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High Prolidase Levels in Patients with Familial Mediterranean Fever (FMF)


İntroduction: Familial Mediterranean Fever (FMF) is an autoinflammatory disease. Prolidase is a specific imidodipeptidase that plays a role in collagen degradation. Prolidase plays an important role in inflammation and wound healing. Hypoxia-inducible factor-1α (HIF-1) is an important protein in the regulation of immunological response, hemostasis, vascularization. The aim of the study was to compare serum prolidase and HIF-1α levels in patients with FMF in attack-free period and healthy control group.

Methods: Between August 2017 and December 2017, sixty patients who diagnosed FMF according to the criteria of the Tel-hashomer who admitting to Sivas Cumhuriyet University Medical Faculty Internal Medicine Rheumatology Department and sixty healthy volunteers were enrolled in the study.

Results: Median serum prolidase level were 72.1 (25.1-114.9) ng/ml in FMF group and 30.7 (21.3-86.2) ng/mL in healthy control (HC) group (p=0.018). ROC analysis showed that the sensitivity was 65% and the specificity was 68.3% at serum prolidase levels 54.03 ng/mL (p<0.05). The median serum levels of HIF-1α in the FMF group was 482.0(292.0-3967.0) pg/mL and 632.0(362.0-927.0) pg/mL in the HC group (p>0.05). There was no significant correlation between laboratory findings, sex, age, and prolidase (p>0.05).

\Conclusion: Serum prolidase enzyme levels in FMF patients with attack-free period were significantly higher than in the HC group. However, the role of prolidase and HIF1-α in the FMF disease needs to be clarified with more extensive and comprehensive studies.

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Abdominal Contrast Enhanced Ultrasound, A Practical Review


Abdominal contrast enhanced ultrasound (CEUS) is a relatively new investigation method that combines conventional ultrasound with a small amount of intravenous contrast through a peripheral vein (usually the cubital vein). The contrast is made by very small gas microbubbles floating in a phospholipid suspension. The size of microbubbles are between 1-10 micrometers, being to large to go out of the vessels, but sufficiently small to stay into the capillaries, and this is the reason for they can be used as vascular tracers. So, it is possible to obtain images with microvessels inside of different organs in different vascular phases (arterial, portal, venous), images that are similar with the one obtained in CECT and CEMRI.

The intravenous contrast used in CEUS eliminates trough the lungs, during expiration. These is the reason why the most important contraindication for using iv contrast is severe respiratory failure. Also, it is important that intravenous contrast is not allergenic, the percentage of allergic reaction being extremly small (0,001%).

The most important advantages of CEUS are:

• It can be safely used for the pacients that are allergic to intravenous contrast used in CECT and CEMRI;

• It can be used in pacients with chronic kidney disease;

Abdominal contrast enhanced ultrasound is used in day-to-day practice mainly for evaluation of hepatic lesions, but also for pancreatic, kidney, testis pathology, as well as for inflammatory bowel diseases.

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Advanced Heart Failure


Advanced heart failure (AHF) is the stage of heart failure (HF) refractory to maximal medical treatment, cardiac devices (CRT - cardiac resynchronization, ICD - implantable defibrillator) and surgical treatment. AHF has become of interest through the experience and favorable results of treatment by mechanical circulatory support (MCS) and cardiac transplant (CT). The article reviews the criteria for defining the AHF (2018 ESC statement), natural history and prognosis outside the advanced treatment forms. Evaluation of risk and prognostic factors is required before the decision of advanced therapy: clinical factors (HF severity and reduction of cardiorespiratory functional capacity), RV function, biological markers and elements of organ dysfunction, as well as reduction of tolerance to conventional medication.

Finally, the principles of treatment and the results of mechanical circulatory support and cardiac transplant are presented.

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Analysis of the Differences Given by the Presence / Absence of Peripheral Manifestations of Ankylosing Spondylitis


Objectives. Our study aimed to compare to what extent the characteristics of patients with ankylosing spondylitis (AS) differ, depending on the presence / absence of peripheral manifestations of the disease.

Materials and method. We analyzed a batch of 124 patients admitted to the rheumatology clinics of two hospitals, with ankylosing spondylitis according to the modified New York criteria. All individual patient characteristics were documented from patient observation sheets. We divided the population into two groups: the P + group representing the patients with peripheral manifestations of arthritis or enthesitis (N = 56) and the P- group representing the patients without the peripheral manifestations (N = 68). Statistical processing was performed using IBM SPSS and Microsoft Excel.

