Time for micro-RNAs in steatotic liver disease: a case-control study.

One of the challenges of modern-day living is to resist the temptation of overfeeding and sedentariness and maintain a healthy body and mind. On a favorable genetic and epigenetic background, a high-fat diet combined with lack of physical exercise constitutes the foundation for severe metabolic disturbances including steatotic liver disease. In our case-control study, we had the aim of establishing the role of selected micro-RNAs-miR-122, miR-192, miR-33a, and miR-33b-as superior biomarkers for the diagnosis and prognosis of steatotic liver in a 36-patient cohort compared to 12 healthy controls. Initial results confirmed the decline in miR-122 expression as fatty liver is progressing. However, combinations of ΔmiRs, such as ΔmiR33a_192, ΔmiR33a_122, and ΔmiR33b_122, correlate with ultrasound steatosis grade (R 2 = 0.78) while others such as ΔmiR33b_122 provide a high specificity and sensitivity in fatty liver disease with an area under the curve (AUC) of 0.85. Compared to classical biomarkers, micro-RNAs can be used for both diagnostic and prognostic purposes as their diminished expression in severe cases of steatosis is associated with higher risk of emerging hepatocellular carcinoma. Manipulating micro-RNAs through agomirs or antagomirs can be the answer to the yet unsolved problem of efficient therapy in MAFLD.

Design and Manufacturing of Equipment for Investigation of Low Frequency Bioimpedance.

The purpose of this study was to highlight a method of making equipment for the investigation of low frequency bioimpedance. A constant current with an average value of I = 100 µA is injected into the human body via means of current injection electrodes, and the biological signal is taken from the electrodes of electric potential charged with the biopotentials generated by the human body. The resulting voltage, ΔU is processed by the electronic conditioning system. The mathematical model of the four-electrode system in contact with the skin, and considering a target organ, was simplified to a single equivalent impedance. The capacitive filter low passes down from the differential input of the first instrumentation amplifier together with the isolated capacitive barrier integrated in the precision isolated secondary amplifier and maintains the biological signal taken from the electrodes charged with the undistorted biopotentials generated by the human body. Mass loops are avoided, and any electric shocks or electrostatic discharges are prevented. In addition, for small amplitudes of the biological signal, electromagnetic interferences of below 100 Hz of the power supply network were eliminated by using an active fourth-order Bessel filtering module. The measurements performed for the low frequency of f = 100 Hz on the volunteers showed for the investigated organs that the bioelectrical resistivities vary from 90 Ωcm up to 450 Ωcm, and that these are in agreement with other published and disseminated results for each body zone.

Reliability, Validity, and Sensitivity to Change of the Cochin Hand Functional Disability Scale and Testing the New 6-Item Cochin Hand Functional Disability Scale in Systemic Sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease causing complex hand disability. A reliable tool for hand function assessment in SSc is the Cochin Hand Functional Disability Scale (CHFS). More recently, a short-form CHFS of 6 items (CHFS-6) has been developed. OBJECTIVES: To validate the CHFS and the new CHFS-6 in Romanian patients with SSc. PATIENTS AND METHODS: Consecutive patients with SSc who completed the CHFS were included. All patients were assessed according to the recommendations of the European Scleroderma and Research Trials and also completed the Scleroderma Health Assessment Questionnaire and the Hand Mobility in Scleroderma questionnaire. Finger range-of-motion distances were measured. RESULTS: Seventy patients, 63 female and 7 male patients (age median, 53.0 years; interquartile range [IQR], 21.0 years), were included. Twenty seven had diffuse cutaneous involvement (dcSSc). Median CHFS and CHFS-6 at baseline were 25.0 (IQR, 37.0) and 8.0 (IQR, 13.0), respectively.The internal consistency (Cronbach α = 0.96, respectively, 0.90, in all 70 patients) and test-retest reliability (intraclass correlation coefficient = 0.98 for both, in 38 patients) of both CHFS and CHFS-6 were excellent. The CHFS-6 had a very high correlation with the CHFS. There were moderate to good correlations with Hand Mobility in Scleroderma, Scleroderma Health Assessment Questionnaire, and the anthropometric measurements (construct validity). In patients with early dcSSc with a second evaluation, we found good to moderate sensitivity to change (standardized response mean of 0.8 and effect size of 0.4 for CHFS, and standardized response mean of 1.1 and effect size of 0.6 for CHFS-6). CONCLUSIONS: The CHFS and CHFS-6 are valid and easy-to-use tools for hand involvement in SSc, which can be used in clinical or research setting.

