European Journal of Internal Medicine

Editorial Board

2010-02-01

European examinations in internal medicine

Colin G. Semple, Stefan Lindgren — 2009-11-18

The European Board of Internal Medicine (EBIM) is a joint venture between the UEMS Section of Internal Medicine and EFIM. In 2005, a decision was made to promote a Diploma in Internal Medicine in order to provide an assessment of the core knowledge required of trainees in this specialty. The Diploma is built on documented knowledge in Internal Medicine together with a support for the candidate from his/her National Society regarding completion or near completion of specialist training in Internal medicine and confirming that the candidate currently holds a post covered by UEMS/EFIM .

Inherited and acquired predispositions for thrombosis in immunocompetent patients with cytomegalovirus-associated thrombosis

Lihi Atzmony, Anat Grosfeld, Nili Saar, Dan Justo — 2009-11-02

Abstract: Background: Thrombosis is a rare complication of cytomegalovirus (CMV) infection in immunocompetent patients. The clinical circumstances of this complication have never been studied, to the best of our knowledge.Aim: We reviewed all reports on CMV-associated thrombosis in immunocompetent adults found in the literature, in search for thrombosis risk factors other than CMV.Methods: Our search yielded 32 case reports and case series on CMV-associated thrombosis in immunocompetent adults. Reports on immunocompromised patients, infants and elderly patients were excluded. All reports were reviewed for other, acquired as well as inherited, predispositions for thrombosis.Results: Reports on 39 immunocompetent adults were reviewed, mean age for which was 34.9±10.8years. Overall, 14 (35.9%) patients had one or more acquired predispositions for thrombosis; 16 (45.7%) of the 35 patients that were investigated for inherited thrombophilias had one or more inherited predispositions for thrombosis. Only 12 (34.3%) patients were found to have no acquired or inherited predispositions for thrombosis other than CMV. The most common (n=13; 33.3%) acquired predisposition for thrombosis was daily use of oral contraceptives. The most common (n=6; 17.1%) inherited predisposition for thrombosis was factor V Leiden mutation.Conclusions: Most immunocompetent adults with CMV-associated thrombosis have other acquired or inherited predispositions for thrombosis. Hence, addressing these predispositions in patients with CMV-associated thrombosis may be of great clinical importance.

Lung cancer screening – are we there yet?

Eiran Warner, Alan Jotkowitz, Nimrod Maimon — 2009-11-27

Abstract: Background: Lung cancer is the most lethal cancer and most cases are the result of cigarette smoking. Although a high risk target population for screening can be defined, and although early stage lung cancer has a much better prognosis than advanced disease, there is still no clear evidence that lung cancer screening decreases mortality. Accordingly, current guidelines suggest that there is no evidence to support routine screening. Although randomized studies in the 1970′s which used chest x-ray and sputum for screening were clearly negative in the last 20years more sensitive screening tools such as chest computed tomography have revolutionized the field. However, randomized controlled trials of computed tomography have only recently been launched.Aims of this review: Our objectives are to provide the reader with the rationale for screening for lung cancer, to review the older screening studies and their limitations, and to summarize the current knowledge and ongoing trials of lung cancer screening.Literature search: A literature search using Medline was conducted from 1966 onwards searching for articles with relevant key words such as lung cancer screening chest X – ray low dose computerized tomography cancer screening guideline. When appropriate additional references were found from the bibliographies of identified papers of interest.Conclusions: Recent uncontrolled multicenter studies of chest computed tomography scans show encouraging results. However, until data from, large properly designed and appropriately analyzed randomized controlled trials which may overcome research biases is available, the benefit of lung cancer screening, if any is still unknown.

