How Dexamethasone Used in Anti-COVID-19 Therapy Influenced Antihypertensive Treatment in Patients with SARS-CoV-2.

BACKGROUND: During the SARS-CoV-2 pandemic period, in the treatment approved by the WHO, along with antivirals, antibiotics, nonsteroidal anti-inflammatory drugs and anticoagulants, dexamethasone was always used. This study started from the professional concern related to the vasopressor effect of cortisone on blood pressure (BP). METHODS: The study group was achieved by selecting, from a total of 356 patients hospitalized in the clinic, the patients with known hypertensive status at admission for SARS-CoV-2. Dexamethasone was part of the anti-COVID-19 treatment, with an administration of 4-6-8 mg/day, depending on bodyweight, for 10 days. All patients with hypertension received antihypertensive treatment in adjusted doses according to the recorded BP values. RESULTS: Monitoring of BP in hospitalized patients was performed daily, in the morning and evening. If on the 2nd day of treatment, 84% of the patients partially responded to the treatment with a moderate decrease in BP, on the 3rd therapy day, the situation clearly improved: more than 75% of the patients had values of BP that can be classified as high-normal (38.23%) and normal (40.03%). CONCLUSIONS: Dexamethasone for treatment of SARS-CoV-2 infection did not have a notable influence on increasing BP, because the doses were low-moderate and prescribed for a short time.

Analysis of Risk Factors for the Development of Gestational Diabetes Mellitus in a Group of Romanian Patients.

Introduction: Gestational diabetes mellitus (GDM) is caused by numerous risk factors, the most common being old age, obesity, family history of diabetes mellitus, GDM, history of fetal macrosomia, history of polycystic ovary syndrome or treatment with particular drugs, multiple births, and certain races. The study proposed to analyze the risk factors causing GDM. Method: In the study, we included 97 pregnant women to whom there was an OGTT performed between weeks 24th and 28th of pregnancy, divided into two groups, with GDM and without GDM. The statistical analysis was performed with SPSS 26.0, the tests being statistically significant if p value < 0.05. Results: The favoring risk factors for the onset of GDM were analyzed, with statistically significant differences between the GDM group and the group without GDM related to the delivery age (32.39 ± 4.66 years old vs. 28.61 ± 4.71 years old), history of fetal macrosomia (13.7% vs. 0%), presence of GDM during previous pregnancies (7.8% vs. 0%), HBP before pregnancy (9.8% vs. 0%), gestational HBP (17.6% vs. 0%), glycemia value at first medical visit (79.37 ± 9.34 mg/dl vs. 71.39 ± 9.16 mg/dl), and weight gain during pregnancy (14.61 ± 4.47 kg vs. 12.48 ± 5.87 kg). Conclusions: Identifying the risk factors for the GDM onset has a special importance, implying an early implementation of interventional measures in order to avoid the onset of GDM and associated maternal and fetal complications.

Maternal and Fetal Metabolites in Gestational Diabetes Mellitus: A Narrative Review.

Gestational diabetes mellitus (GDM) is a major public health issue of our century due to its increasing prevalence, affecting 5% to 20% of all pregnancies. The pathogenesis of GDM has not been completely elucidated to date. Increasing evidence suggests the association of environmental factors with genetic and epigenetic factors in the development of GDM. So far, several metabolomics studies have investigated metabolic disruptions associated with GDM. The aim of this review is to highlight the usefulness of maternal metabolites as diagnosis markers of GDM as well as the importance of both maternal and fetal metabolites as prognosis biomarkers for GDM and GDM's transition to type 2 diabetes mellitus T2DM.

Systemic and adipose tissue inflammation in NASH: correlations with histopathological aspects.