Capillary loss reflects disease activity and prognosis in patients with systemic sclerosis.

Capillary density on nailfold capillaroscopy (NFC) is considered a promising instrument for assessing disease characteristics in patients with systemic sclerosis (SSc), however, there is no agreement yet over how to analyze and interpret the results. The objective of this study was to investigate the possible associations of the mean number of capillaries with disease characteristics, disease activity [measured by the European Scleroderma Study Group (EScSG) disease activity score] and survival in a single-center cohort of patients with SSc. Sixty-eight patients were included; 54 had follow-up at 6 months. Thirty-two images per patient were assessed independently by two raters, scoring the mean number of capillaries in all fingers (N), in the 3rd finger of the dominant hand (dN3) and in the 4th finger of the non-dominant hand (ndN4) for each patient. NFC 'early', 'active' and 'late' patterns were also assessed. Two thousand and seventy-six images were scored at baseline, 1,728 at follow-up. Baseline N was median (IQR) 5.1 (2.7) for rater 1, and 4.9 (1.7) for rater 2, respectively. N was significantly lower in patients with a history of digital ulcers (DUs), vs. those who never had DUs 4.8 (1.4) vs. 6.4 (3.1), P=0.016. A lower N was associated with higher disease activity at baseline and follow-up (linear regression adjusted for age, sex and history of DUs). A lower ndN4 was associated with increased mortality (logistic regression adjusted for age and sex). In conclusion, in patients with SSc, a lower mean number of capillaries assessed by NFC was associated with higher disease activity after 6 months of follow-up and with shorter survival.

Current Trends on Glomerulosclerosis Regression.

The role of the renin-angiotensin system in hypertension and end-organ damage has long been recognized. Angiotensin l converting enzyme inhibitors are superior to other antihypertensive agents in protecting the kidney against progressive deterioration, even in normotensive persons. Likewise, angiotensin II type 1 receptor antagonists improve or even reverse glomerulosclerosis in rat animal models. These findings suggest that Angiotensin II has nonhemodynamic effects in progressive renal disease. The renin-angiotensin system is now recognized to be linked to the induction of plasminogen activator-inhibitor-1, possibly via the AT4 receptor, thus promoting both thrombosis and fibrosis. Interactions of the renin-angiotensin system with aldosterone and bradykinin may impact both blood pressure and tissue injury. The beneficial effect on renal fibrosis of inhibiting the renin-angiotensin system likely reflects the central role that angiotensin has in regulating renal function and structure by its various actions. This article explores the renin-angiotensin-aldosterone system with plasminogen activator-inhibitor-1 interaction and the potential significance of these interactions in the pathogenesis of progressive renal disease and remodeling of renal sclerosis.

Transgenerational Effects of Traumatic Historical Events on the Incidence of Metabolic Syndrome/ Nonalcoholic Fatty Liver Disease in the Romanian Population.

