Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.

Mitochondrial dysfunction is currently acknowledged as a central pathomechanism of most common diseases of the 21st century. Recently, the assessment of the bioenergetic profile of human peripheral blood cells has emerged as a novel research field with potential applications in the development of disease biomarkers. In particular, platelets have been successfully used for the ex vivo analysis of mitochondrial respiratory function in several acute and chronic pathologies. An increasing number of studies support the idea that evaluation of the bioenergetic function in circulating platelets may represent the peripheral signature of mitochondrial dysfunction in metabolically active tissues (brain, heart, liver, skeletal muscle). Accordingly, impairment of mitochondrial respiration in peripheral platelets might have potential clinical applicability as a diagnostic and prognostic tool as well as a biomarker in treatment monitoring. The aim of this minireview is to summarize current information in the field of platelet mitochondrial dysfunction in both acute and chronic diseases.

Migraine without aura is frequently reported in female patients with irritable bowel syndrome (IBS), but knowledge about the relationship between these two conditions is still lacking. This study was aimed to explore the particularities of migraine without aura in young female patients with IBS in order to establish a possible link between them. From a cohort of young female patients hospitalized with IBS in the Internal Medicine Department, 30 joined this pilot study, and they were assigned into two groups on the basis of presence or absence of migraine. In this sample, 15 patients have mild to moderate migraine without aura, with a recently taken normal brain scan, and 15 were without migraine. Diseases and conditions not related to migraine and other possible specific female comorbidities were ruled out. Patients undertook a thorough clinical examination in order to assess fibromyalgia (FM) and chronic pelvic pain (CPP), Questionnaires for migraine disability assessment (MIDAS) and generalized anxiety disorder (GAD) were performed. Laboratory testing of blood, urine, and stool were also performed. Optimized lymphocyte proliferation test for food allergy (FA) and a fecal microbiota (microbiological semiquantitative method) for dysbiosis (DB) assessment were performed. Based on the results, migraine-positive group displayed more severe comorbidities: FM (p=0.0002), FA (p=0.0006), CPP (p=0.026), higher scores of anxiety (GAD, p=0.0008), and more severe DB (p=0.0009). We noticed a strong positive correlation between MIDAS and GAD (r=0.83), a good positive correlation between MIDAS and DB (r=0.56), and a moderate positive correlation between MIDAS, FM, and FA (r=0.46 and 0.41). In conclusion, young female patients with IBS and migraine without aura displayed more severe associated issues – anxiety, intestinal DB, FM, FA, and CPP. The severity of migraine correlated well with anxiety range and DB magnitude and moderately with FM and FA.

Background: The complexity of myeloproliferative neoplasms (MPNs) cannot be characterized by acquired somatic mutations alone. Individual genetic background is thought to contribute to the development of MPNs. The aim of our study was to assess the association between the TET2 rs1548483 single nucleotide polymorphism (SNP) and the susceptibility to polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) or chronic myeloid leukemia (CML). Methods: We evaluated the TET2 rs1548483 SNP through real-time PCR in 1601 MPN patients out of which 431 with PV, 688 with TE, 233 with PMF, 249 with CML and 197 controls. We included only patients with a molecularly proven driver mutation, such as JAK2 V617F, CALR or BCR-ABL1. Results: Significant association between TET2 rs154843 variant allele and JAK2 V617F-positive PV and PMF (OR = 1.70; 95% CI: 1.01–2.91; p-value = 0.046, and OR = 2.04; 95% CI: 1.10–3.77; p-value = 0.024, respectively), and type 2 CALR-positive PMF (OR = 2.98; 95% CI: 1.12–7.93; p-value = 0.035) was noted. Conclusions: The TET2 rs1548483 SNP is associated with the susceptibility to molecularly annotated PV and PMF.

What is presently known is that thromboembolic disease represents a major cause of morbidity and mortality during pregnancy. To this we add a rare but not negligible pathology, acquired and inherited thrombophilia, which increases the predisposition for thrombotic events during pregnancy. In this article, what has been studied is the impact that LMWH has on patients with inherited thrombophilia, both the conventional FV, FII and the newly introduced MTHFR, PAI, FXII, factors which are often combined.81 patients have been taken into consideration / included in study, with the following anterior results, before the patients discovered their illnesses, thus before following treatment: first trimester or advanced pregnancy loss, IUGR, premature birth or secondary placental thrombotic complications such as: preeclampsia, DPPNI or dead fetuses, as well as maternal thrombotic accidents. The administration of LMWH decreased the rate of pregnancy loss compared to untreated pregnancies is statistical significant (p= 0.004), there were fewer DPPNI (p= 0.006), and no intrauterine deaths. We also compared the occurrence of thrombotic events during treated and untreated pregnancies and we observed significant differences in this groups (p= 0.001). There was also a sufficient number of patients with new types of thrombophilia included in the study to demonstrate the impact it has on pregnancy. LMWH improves the situation of women with thrombophilia during pregnancy.