Results. In the subtype of patients P+ the mean age was 45.14 14.16 years, and in the subtype P- mean age was 43.84 years 12.58 years. Gender distribution of patients in the two subgroups shows higher frequencies for patients without peripheral manifestations P- in both genders, respectively 55.4% in males and 52.2% in females. The highest frequencies were registered at the normal BMI of 18.5-24.9 in both sublots, respectively 51.8% for the P+ patients and 45.6% for the P- patients. The degree of activity of the disease, based on the ASDAS - CRP score, within both P + and P- subgroups, revealed a majority of patients with inactive disease (≤ 1.3). Within the P+ and P- sublots, most patients had the BASDAI index in the range 0-0.9, that is 67.9% of the patients in the P+ sublot and 64.7% of those in the P- sublot, respectively. This shows that the majority of patients in both subgroups had a good therapeutic response to biological treatment, with symptoms such as pain and / or fatigue absent or very low in intensity.

There were no statistically significant differences between the two subgroups.

Conclusion. Even though there were no major paraclinical differences between the patients with pure axial ankylosing spondylitis and patients with AS with peripheral manifestations, the patients with peripheral manifestations of the disease should be approached by a multidisciplinary team.

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Comparison of three risk scores to predict outcomes in upper gastrointestinal bleeding; modifying Glasgow-Blatchford with albumin


Introduction. Management of upper gastrointestinal bleeding (UGIB) is of great importance. In this way, we aimed to evaluate the performance of three well known scoring systems of AIMS65, Glasgow-Blatchford Score (GBS) and Full Rockall Score (FRS) in predicting adverse outcomes in patients with UGIB as well as their ability in identifying low risk patients for outpatient management. We also aimed to assess whether changing albumin cutoff in AIMS65 and addition of albumin to GBS add predictive value to these scores.

Methods. This was a retrospective study on adult patients who were admitted to Razi hospital (Rasht, Iran) with diagnosis of upper gastrointestinal bleeding between March 21, 2013 and March 21, 2017. Patients who didn’t undergo endoscopy or had incomplete medical data were excluded. Initially, we calculated three score systems of AIMS65, GBS and FRS for each patient by using initial Vital signs and lab data. Secondary, we modified AIMS65 and GBS by changing albumin threshold from <3.5 to <3.0 in AIMS65 and addition of albumin to GBS, respectively. Primary outcomes were defined as in hospital mortality, 30-day rebleeding, need for blood transfusion and endoscopic therapy. Secondary outcome was defined as composition of primary outcomes excluding need for blood transfusion. We used AUROC to assess predictive accuracy of risk scores in primary and secondary outcomes. For albumin-GBS model, the AUROC was only calculated for predicting mortality and secondary outcome. The negative predictive value for AIMS65, GBS and modified AIMS65 was then calculated.

Result. Of 563 patients, 3% died in hospital, 69.4% needed blood transfusion, 13.1% needed endoscopic therapy and 3% had 30-day rebleeding. The leading cause of UGIB was erosive disease. In predicting composite of adverse outcomes all scores had statistically significant accuracy with highest AUROC for albumin-GBS. However, in predicting in hospital mortality, only albumin-GBS, modified AIMS65 and AIMS65 had acceptable accuracy. Interestingly, albumin, alone, had higher predictive accuracy than other original risk scores. None of the four scores could predict 30-day rebleeding accurately; on the contrary, their accuracy in predicting need for blood transfusion was high enough. The negative predictive value for GBS was 96.6% in score of ≤2 and 85.7% and 90.2% in score of zero in AIMS65 and modified AIMS65, respectively.

Conclusion. Neither of risk scores was highly accurate as a prognostic factor in our population; however, modified AIMS65 and albumin-GBS may be optimal choice in evaluating risk of mortality and general assessment. In identifying patient for safe discharge, GBS ≤ 2 seemed to be advisable choice.

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Eosinophilic pancreatitis versus pancreatitis associated with eosinophilic gastroenteritis – a systematic review regarding clinical features and diagnosis


Background. Over the past years, eosinophil infiltration involving the gastrointestinal tract and pancreas leading to eosinophilic pancreatitis, eosinophilic gastroenteritis and hypereosinophilic syndrome has been reported in the literature.