INTRODUCTION: Non-alcoholic steatohepatitis (NASH) is a progressive form of liver steatosis that involves a risk of progression towards fibrosis, cirrhosis, and end-stage liver disease. Low-grade inflammation is recognized to be involved in non-alcoholic fatty liver disease (NAFLD) pathogeny. Additionally, adipose tissue dysfunction plays an important role in the development of metabolic diseases. PATIENTS, MATERIALS AND METHODS: We conducted a study on 68 patients with liver steatosis confirmed through liver biopsy during the surgery. In all the patients, we recorded anthropometric parameters and we performed blood tests for systemic inflammation [high-sensitivity C-reactive protein (hs-CRP), fibrinogen] and serum adipokines related to adipose tissue inflammation (leptin, adiponectin). Additional to histopathological examination, we also performed the immunohistochemical study of inflammatory mononuclear cells. RESULTS: The 68 patients had a mean age of 56.57±4.94 years old, had a mean value of hs-CRP of 2.30±0.91 mg∕L, a mean value of leptin of 14.02±17.02 ng∕mL and a mean value of adiponectin of 7.54±0.38 mg∕L. In all the cases studied by liver biopsy, the steatosis exceeded 5% of hepatocytes, but the frequency of NASH was 26.47%. Cluster of differentiation (CD)45-positive, CD4-positive, and CD8-positive T-lymphocytes predominated in the studied cases. We obtained a statistically significant high association between definite NASH and the values of hs-CRP, serum adiponectin and leptin∕adiponectin ratio (p<0.0001). CONCLUSIONS: Systemic and adipose tissue inflammation was statistically significant associated with histological lesions of steatosis and NASH, suggesting that the determination of hs-CRP and serum adipokines in dynamics in patients with NAFLD is predictive for the progression of the disease.

Triglyceride and glucose index: a useful tool for non-alcoholic liver disease assessed by liver biopsy in patients with metabolic syndrome?

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic impairments, being a component of metabolic syndrome. Considering the involvement of fat accumulation and insulin resistance in NAFLD, triglyceride and glucose (TyG) index was proposed as a marker of NAFLD progression. The "gold standard" for the evaluation of liver lesions characteristic for NAFLD remains the liver biopsy. The aim of this study was to establish the links between TyG index, assessing insulin resistance, and histopathological lesions of liver samples obtained by liver biopsy in patients with metabolic syndrome. PATIENTS, MATERIALS AND METHODS: We conducted a study over a period of three years, including 113 adult patients with metabolic syndrome in whom hepatic disorders were assessed by liver biopsy and insulin resistance was evaluated by TyG index. RESULTS AND DISCUSSIONS: In our study, steatosis had a frequency of 92.03%, being identified 26 cases with mild steatosis, 48 with moderate steatosis and 31 with severe steatosis. Regarding non-alcoholic steatohepatitis (NASH), the frequency of this disorder in our study group was 29.2% in the subjects with liver steatosis, while liver fibrosis had a frequency of 53.09%. When we analyzed the relationships between TyG index and the presence of each type of lesion necessary for NASH diagnosis, we obtained statistically significant differences for the presence of hepatocyte ballooning (p=0.01) and a high statistically significance for the NAFLD activity score (NAS) (p<0.0001). CONCLUSIONS: TyG index is a facile tool that can be used to identify patients at risk for advanced NAFLD lesions evaluated by liver biopsy.

The role of skin and muscle biopsy in the diagnosis of main connective tissue diseases.

Systemic involvement in autoimmune diseases is often unclear and organ changes are confounding, thus making it difficult to have an early accurate diagnosis. In those situations, both clinical and paraclinical findings might orientate the diagnosis, but only histological or immunohistochemistry changes might be accurate enough. The skin histological changes are relevant and sometimes might have a tremendous role in the accurate diagnosis of autoimmune rheumatic diseases, due to the correlation with the clinical systemic manifestations of the diseases and through the accessibility of biopsy. In the same time, muscle biopsy can provide important support for physicians improving diagnosis and optimizing management of connective tissue diseases.

An extremely rare case of distal common bile duct adenocarcinoma in a 65-year-old male patient.

Cholangiocarcinoma is an extremely rare and highly aggressive primary malignancy of the biliary tract. The current report illustrates a rare case of distal common bile duct adenocarcinoma encountered in a 65-year-old male patient who was thoroughly investigated after presenting with a two weeks history of pain in the right hypochondrium, jaundice and unintentional weight loss (6 kg in two weeks). The medical team opted for a pancreaticoduodenectomy (Whipple procedure) managing to obtain negative resection margins of the tumor with a favorable immediate postoperative evolution. However, the surgical team was forced to reintervene twice due to complications caused mainly by the patient's disregard.