Concerns for successful public health management are integrated into the core business of government-responsible institutions. Diseases associated with metabolic syndrome are very common in the Romanian population. In our study, we focused on the cardiovascular and non-alcoholic fatty liver disease (NAFLD). The article starts from the hypothesis that the increased incidence of such diseases is determined today by the cumulative effect of traumatic historical events such as the famine of 1946-47 and the communist political regime specific to the 80s and 90s. This study aims to present the arguments that indicate the correlation of economic variables whose variation can be easily determined by traumatic events that affected the economy, with variables able to measure the incidence of various diseases usually associated with metabolic syndrome or NAFLD. A series of statistical data were analyzed from the official sources available in the form of consecutive value data for the 1995-2018 period. The results highlighted a direct and strong link between the variable gross domestic product (GDP) per capita in USD, 2011 purchasing power parity (PPP) and specific incidence of circulatory, nutritional endocrine and metabolic diseases, as well as a strong and inverse link between GDP and infant's deaths per 1000 live births. Conclusions highlight that the effects of traumatic historical events must be made aware through medical education of the population, supporting the idea according to which the incidence of various metabolic diseases is greater for the offspring of those who have actively suffered during such events.

Risk of active tuberculosis in patients with inflammatory arthritis receiving TNF inhibitors: a look beyond the baseline tuberculosis screening protocol.

Tuberculosis (TB) is a major concern in patients receiving TNF inhibitors (TNFi). This study aimed to assess the incidence of active TB and the efficacy of TB prevention measures used over the years, and to determine risk factors for developing TB, in a single-centre cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNFi. Data of all patients in whom treatment with TNFi was initiated in our rheumatology clinic until December 1st 2014 have been retrospectively analysed. The cohort was divided into 3 groups per the mandatory LTBI screening method at baseline: tuberculin skin test (TST) with a positive threshold of either 10 mm (group TST1), or 5 mm (group TST2), and QuantiFERON®-TB Gold test (group QFT). The incidence of active TB was analysed for each group and compared to TB incidence data in general population. Five hundred fifty patients were included (305 RA, 42 PsA, 203 AS); 97 patients belonged to the TST1, 229 to the TST2 and 224 to the QFT group. The number of active TB cases/time of exposure to TNFi (person-years, PY) was 8/593.5, 9/1044.0 and 3/555.3, respectively, accounting for an incidence of 1348.0, 862.1 and 540.2 cases per 105 PY. Active TB cases occurring in the first year of TNFi treatment (early TB) per total TB cases were only 3/8, 1/9 and 1/3, respectively, too few to identify statistically significant differences between the 3 LTBI screening protocols. However, less TB cases per total observation time were registered in the QFT group, probably due to the reduced duration of exposure to TNFi. All cases of active TB were registered among patients receiving monoclonal antibodies TNFi agents. We have found no significant risk factors for developing active TB. In our cohort, TB occurring after 1 year of TNFi treatment exceeds 'early TB', suggesting the necessity of further TB prevention measures besides baseline screening for LTBI.

A Romanian version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument.

OBJECTIVES: UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) Instrument is a comprehensive, self-administered survey for the assessment of gastrointestinal involvement in scleroderma patients, developed and validated in English. Our objective was to translate and validate a Romanian version of UCLA SCTC GIT 2.0. METHODS: Translation from English into Romanian has been made using the forward-backward method. Sixty-four patients, attending a referral centre as part of an extensively studied cohort, were approached in a consecutive manner over a period of two years for administration of the questionnaire. We evaluated the reproducibility, internal consistency, construct validity and discriminative capacity of the translation (Romanian GIT). RESULTS: Fifty-four patients returned completed questionnaires. Internal consistency was demonstrated by Cronbach's alpha coefficient (0.931). Construct validity is supported by moderate, but significant correlations of Romanian GIT total score with the Mental Component Summary (MCS) of SF-36 (r=0.541, Spearman correlation) and among subscales, by significant correlations with SHAQ total score (r=0.559, Spearman correlation) and by strong correlations with gastrointestinal subscale of SHAQ (SHAQ GI) (r=0.726, Spearman correlation). Reproducibility was good as well. Divergent validity was supported by significant differences between patients with or without a clinical diagnosis of gastrointestinal disease. Other differences in the Romanian GIT total score were tested among subgroups of patients. CONCLUSIONS: The Romanian GIT has acceptable reliability and validity. This questionnaire can be used for the assessment of gastrointestinal involvement in scleroderma patients.

