic methods to assess adhesion to and invasion of eukaryotic cells, biofilm development, and expression of soluble virulence factors in 92 Staphylococcus spp. strains. The adhesion index, invasion capacity, biofilm formation and expression of soluble factors did not differ significantly between clinical and commensal strains. The major bacterial traits we found to be significantly more prevalent in clinical staphylococci were the aggregative adhesion pattern (P = 0.012), cluster adhesion (P = 0.001) and tetrad morphology (P = 0.018). The aggregative adhesion pattern was correlated with higher cyto-adhesion (P

Bacillary angiomatosis represents a cutaneous and systemic infection caused by Bartonella species, typically described in the past in HIV-positive patients or associated with immunodeficiencies. More recent case reports had brought into attention the probability that this entity may manifest in otherwise healthy individuals, triggered by trauma and skin burns. The physiopathology of this neoproliferative process is based on the production of angiogenetic molecules, such as vascular endothelial growth factor (VEGF) and IL-8. In case of an inadequate treatment, the evolution can be fatal, with a systemic dissemination of the abscesses within the gastro-intestinal tract, respiratory tract, brain and bones. The appropriate therapy is with oral erythromycin and doxycycline, but several treatments such as cephalosporins, penicillins, macrolides, aminoglycosides, rifampin, dapsone, ciprofloxacin, have been tried with favorable results. Herein we present the case of a Caucasian patient, seronegative for HIV, who developed multiple vascular papules and nodules on the face, after a severe trauma and which healed after an adequate antibiotic therapy with oral clarithromycin.

Melanoma is the most severe type of skin cancer and its incidence has increased in the last decades. In the United States, it is the 6th most common cancer in both men and women. Prognosis for patients with melanoma depends on the stage of the disease at the time of diagnosis and it can be influenced by the immunologic response. Melanoma has been historically considered an immunogenic malignancy. It often contains great amount of immune cells (different subsets of T-cells, dendritic cells, macrophages, neutrophils, mast cells, B lymphocytes), which may reflect a continuous intercommunication between host and tumor. It is not established if tumor-infiltrating lymphocytes (TILs) are induced by tumor cells or by other components of the microenvironment or when they are a host direct immunologic reaction. It has been observed that in many cases, the presence of a dense TIL is associated with good prognosis. The pattern and activation state of the cells which constitute TIL is variable and modulates the clinical outcome. An important step in the understanding of tumor immunobiology is the analysis of the populations and subsets of immune cells that form TIL. Besides its prognostic significance, after approval of cytotoxic T lymphocyte antigen 4, programmed cell death-1 and programmed death-1 ligand antibodies for the treatment of melanoma, the assessment of immune infiltrate composition has become even more captivating, as it could provide new target molecules and new biomarkers for predicting the effect of the treatment and disease outcome in patients treated with immunotherapy. In this review we discuss current state of knowledge in the field of immune cells that infiltrate melanoma, resuming the potential of TIL components to become prognostic markers for natural evolution, for response to drugs or valuable targets for new medication.

The development of combination antiretroviral therapies (cART) represents a significant advance in the treatment of (human immunodeficiency virus) HIV infection. However, several studies report that a large percentage of individuals with HIV, particularly those receiving cART, present body composition differences compared with the general population. The aim of this study was to explore body composition differences by dual-energy X-ray absorptiometry (DEXA), among HIV-positive patients receiving cART, in comparison to healthy controls.The cross-sectional study included 60 HIV-infected patients (all under 50 years old). We analyzed the association of antiretroviral medication use and different HIV-related factors, to the body composition parameters.Our cohort had significantly lower fat mass and lower bone mass compared to non HIV-infected persons. Median time since HIV infection diagnosis was 5 years (interquartile range, [IQR], 2-10.25) and viral suppression was achieved in 49 (81.66%) patients. Treatment with protease inhibitors (PIs) was strongly correlated with low fat mass, reduced lean mass and loss of bone mineral density. Nucleoside reverse transcriptase inhibitors (NRTIs)-containing treatment was associated with decrease of lean tissue mass (LM). The prevalence of osteopenia was 41.67% at the lumbar spine (L1-L4) and 36.7% at the hip. We found osteoporosis in 10% of the patients at the lumbar spine. Reduced bone mass was associated, in the patient group, with the duration of PIs use and with smoking (in the males group).In our research, HIV-infected individuals compared to healthy controls had body composition differences, including fat mass atrophy and reduced bone mineral content.