Mortality risk in splenectomised patients: A Danish population-based cohort study

2009-11-04

Abstract: Background: The extent and magnitude of mortality risk among patients splenectomised for a variety of indications is not well-described in the literature. We assessed mortality risk among splenectomised patients compared to the general population and to un-splenectomised patients with similar underlying medical conditions.Methods: We conducted a historical population-based cohort study in Denmark between January 1, 1996 and December 31, 2005. Mortality risk was evaluated within 90days, 91–365days, and >365days post-splenectomy, controlling for age, sex, and comorbid conditions using Cox proportional hazards models for a splenectomised cohort compared to the general Danish population and a matched indication cohort.Results: We identified a total of 3812 splenectomised patients, 38,120 population comparisons, and 8310 matched indication comparisons. Within 90days post-splenectomy, the adjusted relative risk (RR) for death, regardless of indication, was highly elevated compared to the general population: RR 33.6 [95% confidence interval (CI): 6.9, 35.0]. This risk declined substantially after 90days post-splenectomy but remained higher 365days post-splenectomy for all indications compared to the general population. When compared to the matched indication cohort, short- and long-term mortality risk with splenectomy was not increased.Conclusion: Regardless of indication, the adjusted short- and long-term risk of death for splenectomised patients was higher than the general population. Most of this risk seems to be due to the underlying splenectomy indication and not to splenectomy alone.

Serum albumin as an outcome predictor in hospital emergency medical admissions

Owen Lyons, Bryan Whelan, Kathleen Bennett, Deirdre O'Riordan, Bernard Silke — 2009-11-30

Abstract: Background: To examine the relationship between admission serum albumin and 30-day mortality during an emergency medical admission.Methods: An analysis was performed of all emergency medical patients admitted to St. James's Hospital (SJH), Dublin between 1st January 2002 and 31st December 2008, using the hospital in-patient enquiry (HIPE) system, linked to the patient administration system, and laboratory datasets. Mortality was defined as an in-hospital death within 30days. Logistic regression was used to calculate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals for defined albumin subsets.Findings: Univariate analysis using predefined criteria based on distribution, identified the groups of <10% and between 10 and 25% of the serum albumin frequency distribution as at increased mortality risk. Their mortality rates were 31.7% and 15.4% respectively; their unadjusted odds rates were 6.35 (5.68, 7.09) and 2.11 (1.90, 2.34). Patients in the lowest 25% of the distribution had a 30-day mortality of 19.9% and this significantly increased risk persisted, after adjustment for other outcome predictors including co-morbidity and illness severity (OR 2.95 (2.49, 3.48): p<0.0001).Interpretation: Serum albumin is predictive of 30-day mortality in emergency medical patients; mortality is non-linearly related to baseline albumin. The disproportionate increased death risk for patients in the lowest 25% of the frequency distribution (<36g/L) is not due to co-morbidity factors or acute illness severity.

Esophageal motility and 24-h pH profiles of patients with heterotopic gastric mucosa in the cervical esophagus

2009-11-30

Abstract: Background: Heterotopic gastric mucosa occurs as a flat island of red mucosa in the proximal third of the esophagus where it gives rise to the cervical inlet patch. The aims of this study were to investigate the esophageal motility pattern and 24-h pH profiles of patients with cervical inlet patch.Methods: Thirty patients (16 women, mean age: 44.9years, range: 23–72) diagnosed as having heterotopic gastric mucosa in the cervical esophagus with upper gastrointestinal symptoms had undergone esophageal motility testing and 24-h pH monitorisation with a double-channel pH probe.Results: Manometric investigation was abnormal in 7 patients (non-specific esophageal motor disorder in 4 patients, esophageal hypomotility in 1 patient, and hypotensive LES in 2 patients). Pathological acid reflux (pH<4) was found in 9 (30%) of 30 heterotopic gastric mucosa patients during pH monitorisation from the distal probe. Pathological acid reflux in the proximal esophagus (percentage of total time of pH<4) was seen in four of these nine patients. Only four of the 30 patients (13.3%) presented with “acid independent episodes” during the 24-h esophageal pH monitorisation.Conclusion: Manometric investigation and 24-h pH monitorisation revealed that some of the patients with HGM have signs of esophageal motor dysfunction and “acid independent episodes” from the patches. These abnormalities may be responsible for some of the symptoms of HGM patients.