Development of a prognostic score for work disability in Romanian patients with ankylosing spondylitis.

PURPOSE: To develop a prognostic score for predicting work disability (WD) in patients with ankylosing spondylitis (AS) as strong indicator for poor vocational rehabilitation. METHOD: A cross-sectional study was performed in a group of 170 patients with AS, 120 work disabled and 50 still employed. The variables strongly associated with WD were quantified (scored 0-30) - abnormalities of: anterior-posterior radiograph of pelvis, lateral cervical spine radiograph and lung function tests, certain work factors (occupation, physical strain and microclimate), Bath Ankylosing Spondylitis Mobility Index and Bath Ankylosing Spondylitis Functional Index tests. RESULTS: The eight-item score identifies WD with sensitivity of 91.7% and specificity of 85.7%. The scaling properties were fulfilled: internal consistency - Chronbach's alpha 0.73; reliability - intraclass correlation coefficient 0.73; redundancy weak-moderate, with coefficients ranging from 0.032 to 0.797; the discriminative capacity by the significant variations of the score according to the statute (employed or work disabled) and the degree of WD. CONCLUSIONS: The score is a reliable method for assessing the WD risk in patients with AS. It allows a complex evaluation by performing minimal investigations and it is easy to perform. IMPLICATIONS FOR REHABILITATION: Work disability is an important outcome in AS, determined by numerous variables but highly dependent on the national characteristics of economy, social security and healthcare system. The prognostic score for work disability in AS not only contains medical but also socio-demographic and work-related factors and is expected to be a useful tool for specialists to guide the tertiary prevention-oriented rehabilitation measures. Our study suggests the prognostic score to be comprehensive, useful and a reliable method to assess the risk of work disability in AS.

Composite diffuse large B-cell lymphoma and follicular B-cell lymphoma - case report and review of literature.

Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presenting a case of diffuse non-Hodgkin large B-cell lymphoma with areas of low grade and high grade follicular non-Hodgkin B-cell lymphoma in a retroperitoneal lymph node and spleen of an 62 year old woman. Histopathological examination and immunohistochemistry features proved the diagnosis of composite lymphoma.

The role of distubances of phosphate metabolism in metabolic syndrome.

BACKGROUND: Metabolic syndrome represents a cluster of cardiovascular risk factors that has become a public health problem of epidemic proportions. It was proposed that disturbances in phosphate metabolism may represent a key feature of metabolic syndrome, with a high contribution of cardiovascular risk factors. OBJECTIVES: The aim of the study is to investigate the relationship between phosphate levels and the presence of the characteristics of metabolic syndrome, as well as the mechanisms that may responsible for reduced phosphate levels in patients with metabolic syndrome. METHODS: One hundred fifty five subjects are enrolled in the study: 64 with metabolic syndrome and 91 without this syndrome. Biochemical parameters of the metabolic syndrome study populations were compared with healthy population study. RESULTS: Patients with metabolic syndrome showed significantly lower phosphate (46%) and magnesium levels compared with controls (22.7%) (p<0.001).Because fractional excretion of phosphate was similar in both groups, we think that hypophosphatemia in patients with metabolic syndrome can be attributed to decreased dietary intake, as well as internal redistribution of this element. Lower magnesium hyperinsulimemia-induced renal magnesium wasting also may be a contributory factor. CONCLUSIONS: Patients with metabolic syndrome show significantly lower phosphate and magnesium concentrations compared with individuals who do not fulfill criteria for diagnosis of this syndrome. This reduction is likely to be attributed to reduced dietary intake and internal redistribution of phosphate and is more pronounced as the number of components of metabolic syndrome increases. The clinical significance of these disturbances, as well as their importance as targets for preventive or therapeutic interventions, remains to be established.

Effects of lifestyle changes including specific dietary intervention and physical activity in the management of patients with chronic hepatitis C--a randomized trial.

