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Objective: The clinical profile, management and outcome of infective endocarditis (IE) may be influenced by socioeconomic issues. Methods: A nationwide prospective study evaluated IE during the era of deep economic crisis in Greece. Epidemiological data and factors associated with 60-day mortality were analyzed through descriptive statistics, logistic and Cox-regression models. Results: Among 224 patients (male 72.3%, mean age 62.4 years), Staphylococcus aureus (n = 62; methicillin-resistant S. aureus (MRSA) 33.8%) predominated in the young without impact on mortality (p = 0.593), whilst Enterococci (n = 36) predominated in the elderly. Complications of IE were associated with mortality: heart failure [OR 2.415 (95% CI: 1.159–5.029), p = 0.019], stroke [OR 3.206 (95% CI: 1.190–8.632), p = 0.018] and acute kidney injury [OR 2.283 (95% CI: 1.085–4.805), p = 0.029]. A 60-day survival benefit was solely related to cardiac surgery for IE during hospitalization [HR 0.386 (95% CI: 0.165–0.903), p = 0.028] and compliance with antimicrobial treatment guidelines [HR 0.487 (95% CI: 0.259–0.916), p = 0.026]. Compared with a previous country cohort study, history of rheumatic fever and native valve predisposition had declined, whilst underlying renal disease and right-sided IE had increased (p < 0.0001); HIV infection had emerged (p = 0.002). No difference in rates of surgery and outcome was assessed. Conclusions: A country-wide survey of IE highlighted emergence of HIV, right-sided IE and predominance of MRSA in the youth during a severe socioeconomic crisis. Compliance with treatment guidelines promoted survival.

Background: Patients with diabetes mellitus (DM) exhibit alterations in their immune response when infected by several types of micro-organisms. The increased susceptibility of diabetics to infections is particularly related to abnormalities in the function of neutrophils such as chemotaxis, adhesion and intracellular killing, leading to increased mortality rates. Aims of the study were to assess the phagocytic activity and the expression of antigens HLA-DR and CD64 of monocytes and neutrophils in diabetics with sepsis and evaluate their significance as prognostic factors. Methods: This is an observational prospective study conducted in a tertiary medical center, referring to a population of 51 diabetic patients who were treated for sepsis. Samples of whole blood were received from the selected patients and were evaluated for the expression of surface antigens HLA-DR and CD64 on monocytes and neutrophils, and for their phagocytic activity as well. Results: Alterations in the phagocytic activity were found in the diabetic patients who developed sepsis, and these were addressed as an elevation in the expression of CD64 on monocytes (CD64M), and a reduction in the expression of HLA-DR on monocytes (HLA-DRM) at least in the initial phase of the acute infection. A significant elevation was also noticed in the phagocytosis rate of both neutrophils and monocytes on day of admission. Survivors had higher rates of both CD64 and HLA-DR on monocytes when compared to non-survivors. No correlation was found between glycemic control, values of inflammatory markers on admission, phagocytosis rate and the survival of diabetics with sepsis. A reduced expression of CD64O, HLA-DRM and the co-expression of CD64/HLA-DR on monocytes in the initial phase of sepsis and poor glycemic control (hemoglobin A1c (HbA1c) > 8.5) was found. Conclusions: In the present study of diabetic patients with sepsis the phagocytic activity of neutrophils and monocytes is elevated at the initial phase of an acute infection and only the values of CD64 and HLA-DR on monocytes were significantly related to outcome. Further evaluation of these results with large prospective studies is warranted. J Clin Med Res. 2020;12(3):157-164 doi: https://doi.org/10.14740/jocmr4068

Objective Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. Methods Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2, Graphical abstract Image 1

