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Romanian Journal of Internal Medicine

<trans-abstract xml:lang="ro">Eozinofilele sunt leucocite care intervin în răspunsurile imune înnăscute, fiind asociate în general cu inflamaţia alergică şi infecţiile parazitare. Studii recente evidenţiază efecte pleiotrope adiţionale ale eozinofilelor în procese imunomodulatoare, de homeostazie şi reparare tisulară. Afecţiunile însoţite de hipereozinofilie sunt relativ frecvente în practica medicală şi ridică adesea probleme de diagnostic diferenţial greu de rezolvat, care necesită o abordare multidisciplinară. Hipereozinofilia poate fi secundară, reactivă în cadrul altor boli sau primară, reprezentând sindroamele hipereozinofilice. Acestea sunt diagnosticate pe baza unor criterii clinice şi paraclinice definite, conform ghidurilor internaţionale actuale. Diagnosticul etiologic este de multe ori dificil şi tardiv, iar evoluţia poate fi severă, cu afectare multiorganică şi deces. Unele cazuri pot rămâne idiopatice, în ciuda investigaţiilor exhaustive. Articolul de faţă îşi propune o evaluare a celor mai recente date din literatură privind rolul eozinofilelor în patologia umană, abordarea diagnostică şi terapeutică a sindroamelor hipereozinofilice şi unele consideraţii utile în practica medicală.</trans-abstract>

<abstract><title style='display:none'>Abstract</title>Eosinophils are innate immune leukocytes recruited in large numbers to sites of allergic inflammation and parasitic infections. Recent studies show additional pleiotropic effects of recruited eosinophils impacting immunomodulation, tissue homeostasis and repair. Pathologic conditions accompanied by blood eosinophilia are quite frequent in medical practice and may raise serious differential diagnosis problems in severe cases, that require a multidisciplinary approach. Hypereosinophilia may be reactive to other diseases or primary, representing hypereosinophilic syndromes, that are diagnosed based on clinical and laboratory criteria, according to actual international guidelines. The etiopathogenic diagnosis is difficult and delayed in many cases and clinical evolution may be severe, with multiorgan involvement and poor prognosis. Some cases remain idiopathic, despite exhaustive investigation. This paper aims to review the most recent data in the literature referring to the role of eosinophils in human pathology, diagnostic criteria and treatment strategies of hypereosinophilic syndromes, actual classification and to draw some useful recommendations in clinical practice.</abstract>

Abstract

“Colentina” Clinical Hospital, Bucharest, Romania

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

Keywords

<article-title>Eosinophilia and Hypereosinophilic Disorders – Update on Etiopathogeny, Classification and Clinical Approach</article-title>

Eosinophilia and Hypereosinophilic Disorders – Update on Etiopathogeny, Classification and Clinical Approach

<trans-abstract xml:lang="ro"><bold>Nefropatia diabetică</bold>. În anul 2014 (conform datelor publicate de Organizaţia Mondială a Sănătăţii), 9% din populaţia adultă a globului a fost afectată de diabet, care a fost considerat direct responsabil de 1,5 milioane de decese cu doar doi ani în urmă (în anul 2012). Din totalitatea pacienţilor cu diabet, aproximativ un sfert dezvoltă în timp afectare renală. Nefropatia diabetică are caracteristici similare din punct de vedere al mecanismelor fiziopatologice şi leziunilor ultrastructurale, atât în tipul 1 cât şi în tipul 2 de diabet zaharat. În cazurile de diabet tip 2 există însă posibilitatea ca rinichiul să fie afectat suplimentar de unii factori nocivi de tipul obezităţii, hipertensiunii arteriale, dislipidemiei şi bolii renale ischemice macrovasculare survenite independent de prezenţa diabetului.Modificările morfologice specifice se regăsesc la nivelul tuturor structurilor renale (glomerulare, tubulare, vasculare, interstiţiale), determinând o constelaţie de aspecte imunohistochimice caracteristice diabetului, un eveniment cheie fiind reprezentat de depleţia celulară.<bold>Moartea celulară</bold>. Moartea celulară a fost puţin studiată în boala renală diabetică, deşi ar putea reprezenta un mecanism patogenic important în apariţia şi progresia nefropatiei. La nivel renal pierderea celulară poate fi explicată prin mai multe mecanisme; diferiţi stimuli cu potenţial lezional celular pot declanşa semnalizarea apoptotică cu apariţia de proteine reglatoare cu dublu rol (participă la iniţierea căilor apoptozei şi la moartea celulară sau la oprirea acestui proces). Tipurile de moarte celulară precum şi proporţia relativă dintre acestea în ţesutul renal (apoptoză, necroză, autofagie, catastrofă mitotică), nu au fost pe deplin elucidate. Fenomenele care conduc la moartea celulară depind de tipul şi intensitatea semnalelor nocive, tipul de celulă afectată, dar şi de bagajul energetic al acesteia.<bold>Caspazele</bold>. Descoperite la mijlocul anilor 1990, caspazele fac parte din familia cistein-proteazelor şi sunt implicate în numeroase aspecte ale fiziologiei (având rol în dezvoltare, îmbătrânire şi apoptoză), dar şi ale fiziopatologiei unor afecţiuni degenerative, boli autoimune, afecţiuni oncologice - având un rol esenţial atât în apoptoză şi necroză, cât şi în inflamaţie. Termenul de caspază provine de la C-simbol al cisteinei care este localizată în centrul activ al enzimei, ASP – acidul aspartic (substratul este clivat specific imediat după acidul aspartic), AZĂ – protează.</trans-abstract>