BACKGROUND Aging of persons with human immunodeficiency virus (HIV) resulted in high rates of osteopenia and osteoporosis. Multiple cohort studies have reported an increased prevalence of bone demineralization among HIV-infected individuals. The aim of this study was to evaluate bone mineral density (BMD) and risk factors for osteopenia/osteoporosis among HIV-positive patients attending the National Institute for Infectious Diseases "Prof.Dr. Matei Balș", Bucharest, Romania. METHODS We performed a cross-sectional study that enrolled 60 patients with HIV. The association between BMD and lifestyle habits (smoking), body mass index (BMI), nadir cluster of differentiation 4 (CD4) cell count, current CD4 cell count, HIV viral load and history of combination antiretroviral therapy (cART) were investigated. The BMD was measured at the lumbar spine, hips and total body using dual-energy X-ray absorptiometry (DEXA). RESULTS In the present study, DEXA evaluation showed an overall prevalence of osteoporosis of 16.66% (ten patients) and a prevalence of osteopenia of 48.33% (29 patients). In men, low BMI and cigarette smoking showed significant association with the diagnosis of lumbar spine demineralization (p=0.034 and p=0.041, respectively). Duration of exposure to cART classes in relation to BMD was also evaluated. The use of non-nucleoside reverse-transcriptase inhibitors (NNRTIs) was associated with low lumbar spine BMD in all patients (p=0.015). Reduced BMD was significantly associated with protease inhibitors (PIs)-containing treatment (p=0.043) in women. CONCLUSION At lumbar spine DEXA, male gender was statistically associated with reduced BMD. At the left hip Ward's area, decreased BMD T scores were significantly associated with aging. The reduced BMD was higher in patients receiving PI- or NNRTI-containing regimens.

Regression in melanoma is a frequent biological event of uncertain prognostic value as the lesion exhibits heterogeneous phenotypical features, both at the morphological and immunohistochemical level. In the present study, we examined the expression of tissue inhibitors of metalloproteinases (TIMP1, TIMP2 and TIMP3) in melanoma with regression. We specifically examined the expression levels of these TIMPs in regressed components (RC) and non-regressed components (NRC) of the tumor and compared their expression levels with those in non-regressed melanomas. We found that TIMP1 was overexpressed in the NRC of melanomas with partial regression (PR) compared with the NRC in melanomas with segmental regression (SR) (P=0.011). TIMP2 was overexpressed in the NRC of melanomas with PR compared with the NRC in melanomas with SR (PR/SR, P=0.009); or compared with the NRC in melanomas with simultaneous SR-PR (P=0.002); or compared with melanomas without regression (absence of regression) (P=0.037). Moreover, TIMP3 was overexpressed in the NRC of all melanomas with SR as compared to the RC component (P=0.007). Our findings on the differential expression of TIMP1, TIMP2 and TIMP3 in melanomas with regression support the hypothesis that the morphological differences identified in the melanoma regression spectrum may have a correlation with prognosis. This may explain the controversial findings within the literature concerning the biological and prognostic role of regression in melanoma.

Introduction. Diabetes Mellitus causes ultrastructural changes triggered by partially clarified cellular mechanisms. Since cell death is an important mechanism in the appearance and progression of diabetic nephropathy, we studied alteration of several markers of apoptotic pathways signaling in renal tissue of diabetic or prediabetic patients. Methods. We analyzed 48 human kidney tissue samples divided into two study groups: the research group (43 renal tissue samples from diabetic or prediabetic patients), and the control group (5 renal tissue samples from patients without diabetes). Immunohistochemistry revealed expression of Bcl-2, APAF-1, CD-95 and Caspase-9 in the renal cortical structures. Statistical analysis was also performed (significance level P Results. We found a variable expression of the antiapoptotic Bcl-2 with a decrease of Bcl-2 expression in diabetes. The control samples render evident intensely positive immunostaining for CD-95. In diabetes and diabetic nephropathy, there was positive immunostaining for APAF-1 at tubular cell level. Nuclear and cytoplasmic positivity for Caspase-9 was more frequently recorded as kidney damage progresses. APAF-1 and Caspase-9 positivity are arguments for an intrinsic apoptotic mechanism of cell death in diabetic nephropathy. Conclusion. The mechanisms of apoptotic cell death identified in diabetic kidney samples prove that Bcl-2, CD-95, APAF-1 and Caspase-9 represent reliable markers of cell death in human renal tissue. Our results support the hypothesis that apoptosis is a pathogenic and initiator mechanism of renal remodeling in diabetic kidney disease.

