<abstract><title style='display:none'>Abstract</title>Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality, which requires urgent interventions in order to improve outcomes.<italic>Surviving Sepsis</italic> is an international campaign that aims to improve sepsis outcomes. The 2016 guideline modifies the previous definition of sepsis and proposes some specific diagnostic and therapeutic measures, such as the protocolized use of fluid resuscitation and antibiotics.We aim to summarize the main recommendations of the 2016 guideline that are relevant to the internist and evidence-base update them to the year 2020. In the current context, this review doesn’t address patients affected by SARS-COV2 induced disease.</abstract>

Sepsis, a 2020 review for the internist

<abstract><title style='display:none'>Abstract</title><bold><italic>Background</italic></bold>. In the last years an uprising interest for a relatively unknown entity, eosinophilic ascites (EA), has been recorded.Our aim is to investigate the potential causes of EA development, as well as clinical, laboratory, endoscopic and radiologic features, management and outcome in these patients.<bold><italic>Methods</italic></bold>. The following research was performed on PubMed (MEDLINE) database using the medical subject headings [Mesh] terms “Ascites” AND “Eosinophils”.<bold><italic>Results</italic></bold>. A total of 284 results, dating from 1962 onwards, were found and abstracts were examined. 131 papers were excluded and the remaining 153 publications, consisting in case reports and series of cases, were analyzed.From 171 patients with EA, 127 subjects (74%) had EGE, 17 (10%) parasitic and fungal infections, 11(7%) Hypereosinophilic syndrome and 16 patients (9%) less common diseases (eosinophilic pancreatitis, chronic eosinophilic leukemia, myelofibrosis, T-cell lymphoma, Churg Strauss Syndrome, Systemic lupus erythematosus, Familial paroxysmal polyserositis and Ménétrier’s disease). High eosinophil blood count and IgE levels as well as gastrointestinal symptoms are frequent. The diagnosis is based on ascitic fluid analysis, imaging and endoscopic biopsies. Therapy with corticosteroids results in resolution of eosinophilic ascites in almost all patients.<bold><italic>Conclusion</italic></bold>. In most cases, in the absence of allergy, parasitic infections, malignancy, hematological disorders, peritoneal tuberculosis, inflammatory bowel disease or autoimmune disease, EA develops as a manifestation of eosinophilic gastroenteritis.</abstract>

Causes of eosinophilic ascites – A systematic review

<abstract><title style='display:none'>Abstract</title><bold>Introduction</bold>. In forensic pathology the autolytic process has been observed and documented in order to determine the postmortem interval as accurately as possible. The observation and experiments have been carried out on cadavers exposed to environmental conditions – heat, humidity, air currents, soil, water.<bold>Methods</bold>. For this study hematoxylin and eosin (HE) stained sections of organ samples from 30 autopsied bodies were examined under the microscope. Modifications of tissue and cell structures were noted in correlation with the bodies’ time spent in the Morgue’s mortuary refrigerator until the autopsy was performed, which varied between 24 hours and 22 days.<bold>Results</bold>. All the organs sampled (lung, heart, liver and pancreas) showed severe autolytic alterations after 5 to 8 days. The most heavily affected was the pancreas, cells within Langherhans islets becoming complete autolyzed at the 36 hours mark. Inside organs, autolytic processes occur at different rates depending on the locations within that organ –deeply or superficial; in the heart after 4 or more days subendocardic myocardium shows less severe autolytic changes than the subepicardial one.<bold>Conclusion</bold>. Autolytic processes have a delayed onset and a much lower progression rate in a cold controlled environment. Different organs suffer different rates of autolysis in correlation to their structure and enzymatic content.</abstract>

County Forensic Pathology Department Giurgiu, 5-7Alexandriei 5-7 Bvd, Giurgiu, Romania

Pathology Department of “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd, Bucharest, Romania

UMF “Carol Davila”, School of Medicine, Eroii Sanitari Bvd, Bucharest, Romania

Correlations Between the Autolytic Changes and Postmortem Interval in Refrigerated Cadavers