Anti-t-PA antibodies in acute myocardial infarction after thrombolysis with rt-PA

2009-10-19

Abstract: Background: Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is successfully used in acute myocardial infarction with ST elevation (STEMI). Reocclusions follow rt-PA treatment in up to 30% of patients within one year. The infusion of rt-PA may induce the production of anti-t-PA antibodies which could interfere with the function of the native t-PA molecule.Methods: In order to detect and characterise anti-t-PA antibodies, plasma samples were collected from 30 STEMI patients (20 treated and 10 not treated with rt-PA) at baseline before rt-PA infusion and then 15, 30, 90 and 180days after STEMI and from 40 healthy subjects at baseline only. Immunoenzymatic, chromatographic and chromogenic methods were employed.Results: An increase of anti-t-PA antibodies was observed 15days (IgM, p=0.0001) and 30days (IgG, p=0.0001) after rt-PA infusion. Six patients had large increases of anti-t-PA IgG which bound the catalytic domain of t-PA (two cases) or kringle 2 domain (four cases), were of IgG1 or IgG3 subclasses and interacted with the t-PA molecule in fluid phase.Conclusion: The infusion of rt-PA may induce the production of specific antibodies that bind active sites of t-PA, thus potentially reducing its in vivo function.

Predictors of mortality within three months in the patients with malignant pleural effusion

Mehmet Oğuzhan Özyurtkan, Akın Eraslan Balcı, Muharrem Çakmak — 2009-11-18

Abstract: Background: Malignant pleural effusion (MPE) has a limited life expectancy (3–12months). We investigated the predictors of the early mortality (EM) within three months.Methods: The patients were retrospectively grouped according to the death within three months (Group I) and survival more than three months (Group II). Demographical, clinical, and biochemical parameters in the fluid were analysed to determine their effects on the EM. The 30-day response rate of talc pleurodesis was investigated.Results: The study included 85 patients (Group I/Group II=40/45). The patients in Group I died within a median of 28days. Twenty-six patients in Group II died in a median of 205, but 19 were still alive (median 200days). The median survival was longer in renal cell, colorectal, breast, liver, ovarian and oropharynx carcinoma, and mesothelioma. Sixty-two patients (63%) underwent talc pleurodesis, which prevented the fluid reaccumulation (p=0.04). The significant factors of the EM in the univariate analysis were the presence of high-risk tumors (lung, stomach, soft tissue, bladder, esophagus, prostate, cervix, and lymphoma), the low Karnofsky performance score (KPS) (p<0.0001), the low pH value of the fluid (p=0.05), and the low concentration of glucose (p=0.01), total protein (p<0.0001), and albumin (p<0.0001) in the fluid. According to the multivariate analysis high-risk tumors (p=0.03), a lower KPS (p<0.001), and glucose value (p=0.04) were the predictors of the EM.Conclusion: Talc pleurodesis prevents the fluid reaccumulation. High-risk tumors, a poor performance status, and lower pleural fluid glucose concentration are predictors of the EM within three months in the patients with a MPE.

Accuracy of carotid plaque detection and intima–media thickness measurement with ultrasonography in routine clinical practice

