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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..

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.

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.

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.

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.

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.

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.

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.

Polymorphisms in IL6, ACE and ATR genes are associated with obesity. Torque Teno virus (TTV) seems to be able to interfere with production of some proinflammatory cytokines associated with obesity and related phenotypes. The aim of this study was to test the potential association between obesity, TTV infection and the IL6 G-174C (rs1800795), ACE I/D (rs4646994), AT1R A1166C (rs5186) polymorphisms. The polymorphisms and the presence of TTV were detected in blood samples from 150 obese and 150 normal-weight, healthy subjects using PCR based methods. IL6-174 CC genotype was more frequent in all obese patients (P=0.02) and in patients without TTV infections (P=0.03) than in controls. Obese women had more frequent TTV infections compared with normal-weight women (P=0.046). Obese subjects, regardless of gender (women P=0.03, men P=0.04), and healthy normal-weight men (P

Present day increasing dependence on electricity, in both home and work environments, can lead, if the necessary precautions are not met, to a wide type of injuries, from cutaneous burns to important visceral lesions. We report the case of a 44 year-old male with cutaneous and severe visceral lesions, paresis and paresthesia of the right upper limb induced by a high energy electrical shock. No psychiatric manifestations were observed. This case followed an unusual course due to the particular evolution of the hepatic lesions, which included necrosis, abscesses, thrombosis and angiocholitis.

Aims: We aimed to quantify global and regional body composition changes in chronic hepatitis C (CHC) patients, compare them to healthy controls and identify possible association between body composition changes and CHC. To our knowledge, this study is the first one comparing CHC patients to controls with regard to soft tissue body composition changes. Methods: We assessed 60 CHC patients and 60 healthy controls by Dual Energy X-Ray Absorptiometry. Soft tissue and bone body composition parameters were compared between the groups (using the Mann-Whitney test). These parameters were correlated (using Spearman’s rank correlation coefficient – rho) with independent variables (age, gender, body mass index – BMI, cigarette smoking, time since CHC diagnosis, viral load, fibrosis grade, type of treatment, time of treatment) for the entire CHC group and also for subgroups according to gender. Results: Total fat mass, trunk fat mass and percent body fat were lower in CHC patients as compared to controls. Several risk factors were associated with the reduced fat mass: low BMI, cigarette smoking and peginterferon alpha 2a plus ribavirin treatment. Peginterferon alpha 2a and ribavirin treatment negatively correlated with lean body parameters, especially in CHC males group. Bone mineral density (BMD) was lower as compared to controls and was correlated with low BMI, cigarette smoking and peginterferon alpha 2a and ribavirin treatment. Conclusions: Patients with CHC have an acquired type of lipodystrophy (particularly in the trunk region), and also a reduced BMD as compared with controls. A low BMI, cigarette smoking and peginterferon alpha 2a and ribavirin therapy were associatd with a low fat mass and low BMD. Abbreviations: BMD: bone mineral density; BMI: body mass index; CHC: chronic hepatitis C; DXA: Dual Energy X ray Absorptiometry; FM: fat mass; FMR: fat mass ratio; HCADS: hepatitis C associated dysmetabolic syndrome; HCV: hepatitis C virus; HO: hepatic osteodystrophy; LS: lumbar spine; LM: lean mass; PBF: percent body fat.