<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

<article-title>Caspases, Cell Death and Diabetic Nephropathy</article-title>

Caspases, Cell Death and Diabetic Nephropathy

{"article-title":"Caspases, Cell Death and Diabetic Nephropathy"}

<trans-abstract xml:lang="ro">Fibrogeneza hepatică este rezultatul final al leziunii hepatice. Fibroza duce la disfuncţie hepatică ce determină alte comorbidităţi. Înţelegerea aşadar a mecanismelor fibrogenetice, realizarea unui diagnostic corect încă din stadiile timpurii duce la scăderea prevalenţei cirozei hepatice. Strategiile terapeutice şi metodele de detecţie depind de progresia fibrozei hepatice şi de rata dezvoltării cirozei. Tradiţional, standardul de aur pentru evaluarea cirozei hepatice este puncţia, biopsia hepatică, o manvera invazivă. În ultimul timp însă au fost dezvoltate mai multe metode non-invazive pentru a putea evalua mai uşor fibroza hepatică. Iniţial aceste metode au fost dezvoltate pentru pacienţii cu hepatită cronică cu virus hepatitic C. Astfel că necesitatea biopsiei a scăzut foarte mult în ultima vreme.În acest articol tip review sunt trecute în revistă principalele mecanisme fibrogenetice, diagnosticul fibrozei hepatice, strategiile pentru evaluarea şi tratamentul fibrozei hepatice.</trans-abstract>

<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>

Shahid Beheshti University Hospital, Guilan University of Medical Sciences, Gilan, Iran

<article-title>Liver Fibrosis: Causes and Methods of Assessment, A Review</article-title>

Liver Fibrosis: Causes and Methods of Assessment, A Review

{"article-title":"Liver Fibrosis: Causes and Methods of Assessment, A Review"}

<trans-abstract xml:lang="ro"><bold>Introducere</bold>. Boala cronică pulmonară obstructivă (BPOC) asociază o incidenţă crescută a tahiaritmiilor supraventriculare. Potenţialele atriale tardive (ALP) detectate prin metoda „P-wave signal-averaged electrocardiography” (SAECG) ar putea fi utilă pentru identificarea pacienţilor aflaţi la risc pentru tahiaritmii supraventriculare. Obiectivul studiului a fost de a determina rolul metodei P-wave SAECG pentru evaluarea riscului aritmic la pacienţii cu exacerbare a BPOC.<bold>Metode</bold>. Au fost incluşi prospectiv 45 de pacienţi cu exacerbare a BPOC şi 58 de pacienţi fără antecedente de boală pulmonară. Au fost analizate funcţia pulmonară, valorile gazelor sanguine, ecocardiografie, monitorizare Holter pe parcursul a 24 de ore şi P-wave SAECG. Au fost măsurate duratele undei P filtrate (FPD), voltajul root mean în ultimele 40, 30 şi 20 de ms ale undei P filtrate (RMS 40, RMS 30 şi RMS 20), voltajul potenţialelor root mean square ale undei P 9RMS-p) şi integrala potenţialelor din timpul undei P filtrate (Integral-p). ALP au fost definite ca FPD &gt; 132 ms şi RMS 20 &lt; 2.3 µV.<bold>Rezultate</bold>. Bătăile premature isolate atriale (APB) şi tahiaritmiile supraventriculare (SVT) au fost mai frecvente în grupul cu BPOC. Nu a fost observată nicio diferenţă privind parametrii P wave SAECG între cele două grupuri. În grupul cu BPOC niciuna dintre tahiaritmiile supraventriculare nu s-a corelat cu ALP sau cu parametrii P-wave SAECG.<bold>Concluzii</bold>. Pacienţii cu exacerbare a BPOC dar fără boală cardiacă aparentă au o incidenţă mai mare a aritmiilor supraventriculare. Analiza P-wave SAECG şi identificarea ALP au o valoare redusă pentru evaluarea riscului aritmic al acestor pacienţi.</trans-abstract>

<abstract><title style='display:none'>Abstract</title><bold>Introduction</bold>. Chronic obstructive pulmonary disease (COPD) is associated with higher incidence of supraventricular arrhythmias. Atrial late potentials (ALP) detected by P-wave signal-averaged electrocardiography (SAECG) could be useful in detecting the patients at risk for supraventricular arrhythmias. Our objective was to assess the role of P-wave SAECG and ALP detection for arrhythmic risk evaluation of the patients with exacerbated COPD.<bold>Methods</bold>. We prospectively included 45 patients with exacerbation of COPD and 58 age-matched patients with no history of pulmonary disease in a control group. We performed pulmonary function tests, arterial blood gases, echocardiography, 24-hour Holter monitoring and P-wave SAECG. We measured filtered P-wave duration (FPD), the root mean square (RMS) voltages in the last 40, 30 and 20 ms of the filtered P-wave (RMS 40, RMS 30 and RMS 20), the root mean square voltage of the filtered P-wave potentials (RMS-p), and the integral of the potentials during the filtered P-wave (Integral-p). ALP was defined as FPD &gt; 132 ms and RMS 20 &lt; 2.3 µV.<bold>Results</bold>. Isolated atrial premature beats (APB) and supraventricular tachycardias (SVT) were more frequent in the COPD group. There were no significant differences between groups regarding the P wave SAECG parameters. In the COPD group none of the supraventricular arrhythmias was correlated with ALP or any P-wave SAECG parameters.<bold>Conclusions</bold>. The patients with acute exacerbation of COPD but no apparent cardiac disease have a higher incidence of supraventricular arrhythmias. P-wave SAECG analysis and ALP detection have little value in the arrhythmic risk evaluation of these patients.</abstract>

“Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu, Bucharest, District 1, 020022 Romania

“Colentina” Clinical Hospital,19-21Ştefan cel Mare, Bucharest, District 2, 020125, Romania

<article-title>P Wave Signal-Averaged Electrocardiography in Patients with Chronic Obstructive Pulmonary Disease</article-title>

P Wave Signal-Averaged Electrocardiography in Patients with Chronic Obstructive Pulmonary Disease

<trans-abstract xml:lang="ro"><bold>Introducere</bold>. Sindromul antifosfolipidic (SAFL) este unul dintre cele mai frecvente fenomene autoimune asociate lupusului eritematos sistemic (LES), iar patogeneza celor două entităţi pare a fi intricată.<bold>Obiective</bold>. Investigarea asocierii dintre titrul anticorpilor antifosfolipidici (AAFL) şi prezenţa SAFL secundar în cadrul LES.<bold>Material şi metode</bold>. Au fost incluşi în studiu 65 pacienţi ce au îndeplinit criteriile SLICC din 2012. Diagnosticul SAFL a fost susţinut conform criteriilor Sydney din 2006. Au fost definite trei grupuri: pacienţi cu LES şi SAFL secundar, pacienţi cu LES şi AAFL pozitivi însă fără manifestări clinice specifice SAFL şi pacienţi cu LES fără AAFL pozitivi sau manifestări clinice ale SAFL. Pacienţilor le-a fost analizat un panel extins de AAFL: anticorpi tip IgM şi IgG anti-cardiolipidici (aCL), anti-β2 glicoproteină I (aβ2GPI), anti fosfatidiletanolamină (aPE), antifosfatidilserină (aPS) şi antiprotrombină (aPT).<bold>Rezultate</bold>. Numai anticorpii aβ2GPI (atât IgM cât şi IgG) au avut niveluri semnificativ mai mari la pacienţii cu SAFL secundar comparativ cu celelalte două grupuri [mediană (min; max) IgM: 7.0 (0.0-300.0) vs. 1.0 (0.0-28.0) vs. 1.0 (0.0-12.0), IgG: 3.0 (0.0-79.0) vs. 1.0 (0.0-3.0) vs. 1.0 (0.0-12.0) (p&lt;0.001, test Kruskal-Wallis)]. În cadrul analizei regresiei logistice numai anticorpii aβ2GPI (IgM şi IgG) au fost identificaţi ca factor de risc pentru diagnosticul SAFL secundar la pacienţii cu LES [OR(95%CI) 5.9 (2.2-15.7) pentru IgM, respectiv 1.3 (1.1-1.5) pentru IgG]. Titrurile anticorpilor aPS, aPT şi aPE IgG s-au corelat pozitiv cu cel al anticorpilor anti DNAdc pe când concentraţia anticorpilor aPS, aPT şi aPE IgM a fost invers corelată cu nivelurile C3 ale complementului.<bold>Concluzii</bold>. Anticorpii tip IgG aβ2GPI au crescut riscul de aproximativ 6 ori pentru dezvoltarea SAFL secundar. AAFL ce nu sunt incluşi în criteriile de diagnostic nu par să fie asociaţi cu diagnosticul SAFL secundar la pacienţii cu LES. Aceştia sunt însă corelaţi cu titrul anticorpilor anti DNAdc şi cu nivelurile serice ale componentei C3 a complementului seric.</trans-abstract>

<abstract><title style='display:none'>Abstract</title><bold>Background</bold>. The antiphospholipid syndrome (APS) is one of the most encountered autoimmunity in systemic lupus erythematosus (SLE) patients and pathogenesis of these two seems to be intricate.<bold>Aim</bold>. To investigate the association of antiphospholipid antibodies (APLAs) titer with the presence of secondary APS diagnosis in SLE patients.<bold>Methods</bold>. 65 patients fulfilling the 2012 Systemic Lupus Collaborating International Clinics (SLICC) SLE’s criteria were included. The APS diagnosis was sustained according to the 2006 Sydney APS’s criteria. Three groups of patients were defined: SLE patients with secondary APS, SLE with history of positive “criteria” APLAs but without APS clinical features, respectively SLE patients without positive APLAs or clinical APS criteria. An extended APLAs panel was searched in all cases: both IgM and IgG of anticardiolipin antibodies (aCL), anti-β2 glycoprotein I antibodies (aβ2GPI), antiphosphatidylethanolamine antibodies (aPE), antiphosphatidylserine antibodies (aPS), respectively antiprothrombin antibodies (aPT).<bold>Results</bold>. Only the aβ2GPI, both IgM and IgG serotypes, had significantly higher titers in patients with SLE and secondary APS compared to no APS (with/without positive APLAs): median (min; max) 7.0 (0.0-300.0) <italic>vs</italic>. 1.0 (0.0-28.0) <italic>vs</italic>. 1.0 (0.0-12.0), respectively 3.0 (0.0-79.0) <italic>vs</italic>. 1.0 (0.0-3.0) <italic>vs</italic>. 1.0 (0.0-12.0) (p&lt;0.001, Kruskal-Wallis test)]. Also, in regression logistic models, only the aβ2 GPI (IgG and IgM) were identified as risk factors for secondary APS diagnosis in the SLE patients: OR(95%CI) 5.9 (2.2-15.7), respectively 1.3 (1.1-1.5). In regard with the SLE markers, the IgG serotypes of the “non-criteria” APLAs analyzed (aPS, aPT, aPE) were correlated with the antiDNA titers while the IgM serotypes inversely associated with the complement C3 levels.<bold>Conclusions</bold>. IgG aβ2 GPI are accompanied by almost 6-fold increase risk of secondary APS when screening SLE patients. On the contrary, the “non-criteria” APLAs do not seem associated with the APS diagnosis in SLE patients. Some correlates of the “non-criteria” APLAs with the antiDNA and complement C3 levels were also observed.</abstract>