We aimed to analyze and compare the features involving patients with eosinophilic pancreatitis and pancreatitis associated with eosinophilic gastroenteritis and to determine if there is a connection between the two disorders or if they in fact meet the diagnostic criteria for hypereosinophilic syndrome.

Material and methods. The following search was performed in March 2019 on PubMed (MEDLINE) database using the medical terms “pancreatitis”, “eosinophilic pancreatitis”, “eosinophilic gastroenteritis” and “hypereosinophilic syndrome”.

Results. The search revealed 119 publications from 1970 onwards. A total of 83 papers were excluded, and the remaining 36 publications, consisting in case reports and case series, were analyzed. From 45 patients, 20 subjects with eosinophilic gastroenteritis developed pancreatitis, 20/45 had eosinophilic pancreatitis, and 5/45 hypereosinophilic syndrome involving the pancreas. There was no significant difference regarding clinical, laboratory and imaging features between the three groups, despite the multiple theories that explain the association of pancreatic and gastrointestinal eosinophilic infiltration. Although there was a strong resemblance between the three groups, histological evidence of eosinophilic gastrointestinal infiltration guided the treatment towards a less invasive way, while subjects with eosinophilic pancreatitis underwent pancreatic surgery to exclude potentially malignant lesions.

Conclusion. Although there are various theories that explain pancreatitis development in patients with eosinophilic gastroenteritis, hypereosinophilia diagnostic work-up should be taken into account in all patients with high number of blood eosinophils, even in those with eosinophilic pancreatitis in order to establish the diagnosis using a minimally invasive approach and to apply an adequate treatment.

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Idiopathic thrombocytopenic purpura (ITP) – new era for an old disease


Immune thrombocytopenia is an autoimmune hematological disorder characterized by severely decreased platelet count of peripheral cause: platelet destruction via antiplatelet antibodies which may also affect marrow megakaryocytes. Patients may present in critical situations, with cutaneous and/or mucous bleeding and possibly life-threatening organ hemorrhages (cerebral, digestive, etc.) Therefore, rapid diagnosis and therapeutic intervention are mandatory.

Corticotherapy represents the first treatment option, but as in any autoimmune disorder, there is a high risk of relapse. Second line therapy options include: intravenous immunoglobulins, thrombopoietin receptor agonists, rituximab or immunosuppression, but their benefit is usually temporary. Moreover, the disease generally affects young people who need repeated and prolonged treatment and hospitalization and therefore, it is preferred to choose a long term effect therapy. Splenectomy – removal of the site of platelet destruction – represents an effective and stable treatment, with 70–80% response rate and low complications incidence.

A challenging situation is the association of ITP with pregnancy, which further increases the risk due to the immunodeficiency of pregnancy, major dangers of bleeding, vital risks for mother and fetus, potential risks of medication, necessity of prompt intervention in the setting of specific obstetrical situations – delivery, pregnancy loss, obstetrical complications, etc.

We present an updated review of the current clinical and laboratory data, as well as a detailed analysis of the available therapeutic options with their benefits and risks, and also particular associations (pregnancy, relapsed and refractory disease, emergency treatment).

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In-hospital screening for diabetes mellitus with HbA1c in an internal medicine department was not useful; a prospective pilot study


Background. Screening inpatients for diabetes mellitus may be a good opportunity to detect undiagnosed cases and several studies have demonstrated the feasibility and usefulness of this practice. HbA1c has been suggested as the method of choice due to the effects of acute illness on glucose. The aim of this study was to evaluate a screening protocol based on HbA1c to identify inpatients with undiagnosed diabetes mellitus in an internal medicine department.

Methods. We conducted a prospective study of all admissions in the internal medicine department of a 412-bed community hospital in Greece during a 6-month period. Candidates for screening based on the American Diabetes Association’s recommendations were screened with HbA1c. Patients with very poor health status and patients with conditions that may interfere with HbA1c measurement or interpretation were excluded.

Results. Of 463 patients (median age 74) only a small proportion (14.9%) were candidates for screening with HbA1c. Known diabetes mellitus, a low admission glucose, severe anemia or blood loss and poor health status were the most common reasons of exclusion. Among the 55 screened patients, 7 had diabetes (based on HbA1c ≥ 6.5%). However, in only 1 of them HbA1c was above target considering the patients’ health status. Categorical agreement (no diabetes, prediabetes, diabetes) between morning glucose and HbA1c was low. However, the concordance between a morning glucose < 125 mg/dl and HbA1c < 6.5% was > 90%.