A. Ray, J.T. Tamsma, M.M.C. Hovens, J. op 't Roodt, M.V. Huisman — 2009-11-18

Abstract: Background: Current guidelines in cardiovascular disease prevention advocate the use of carotid ultrasound measurements for risk stratification. Carotid abnormalities (plaques or increased intima–media thickness (IMT)) are associated with high risk of coronary and peripheral artery disease. An office-based measurement by clinicians would considerably broaden the clinical applicability of carotid ultrasound. In the present study we have assessed the accuracy of ultrasound detection of carotid plaques and intima–media thickness by trained internists in a routine outpatient setting.Methods and results: Carotid ultrasound was performed in 112 vascular outpatients by internists, after a six-week training period. The internists' results were independently compared to the reference standard, consisting of carotid ultrasound performed in a specialized vascular laboratory. Sensitivity and specificity were calculated for plaque detection and IMT determination. The mean time required to perform the scans on the outpatient department was 7.3min (range 4.5 to 16.7min). A high level of accuracy for detecting plaques (sensitivity 78.5%; specificity 93.6%) was achieved. Identifying abnormal IMT had lower sensitivity but adequate specificity of 46.7% and 87.6%, respectively.Conclusions: In conclusion, our findings demonstrate that clinicians can be trained well enough in six weeks to accurately and efficiently detect carotid plaques in an outpatient setting. IMT abnormalities were less accurately detected in the office-based approach and may require a specialized vascular laboratory.

Data integrity, reliability and fraud in medical research

Mark Otto Baerlocher, Jeremy O'Brien, Marshall Newton, Tina Gautam, Jason Noble — 2009-11-30

Abstract: Background: Data reliability in original research requires collective trust from the academic community. Standards exist to ensure data integrity, but these safeguards are applied non-uniformly so errors or even fraud may still exist in the literature.Objective: To examine the prevalence and consequences of data errors, data reliability safeguards and fraudulent data among medical academics.Methodology: Corresponding authors of every fourth primary research paper published in the Journal of the American Medical Association (2001–2003), Canadian Medical Association Journal (2001–2003), British Medical Journal (1998–2000), and Lancet (1998–2000) were surveyed electronically. Questions focused on each author's personal experience with data reliability, data errors and data interpretation.Results: Sixty-five percent (127/195) of corresponding authors responded. Ninety-four percent of respondents accepted full responsibility for the integrity of the last manuscript on which they were listed as co-author; however, 21% had discovered incorrect data after publication in previous manuscripts they had co-authored. Fraudulent data was discovered by 4% of respondents in their previous work. Four percent also noted ‘smudged’ data. Eighty-seven percent of respondents used data reliability safeguards in their last published manuscript, typically data review by multiple authors or double data entry. Twenty-one percent were involved in a paper that was submitted despite disagreement about the interpretation of the results, although the disagreeing author commonly withdrew from authorship.Conclusions: Data reliability remains a difficult issue in medical literature. A significant proportion of respondents did not use data reliability safeguards. Research fraud does exist in academia; however, it was not reported to be highly prevalent.

The European Diploma of Internal Medicine — Perspectives on the exam from across Europe1

Roger Duckitt, Mine Durusu Tanriover, Lenka Bosanka, Lorenzo Dagna, Moshe Vardi — 2009-11-09

Professionalism in Medicine and its implementation has been the subject of discussions among practitioners for many years . Assessment of the competencies required is achieved throughout the training curves of medical professionals , aiming at providing motivation and direction for future learning, protecting the public by identifying incompetent physicians and providing a basis for choosing applicants for advanced training . In particular, licensing bodies have developed and continue to develop assessment models to grant permission to practice with an ongoing search for the form which will ensure professionalism, competency, and lifelong durability of medical excellence .

Management of complication in post-lumbar puncture

Weekitt Kittisupamongkol — 2009-02-04

I read with interest the article by Anwar and colleagues . The authors cite that treatment for post-lumbar puncture cranial nerve palsy is intravenous or oral fluid administration, I disagree. There is no evidence that increased fluid intake affects cerebrospinal fluid production . Moreover, caffeine usages for post-lumbar puncture nerve palsy require further studies. At therapeutic dose, such usages are associated with atrial fibrillation .