Streptococcal tonsillitis related reactive arthritis - clinical, ultrasound imaging and immunohistochemical study.

In clinical practice and literature studies, the most common condition associated to streptococcal tonsillitis used to be acute rheumatic fever (ARF). Several publications in the late years report a more frequent and distinctive entity from ARF following ß-hemolytic group A streptococcus infection in patients with post-infectious arthritis, that do not fulfill the modified Jones criteria, the so-called post-streptococcal reactive arthritis (PSRA). A distinctive pattern of clinical framing and biological profile in patients with PSRA following streptococcal tonsillitis is described, with a non-migratory, additive, recent onset (7-10 days) arthritis that affects small and large joints as well, with a bimodal peak of incidence at 8-14 and 21-37 years of age, with variate response to non-steroidal anti-inflammatory drugs and has a tendency for recurrence and persistence. Sacroiliitis, although rare, is described in human leukocyte antigen (HLA)-B27 positive PSRA patients. The main objective of the current study was to evaluate various immunohistochemical patterns of streptococcal tonsillitis in patients with PSRA and find possible correlations with the clinical, biological and ultrasound profile.

Difficulty in positive diagnosis of ascites and in differential diagnosis of a pulmonary tumor.

Ascites is the most frequent complication of cirrhosis and occurs only when the portal hypertension has already installed but ascites is caused by neoplasms, heart failure, tuberculosis, pancreatic illnesses, as well as other kind of affections. We describe the case of a 67-year-old patient, a retired person, without significant personal or familial history, nonsmoker, infrequent alcohol and coffee consumer with following chief complaints at onset: loss of appetite, weight loss, serious physical asthenia, delayed intestinal transit, diffuse abdominal pain and increase of abdominal circumference. Initially was misdiagnosed with liver cirrhosis. After discharged from our Clinic, suspicion of diagnosis was mesothelioma as well as after first thoracoscopy and pleural biopsy performed in a Clinic of Thoracic Surgery. Several pleural fragments collected by biopsy were sampled for the histopathological exam. The stainings used were Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) for the mucopolysaccharides. For the immunohistochemistry was used the labeled Streptavidin-Biotin (LSAB)-Horseradish peroxidase (HRP) method, as well as the antibodies: cytokeratin (CK) cocktail (AE1÷AE3), vimentin, calretinin, CK7, CK5÷6, CK20, epithelial specific antigen/epithelial cell adhesion molecule (Ep-CAM) (BerEP4), thyroid transcription factor-1 (TTF-1), E-cadherin, CDX2, carcinoembryonic antigen (CEA) and the Hector Battifora mesothelial antigen-1 (HBME-1). The aspect at immunohistochemistry establishes a positive diagnostic of poorly differentiated mucinous pulmonary adenocarcinoma, with "signet ring" cells. The rapid and accurate determination of the diagnostics will allow not only for a decrease in the expenses for inefficient treatments, but also for the guidance of the patients towards clinics or centers able to provide and supervise these treatments.

Histopathological and immunohistochemical profile in primary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by hypofunction of the salivary and lachrymal glands. Main clinical features of SS are sicca symptoms, due to the altered glandular function. Also, in advanced stages, bilateral swelling of the parotid glands can be noted, indicative of severe glandular involvement. Phenotypic expression of various mononuclear cells present in the affected tissue offers additional insight into cellular proliferation, survival, migration, antibody secretion and also the potential of forming tertiary lymphoid tissue, i.e., germinal centers. The main objective of the present study was to evaluate various autoimmune activity patterns present in salivary glands by means of immunohistochemistry (IHC) analysis. The study group comprised of 10 primary SS patients, with various degrees of lymphocytic infiltrates confirmed on minor salivary gland (MSG) biopsy. We could identify both morphological changes, i.e., ductal system abnormalities or increased interstitial fibrosis, and immunological patterns associated with SS pathogenesis. CD3+ T-cells displayed a more intense reaction in specimens with mild to intermediate focus score (FS) grade. Specimens with important CD20+ B-cell component of lymphocytic infiltrate were associated with intermediate and severe FS grade. Specimens showed varying degrees of CD68+ cells, with more intense IHC reactions in slides displaying a more advanced mononuclear infiltration. Immunoreactivity was strong for both MMP-2 and MMP-8 matrix metalloproteinases, throughout the gland, in areas of acini, without it being linked with proximity of mononuclear cell infiltration. We could also establish some correlations between the degree of lymphocytic infiltration and clinical profile.