INTRODUCTION Several studies have reported that cytokines secreted by adipose tissue (adipokines) may be linked to HIV replication. The aim of the study was to evaluate the relationship between HIV replication and serum levels of adipokines, in a Caucasian HIV-infected population of men and women undergoing complex antiretroviral therapy. METHODS A cross-sectional study was conducted in an unselected sample of 77 HIV-1-positive patients. Serum adipokines levels were measured including circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Patients were divided into two groups: Group 1 - with undetectable viral load and Group 2 - with persistent HIV viral replication. Differences between groups ? were tested using independent-sample t-test for Gaussian variables and Mann-Whitney-Wilcoxon test for non-parametric variables. Pearson's chi-squared test was used for correlation analysis. RESULTS A total of 77 patients (age range: 17-65, mean: 32.5 years) including 44 men (57.1% men, age range: 17-63 years, mean: 34.1 years) and 33 women (42.9% women age range: 19-65 years, mean: 30.3 years) were included in the study. TNF-alpha had significantly higher serum levels in patients with detectable viral load (16.89 vs. 9.35 pg/mL), (p=0.043), but correlation analysis lacked statistical significance. Adiponectin had median serum levels of 9.22 ig/mL in Group 1 vs. 16.50 ig/mL in Group 2 but the results lacked statistical significance (p=0.059). Higher leptin, IL-6 and resistin serum levels were noted in patients with undetectable HIV viral load, without statistical significance. CONCLUSIONS The present study reported higher TNF-alpha serum levels in patients with persistent HIV viral load. We found no statistically significant correlations between adiponectin, leptin, resistin and IL-6 and HIV viral load in our Caucasian HIV-positive study population, undergoing antiretroviral therapy.

Introduction. Little is known about the relationship between insulin resistance and proliferative diabetic retinopathy in type 1 diabetes. The aim of this article is to explore the relationship between sight-threatening proliferative diabetic retinopathy and insulin resistance. Methods. This was a cross-sectional study that included 167 type 1 diabetes patients. Insulin resistance was assessed using eGDR (estimated glucose disposal rate) formula. Diabetic retinopathy was assessed by ophthalmoscopy using Early Treatment Diabetic Retinopathy classification. The association between eGDR and proliferative diabetic retinopathy was assessed in uni- and multivariate models using stepwise logistic regression of covariates. The contribution of individual predictors in the final regresion model was examined using Wald statistic. Results. Significantly lower eGDR’s values were observed in patients with proliferative diabetic retinopathy: 5.5 vs. 7 (p = 0.002). The results remained significant (p < 0.001) after adjusting for multiple covariates (sex, diabetes duration, body mass index, HDL cholesterol, LDL cholesterol, triglycerides, smoking). eGDR variable was retained in the final model of stepwise logistic regression (p < 0.001) and showed the strongest association with proliferative diabetic retinopathy (Wald = 12.73). Conclusions. In type 1 diabetes patients insulin resistance was the most important independent risk factor associated with diabetic proliferative retinopathy.

Matrix metalloproteinases (MMPs) are well-recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non-nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra-cytoplasmic or intra-nuclear compartments, with no clear-cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP-9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP-9 nuclear expression, and there was no evidence of a clear-cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP-9 in the nuclear compartment also co-expressed activated-caspase 3, indicating a possible link between nuclear MMP-9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP-9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology.

Background: There are only a few studies involving the use of melatonin for premedication for anaesthesia. The goal of our study was to compare the effects of melatonin and midazolam administered a...

Background After the introduction of highly active antiretroviral therapy for the treatment of HIV infection, metabolic abnormalities were increasingly observed, associated with both protease inhibitors and nucleoside reverse transcriptase inhibitors, characterized by abnormal fat distribution in the body (lipoatrophy, lipohypertrophy or both), hyperglycemia and lean tissue mass wasting. However such metabolic changes are not always treatment related, having a multifactorial etiology. Dual-energy X-ray absorptiometry (DXA) evaluates the quantity of body fat and lean tissue and their distribution, allowing the diagnosis of both quantitative and qualitative changes.

Methods We performed a cross-sectional study on patients with CHC, in a tertiary-care hospital in November 2011 – April 2012. We staged liver fibrosis using FibroMax (BioPredictive) and we used CobasTaqman (Roche) for HCV-RNA quantification. Patients were also evaluated by ALT, platelets, erythrocyte sedimentation rate (ESR), fibrinogen, C-reactive protein (CRP) and tumor necrosis factor alpha (TNFa) plasma levels. For TNFa quantification we used Kamiya Biomedical Company ELISA kits.