Conclusions. In settings similar to ours (very elderly patients, high rate of conditions that confound the use of HbA1c and high rate of patients with poor health status), untargeted screening of inpatients with HbA1c is unlikely to be cost-effective. A morning glucose during hospitalization may be a better first step for screening.

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The neutrophil to lymphocyte ratio in heart failure: a comprehensive review


Introduction. Heart failure (HF) and systemic inflammation are interdependent processes that continuously potentiate each other. Distinct pathophysiological pathways are activated, resulting in increased neutrophil count and reduced lymphocyte numbers, making the neutrophil to lymphocyte ratio (NLR) a potential indirect marker of severity. We conducted this comprehensive review to characterize the role of NLR in HF.

Methods. We searched the PubMed (MEDLINE) database using the key words “neutrophil”, “lymphocyte”, “heart failure”, “cardiomyopathy”, “implantable cardioverter defibrillator”, “cardiac resynchronization therapy” and “heart transplant”.

Results. We identified 241 publications. 31 were selected for this review, including 12,107 patients. NLR was correlated to HF severity expressed by clinical, biological, and imaging parameters, as well as to short and long-term prognosis. Most studies reported its survival predictive value. Elevated NLR (>2.1–7.6) was an independent predictor of in-hospital mortality [adjusted HR 1.13 (95% CI 1.01–1.27) – 2.8 (95% CI 1.43–5.53)] as well as long-term all-cause mortality [adjusted HR 1.43 (95% CI 1.1–1.85) – 2.403 (95% CI 1.076–5.704)].

Higher NLR levels also predicted poor functional capacity [NLR > 2.26/2.74, HR 3.93 (95% CI 1.02–15.12) / 3.085 (95% CI 1.52–6.26)], hospital readmissions [NLR > 2.9/7.6, HR 1.46 (95% CI 1.10–1.93) / 3.46 (95% CI 2.11–5.68)] cardiac resynchronization therapy efficacy [NLR > 3.45/unit increase, HR 12.22 (95% CI 2.16–69.05) / 1.51 (95% CI 1.01–2.24)] and appropriate implantable cardioverter defibrillator shocks (NLR > 2.93), as well as mortality after left ventricular assist device implantation [NLR > 4.4 / quartiles, HR 1.67 (95% CI 1.03–2.70) / 1.22 (95% CI 1.01–1.47)] or heart transplant (NLR > 2.41, HR 3.403 (95% CI 1.04–11.14)].

Conclusion. Increased NLR in HF patients can be a valuable auxiliary biomarker of severity, and most of all, of poor prognosis.

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Particularities of the Evolution and Therapeutic Response in Men with Systemic Lupus Erythematosus and Lupus Nephritis


Aim. The prevalence ratio of systemic lupus erythematosus in men compared to women is 1:10, with more aggressive forms in men and in children. The incidence of lupus nephritis is of 50-60% in patients with lupus.

In this paper, we aim to report on a series of cases that include male patients who had lupus nephritis via renal biopsy and were admitted between January 2011 - December 2017, with or without other SLE manifestations. The aim is to review the particularities and the therapeutic response: age at onset, disease duration, lupus nephritis class, extra-renal organ involvement of lupus disease, paraclinical findings – proteinuria, inflammatory syndrome, renal function, therapeutic response – immunosuppressive regimens used for induction and maintenance, remission onset, remission type, number of flares, side effects of immunosuppressive therapy.

Materials and method. We have reviewed the histopathology database of male patients with lupus nephritis revealed via renal biopsy, medical charts and the Hippocrates information system in order to collect patient data.

Outcomes. Out of 68 renal biopsies positive for lupus nephritis, 9 were from male patients, which reveals a 6.5:1 ratio. The average age at the time of the renal biopsy is 37. 33 years old. Lupus nephritis class - 8 out of 9 patients were class IV, 1 sample was class IV+V. The duration of the corticosteroid therapy is 6.6 years. In addition, we also reviewed the immunosuppressive agents used, the number of flares, and the side effects of the medication.

Conclusions. Our data are similar to the literature data.

Open access