“Carol Davila” University of Medicine and Pharmacy, Bucharest

“Colentina” Research Center, Colentina Clinical Hospital, Bucharest

“Dr. Carol Davila” Central University Emergency Military Hospital, Bucharest

“Cantacuzino” National Institute of Research and Development in Microbiology-Immunology, Bucharest, Romania

<article-title>Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients</article-title>

Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients

<trans-abstract xml:lang="ro"><bold>Introducere</bold>. Asocierea unor medicamente care pot interacţiona cu statinele rezultând în concentraţii serice crescute ale statinelor reprezintă un factor de risc important pentru afectările musculare determinate de statine. Obiectivul studiului a fost de a determina prevalenţa acestor asocieri la pacienţii spitalizaţi, cu statine în terapia dinainte de internare sau din timpul spitalizării şi de a determina frecvenţa cu care acestea sunt asociate cu afectare musculară.<bold>Metode</bold>. Acest studiu prospectiv observaţional a inclus pacienţii cu statine în terapie din 2 secţii de medicină internă. Date referitoare la caracteristicile pacienţilor, co-morbidităţile şi terapia medicamentoasă au fost colectate din fişa pacientului şi interviul cu acesta. Terapia a fost evaluată pentru interacţiuni medicamentoase potenţiale (IMp) cu programul informatic Thomson Micromedex Drug Interactions. Fiecare pacient cu statină în terapia dinainte de internare a fost intervievat suplimentar pentru identificarea eventualelor afectări musculare.<bold>Rezultate</bold>. În terapia celor 109 pacienţi trataţi cu statine am identificat 35 de IMp la 30 (27.5%) de pacienţi, majoritatea în terapia dinainte de internare (n = 27). Severitatea IMp a fost moderată (n = 20) şi majoră (n = 15), iar 24 IMp vizau sistemul muscular. Medicamentele cele mai frecvent implicate în IMp ale statinelor au fost amiodarona şi fenofibratul. Doi dintre pacienţii cu IMp au raportat dureri musculare, ambii având factori de risc suplimentari pentru afectarea musculară determinată de statine.<bold>Concluzie</bold>. Prevalenţa IMp ale statinelor a fost mare în studiul nostru, îndeosebi în terapia dinainte de internare. Un număr mic de IMp au fost asociate cu afectare musculară.</trans-abstract>

<abstract><title style='display:none'>Abstract</title><bold>Introduction</bold>. The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects.<bold>Methods</bold>. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients’ therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms.<bold>Results</bold>. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins’ pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects.<bold>Conclusion</bold>. The prevalence of statins’ pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.</abstract>

Drug Information Research Center, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

Department of Medical Informatics and Biostatistics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

<article-title>Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients</article-title>

Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients

<trans-abstract xml:lang="ro"><bold>Introducere</bold>. Disfuncţia uşoară cognitivă (MCI) este stadiul prodromal al bolii Alzheimer (AD) aşadar identificarea factorilor de risc poate fi utilă. În literatură sunt date controversate legate de statusul antioxidant seric, micro-nutrienţi şi homocisteina (HCy) drept parametrii de analizat în AD aşadar aceşti factori au fost determinaţi în acest studiu.<bold>Materiale şi metode</bold>. Au fost recrutaţi 120 de pacienţi vârstnici cu disfuncţie cognitivă şi 120 de pacienţi vârstnici sănătoşi. Acestora le-a fost administrat Mini-mental state examination (MMSE) şi pacienţii cu disfuncţie cognitivă au fost împărţiţi în grup cu disfuncţie uşoară şi disfuncţie moderat severă. Au fost analizate nivelurile serice ale cuprului, ale manganului, zincului, Hcy precum şi statusul antioxidant seric.<bold>Rezultate</bold>. Nivelurile oxidanţilor au fost mai mari la pacienţii cu disfuncţie cognitivă, iar nivelurile antioxidanţilor au fost semnificativ mai mici în cadrul acestui grup comparat cu martorii sănătoşi (p&lt;0.001). După ajustarea pentru vârstă, gen, statusul educaţional nu s-au observat diferenţe semnificative între nivelurile serice ale Hcy între cele două grupuri. Nu au fost diferenţe semnificative nici între concentraţiile microelementelelor.<bold>Concluzii</bold>. Rezultatele confirmă asocierea dintre stresul oxidativ şi apariţia disfuncţiei cognitive. Acesta ar putea fi implicat în etiologia AD. Identificarea unor astfel de biomarkeri este importantă pentru selecţia tratamentului adecvat.</trans-abstract>