Background Insulin resistance is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy. Cytokines secreted by adipose tissue (adipokines) are linked to insulin sensitivity. The present study is aimed to assess the prevalence of insulin resistance (IR) and its association with several adipokines, in a non-diabetic Romanian cohort of men and women with HIV-1 infection, undergoing combination antiretroviral therapy (cART). Methods A cross-sectional study was conducted in an unselected sample of 89 HIV-1-positive, non-diabetic patients undergoing stable cART for at least 6 months. Metabolic parameters were measured, including fasting plasma insulin, and circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Insulin resistance was estimated by measuring the Quantitative Insulin Sensitivity Check Index (QUICKI), using a cut-off value of 0.33. A linear regression model was fitted to QUICKI to test the association of IR and adipokines levels. Results A total of 89 patients (aged 18–65, median: 28 years) including 51 men (57.3%) and 38 women (42.7%) were included in the study. Fifty nine patients (66.3%) were diagnosed with IR based on QUICKI values lower than the cut-off point. IR prevalence was 72.5% in men and 57.6% in women. The presence of the IR was not influenced by either the time of the HIV diagnosis or by the duration of cART. Decreased adiponectin and increased serum triglycerides were associated with increased IR in men (R=0.43, p=0.007). Hyperleptinemia in women was demonstrated to be associated with the presence of IR (R=0.33, p=0.03). Conclusions Given the significant prevalence of the IR in our young non-diabetic cohort with HIV infection undergoing antiretroviral therapy reported in our study and the consecutive risk of diabetes and cardiovascular events, we suggest that the IR management should be a central component of HIV-infection therapeutic strategy. As adipokines play major roles in regulating glucose homeostasis with levels varying according to the sex, we suggest that further studies investigating adipokines should base their analyses on gender differences.

Both diabetes mellitus and allergic diseases presented an ascendant trend in the last years. The association between the two diseases represents an extremely discussed subject from the pathophysiological and clinical point of view, since the two diseases should exclude each other, but a unitary conclusion has not been reached yet. Objectives. The aim of this study is to perform a systematic review and a meta- analysis of the existent studies regarding the association between these two pathologies. Material and Method. We carried out an extensive search in the international databases, where we identified 557 articles treating these subjects, but only 12 articles have analyzed the relation between type 1 diabetes and atopic dermatitis. Results. The meta-analysis comprised 81519 subjects and suggests that the occurrence of type 1 diabetes is protective for atopic dermatitis (OR=0,68, CI=0,61-0,77, p

Objectives The presence of c-kit positive neurons in sensory ganglia has been verified in various species but not in humans. Our aim has been to identify whether human primary trigeminal neurons label with c-kit/CD117 and thus, whether data gathered in animal studies can be extrapolated to humans. We also intended to establish whether, and which non-neuronal cells also label with c-kit in the trigeminal ganglion. Methods Human adult trigeminal ganglia from eight cadavers were processed for immunohistochemistry on paraffin embedded samples using monoclonal antibodies for CD117/c-kit, and three additional trigeminal ganglia were used for transmission electron microscopy (TEM). To evaluate which neuronal type (A or B) was labeled with c-kit, we evaluated the same neurons on adjacent sections labeled with antibodies for neurofilaments (NF). Results c-kit has labeled trigeminal neurons (TNs), mast cells and interstitial cells (ICs) within the trigeminal ganglion. c-kit + TNs were NF–and thus were strongly presumed to be nociceptive, as such neurons are known to be NF-poor. c-kit + ICs with long and moniliform processes intermingled with the satellite glial cells (SGCs) of the neuronal envelopes. TEM evaluations confirmed this mixed composition of the neuronal envelopes and demonstrated that the perineuronal ICs are in fact interstitial Cajal-like cells (ICLCs) and/or telocytes. Conclusions c-kit + TNs were objectified in humans and strongly presumed to be nociceptive. TNs envelopes mostly consist of SGCs, but are also combined with ICLCs/telocytes.