Intramuscular human Dirofilaria repens infection of the temporal region - case report and review of the literature.

Dirofilariasis is a zoonotic worldwide-distributed disease, especially in regions with warm to temperate climate, where it recently recorded a significant increase of prevalence. A 61-year-old female, a dog owner, residing in the Southwest of Romania, near a swamp, developed a painless nodule in the left temporal region. The contrast-enhanced computed tomography (CT) scan revealed a temporal intramuscular cystic lesion. The surgical exploration confirmed the lesion as with intramuscular localization. The histopathology and biochemistry investigations established as a cause of the lesion an infestation with Dirofilaria repens species. The patient underwent an anthelmintic treatment with Diethylcarbamazine and the clinical and radiological follow-up did not revealed any recurrences within a period of 15 months after surgery. This is the second case reported in Craiova (Romania), the seventh worldwide reported case with localization in the temporal region, and the second one with intramuscular development in this region. The existence of such cases should alert the clinician to include parasitosis in the differential diagnosis of atypical space-occupying lesions of the head regions.

Apert syndrome - clinical case.

Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert syndrome are early craniostenosis, microviscerocranium and II-V finger syndactyly of hand and toes with proximal phalanx of the bilateral thumb "in delta". It is difficult to determine prenatal diagnosis in the second quarter, when examining the morphology of fetal signs; the dysmorphism signs appeared in the third pregnancy quarter. We present here the case of a newborn with Apert syndrome that was born prematurely in our Clinic after a monitored pregnancy, where there was issued a suspicion of cranio-facial dysmorphism, malposition and malformation of the feet and hands in the third quarter of prenatal pregnancy. The diagnosis of Apert syndrome was placed on clinical signs, laboratory and genetic tests. The clinical outcome of the baby in the maternity was favorable, the therapeutic management being established by a multidisciplinary team. Immediate complications were due to the case of prematurity: respiratory distress syndrome and the characteristics of the syndrome: micrognathia and naso-facial dysmorphism, syndactyly, bilateral foot metatarsus adductus.

Determination of VEGFR-2 (KDR) 604A>G Polymorphism in Pancreatic Disorders.

Pancreatic disorders have a high prevalence worldwide. Despite the fact that screening methods became more effective and the knowledge we have nowadays about pancreatic diseases has enhanced, their incidence remains high. Our purpose was to determine whether single nucleotide polymorphism (SNP) of VEGFR-2/KDR (vascular endothelial growth factor receptor 2/kinase insert domain receptor) influences susceptibility to develop pancreatic pathology. Genomic DNA was extracted from blood samples collected from patients diagnosed with acute pancreatitis (n = 110), chronic pancreatitis (n = 25), pancreatic cancer (n = 82) and healthy controls (n = 232). VEGFR-2 (KDR) 604A>G (rs2071559) polymorphism frequency was determined with TaqMan allelic discrimination assays. Statistical assessment was performed by associating genetic polymorphism with clinical and pathological data. In both pancreatic disorders and healthy control groups the polymorphism we studied was in Hardy-Weinberg equilibrium. Association between increased risk for pancreatic disorders and studied polymorphism was statistically significant. KDR 604AG and AG + GG genotypes were more prevalent in acute pancreatitis and pancreatic cancer patients than in controls. These genotypes influence disease development in a low rate. No association was found between chronic pancreatitis and KDR 604AG and AG + GG genotypes. In Romanian cohort, we found an association between the KDR 604A→G polymorphism and acute pancreatitis and pancreatic cancer. Carriers of the -604G variant allele were more frequent among acute pancreatitis and pancreatic cancer than among controls, suggesting that KDR 604G allele may confer an increased risk for these diseases. In the future, more extensive studies on larger groups are necessary, in order to clarify the role of VEGFR2 polymorphisms in pancreatic pathology.