<abstract><title style='display:none'>Abstract</title>Patients with chronic liver disease have associated comorbidities that require treatment, including cardiovascular disease, arrhythmias, cerebrovascular accidents and pain. These medications may affect the liver disease. Due to the complexity of medical problems in patients with chronic liver disease, treating clinicians benefit from targeted guidance for their care.</abstract>

Use of statins, amiodarone, direct oral anticoagulants and NSAIDs in chronic liver disease: a guide for general clinicians

<abstract><title style='display:none'>Abstract</title><bold>Background and Aims</bold>. Sulodexide has been reported to have antiproteinuric and nephroprotective properties. We investigated the effects of long-term low-dose Sulodexide on proteinuria and renal function in patients with chronic kidney disease (CKD) caused by diabetic nephropathy (DN), hypertensive nephropathy (HN) and primary glomerulonephritis (GN).<bold>Material and Methods</bold>. 100 patients with CKD received low-dose Sulodexide 50 mg/day for 12 months. Treatment efficacy was evaluated as proteinuria reduction compared to baseline; response was defined as a decline in proteinuria below 0.3 g/d. Renal function evolution was assessed by eGFR variation from baseline.<bold>Results</bold>. All patients presented reduction of proteinuria, with global mean value of proteinuria decrease of 0.85 ± 1.34 g/d (p&lt;0.0001). Patients with HN had the highest mean percentage of proteinuria reduction (73±29%) and the lowest mean time period to achieve responder status (6.6±2.4 months), compared to patients with DN (57±29%, 8±2.9 months) and GN (63±24%, 10.7±1.2 months). Renal function as mean eGFR remained stable or improved during the study; significant increase was found only in HN group (3.41 ± 6.38 ml/min/1.73m2, p=0.043). Multivariate regression analysis identified that responder status was significantly associated with gender, baseline eGFR, baseline proteinuria and etiology of CKD. Concomitant administration of ACEIs or/and ARBs did not influence the response to Sulodexide therapy.<bold>Conclusions</bold>. Independently of ACEIs or/and ARBs therapy, long-term low-dose Sulodexide is efficient as antiproteinuric and renoprotective therapy in patients with CKD caused by DN, GN and HN. Better response is achieved in patients with lower degree of renal dysfunction.</abstract>

Center of Internal Medicine and Nephrology, Fundeni Clinical Institute, Bucharest

“Carol Davila” University of Medicine and Pharmacy, Bucharest

Efficacy of long-term low-dose sulodexide in diabetic and non-diabetic nephropathies

<abstract>
<title style='display:none'>Abstract</title>
Nailfold capillaroscopy (NFC) is now one of the main imaging tools in systemic sclerosis and imposed over time as an easy, non-invasive method for the nailfold microvascular bed assessment.
In qualitative NFC normal pattern is characterized by homogeneous, parallel fashion arrangement of the last capillaries row as well as by capillaries with hairpin or non-specific variations like tortuous and/ or crossing shape.
Nailfold capillaroscopy is strongly recommended for evaluation of all patients with Raynaud phenomenon. Appearance of giant capillaries is chronologically the first relevant finding for scleroderma spectrum disorders development (systemic sclerosis, dermatomyositis, undifferentiated and mixed connective tissue disease). Collapses of the giant loops generate microhemorrhages and further capillary loss with subsequent hypoxia, and neoangiogenesis seen as ramified/ bushy capillaries. Nailfold capillaroscopy is indicated especially in systemic sclerosis, being also included in the classification criteria.
Based on these major NFC pathologic findings (giant capillaries, microhemorrhages, avascularity and neoangiogenesis), three evolutive stages were described in systemic sclerosis, namely the early, active, and late scleroderma pattern.
In other connective tissue diseases than those scleroderma-related, like systemic lupus erythematosus, psoriatic arthritis, or antiphospholipid syndrome, the interest for capillaroscopy is growing, but the attempts of defining specific characteristics failed until now.
Besides qualitative NFC, semiquantitative and quantitative capillaroscopic assessments were proposed for more accurate evaluation. Lately, automated systems are under development. There is still need of more studies to sustain the nailfold capillaroscopy validity as diagnostic and prognostic test.
</abstract>