November 12th 2014: the opening conference for the project “Doctoral and post-doctoral research – a priority of the Romanian postgraduate education system (Doc-Postdoc)” took place in Bucharest, Romania. The project aims to support doctoral and post-doctoral research in Romania, and is cofinanced by the European Social Fund through the Sectoral Operational Programme for Human Resources Development 2007-2013; priority axis 1. “Education and training in support for growth and development of a knowledge based society“; key area of intervention: 1.5. “Doctoral and post-doctoral programs in support of research”; contract code: POSDRU/159/1.5/S/137390. The Carol Davila University of Medicine and Pharmacy in Bucharest is the project beneficiary, partnering with two other major universities in Romania: The University “Politehnica” of Bucharest, and the University of Medicine and Pharmacy Târgu Mures. The conference presented the aims and objectives of the project, but it was also packed with scientific sessions where young PhD candidates and post-doctoral researchers had the opportunity to present the studies they are conducting within this project. The topics discussed spanned through the interdisciplinary fields of biomedicine and bioengineering. Of particular interest to the readers of the Journal GERMS, Dr. Catalin Tiliscan presented data on adipocyte dysfunction in HIV-positive patients undergoing antiretroviral therapy, his study showing that almost half of patients had hyporesistinemia, and resistin was correlated with the inflammatory profile. Also, an unfavorable immune status appeared to be inversely proportional to the values of monocyte chemoattractant protein-1 MCP-1, while leptin values were not correlated with CD4 cell count or virologic status, but rather with HDL-cholesterol and waist circumference. Dr. Ramona Popescu presented an interdisciplinary study protocol for determining the incidence of intercurrent and opportunistic infections in rheumatologic patients undergoing treatment with biologic agents. Dr. Oana Sandulescu presented the preliminary results of a study aimed to determine the capacity of staphylococcal species to adhere to and internalize in eukaryotic cells. By comparing two different types of bacterial strains, collected from patients with clinically-relevant infections and from asymptomatic nasal carriage, the study showed that despite a similar rate of internalization, staphylococci from the two groups displayed statistically significant differences regarding intracellular growth after internalization. Dr. Daniela Talapan presented significant data on the emergence of carbapenemase-producing Enterobacteriaceae, with Klebsiella spp. ranking first among bacteria with resistance to carbapenems, followed by E. coli, E. cloacae, and E. aerogenes, leaving a considerably low number of active antibiotics in play, namely colistin, tigecycline and fosfomycin. Based on the preliminary data presented at the conference, the research conducted within this project is bound to generate information with a significant clinical impact, leading to a better understanding of medical issues currently understudied, with the potential to reshape clinical practice.

Methods We performed a transversal study that used the following inclusion criteria: non-diabetic patients with documented HIV infection, undergoing stable cART for at least 6 months. Clinical, metabolic, inflammatory and immuno-virological patterns were assessed (age, sex, body mass index, HIV load, actual and nadir CD4, duration of HIV infection and antiretroviral therapy, lipid panel, C-reactive protein CRP). Resistin levels were evaluated using KAPME Biosource EASIA. In order to test the sensitivity to insulin we used the QUICKI index, the best surrogate marker after glucose clamp index. Parametric and non-parametric variables were described using means (±Standard Deviation SD) and medians (Interquartile Ratio IQR), respectively.

Background Reports show that 1.8–8.4% of male patients receiving efavirenz (EFV) develop gynecomastia by unclear multiple mechanisms, one of them being a direct binding to estrogen receptors. However, EFV can independently cause gynecomastia by increasing prolactin levels and we postulate that this mechanism is a dopaminemediated one. Dopamine is a strong prolactin inhibitor. Conversely, a lack of dopamine can cause hyperprolactinemia. On the other hand, dopamine is an antidepressant neurotransmitter and depression is one of the very frequent adverse reactions to EFV. We present the case of an HIV-positive newly diagnosed male patient who developed mild depression and amplified a preexistent gynecomastia after the introduction of an EFV-containing antiretroviral regimen.