<abstract><title style='display:none'>Abstract</title><bold>Introduction</bold>. Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer’s disease (AD), so identification of the related risk factors can be helpful. There are controversial data regarding the serum oxidant/antioxidant status, trace elements and homocysteine (Hcy) as effective parameters in this disease, therefore the status of these factors was determined in this study.<bold>Methods</bold>. One hundred-twenty elderly persons with cognitive impairment and 120 elderly healthy persons who were differentiated using Mini-mental state examination (MMSE) participated in this study. The patients were divided into mild and moderate-to-severe cognitive impairment group. Serum antioxidant/oxidant, copper (Cu), manganese (Mn), zinc (Zn) and Hcy concentrations were measured using routine methods.<bold>Results</bold>. Oxidant and antioxidant levels increased and decreased based on the severity of the disease and were higher and lower in patients than in control group, respectively (p&lt;0.001). With adjusting for age, gender and education, significant difference in Hcy levels was not observed. There was no significant difference in trace elements levels among groups.<bold>Conclusions</bold>. Results confirmed the association between oxidative damage with increasing the severity of cognitive impairment. These factors may be involved in the etiology of cognitive impairment and AD. Identification of such biomarkers is important to select appropriate treatment goals before the onset of irreversible clinical signs.</abstract>

Department of Biochemistry and Biophysics, Babol University of Medical Sciences, Babol, Iran

Social Determinant of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

Department of Social Medicine, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran

<article-title>Homocysteine, trace elements and oxidant/antioxidant status in mild cognitively impaired elderly persons: a cross-sectional study</article-title>

Homocysteine, trace elements and oxidant/antioxidant status in mild cognitively impaired elderly persons: a cross-sectional study

<trans-abstract xml:lang="ro"><bold>Introducere</bold>. Hipoxia este un factor important pentru retenţia sodiului şi boala pulmonară cronică obstructivă (BPOC) deşi şi hipercapnia este asociată cu retenţia de sodiu la aceşti pacienţi. Articolul se concentrează pe rolul pe care îl joacă PaCO2 pentru apariţia edemelor la pacienţii cu BPOC.<bold>Materiale şi metode</bold>. Au fost incluşi în studiu pacienţi spitalizaţi cu BPOC. Aceştia au fost împărţiţi în două grupe – cu şi fără edeme. Criteriile de excludere au fost boli hepatice, sindrom nefrotic sau alte afectări renale, insuficienţă cardiacă stângă, sau medicaţie care ar fi putut să interfere cu funcţia endocrină. Datele au fost analizate utilizând softul SPSS. Au fost studiate gazele sanguine (PaO2, PaCO2), pH, nivelurile ionului bicarbonat alături de VEMS (volumul expirator maxim în prima secundă), CVF (capacitatea vitală forţată) şi raportul VEMS/FVC.<bold>Rezultate</bold>. Nu au fost găsite diferenţe semnificative între cele două grupuri exceptând valorile PaCO2 care au fost mai mari la grupul de pacienţi cu edeme (p = 0.05).<bold>Concluzii</bold>. Studiul sugerează că hipercapnia este şi ea un factor determinant important pentru dezvoltarea edemelor la pacienţii cu BPOC.</trans-abstract>

<abstract><title style='display:none'>Abstract</title><bold>Introduction</bold>. Studies often suggest hypoxemia is an important factor for sodium retention in chronic obstructive pulmonary disease (COPD), although hypercapnia is also associated with sodium retention in these patients. Hence, we have presented the major role of PaCO2 in edema due to COPD.<bold>Method</bold>. COPD patients who were hospitalized due to exacerbation were enrolled in the study and divided into two groups: with and without edema. Exclusion criteria included primary hepatic diseases, nephrotic syndrome and other renal diseases, left heart failure, or using drugs that would interfere with these organs or endocrine function. Data were coded and analyzed by SPSS software. Arterial blood gas variables including bicarbonate, pH, and PaO2, PaCO2 and O2 saturation, and FEV1, FVC, FEV1/FVC were measured and compared between the groups.<bold>Results</bold>. No significant difference was found between the averages of bicarbonate, pH, PaO2, O2 saturation, FEV1, FVC and FEV1/FVC in COPD in the two groups. PaCO2 levels were significantly higher in patients with edema, compared to those without edema (p = 0.05). A reverse and significant correlation between PaCo2 and FEV1 levels (p = 0.03) (r = −0.501) was observed in patients with edema.<bold>Conclusion</bold>. This study suggests that hypercapnia is a major factor in causing edema in COPD patients compared to hypoxemia.</abstract>

Lung Disease Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Research Center for Patient Safety & Health Quality, Mashhad University of Medical Sciences, Mashhad, Iran

Preventive Cardiovascular Care Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

<article-title>The Effect of Arterial PaCO2 in COPD Exacerbations with and without Peripheral Edema</article-title>