Oral and cutaneous findings are valuable diagnostic aids in Wegener's granulomatosis

Angelo Valerio Marzano, Daniele Fanoni, Emilio Berti — 2009-11-02

Wegener's granulomatosis (WG) is a rare granulomatous necrotizing vasculitis of small vessels which has predilection for upper airways, lung and kidney, but can involve any other organ. Without treatment, the mainstay of which is the combination of cyclophosphamide and systemic corticosteroids, it may run a fatal course. In a previous issue, Ruokonen et al. have reported a case presenting with oral lesions as the sole sign of WG . In the abovementioned case, the patient had hyperplastic granular gingivitis called as strawberry gingivitis which is a rare manifestation of WG, but may be the first sign and nearly pathognomonic for this autoimmune vasculitis in around 5% of patients with WG . Interestingly, also the histopathological features of the so-called strawberry gingivitis, albeit non-specific, are very suggestive of WG and can be seen in only few other conditions affecting the gingiva: they are characterized by the combination of pseudoepitheliomatous hyperplasia, epithelial micro-abscesses, and intense inflammatory infiltrate of neutrophils, eosinophils and multinucleated giant cells . It is noteworthy that the differential diagnosis of WG based on oral manifestations is wide and includes most notably other vasculitis such as microscopic polyangiitis, specific granulomatous diseases such as sarcoidosis and Crohn's disease, granulomatous infectious processes such as tuberculosis and deep mycoses, blood dyscrasias such as leukemia and lymphoma, and drug-induced gingival changes. As dermatologists, in addition to the differential diagnoses mentioned above, we would highlight a rare condition, namely Langerhans cell histiocytosis (LCH), which is a multisystem disorder characterized by the proliferation of a distinct cell type — the so-called Langerhans cell — and presenting with distinctive mucocutaneous manifestations. In LCH, vegetating nodulo-ulcerative lesions closely resembling those of WG may involve the gums and be accompanied by tooth mobility as in strawberry gingivitis . As reported by Ruokonen et al., it has been suggested that oral manifestations as well as cutaneous findings are valuable diagnostic aids in WG. In fact, about 15% of patients with WG develop specific skin lesions at some time during the course of the disease or more rarely at disease onset . The most common skin lesion is palpable purpura with the histopathological correlate of leukocytoclastic vasculitis. Nodules, papules, ulcerations and deep erythema nodosum-like subcutaneous nodules complete the wide clinical spectrum. In conclusion, the case on Ruokonen et al. emphasizes the importance to recognize the oral and cutaneous manifestations of WG, which may also precede systemic involvement, to start proper treatment as soon as possible so improving the outcome of this potentially lethal disease.

A new cause of cavitated bilateral pulmonary nodules: Influenza A (H1N1) virus

B.C. Finn, Edwing M. Rodríguez Pabón, P. Young — 2009-11-24

The 2009 pandemic Influenza A (H1N1) virus, which was first identified in the United States and Mexico, was imported into Argentina from Mexico in late April 2009 . We report a patient with Influenza A (H1N1) virus presenting with cavitated pulmonary nodules.

Predictors of positive temporal artery biopsy in patients with giant cell arteritis and polymyalgia rheumatica (comment on the article by Marí et al.)

Miguel A. Gonzalez-Gay, Jose A. Miranda-Filloy, Javier Llorca — 2009-11-16

We have read with great interest the elegant study by Marí et al. titled “Analysis of temporal artery biopsies in a 18–year period at a community hospital” . In this study the authors sought for clinical variables that may predict a positive temporal artery biopsy (TAB). The authors also described the best set of clinical features that may predict a positive TAB in their community hospital. They found that headache, jaw claudication, and abnormal temporal artery on palpation were the best positive predictors of positive TAB in patients on whom a biopsy was performed to make a diagnosis of giant cell arteritis (GCA) . Apart from these interesting data, the authors established clinical differences between biopsy-proven GCA and biopsy-negative GCA patients diagnosed as having this systemic vasculitis according to well-defined classification criteria . Interestingly, Marí et al. found a significantly increased frequency of severe visual ischemic complications (transient or permanent visual loss or diplopia) in the group of biopsy-proven GCA patients compared to those GCA patients with a negative TAB . Moreover, they found a non-significantly increased frequency of abnormal palpation of temporal artery on physical examination in biopsy-proven GCA patients (73.3%) compared with those biopsy-negative GCA patients (54.2%) .