BACKGROUND: In patients with chronic hepatitis C (CHC), obesity is involved in the pathogenesis of insulin resistance, fatty liver disease and progression of fibrosis. The objective of this study was to compare a normoglucidic low-calorie diet (NGLCD) with a low-fat diet (LFD) among participants with CHC. Aimed to measure the impact of dietary changes in reduction of insulin resistance, obesity but also in steatosis and fibrosis. METHODS: Randomized, controlled trial in three medical centers with assessments at baseline, 6 months and 12 months. Participants were patients over 35 years with chronic hepatitis C (n = 120) with BMI over 25 kg/m². We evaluated the effects of NGLCD vs. LFD in weight management and metabolic improvement. The primary endpoint was to measure the impact of dietary changes through nutritional intervention in reversibility of insulin resistance, obesity, steatosis, and fibrosis. We performed anthropometric measurements, fasting glucose profile, serum lipids, liver profile, blood count at baseline, 6 and 12 months. Steatosis was evaluated using ultrasonographic criteria. Liver fibrosis was non-invasively assessed. RESULTS: After 6 and 12 months of intervention, both groups had a significant decrease in caloric consumption. At 6 months, weight loss was greater in the NGLCD group (-5.02 ± 3.43 kg vs. -4.1 ± 2.6 kg; p = 0.002) compared to the LFD group. At 1-year, however, weight loss was similar in both groups (-3.9 ± 3.3 kg vs. -3.1 ± 2.6 kg; p = 0.139). At 12 months, fasting plasma glucose, fasting plasma insulin, and HOMA-IR had significant improvements in both groups. With both diets aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) decreased with significant differences; also there were significant improvements in AST/ALT ratio, Forns fibrosis index. The two diets were associated with reduction of both the prevalence and the severity of steatosis (all p < 0.001). At 12 months, total cholesterol, HDL-cholesterol, triglycerides improved in both groups (all p < 0.05). CONCLUSIONS: The present study establishes the benefits of low-calorie diet and low-fat diet in management of patients with hepatitis C regarding improvement of insulin resistance, steatosis and also fibrosis.Overweight or obese patients with CHC undergoing a lifestyle intervention (specific dietary intervention and physical activity) for 1-year had significant improvements in body weight, lipid and hepatic profile. TRIAL REGISTRATION: PNCI2-3343/41008/2007.

Gastric and colonic mantle cell lymphoma - incidental discovery.

A 65-year old patient, with no medical history, was admitted for lower gastrointestinal bleeding. On clinical examination the patient seemed to be in good health. However the examination was completed with a rectosigmoidoscopy revealing the presence of mucosal erosions, ulcerations, multiple papulae. The histopathological examination raised the suspicion of a colonic lymphoma. Gastric biopsies suggested a gastric MALT type lymphoma associated to the colonic lymphoma, but the immunohistochemical profile corresponded to a mantle cell lymphoma. In spite of the general poor prognosis of mantle cell lymphoma, our patient had a good clinical and endoscopic response to the standard cyclophosphamide, vincristine, prednisone (CVP) therapy. The cases of gastric and colonic mantle lymphoma are rare, the response to therapy is poor; fortunately, our patient had a complete resolution after completion of the six cycles of chemotherapy.

Hepatitis virus C infection, adipokines and hepatic steato-fibrosis.

Hepatitis C viral infection is accompanied by various serum alterations that could explain its molecular impact on hepatic structure and metabolic homeostasis. Recently it has been shown that adipocytokines play a pivotal role in development of hepatic steato-fibrosis, different studies giving a support of the hypothesis that the balance of adipocytokine expression is a key regulator for the progression of hepatic steatosis and fibrosis. The association between insulin resistance and hepatitis C virus genotypes and liver fibrosis stage foreshadowed that virus-induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. The main importance of adipocytokine profile detection consists in the prediction of steatosis induction that has clinical relevance, being associated with advanced fibrosis and hyporesponsiveness to antiviral therapy.