Nailfold capillaroscopy in systemic diseases: short overview for internal medicine

<abstract>
<title style='display:none'>Abstract</title>
Background: Respiratory allergies mostly allergic rhinitis and asthma represent an important and increasing public health problem and one of the priorities for the European health systems. There is an increasing public concern regarding the persistence and severity of allergic diseases and many difficulties of health systems in providing prompt specialized medical assistance. Our study aims to highlight the main results of the Alliance 4Life project focused on the evaluation of the burden and management of respiratory allergies in primary care from Romania and comparative health-related data from four Central and Eastern European countries.
Method: We developed a questionnaire focused on patients with allergic rhinitis and asthma directly addressed to general practitioner (GP) specialists from Romania who attended the annual national conference in Bucharest.
Results: The main results showed that patients with respiratory allergies are frequently encountered in primary care practice, only a few patients are evaluated by allergists and there is a clear need for education in this field.
Conclusions: This preliminary study confirms that respiratory allergies represent a considerable burden in primary care and the questionnaire may be a useful tool in further studies considering the experience of other healthcare systems. More advanced studies integrating epidemiology with data on air pollution and environmental conditions should be envisaged.
</abstract>

Evaluation of respiratory allergies burden and management in primary care and comparative analysis of health care data from Romania, Poland, Czech Republic and Bulgaria – preliminary study

<abstract>
<title style='display:none'>Abstract</title>
Background: Metabolic-associated fatty liver disease and liver fibrosis are intimately linked to insulin resistance, type 2 diabetes, obesity, and metabolic syndrome. Transient elastography (TE) and point shear wave elastography (pSWE) were used to measure liver stiffness in patients who met the ultrasound criteria for steatotic liver diseases (SLD). This study compared two methods for estimating liver stiffness in patients with SLD, which in turn correlated with liver fibrosis. Method: Ultrasound B-mode imaging was used to identify SLD. In total, 250 MAFLD patients were recruited. Patient characteristics, laboratory investigations, and liver stiffness measurements using TE and pSWE were assessed on the same day.
Results: In the study, 56.0% of the patients were male, with a mean age of 41.5 ± 10.7 years. The correlation between TE and pSWE was significant (Spearman’s r = 0.867*, p &lt; .001). The Bland-Altman Plot analysis confirmed this, with 97.5% of variations in LSM falling within 95% agreement ranges. Cohen’s κ was used to assess the agreement between TE and pSWE fibrosis stages, showing almost perfect agreement (83.5% kappa agreement) and a strong association between pSWE and TE in the assessment fibrosis stages.
Conclusion: In patients with MAFLD, TE, and SWE are reliable methods for measuring liver stiffness and can be used as non-invasive screening tools for the assessment of fibrosis in SLD.
</abstract>

Comparison of transient elastography and shear wave elastography in patients with MAFLD: A single-center experience

<abstract>
<title style='display:none'>Abstract</title>
<sec>
<title style='display:none'>Introduction:</title> The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represented a disruptive pathology that emerged in late 2019 with profound implications ranging from individual health to health systems and world economy. Our study aimed to evaluate clinical, biochemical and computerized tomography (CT) parameters values in determining the severity of pulmonary embolism (PE) associated with COVID-19.
</sec>
<sec>
<title style='display:none'>Methods</title>We performed an observational cohort study evaluating demographic, clinical, biochemical, coagulation markers, as well as CT imaging parameters.
</sec>
<sec><title style='display:none'>Results</title>
In our study on 186 patients with COVID-19, we found that 31 patients (16,66%) had pulmonary embolism. Significant correlations for the patients with PE were detected in C-reactive protein, lactate dehydrogenase, serum ferritin, IL-6, serum myoglobin, NT-proBNP, D-dimers, serum proteins, transaminases as well as white cell blood counts. Patients with pulmonary embolism had a more severe lung involvement, with thrombi distribution mainly involving the lower lobes.
</sec>
<sec><title style='display:none'>Conclusion</title>
Early identification of PE is an important step for timely and efficient treatment in the intensive care management of COVID-19 patients. Our study showed that high plasmatic values of lactate dehydrogenase, ferritin, IL-6, white blood cells and D-dimers and low proteins serum levels are strongly linked with COVID-19-associated pulmonary embolism.
</sec>
</abstract>

