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

Abstract

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

Abstract

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.

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

Abstract

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

Abstract

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

Abstract

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.

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

Abstract

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.

Open access
The role of spleen stiffness using ARFI in predicting esophageal varices in patients with Hepatitis B and C virus-related cirrhosis

Abstract

Introduction. Current guidelines recommend that all patients with cirrhosis undergo upper gastrointestinal endoscopy (UGE) screening for esophageal varices (EV). Unfortunately, UGE has a lot of disadvantages, consequently various non-invasive methods of diagnosing EV have been proposed. We evaluated if spleen stiffness (SS) measured by Acoustic Radiation Force Impulse (ARFI) is a viable technique in diagnosing EV.

Methods. We recruited 178 patients with cirrhosis caused by Hepatitis B and C who underwent biochemical tests, abdominal ultrasound, UGE, LS and SS measurements using ARFI elastography. Based on the endoscopic results the patients were divided in 3 groups: without EV, with small EV (<5 mm) and with large EV (>5 mm).

Results. ARFI SS was the only non-invasive parameter associated with the presence of EV (2.7±0.30 vs. 3.4±0.52, p<0.001) and large EV (2.91±0.36 vs. 3.86±0.37, p=0.001) after multivariate logistic regression (p<0.001). ARFI SS for predicting EV showed an AUROC of 0.872 (CI 95%: 0.799–0.944), for a cut-off value of 2.89 m/s: Sensitivity (Se) 91.4% (CI 95%: 81–97%), Specificity (Sp) 67.7% (CI 95%: 51–85%). ARFI SS for diagnosing large EV (>5mm) had better results with an AUROC 0.969 (CI 95%:0.935–0.99), and for a cut-off of 3.30 m/s: Se 96.4% (CI 95%: 82–99.9%), Sp 88.5% (CI 95%: 78–95%).

Conclusions. SS measured using ARFI is a good method of detecting EV and is an excellent method of diagnosing large EV in patients with virus-related cirrhosis.

Open access
Will imaging change the diagnosis and management of giant cell arteritis?

Abstract

Giant cell arteritis is a common systemic vasculitis affecting the elderly, with maximum prevalence in the 7th decade of age, targeting aortic derived medium and large vessels of the neck and head. Diagnosis is established on a biopsy specimen of the temporal artery wall, through pathological confirmation of panarteritis, typically characterized by mononuclear cell infiltrate, with the 1990 ACR criteria often used in clinical practice.

We present the case of a patient with a new onset headache and systemic inflammation, who did not fulfil the classical diagnostic criteria, nor did the temporal artery biopsy (TAB) provide a positive result. However, the ultrasonographical features, clinical evolution and response to corticosteroid therapy confirmed the diagnosis. This patient had bilateral presence of the halo sign on color duplex ultrasonography (CDUS), cited as a highly specific feature, when compared to the ACR criteria as a standard reference. We employed its positive likelihood-ratio (LR+) of 43 as previously estimated, while considering a low pre-test probability for a positive diagnosis (15%), to calculate a post-test probability of 88%, leading to our decision to treat him as having giant cell arteritis. Remission of the headache and rebound phenomena when tapered off steroid therapy substantially contributed to the positive diagnosis, underlining the importance of future studies needing to use clinical evolution as a reference standard.

Open access
Autoimmune polyglandular syndrome type 3 variant in rheumatoid arthritis

Abstract

Introduction: Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant.

Case report: A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves' disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy.

Conclusion: In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.

Open access
A rare case of Diffuse Alveolar Hemorrhage (DAH) due to Warfarin Toxicity

Abstract

Introduction: Warfarin is one of the most frequently used anticoagulant agents in the clinic. The most important adverse effect of warfarin is hemorrhage of vital organs, such as lung and brain. Diffuse Alveolar Hemorrhage (DAH) is a rare clinical condition which occurs due to variety of medical disorders. Although it’s rarely reported, DAH can be a result of coagulopathy prompted by warfarin therapy. In this study we present a case of DAH, caused by warfarin toxicity which referred to the hospital with non-specific respiratory symptoms.

Case Presentation: A 41-year-old female patient referred to the hospital complaining of shortness of breath, cough and dizziness. She had been taking warfarin due to mitral valve replacement for the past 10 years. Her recent symptoms began shortly after taking amoxicillin, a few days before admission. Early clinical examination and paraclinical studies reveal DAH as the cause of respiratory symptoms. The patient was then intubated and received Fresh Frozen Plasma, Packed Cells and oral vitamin K. Laboratory findings apart from increased INR, PT, ESR and CRP were all within normal range. After the initiation of treatment patient’s INR decreased and her clinical condition improved. Follow-up CT-Scan and bronchoscopy also confirmed resolving DAH.

Conclusions: The usage of warfarin in anticoagulation should be closely monitored due to its narrow therapeutic window and other factors, including its interaction with other medications such as antibiotics. Warfarin toxicity can lead to DAH, a life-threatening condition which can be presented with non-specific symptoms and deteriorate patient’s clinical condition in a short time. Therefore, it is of utmost importance to watch closely for primary symptoms of such rare incident in patients under warfarin therapy and initiate treatment as soon as possible, to prevent mortality.

Open access