Introduction: Sclerosing Extramedullary Hematopoietic Tumor (SEHT) is a very rare lesion associated with chronic myeloproliferative disorders (CMPD). SEHT can mimic morphologically, both macroscopically and microscopically, a wide variety of tumors/lesions. Case presentation: We present the case of a female patient diagnosed with gallstones for which surgery was decided. Intraoperatively, a malignant tumor of extrahepatic bile ducts was suspected. A frozen section examination raised the suspicion of a mesenchymal tumor or an inflammatory pseudotumor. The histological evaluation of the permanent sections, supplemented with an immunohistochemical investigation (IHC), was the one that established the diagnosis of SEHT, based on the presence of areas of sclerosis, atypical CD31+ megakaryocytes, myeloid and erythroid elements. Conclusions: The authors present the difficulties of a morphological diagnosis on the frozen section and on permanent sections in the absence of relevant clinical information and make a review of the literature data dedicated to the subject.

Background Gallstone disease (GSD) is more commonly presented in aged people. Purpose The purpose of the study was to explore the insights of metabolic performance of bacterial species from gut microbiota as well as the clinical background in middle-aged and elderly patients with GSD. Patients and Methods This is an observational study concerning 120 research participants. Of those, 90 patients with symptomatic GSD addressed for cholecystectomy, average age 59.83 ± 15.32 years: 45 with cholesterol rich gallstones (CGSs), 45 with pigment gallstones (PGSs) and 30 healthy controls joined this observational study. Clinical examination, lab work-ups, upper and lower digestive video-endoscopies, abdominal ultrasound/CT and gallbladder motility assessment by Dodd’s method were performed. Overall stool dysbiosis (DB) was assessed as 1 = minor, 2 = mild, 3 = severe, species being identified by matrix-assisted laser desorption ionization method. Stool samples from dysbiotic patients were analyzed by a next generation sequencing method with operational taxonomic unit identification. Results Patients with GSD presented with a significant high range of overall gut DB (p < 0.0001) when compared with controls. Those with CGSs compared with those having PGSs displayed significant clinical differences related to elderly age, lifestyle and diet particularities, obesity, dyslipidemia, nonalcoholic fatty liver disease, hypertension, type 2 diabetes mellitus or impaired glucose tolerance, as well as motility disturbances of gallbladder with a decrease of the ejection fraction. Significant increase of overall DB range and alterations of several functional bacterial species with a decrease of butyrate, lactate, acetate/propionate and methane producers, mucin degrading bacteria, biodiversity index of microbiota, as well as an increase of lipopolysaccharide positive bacteria were significantly present in patients with CGSs. Conclusion Middle-aged and elderly patients with GSD and a clinical background characterized by particular lifestyle, metabolic and gallbladder motility issues displayed significant modifications of biodiversity, overall gut DB and alterations of several functional bacterial species, with a decrease of their metabolic performance.

Background and Objectives: Migraine with aura (MA) could be considered a risk factor for developing atherosclerosis and cardio-vascular events. However, less is known about the relation between migraine without aura (MWA) and atherosclerosis. Our study aimed to assess whether young female migraineurs, with alterations of gut microbiota could associate early atherosclerosis. Materials and Methods: We conducted an exploratory cross-sectional, pilot study concerning 105 consecutive young females having MWA, with recent normal brain scans, that were free of cardio-vascular risk factors, non-smokers, not on oral contraception, not pregnant, and without thyroid or parathyroid diseases, chronic organ failure, cancer, or on probiotic or antibiotic treatment. Consecutive to assessment of gut microbiota, patients were assigned to two groups: dysbiosis positive (n = 45) and dysbiosis negative (n = 60). All study participants underwent clinical examinations with an assessment of migraine severity, body mass index and carotid intima-media thickness (CIMT), as well as laboratory workups. Statistical analysis was performed using a chi-squared test (χ2), a two-tailed t-test and a nonparametric Spearman’s correlation test. Results: The dysbiosis positive migraineurs showed a significant increase in CIMT along with several anthropometrical, biological and clinical particularities. Significant positive correlations between dysbiosis and CIMT, glycosylated hemoglobin, migraine severity and duration, tumor necrosis factor-alpha, and body mass index were found. Conclusions: Young female migraineurs with significant alterations of gut microbiota experienced early signs of atherosclerosis and displayed severe migraine disability, as well as multiple biological and clinical particularities.