COVID-19 associated pulmonary embolism: clinical, biochemical and CT imaging findings

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>
Acute pulmonary embolism (APE) is a life-threatening condition with a high mortality rate. The pathophysiology involves various complex processes. The systemic immune-inflammatory index (SII) is a well-known biomarker that reflects the intricate balance between pro-inflammatory and anti-inflammatory immune components. In this systematic review, we aim to determine the significance of SII as a potential biomarker for APE.
</sec>
<sec><title style='display:none'>Method</title>
We utilized PubMed, ProQuest, EBSCOHost, and Google Scholar to search for articles. We assessed bias risk using the Newcastle Ottawa Scale (NOS). The outcomes we examined included in-hospital and long-term mortality, the severity of APE, and the sensitivity and specificity of the SII in predicting APE.
</sec>
<sec>
<title style='display:none'>Results:</title> Four studies, involving 2,038 patients, were included for analysis. These studies discuss the use of SII in predicting APE severity, APE mortality, high-risk APE, and the occurrence of APE. SII demonstrates significant results in predicting each of these variables. Furthermore, each study establishes different SII cut-off values. Specifically, a cut-off of 1161 predicts massive APE events with a sensitivity of 91% and a specificity of 90%. A cut-off of &gt;1235.35 differentiates high-risk APE with a sensitivity of 87.32% and a specificity of 68.85%. A cut-off of &gt;1111x109 predicts overall mortality with a sensitivity of 72% and a specificity of 51%. Finally, a cut-off at 1839.91 predicts APE events with a sensitivity of 75.8% and a specificity of 61.9%.
</sec>
<sec><title style='display:none'>Conclusion</title>
The SII can be employed as a potential new biomarker to predict outcomes in APE patients, particularly the occurrence, severity, and mortality of APE.
</sec>
</abstract>

Systemic Immune-Inflammation Index as a Potential Biomarker for Predicting Acute Pulmonary Embolism: A Systematic Review

<abstract>
<title style='display:none'>Abstract</title>
Research advances in the oncology treatment field have led to the widespread use of immunotherapy. The usage of immune checkpoint inhibitor (ICI) has improved the survival of cancer patients with metastases. This has also led to the rapidly expanding indications for ICI use. However, ICI usage may lead to toxicity, which may be immune-related, in different organ-specific targets. The immune-related adverse events (irAEs) of ICI may lead to increased morbidity, decreased quality of life, and early termination of ICI. The clinical manifestations of irAEs in the gastrointestinal system are variable, ranging from self-limited to life-threatening or fatal events. In this review article, we would like to focus on discussing ICI-induced colitis, which is one of the most common ICI irAEs in the gastrointestinal tract.
</abstract>

Immune Checkpoint Inhibitor Colitis, a Rising Issue in Targeted Cancer Therapy Era: A Literature Review

In memoriam: Professor Radu Voiosu

<abstract><title style='display:none'>Abstract</title>Angiogenesis is a crucial event for tumor growth and it is regulated predominantly by several different growth factors. Vascular endothelial growth factor protein family (VEGF) and its receptors are probably the most important tissue factors responsible for angioblast differentiation and tube formation. VEGF protein family currently comprises several members: VEGF (or VEGF-A), VEGF-B, VEGF-C and VEGF-D, VEGF-F, placental growth factor (PlGF), and their receptors VEGFR-1, VEGFR-2 and VEGFR-3. VEGF is a key angiogenic growth factor and its level of expression is a critical marker for detection of the angiogenic diseases. The potent role of VEGF in tumor angiogenesis has been widely described in the past decade, being expressed in most types of nondigestive and digestive cancers. VEGF family members play an important role in the development of pancreatic cancer (especially VEGF-A, VEGF-C, VEGF-D, VEGFR-1 and VEGFR-2). VEGF-A is the most specific and prominent angiogenic factor among all family members and VEGFR-2 is the most important receptor in evaluating the angiogenesis in pancreatic cancer. Thus, VEGF overexpression may be considered as a diagnostic marker and as a poor prognostic factor of the disease.</abstract>