The Effect of Arterial PaCO in COPD Exacerbations with and without Peripheral Edema

<trans-abstract xml:lang="ro">Managementul terapiei antitrombotice la pacientul vârstnic cu boală aterotrombotică instabilă şi cu un risc major de sângerare este o provocare pentru clinician. Prezentăm cazul unui pacient în vârstă de 79 de ani cu artrita reumatoidă şi cu disfuncţie renală uşoară ce urma terapie cu corticoizi orali şi AINS, care se prezintă pentru claudicaţii severe. Anterior internării pacientul a suferit mai multe episoade de AIT (atacuri ischemice tranzitorii). El prezenta rectoragii recurente asociate cu un sindrom anemic uşor datorat bolii hemoroidale. Angiografia a relevat stenoză subocluzivă a arterei carotide interne stângi ce se asocia cu o stenoză semnificativă pe LAD şi cu o boală arterială periferică complexă. În a treia zi de la internare pacientul suferă o hemoragie cataclismică ce a asociat şoc hemoragic. Imediat s-a oprit tratamentul antitrombotic şi s-au administrat transfuzii, realizându-se o sigmoidectomie de urgenţă pentru diverticuloza cronică. Ulterior, s-a reintrodus terapia antiplachetară şi pacientul a fost supus cu success endarterectomiei arterei carotidiene stângi alături de stentarea LAD. A fost externat în cea de-a 24-a zi de la intrenare şi starea sa la 24 de luni este satisfăcătoare.</trans-abstract>

<abstract><title style='display:none'>Abstract</title>Management of antithrombotic therapy in elderly patients with unstable atherothrombotic disease and increased risk of bleeding is a major clinical challenge. We report the case of a 79 year-old diabetic man with rheumatoid arthritis on both oral corticosteroids and NSAID therapy with mild renal dysfunction, who presented to our hospital because of disabling claudication. Prior to admission he had several episodes of TIA. He also had recurrent small rectal bleeding and mild anemia attributed to his long-standing hemorrhoid disease. Angiography showed a sub-occlusive left internal carotid artery stenosis associated with a significant LAD stenosis and complex peripheral artery disease. Cataclysmic bleeding and hemorrhagic shock occurred in the third day post admission. Withdrawal of all antithrombotic treatment, blood transfusion and emergency sigmoidectomy were performed for bleeding colonic diverticulosis. Subsequently antiplatelet therapy was reinitiated and the patient successfully underwent left carotid artery endarterectomy and LAD stenting. He was discharged from hospital on the 21st day post admission and is doing well at 24 months follow-up.</abstract>

Department of Cardiology, Monza Hospital, Bucharest

Department of Cardiovascular Surgery, Monza Hospital, Bucharest

Department of Angiography and Endovascular Interventions, Monza Hospital, Bucharest

<article-title>Acute Atherothrombotic Disease and Severe Bleeding: A Difficult Clinical Presentation in Medical Practice</article-title>

Acute Atherothrombotic Disease and Severe Bleeding: A Difficult Clinical Presentation in Medical Practice

<trans-abstract xml:lang="ro">Un pacient de sex masculin în vârstă de 42 de ani a fost internat în cadrul spitalului nostru în vederea realizării transplantului autolog de celulă stem hematopoietică (auto-HSCT). Acesta fusese diagnosticat în 2003 cu mielom multiplu. La examenul clinic şi la analizele de laborator nu s-au observat modificări. Radiografia toracică de control a arătat o masă radioopacă, bine definită, cu unghiuri obtuze sugerând o leziune extraparenchimatoasă ce se suprapunea cu coastele II şi III. În plus existau modificări osoase caracteristice mielomului multiplu. Biopsia ghidată CT a permis obţinerea materialului bioptic folosind aspiraţie transtoracică pe ac fin. Analiza materialului bioptic a arătat prezenţa ţesutului hematopoietic extramedular contrar aşteptării de mielom multiplu.</trans-abstract>

<abstract><title style='display:none'>Abstract</title>A 42-year-old male patient was admitted to our hospital for planning autologous hematopoietic stem cell transplantation (auto-HSCT). He was diagnosed as multiple myeloma (IgG type Kappa) in 2003. His physical examination was normal with no important abnormality on laboratory evaluation. Chest radiography performed for routine evaluation prior to transplantation revealed a large, well-defined mass, that had obtuse angles with the chest wall consistent with extraparenchymal lesion superposed on second and third ribs. Also, there were multiple bony structures demonstrating changes of destructive effects of multiple myeloma. Computed tomography (CT)-guided biopsy was obtained from the mass by transthoracic fine-needle aspiration (FNAB) method. Biopsy was reported as extramedullary hematopoiesis (EMH) contrary to our expectation of multiple myeloma.</abstract>

Department of Internal Medicine, Faculty of Medicine, Selcuk University, Konya, Turkey

Department of Hematology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

Department of Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

Department of Radiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

<article-title>Pulmonary Extramedullary Hematopoiesis Mimicking Plasmacytoma in a Patient with Multiple Myeloma</article-title>

Pulmonary Extramedullary Hematopoiesis Mimicking Plasmacytoma in a Patient with Multiple Myeloma