The association between chronic pancreatitis and the iNOS-2087A>G polymorphism.

INTRODUCTION: Chronic pancreatitis is morphologically characterized by ductal dysplasia, breeding grounds for the proliferation of the ductal cells, the degenerative changes in pancreatic acinar cells and fibrosis, and it is defined on the basis of the clinical, morphological and functional criteria. AIM: The aim of our study is to examine the existence of a possible correlation between the iNOS-2087A>G polymorphism and chronic pancreatitis by means of the genetic analysis. MATERIAL AND METHOD: We have conducted the study at the Gastroenterology Clinic and the Research Center of Gastroenterology and Hepatology of the University of Medicine and Pharmacy, Craiova, between March 2015 - September 2016. The study had a prospective character. Both for the 58 patients diagnosed with chronic pancreatitis and for the 132 patients in the witness group, the biological material was represented by blood, (around 2.5 - 5 milliliters of venous blood) let on EDTA and kept at 4°C up to the separation of the DNA molecule. All the patients were genotyped for the iNOS - 2087A>G polymorphism, by means of the Real Time PCR technique with TaqMan probes. RESULTS: Analysing the prevalence of the iNOS genotypes within the study group and witness group, we have noticed that, statistically speaking, there are no significant differences between the two groups. CONCLUSION: As a conclusion, in the study lot we can sustain that the risk of developing chronic pancreatitis is not increased by the presence of the iNOS-2087A>G polymorphism.

Histological factors that predict the liver fibrosis in patients with chronic hepatitis C.

In chronic hepatitis, pathologies reveal a prominent inflammatory infiltrate portal consisting mostly of lymphocytes and plasma cells invading the portal spaces, although one can also identify macrophages, neutrophils or eosinophils. In all the forms of chronic hepatitis, fibrosis starts in the portal area, namely periportally, subsequently extends towards the lobules to the central veins, causing septa, followed by fibrosis. We studied 52 patients with chronic hepatitis C, who underwent a hematological, biochemical, virological and histopathological investigation. We found that the severity degree of the portal inflammation was in direct relation to the hepatitis activity index (HAI) and to the degree of fibrosis. The portal inflammation is dependent to the degree of fibrosis. The degree of inflammation significantly changes the distribution of cases with different degrees of fibrosis (chi-square p=0.00011 <0.001). Periportal inflammation, periportal necrosis and focal necrosis are the morphological aspects of the necroinflammatory process best correlated to the occurrence and development of fibrosis.

Histopathological aspects described in patients with chronic hepatitis C.

Chronic hepatitis C affects an estimated 170 million people worldwide and causes approximately 350 000 deaths each year. The current antiviral therapy allows the virus eradication or the permanent inhibition of the virus replication (sustained virological response, SVR), the reduction of the inflammation, and the prevention or the reduction of liver fibrogenesis (histological response). We studied the histopathological aspects found during percutaneous liver biopsy in patients with chronic hepatitis C viral infection who were treated and monitored over a period of two years. The assessment of the histological activity index through Ishak score determined the presence of: mild chronic hepatitis in 12 (23.1%) patients, moderate chronic hepatitis in 21 (40.4%) patients, and severe chronic hepatitis in 19 (36.5%) patients. The percutaneous liver biopsy performed on the patients with chronic viral hepatitis C showed a series of histological alterations, the most frequent being: portal inflammation, periportal necrosis, lobular inflammation, focal necrosis, and hepatic fibrosis (scarring). The severity degree of this histopathological aspect was correlated with the hepatitis activity index. The association of piecemeal with bridging necrosis is the deadline at which the antiviral treatment can still be effective. Evidence of early fibrosis represent the important moment for the antiviral treatment start. The specific histopathological aspects, but not pathognomonic, of chronic hepatitis C (hepatic steatosis, portal lymphoid infiltrates and bile duct damage) had a reduced incidence, occurring in only half (hepatic steatosis), a quarter (portal lymphoid infiltrates) and a fifth (destruction of biliary ducts) of all the patients with chronic viral hepatitis C, and these patterns was correlated with advanced degree of necroinflammatory process of the liver, particularly in the portal tracts.