Gastroenterology Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Romania

Radiology Department, University Hospital, Craiova, Romania

Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Gastrointestinal Unit, Copenhagen University Hospital Herlev, Denmark

“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Surgery I Department, Floreasca Hospital, Bucharest, Romania

Neurology Department, Neuropsychiatry Hospital, Craiova, Romania

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

<abstract><title style='display:none'>Abstract</title>Hepatic fibrogenesis is the final result of injury to the liver. Fibrosis could lead to hepatic dysfunction, important in the pathogenesis of other chronic problems. Therefore, understanding the mechanism, accurate diagnosis and staging of it in early stages accelerates the treatment and reduces the prevalence of chirrosis. Treatment strategies of liver problems and detction methods depend on the amount and progression of liver fibrosis and the rate of cirrhosis development. Traditionally the invasive method, liver biopsy, is reference standard to follow progression and stage of fibrosis. However, during the past decade, progressive development of novel non-invasive methodologies has challenged the invasive method. Non-invasive methods have been initially introduced for chronic hepatitis C with increasing use in other chronic liver diseases. The need for liver biopsy has nowadays decreased significantly as a result of these methodologies. Most of the new non-invasive methods depend on either ‘biological’ or ‘physical’ approaches.In this review, starting from the mechanism of fibrogenesis, the current knowledge about diagnosis, treatment strategies and different methods for its evaluation is discussed. This is followed by a conclusion on what is expected to be known in this field during the future research.</abstract>

Liver Fibrosis: Causes and Methods of Assessment, A Review

<abstract><title style='display:none'>Abstract</title><bold>Background</bold>. Diabetes mellitus is a massive, growing, silent epidemic that has the potential to cripple health services in all parts of the world. Currently, a diagnosis of diabetes is achieved by evaluating plasma glucose levels. Saliva offers some distinctive advantages. Whole saliva can be collected non-invasively and by individuals with limited training. The present study was aimed to estimate and correlate the plasma and salivary glucose levels in diabetic and non diabetic subjects, with special reference to age.<bold>Method</bold>. The study population consisted of three groups: Group 1 consisted of diabetics with BGL&gt;200mg/dl and Group 2 consisted of diabetics with BGL 130-200mg/dl based on their random plasma glucose levels. Group 3 consisted of healthy population as controls with BGL &lt;130 mg/dl. 2 ml of peripheral blood was collected for the estimation of random plasma glucose levels and unstimulated saliva was collected for the estimation of salivary glucose<bold>Results</bold>. The salivary glucose levels were significantly higher in group 1 and group 2 diabetics when compared with controls. The salivary glucose levels show a significant correlation with plasma glucose levels between study populations, suggesting that salivary glucose levels can be used as a monitoring tool for predicting glucose level in diabetic patients.<bold>Conclusion</bold>. The present study found that estimation of salivary glucose levels can be used as a noninvasive, painless technique for the measurement of diabetic status of a patient in a dental set up.</abstract>

Oral Pathology & Microbiology, Forensic Odontology School of Dental Sciences, Krishna Institute of Medical Sciences University, Malkapur, Karad-415539, Satara (Dist.), Maharashtra, India

Public Health Dentistry School of Dental Sciences, Krishna Institute of Medical Sciences University, Malkapur, Karad-415539, Satara (Dist.), Maharashtra, India

Glucose Level Estimation in Diabetes Mellitus By Saliva: A Bloodless Revolution

<abstract><title style='display:none'>Abstract</title>Inflammatory bowel diseases are chronic afflictions, characterized by active and remission periods. Inflammation is the most common type of response that the human body uses as a defense mechanism against aggressors from the environment. The frequency and degree of inflammation depends on the size of the affected tissues. The gastrointestinal tract is, by far, the most susceptible tissue to inflammatory responses, because of its constant exposure to various antigenic, mutagenic and toxic factors.In inflammatory bowel diseases there is a loss of immune tolerance to intestinal flora that is mediated by various substances, including cytokines. Cytokines represent a key signal in the intestinal immune response. Activated dendritic cells and macrophages secrete cytokines that actively intervene in inflammation regulation, in both Crohn’s disease and ulcerative colitis. After their secretion by antigen presented cells, cytokines activate and differentiate T cells, stirring up the adaptive immune response.Cytokines have an important role in the pathogenesis of inflammatory bowel diseases. The identification of new cytokines, as well as the changing of the pathogenesis paradigms in inflammatory bowel diseases has been done on animal tests and clinical studies. Thus, there is promising evidence basis for future therapy research based on cytokines, and anti-cytokine antibodies.</abstract>