We report the case of an adult patient recently diagnosed with cirrhosis. The ultrasound evaluation described a multinodular inhomogeneous liver, requiring a magnetic resonance imaging scan for further characterization. The performed magnetic resonance imaging examination confirmed the diagnosis of cirrhosis associated with portal hypertension and detected a vascular left transdiaphragmatic hernia. Although various types of diaphragmatic hernias have been described - congenital or acquired - to the best of our knowledge, this type of pathology has never been reported.

Leptin is a hormone secreted by the adipose tissue that may be associated in the general population with components of the metabolic syndrome (MS). Our objective was to test the association between dyslipidemia, MS presence and circulating leptin dysfunction in a cohort of HIV-infected non-diabetic patients undergoing combinant antiretroviral therapy (cART). We included HIV-infected non-diabetic consecutive patients undergoing cART, admitted to the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, between 2008-2011. The diagnosis of MS was made using the International Diabetes and American Heart Association harmonized criteria from 2009. Circulating levels of leptin (BioSource EASIA) were measured. We enrolled 95 patients: 53 (55.8%) males (mean age=33.1±13.4 years) and 42 (44.2%) females (mean age=30.5±13.6 years). Most patients (72.5%) had undetectable HIV viral load; median CD4 count was 493.5 (IQR=422)/cmm. The median time from HIV diagnosis was 60 (IQR=73) months. The median time on cART was 58.5 (IQR=70) months, 53.8% of patients had experienced more than one cART regimen. The prevalence of MS was 17.1%. Elevated blood pressure, elevated waist circumference and abnormal fasting glucose prevalences were 30.3%, 17.1% and 6.5%, respectively. Median serum leptin was 1.89 (IQR=3.57) ng/mL. Circulating leptin dysfunction was present in almost half of patients, hypoleptinemia being more frequent (42.%) than hyperleptinemia (8.5%). Hypoleptinemia was more frequent in men (62.3%) comparative to women (17.1%), p=0.000. The prevalence of MS in patients with hypoleptinemia was 25.8% vs 10.8% in persons with normal leptin values (p=0.261). Hypoleptinemia was associated with elevated waist circumference (p=0.004) and abnormal fasting glucose (p=0.05) in women. More than half (65.6%) of men with hypoleptinemia had reduced HDL-cholesterol levels vs 29.4% in men with normal levels of leptin. As expected, hyperleptinemia was associated with the increase of body mass index, both in men (p=0.000) and women (p=0.05). In our cohort of young cART multiexperienced HIV patients leptin dysfunction was not significantly associated with MS presence. Leptin was correlated with several MS components (HDL-dyslipidemia, elevated circumference, abnormal fasting glucose) with significant gender differences, that suggests that leptin may play different roles in the regulation of glucose and lipid metabolism according to the sex.

Correlation between inflammatory biomarkers and metabolic disorders in HIV infected patients undergoing antiretroviral therapy Raluca Mihailescu, Victoria Arama, Catalin Tiliscan, Daniela Munteanu, Viorica Leoveanu, Mihaela Radulescu, Adriana Hristea, Cristina Popescu, Ruxandra Moroti, Violeta Molagic, Raluca Nastase, Loredana Benea, Ana Maria Tudor, Mihai Lazar, Anca-Ruxandra Negru, Irina Lapadat, Ligia Ionescu, Mirela Cernat, Georgeta Juganaru, Doina Cristea, Adriana Manea, Adrian Streinu-Cercel, Daniela Adriana Ion, Sorin Ștefan Arama

We enrolled 103 patients, including 60 males (58.3%) and 43 females (41.7%). The mean age was 32.3±13.3 years (range: 13-65 years). The median Framingham score was 1.2% (IQR=5.8%). Most patients (81.63%) had a low CVR (below 10%) and 18.37% had Framingham score values above 10%. MS and IR prevalences were 16.9% and 61.2%, respectively. CVR in the general population is primarily dependent on age. This observation was valid for our group: the median age was 24 years in people with low CVR, compared with 50 years for those with Framingham score above 10% (p=0.000). None of the antiretroviral drug classes significantly influenced CVR.