Objectives. Chronic viral hepatitis B and C represent an important health burden all over the world. Reduced bone mineral density is an extrahepatic complication which has been found in patients with chronic liver disease. The aim of our study was to identify bone mineral impairment (osteopenia/osteoporosis) and the risk factors that are correlated with its severity, in patients with chronic viral hepatitis B (CHB) and C (CHC). Material and methods. Anthropometric, biological parameters and bone mineral density (BMD) were measured in 60 patients with CHB (n = 30) and CHC (n = 30). BMD was assessed using Dual Energy X-ray Absorptiometry (DEXA) in the hip and lumbar spine regions, inclusively a whole scan (total body). Results. Sixty patients (mean age 44.93 years, range: 20-70) were enrolled, including 30 CHB patients (mean age 46.43 years, range: 20-70) and 30 CHC patients (mean age 43.43 years, range: 28-64). Forty of patients were men (66.66 %). Active smokers were 16 patients (26.66 %). Meanbody mass index (BMI) was 25.38 kg/m2 (range: 16.70-38.40). At baseline, 21 of 60 (35%) of the patients had evidence of osteopenia and 4 of 60 (6.66%) of patients, respectively presented osteoporosis at LS. At total hip, 22 of 60 of the patients (36.66%) recorded osteopenia; osteoporosis was found at 7 patients (11.66%) at total hip assessment. Low BMD values at different regions correlated significantly with low BMI, smoking and liver fibrosis grade. Conclusions. Our results suggest that bone mineral metabolism disorders exist in patients with chronic viral hepatitis B and C who are active smokers, presenting low BMI and advanced liver fibrosis, even without liver cirrhosis.

Diabetic Nephropathy. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to be directly responsible for 1.5 million deaths just two years prior (in 2012). From the entire number of patients suffering from diabetes, approximately a quarter of them develop renal affection. Diabetic nephropathy has similar physiopathology mechanisms and ultrastructural changes in cell injury characteristics in both Type 1 and Type 2 diabetes. Cell Death. Cell Death was less studied in the renal diabetic disease, although it could represent an important pathogenic mechanism in the appearance and progression of nephropathy. At renal level the cellular loss can be explained by several mechanisms; different stimuli with cellular lesion potential can trigger apoptosis signaling with appearance of regulatory proteins having a double role (they participate in the initiation of the apoptosis path and cell death or in the ending of this process). The types of Cell Death and their relative proportion between themselves in the renal tissue have not been completely elucidated. Caspases. Discovered in the middle of the 1990’s, Caspases are a part of the cysteine proteases family and play a role in numerous aspects of physiology (having a role in development, aging and apoptosis), but also in aspects of physiopathology of several degenerative affections, autoimmune diseases, oncologic diseases – having an important part in apoptosis, necrosis and also inflammation.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a glycoprotein belonging to the carcinoembryonic antigen (CEA) family that is expressed on a wide variety of cells and holds a complex role in inflammation through its alternate splicing and generation of various isoforms, mediating intricate mechanisms of modulation and dysregulation. Initially regarded as a tumor suppressor as its expression shows considerable downregulation within the epithelia in the early phases of many solid cancers, CEACAM1 has been linked lately to the progression of malignancy and metastatic spread as various papers point to its role in tumor progression, angiogenesis, and invasion. We reviewed the literature and discussed the various expression patterns of CEACAM1 in different types of tumors, describing its structure and general biologic functions and emphasizing the most significant findings that link this molecule to poor prognosis. The importance of understanding the role of CEACAM1 in cell transformation stands not only in this adhesion molecule’s value as a prognostic factor but also in its promising premise as a potential new molecular target that could be exploited as a specific cancer therapy.