Internal Medicine II and Gastroenterology Clinic, University Hospital Bucharest

Department of Gastroenterology, Fundeni Clinical Institute, Bucharest

Cytokines in inflammatory bowel disease

<abstract><title style='display:none'>Abstract</title> Background. Systemic sclerosis (Ssc) is an autoimmune disease characterized by cutaneous and visceral fibrosis and its pathogenesis is incompletely understood. T helper cells are key regulators of the immune response and they seem to be involved in Ssc clinical manifestations. The aim of the study is to determine key cytokines secreted by Th1 (IFN-γ), Th2 (IL-6) and Th17 (IL-17) in Ssc patients and correlate them with specific manifestations of Ssc patients. Material and methods. 35 consecutive Ssc patients and 20 age and sex matched controls were recruited. Serum IL-17, IFN-γ and IL-6 were determined using ELISA method. Results. Serum IL-17 and IL-6 levels were not significantly different in Ssc patients and controls. Serum IFN-γ levels were higher in Ssc patients when compared to controls. Higher serum IFN-γ levels associated with pulmonary hypertension. After adjusting for gender and age, IL-17 levels remained independently associated with some clinical manifestations of Ssc patients (telangiectasia and high activity score of Ssc). Conclusion. Th17 and Th1 cell responses are active in Ssc patients as their cytokines associated with higher disease activity scores and pulmonary manifestations. Th17 and Th1 specific activity and homing within Ssc patients still needs to be defined and determined in order to target them as potential future therapeutic targets in Ssc patients.</abstract>

Clinical Immunology Department, “Colentina” Clinical Hospital, Bucharest , Romania

Clinical Research Unit RECIF (Réseau d’ Epidémiologie Clinique International Francophone), Bucharest, Romania

“Alfred Rusescu” Institute for Mother and Child Protection, Bucharest, Romania

Department of Internal Medicine, “Colentina” Clinical Hospital, Bucharest, Romania

IL-17, IL-6 and IFN-γ in systemic sclerosis patients

<abstract><title style='display:none'>Abstract</title><bold>Diabetic Nephropathy</bold>. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to be directly responsible for 1.5 million deaths just two years prior (in 2012). From the entire number of patients suffering from diabetes, approximately a quarter of them develop renal affection. Diabetic nephropathy has similar physiopathology mechanisms and ultrastructural changes in cell injury characteristics in both Type 1 and Type 2 diabetes.<bold>Cell Death</bold>. Cell Death was less studied in the renal diabetic disease, although it could represent an important pathogenic mechanism in the appearance and progression of nephropathy. At renal level the cellular loss can be explained by several mechanisms; different stimuli with cellular lesion potential can trigger apoptosis signaling with appearance of regulatory proteins having a double role (they participate in the initiation of the apoptosis path and cell death or in the ending of this process). The types of Cell Death and their relative proportion between themselves in the renal tissue have not been completely elucidated.<bold>Caspases</bold>. Discovered in the middle of the 1990’s, Caspases are a part of the cysteine proteases family and play a role in numerous aspects of physiology (having a role in development, aging and apoptosis), but also in aspects of physiopathology of several degenerative affections, autoimmune diseases, oncologic diseases – having an important part in apoptosis, necrosis and also inflammation.</abstract>

University of Medicine and Pharmacy, Department of Pathophysiology, Bucharest, Romania

“Carol Davila” University of Medicine and Pharmacy, Department of Pathology, Bucharest, Romania

“Colentina” University Hospital, Department of Pathology

Caspases, Cell Death and Diabetic Nephropathy

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