<trans-abstract xml:lang="ro">Dermatoscopia este o tehnică extrem de utilă în diagnosticarea leziunilor pigmentate cutaneo-mucoase, permiţând identificarea leziunilor posibil maligne. Leziunile pigmentate verucoase necesită o evaluare atentă, deoarece alături de leziuni benigne precum keratozele seboreice, nevii melanocitari, includ şi melanomul verucos. În acest articol sunt prezentate aspectele clinice şi dermatoscopice care au stat la baza diagnosticării a trei leziuni pigmentate verucoase cutanate. Influenţa datelor clinice asupra interpretării parametrilor dermatoscopici este un fapt incontestabil, fapt observat şi în cele două cazuri de keratoză seboreică prezentate, ambele încadrate eronat ca leziuni melanocitare (nev verucos, respectiv melanom). În primul caz prezentat, vârsta pacientei şi aprecierea inexactă a duratei de evoluţie au condus spre diagnosticul de nev verucos, deşi parametrii dermatoscopici erau specifici keratozei seboreice. În al doilea caz de keratoză seboreică confirmată histopatologic, amplitudinea aspectelor clinice de melanom au făcut ca examinatorul să identifice parametrii dermatoscopici compatibili cu diagnosticul de melanom, ignorându-i pe cei specifici keratozei seboreice. Cazul de melanom prezentat în acest articol clinic a mimat o keratoză seboreică, iar imaginea dermatoscopică a prezentat doar trăsături subtile specifice melanomului. În toate cele trei cazuri prezentate dermatoscopia a identificat leziunile ca posibil maligne şi a impus biopsia excizională pentru precizarea diagnosticului şi alegerea conduitei terapeutice adecvate.</trans-abstract>

<abstract><title style='display:none'>Abstract</title>Dermatoscopy, as a noninvasive rapid method, which allows the viewing of melanin in the epidermis and papillary dermis, has an important role in diagnosis of the pigmented lesions localized on skin, mucous membrane, scalp and nails. The term of verrucous pigmented lesions includes a series of non-melanocytic and melanocytic, benign and malignant lesions. Among these, the most frequent is the seborrheic keratosis, a common epidermal tumor, affecting the sun exposed areas of adult. At the other end of the spectrum regarding the frequency is the seborrheic keratosis-like melanoma, whose underdiagnosis has a serious impact on the patient’s life. In this work we present the clinical and dermoscopical aspects of three cases of verrucous pigmented lesions (two seborrheic keratoses and one seborrheic keratosis-like melanoma) that determined the diagnostic algorithm as well as the therapeutic approach. The above-presented cases underline the importance of dermatoscopy to determine the malignant potential of the pigmented lesions, the final appropriate treatment being possible after the histopathologic confirmation.</abstract>

First Department of Dermatology, “Colentina” Clinical Hospital, Bucharest, Romania

Department of Pathology, “Colentina” Clinical Hospital, Bucharest, Romania

“Regina Maria” Private Healthcare Network, Bucharest, Romania

<article-title>Dermatoscopy of Verrucous Pigmented Lesions is Essential for Choosing the Appropriate Treatment</article-title>

Dermatoscopy of Verrucous Pigmented Lesions is Essential for Choosing the Appropriate Treatment

<trans-abstract xml:lang="ro">Un pacient de 78 de ani a fost internat în Clinica de Neurologie pentru tulburări de vedere care au început cu două zile în urmă. Ziua următoare pacientul a prezentat cefalee, febră şi tulburări de mers. Ca antecedente personale patologice prezenta HTA, diabet zaharat, un stroke ischemic în urmă cu 13 ani, poliartrită reumatoidă seronegativă cu evoluţie îndelungată (17 ani), guşe polinodulară, fractură ischiopubiană dreaptă şi tromboză a venei femurale drepte în urmă cu un an post accident de maşină, de când urmează tratament cu anticoagulante orale asociate cu antiagregante, hipotensoare, statină şi anti-diabetice orale. Examenul neurologic a evidenţiat redoarea cefei, hemianopsie laterală homonimă stângă, paralizie facială stângă de tip central, ataxia membrelor inferioare cu mers cu bază de susţinere lărgită, reflexul achilian abolit bilateral, indiferenţă plantară bilaterală, apraxie ideomotorie, dizartrie, hipoprosexie şi stare de conştienţă păstrată. Examenul CT cerebral nativ a evidenţiat hemoragii intraparenchimatoase temporale şi parieto-occipitale drepte, o leziune frontală dreaptă sechelară, multiple infarcte lacunare vechi, atrofie corticală. Datele de laborator au relevat sindrom inflamator, absenţa serologiei pozitive pentru poliartrită reumatoidă, coagulograma normală, proteinurie crescută. IRM cerebral efectuat în a şaptea zi de spitalizare a fost sugestiv pentru hemoragie parietală dreaptă subacută. Tratamentul anticoagulant şi antiagregant a fost oprit după survenirea unei crize convulsive tonico-clonice generalizate. S-a iniţiat tratament antiedematos cerebral, hipotensor, anticonvulsivant, betablocant şi simptomatic şi a fost continuat tratamentul antidiabetic. Toate simptomele s-au remis. Argumentele pentru angiopatie amiloidă la pacientul nostru sunt stroke-ul ischemic necardioembolic în antecedente şi o afecţiune inflamatorie cronică-poliartrita reumatoidă în antecedentele personale patologice.</trans-abstract>