Methotrexate (MTX) is a folic acid analog with anti-proliferative (anti-neoplastic, cytotoxic), immunosuppressive and anti-inflammatory properties, which has been used in the treatment of various cutaneous disorders, such as psoriasis, keratoacanthoma, pityriasis rubra pilaris, atopic dermatitis, mycosis fungoides, bullous skin diseases, systemic sclerosis, morphea, lupus erythematosus, dermatomyositis and crusted scabies. Inhibition of cell proliferation is explained through its role in blocking DNA/RNA synthesis, by inhibiting dihydrofolate reductase, necessary for the production of pyrimidine and purine nucleotides. An anticancer effect can be related to α-oxoaldehyde metabolism (MTX increases methylglyoxal levels). Its anti-inflammatory property is based on the inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase, thus increasing intracellular and extracellular adenosine, a purine nucleoside with anti-inflammatory effect. This drug can limit inflammation by scavenging free radicals and decreasing malondialdehyde-acetaldehyde protein-adduct production. Moreover, the anti-proliferative and anti-inflammatory effects can also be related to inhibition of the DNA methylation pathway, thus inhibiting methionine formation. The aim of the present study was to report various dermatological cases from our daily practice that demonstrate the efficacy of MTX in the treatment of cutaneous diseases, highlighting different mechanisms of action: its anti-inflammatory effect in psoriasis and its anti-proliferative, and anti-neoplastic effect in well-differentiated squamous cell carcinoma or in keratoacanthoma. Moreover, different administration pathways and doses are addressed. Assessment of the treatment plan, clinical improvement of cutaneous lesions, biologic evaluation, final aesthetic result, quality of life, as well as potential adverse effects and drug tolerance related to each case mentioned.

Hepatic osteodystrophy is a common and frequently untreated complication, manifested as osteoporosis or osteopenia, encountered in the evolution of chronic liver diseases. Th is article provides a narrative review of hepatic osteodystrophy. Th e aim is to revise the prevalence, pathophysiology, diagnosis and management of hepatic osteodystrophy. We searched medical literature via PubMed, Google Scholar, Wiley, Science Direct, and Springer Link using respective keywords to obtain data on low bone mineral density connected to chronic liver diseases. Many studies have reported an increased prevalence of osteoporosis/osteopenia in patients with chronic liver diseases. Th e pathogenesis is multifactorial, involving genetic factors, vitamin defi ciencies, proinfl ammatory cytokines, hypogonadism, hyperbilirubinemia, antiviral therapy, corticosteroid drugs, and lifestyle factors. Th e management of patients should include individualized assessment for fracture risk factors and bone mineral density. Vitamin D and calcium supplementation should be recommended in all patients with chronic liver diseases and osteoporosis. Bisphosphonates are the most effi cient drugs used in the treatment of hepatic osteodystrophy. In the future, it is necessary to defi ne better the management and specifi c treatment of hepatic osteodystrophy for prevention of fragility fractures and to improve the patient quality of life.

Mechanisms involved in melanoma invasiveness and metastasis are essential to understanding the behavior of this aggressive melanocytic skin cancer. The epithelial-mesenchymal transition (EMT) is considered fundamental for overcoming the in situ stage of melanoma and its proliferation beyond the basal membrane. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are key molecules involved in EMT about whose expression in lentigo maligna (LM) and lentigo maligna melanoma (LMM) little has been studied so far. In this article, our main aim was to review the role of TIMPs in invasiveness and aggressiveness of LM÷LMM in order to detect EMT modifications in this type of melanoma. We also presented some partial personal unpublished results. It is well established by now that progression of melanoma depends on ECM remodeling, TIMPs family being one of the most important regulators of this process. Considering the multitude of molecules involved in cancer invasiveness and their complex interaction, it is too early to analyze and to conclude upon the significance of different expression of TIMPs in LM÷LMM. We consider some correlations are needed to be done also with other consecrated histological (as Clark level, Breslow indexes, presence of ulceration, mitotic index, intratumor inflammatory infiltrate, etc.) and immunohistochemical markers [cadherins, vascular endothelial growth factor (VEGF), bcl-2, etc.] of prognosis and metastasis. In this light, we consider that our study could further clarify the significance of TIMPs expression in this specific type of melanoma.

BACKGROUND: Leptin is an adipokine with complex metabolic, neuroendocrine and immune functions. Our objective was to evaluate leptin serum levels in a cohort of Romanian HIV-infected patients undergoing antiretroviral therapy in relation to their immune-virological status, lipid and glucose metabolic abnormalities and the presence of metabolic syndrome (MS). METHODS: We enrolled consecutive non-diabetic HIV-infected patients aged 18 and over on stable cART for at least 6 months. Blood samples were tested for: leptin, CD4 T cells count, HIV viral load and lipid panel. RESULTS: A total of 90 HIV-infected patients were included in the study: 50 males (55.6%) with a mean age of 33.3 years and 40 females with a mean age of 30.4 years. Most patients (74.4%) had HIV viral load below the limit of detection and the median CD4 count for the cohort was 476 (410) cells/cmm. More than one third of the patients (41.1%) had hypoleptinemia. The prevalence of MS was 13.3%. Hypoleptinemia was significantly more frequent in men. In a subset of patients with undetectable HIV viral load, the median leptin value was 0.6 (6.07) ng/mL in patients with poor immune recovery (CD4 count ≤ 200/cmm) compared to 2 (3.07) ng/mL for those with better immune response (CD4 count > 200/cmm), without statistical significance. The median values of leptin were similar for persons with and without MS criteria. HDL-cholesterol values were positively correlated to leptin values in a linear regression model. CONCLUSION: A significant proportion of patients in our study presented low levels of leptin; this finding was not associated with immune and virological parameters or the presence of MS. Hypoleptinemia was significantly correlated with lower levels of HDL-cholesterol, a key cardiovascular risk factor.