Splenic infarct is a plausible alternative diagnosis in suspected splenic abscess

Oscar M.P. Jolobe — 2009-08-10

In view of the fact that, on computed tomography(CT) there is some overlap between stigmata of splenic infarction and splenic abscess, the presence of “gas in an intrasplenic collection” (a feature in only a minority of cases of splenic abscess), being the only abnormality specific to splenic abscess , splenic infarct was a plausible alternative diagnosis in some of the patients in the recent report by Llenas-Garcia et al. . This is true, not only when suspected splenic abscess is bacterial , but also when it is of mycobacterial origin, given the fact that splenic infarct can complicate abdominal tuberculosis , and can also be closely simulated by tuberculous splenic abscess .

Splenic infarct can coexist with splenic abscess

2009-08-17

We appreciate the suitable comments by Jolobe regarding our recent article . We fully agree that splenic infarct is an alternative diagnosis in suspected splenic abscess and therefore it should be included in the differential diagnosis of splenic lesions. Furthermore, splenic abscess and splenic infarct can present together. A splenic infarct can become overinfected yielding an abscess formation, as well as an acute infection and inflammation of the spleen can cause damage of the vessels and a secondary infarct. In fact, three of the patients in our series (patient numbers 1, 3 and 11) showed areas of splenic infarction in the histopathology. In patient number 1 the splenic infarct was secondary to thrombosis of the splenic vessels; the splenic arteria wall showed an acute inflammatory infiltrate suggesting vasculitis as a cause of the arterial occlusion. The culture of the splenic material was positive for Propionibacterium acnes. In patient number 3 the pathogenic mechanism must be different; the embolization of cardiac material probably caused infarction of some areas, as well as a metastatic spread of the infection. In the pathological exam there were areas of acute inflammation and areas of necrosis with haemorrhage. In patient number 11 there was an ischemic infarct (probably caused during the bypass surgery) secondarily overinfected with abscess formation. Gram negative bacilli and anaerobes were grown by culture.

Nondiagnostic temporal artery histology might also be a feature in some instances of nonclassical giant cell arteritis

Oscar M.P. Jolobe, D. Phil — 2009-08-10

Analysis of temporal artery biopsy-positive (TAB+ve) versus temporal artery biopsy-negative (TAB-ve) giant cell arteritis (GCA) would, in the future, benefit from inclusion of so-called “nonclassical organ involvement”, the latter characterised by GCA involvement of heart, lungs, kidneys, pelvic viscera, and other internal organs . In some of these patients histological examination reveals stigmata of GCA in the internal organs, with concordant stigmata of GCA on temporal artery biopsy . In others, however, stigmata of GCA in the internal organs are not associated with GCA stigmata on temporal artery biopsy. Although, in some of these “discordant” cases, nondiagnostic temporal artery histology is, arguably, attributable to patchy involvement of the temporal artery by GCA, this could hardly have been the case in the 56 year old woman who presented with fever of unknown origin and slight enlargement of the uterus. She was subsequently managed by means of total abdominal hysterectomy and salpingoovariectomy for suspected malignancy.

Agents with antialdosterone properties should be the preferred diuretics for reducing hypertension related atrial fibrillation

Oscar M.P. Jolobe — 2009-05-18

Given the fact that even conventional doses (namely, 25 mg/day) of the widely used antihypertensive thiazide, hydrochlorothiazide, provoke an increase in plasma aldosterone , with attendant profibrotic risk, torasemide should be the preferred antihypertensive diuretic because it has antialdosterone as well as antifibrotic properties . Antifibrotic properties would improve left ventricular diastolic function, thereby reducing the risk of hypertension-related left atrial fibrillation.

Corrigendum to “Hepatitis B remains a major health priority in Western Balkans: Results of a 4-year prospective Greek–Albanian collaborative study” [European Journal of Internal Medicine (2009) 20:698–702]