<abstract><title style='display:none'>Abstract</title>A 78-year-old Caucasian man was admitted in the Department of Neurology for visual disturbances, started two days before. The next day the patient experienced headache, fever and gait disturbances. He had hypertension, diabetes mellitus, an ischemic stroke 13 years ago, longstanding seronegative rheumatoid arthritis (17 years), polynodular goiter, right ischio-pubian fracture and right femoral vein thrombosis a year ago due to a car accident, since he is treated with oral anticoagulants associated to antiaggregant, hypotensors, statin and oral antidiabetics. The neurologic examination had evidenced nuchal rigidity, left homonymous hemianopsia, left central facial palsy, ataxia of the inferior limbs with wide-based gait, achilean reflexes abolished bilaterally, bilaterally abolished plantar reflexes, ideomotor apraxia, dysarthria, hypoprosexia, and preserved consciousness patient. A non-contrast cerebral CT scan had shown right temporal and parieto-occipital intraparenchymatous hemorrhages, a right frontal sequelar lesion, multiple old lacunar infarcts, cortical atrophy. Laboratory findings included an inflammatory syndrome, absence of rheumatoid arthritis positive serology, normal coagulogram, an elevated proteinuria. The cerebral IRM performed on the seventh day of hospitalisation was suggestive for subacute right parietal hemorrhage, old cerebral infarction in the right anterior cerebral artery area, old lacunar infarcts and cerebral atrophy. The anticoagulant and antiaggregant treatment was stopped after a generalized tonic-clonic seizure occurred. Antiedematous, hypotensor, anticonvulsivant, beta-blocker, and symptomatic treatment was started, while the antidiabetic treatment was continued. All symptoms remitted. Arguments for amyloid angiopathy in our patient are previous non-cardioembolic ischemic stroke and a chronic inflammatory disease-rheumatoid arthritis in his personal medical history.</abstract>

Department of Neurology, “Colentina” Clinical Hospital

“Dr. Ion Stoia” Clinical Center for Rheumatic Diseases

“Titu Maiorescu” University, Faculty of Medicine, Bucharest, Romania

<article-title>Multiple Intracerebral Hemorrhages in an Old Patient with Rheumatoid Arthritis</article-title>

Multiple Intracerebral Hemorrhages in an Old Patient with Rheumatoid Arthritis

{"article-title":"Multiple Intracerebral Hemorrhages in an Old Patient with Rheumatoid Arthritis"}

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Editor-in-Chief Gheorghe-Andrei Dan, University of Medicine and Pharmacy "Carol Davila", Colentina University Hospital, Romania †Coman Tanasescu, University of Medicine and Pharmacy "Carol Davila", Romania Deputy/ Managing Editor Cristian Baicus, University of Medicine and Pharmacy "Carol Davila", Colentina University Hospital, Romania Editorial Advisory Board Monica Acalovschi (Romania) Dimitrios Anyfantakis (Greece) Serban Balanescu (Romania) Daniela Bartos (Romania) Antonio Bayes de Luna (Spain) Miron A. Bogdan (Romania) Ion V. Bruckner (Romania) Razvan M. Chirila (USA) Maria Dorobantu (Romania) Pierre Duhaut (France) Dan L. Dumitrascu (Romania) Carmen Fierbinteanu-Braticevici (Romania) Krzysztof J. Filipiak (Poland) Zlatko Fras (Slovenia) Carmen Ginghina (Romania) Alexandru Incze (Romania) Constantin Ionescu-Targoviste (Romania) Juan Carlos Kaski (UK) Petru Manu (USA) Felipe Martinez (Argentina) Antonio Martinez-Rubio (Spain) Mona Munteanu (France) Dana Pop (Romania) Irinel Popescu (Romania) Francesco Portaluppi (Italy) Pietro Portincasa (Italy) Tania Potpara (Serbia) Vlad Ratziu (France) Adalbert Schiller (Romania) Adrian Streinu-Cercel (Romania) Radu Tanasescu (UK) Reimar W. Thomsen (Denmark) Gabriel Ungureanu (Romania) Doina Velican (Romania) Dragos Vinereanu (Romania) Marius M. Vintila (Romania) Victor Voicu (Romania) Mihai Voiculescu (Romania) Radu Voiosu (Romania) Dumitru Zdrenghea (Romania) Editorial Board Anca R. Dan, Colentina University Hospital (Romania) Paul Balanescu, University of Medicine and Pharmacy Carol Davila (Romania) Language Editors Olga Dumitru Technical Editors Iolanda Povara Contact <A href="mailto:editor@intmed.ro">editor@intmed.ro</A> Publisher De Gruyter Poland Bogumiła Zuga 32A Str. 01-811 Warsaw, Poland T: +48 22 701 50 15

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<DIV align=justify> Romanian Journal of Internal Medicine has been published since 1965, and is devoted to promoting internal medicine and its subspecialties in Romania and Eastern Europe. The journal appears quarterly and it publishes, after a peer-review process, original scientific articles, review articles, editorials, case reports and other information relevant to internal medicine and related fields, evidence-based medicine and medical education. Our intended readership includes clinicians, clinical researchers, managers, medical educators and other persons involved in providing medical care. Romanian Journal of Internal Medicine is published by "N Gh Lupu" Foundation of Internal Medicine and Romanian Academy". </DIV>

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Volume 53 (2015): Issue 4 (December 2015)

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