Background and Aims. Insulin resistance is documented in type 1 diabetes and it has been associated with chronic complications. Diabetic nephropathy is a major cause of morbidity and mortality. The purpose of this article is to quantify insulin resistance in type 1 diabetes subjects according to the presence or absence of advanced renal disease. A secondary objective was to study the possible association between insulin resistance and advanced renal disease. Material and Methods. This was a cross-sectional study that included 167 type 1 diabetes patients. Insulin resistance was determined using the eGDR (estimated glucose disposal rate) formula. The association between eGDR and diabetic nephropathy was assessed in uni and multivariate models using stepwise logistic regression analysis of variables. The contribution of individual predictors in the final regression model was examined using Wald statistic. Results. Significantly lower eGDR’s values were observed in patients with nephropathy: 5 vs. 7.3 (p Conclusions. In type 1 diabetes patients insulin resistance was the most important independent risk factor associated with advanced renal disease.

Aquaporin-4 (AQP4) and glutamate transporter-1 (GLT-1) represent the major water and glutamate astrocyte buffering gateways in the brain. Utilizing perilesional ischemic human cortices, we have performed here for the first time an integrative assessment on both AQP4 and GLT-1, and on their proximity to blood vessels and neurons. Counting the relative number of AQP4±/GLT-1±/glial fibrillary acidic protein± cells showed that double-positive variants were overall most frequent, and their number tended to decrease from organized and recent perilesional cortices to controls. AQP4/GLT-1 colocalization showed higher coefficients for the perilesional cortices compared with controls, suggesting an increased water/glutamate-buffering capability. Distance frequency analysis of AQP4/GLT-1 in relationship to neurons showed that both markers were concentrated at 20-40 μm around the perikarya; with AQP4 being more abundant in close proximity, these differences were not being driven by changes in neuropil density alone. Our study suggests a dual, simultaneous astrocytic function depending on the relative distance to neurons and vessels, with increased water and glutamate-buffering capability in the mid perineuronal space, and an increased water-buffering capability in the immediate perineuronal space, even higher than around vessels. Thus, adding specific AQP4/GLT-1 modulator agents selectively depending on the acute/chronic phase of stroke might increase the efficacy of existing treatments.

Impaired production of adipocytokines is a major factor incriminated in the occurrence of lipodystrophy (LD).To evaluate LD prevalence and subtypes in HIV treatment-multiexperienced patients, and to determine the correlations between adipocytokines and LD subtypes.Cross-sectional study in a Romanian tertiary care hospital, between 2008 and 2010, in HIV-positive patients, undergoing cART for ≥6 months. LD diagnosis, based on clinical and anthropometric data, was classified into lipoatrophy (LA), lipohypertrophy (LH) and mixed fat redistribution (MFR). Blood samples were collected for leptin, adiponectin and resistin assessments.We included 100 patients, 44 % with LD, among which LA had 63 %. LA patients had sex ratio, median age, treatment duration and median number of ARV regimens of 1, 20, 93 and 3.5 compared to non-LD patients: 1.65, 31, 44 and 1. LH and MFR patients were older and had higher total and LDL cholesterol versus non-LD patients. For both overall group and female group, LA was associated in univariate and multivariate analysis with increased resistin (p = 0.02 and 0.04) and number of ARV regimens (p0.001). Determination coefficient (Nagelkerke R (2)) of increased resistin and the number of ARV combinations in the presence of LA was 33 % in overall group and 47 % in female patients.In our young HIV-positive population, LD had high prevalence with predominance of LA subtype. LA was associated with high resistin levels and greater number of ARV regimens in overall group and female subgroup. Resistin could be used as a marker of peripheral adipose tissue loss and might be used as a target for new anti-LD therapeutic strategies.