Interrelations between hepatic stellate cells and immune system cells in patients with hepatocellular carcinoma.

OBJECTIVE: Our aim was to identify potential correlations between activated hepatic stellate cells (HSCs) and immune system's cells in patients with viral C hepatocellular carcinoma, by quantifying the percentage of activated HSCs, T-lymphocytes, natural killer cells and B-lymphocytes, in three distinct regions: tumor, transition area and the vicinity tissue (2-5 mm). PATIENTS AND METHODS: We prospectively included 20 samples prelevated at necropsy from patients with HCC and C viral infection. We assessed the percentage of alpha-smooth muscle actin (α-SMA), CD45RO, NK1 and CD20 expression using immunohistochemistry and a semi-quantitative scoring method. RESULTS: We found an inverse correlation between the number of α-SMA-positive HSCs and the number of NK1-positive cells in tumor (p=0.0007), in the transition area/tumor capsule (p=0.024) and in the vicinity tissue (p=0.038). Regarding T-lymphocytes, we have also identified an inverse correlation with the number of α-SMA-positive HSCs in tumor (p=0.0036), in the transition area/tumor capsule (p=0.034) and in the vicinity tissue (p=0.047). We found no correlation between the number of activated HSCs and the number of CD20-positive cells in all three examined areas. CONCLUSIONS: The analysis of HSCs activity within specified areas of tumoral liver tissue may lead to new perspectives in early diagnosis of relapses and in the development of future neoadjuvant therapies.

A pilot study on the role of fractal analysis in the microscopic evaluation of colorectal cancers.

INTRODUCTION: Colorectal cancer (CRC) represents one of the most common cancers worldwide; its growing incidence and prevalence quickly transforming it into a major health burden. Globally, survival varies from one country to another and constantly remains significantly low, despite increasing diagnostic efforts and tools. Fractal geometry and, specifically, fractal dimension (FD) are interesting tools to quantify cellular elements. In this paper, we aimed to identify and quantify by fractal analysis the elements obtained from medical images from pathological and immunohistochemical investigations of colonic biopsy fragments. MATERIALS AND METHODS: We prospectively selected the study group between September 2014 and January 2015, from patients who underwent surgery for previously diagnosed CRC at the Emergency County Hospital, Craiova, Romania. We performed the histological and immunohistochemical studies by following standardized protocols. Anti-Ki67, anti-p53 and anti-VEGF-C antibodies were used for immunostaining. We performed the fractal analysis with an in-house tool and we performed statistical tests on the results. RESULTS: We have included 41 (29 males) consecutive patients with different characteristics; after analyzing the FDs we found significant differences between adenocarcinomas and the other types of colonic cancers (p<0.001). However, we found no significant differences between most types of CRCs. We found significant statistical differences when compared well-differentiated tumors with all other stages (p<0.001). CONCLUSIONS: Fractal analysis with the calculation of FDs is a novel, interesting tool, for determining the pathologic diagnosis of CRCs and may further improve diagnostic and prognostic rates, thus improving patient care.

Hepatocellular carcinoma and metabolic diseases - histological perspectives from a series of 14 cases.

Hepatocellular carcinoma (HCC) represents a major health burden, as curative methods only apply to a select small portion of the affected population. Screening programs are ineffective in the absence of established underlying conditions such as viral hepatitis or alcohol abuse resulting in liver cirrhosis. Thus, overweight or obese, diabetic patients as well as non-alcoholic fatty liver disease (NAFLD) cases are often overlooked as potential candidates for HCC development. Current diagnostic methods for HCC are restricted to non-invasive imaging tests; however, the need for accurate predictive or therapeutic markers make histological studies a necessity; the latest guidelines and recommendations demand an increased effort in obtaining pertinent data from immunohistochemical investigations. Our aim was to retrospectively evaluate a series of patients with common symptoms and manifestations of metabolic syndrome who underwent liver biopsy after imaging revealed suspicious liver masses. We describe the major findings of both common histological evaluation and microvessel density evaluated by positive CD34 immunostaining.