The measurement of total and free cortisol has been studied as a clinical index of adrenal cortisol production in patients with liver cirrhosis. Correlations between free plasma and salivary cortisol have previously been reported in stable cirrhotic patients. Urinary free cortisol constitutes an index of adrenal cortisol production; however, it has never been used in assessing adrenal function in patients with liver cirrhosis.The aim of this observational study was to determine associations between urinary free cortisol, serum total, salivary, measured and calculated plasma free cortisol levels in cirrhotics, determining which of them can be used as an indirect index of free cortisol levels. Moreover, we investigated the potential use of 24 h urinary free cortisol as a prognostic factor for mortality.Seventy-eight outpatients with liver cirrhosis were included. Serum, salivary and urinary free cortisol were measured using the electrochemiluminenscence immunoassay. Plasma free cortisol determination was conducted using a single quadrupole mass spectrometer. The quantification of free cortisol was achieved by determining the signal response on negative ESI-MS mode.Twenty-four hour urinary free cortisol levels correlated with free cortisol determined by mass spectrometer, total cortisol and calculated free cortisol levels. Patients with low levels of urinary free cortisol presented a significantly higher mortality rate compared to those with high levels. The factors associated with death risk were determined by Cox regression. In the multivariate analysis, two models were applied; in the first model, CP score, PVT and urinary free cortisol were found to be significantly related to patients' survival, whereas in the second, MELD score, ascites and urinary free cortisol were independently related to survival.This study suggests that 24 h urinary free cortisol could be considered as a potential index of adrenal cortisol production in patients with liver cirrhosis and it potentially detects patients with a high mortality risk.

Aim: The purpose of this review is to summarize all relevant publications regarding the use and validity of the soluble urokinase plasminogen activator receptor (suPAR) when used by clinicians in the emergency department (ED) for the detection and monitoring of patients with sepsis syndrome. Methods: A PubMed search was conducted in order to identify all publications related to the use of suPAR in sepsis patients in the ED setting. Results: Although suPAR is actively involved in the pathophysiology of sepsis, over the last 15 years, only a few studies have been published referring to its predictive validity in the ED. Conclusions: SuPAR can be easily and rapidly measured in an ED setting, and its role in the exclusion of an infection and the management of sepsis, alone or in combination to other biomarkers, should be further evaluated. The optimal cut-off value, the timing of the measurement and the role of the suPAR in an ED setting should be further investigated.

Background: Sepsis and multi-organ failure remain a major clinical problem with high morbidity and mortality worldwide. Lactate measurement remains part of the initial assessment and management of patients with sepsis. Although arterial blood is most commonly used for lactate measurement, there is increasing use of peripheral venous lactate for initial assessment and for monitoring of response to treatment in patients with sepsis. The aim of this study was to evaluate the relation between lactate levels measured from central line, peripheral vein and arterial line in patients treated for sepsis in the emergency department (ED). Methods: This prospective study enrolled 31 patients with diagnosis of sepsis who were evaluated and treated in the ED of a university hospital. During initial resuscitation, blood samples from the artery, peripheral vein and central vein (when available) were collected and lactate concentrations were measured. Correlation between lactate values from the three different locations was assessed using Pearson correlation. Bland-Altman plots were used to evaluate agreement between lactate measurements in different sampling locations. All patients were eventually admitted to the Internal Medicine Department ward or to the intensive care unit (ICU) for further treatment. Results: Our data showed strong, highly significant correlation between arterial and peripheral venous lactate levels (r = 0.880, P < 0.0001), between arterial and central venous blood lactate (r = 0.898, P < 0.0001) and between central and peripheral venous blood lactate (r = 0.941, P < 0.0001). Conclusions: In this study we observed strong correlation between arterial, central vein and peripheral vein lactate concentrations in 31 patients assessed and treated for sepsis. We suggest that lactate measurement in peripheral venous blood could be used for screening and for monitoring response to therapy in sepsis patients. However, because this is a small study in only 31 patients and published data are limited, larger studies are needed in order to confirm the validity of our findings. J Clin Med Res. 2019;11(9):629-634 doi: https://doi.org/10.14740/jocmr3897

Objective To evaluate the electroencephalographic (EEG) findings and correlate EEG findings with inflammatory biomarkers and the sepsis prognostic scores SOFA, SAPS II and APACHE II in patients who present in the Emergency Department with sepsis without clinical central nervous system involvement. Methods The study included seventeen patients (< 70 years old) with sepsis without central nervous system involvement presenting in the Emergency Department of the University Hospital of Patras, Greece. All patients underwent neurologic examination and EEG analysis on admission to the hospital and were treated according to the international guideline protocols for sepsis. Results Six of seventeen sepsis patients had mild or moderate EEG abnormalities. We did not find any significant correlation between EEG abnormalities and inflammatory biomarkers (CRP, WBC) or commonly used prognostic sepsis scores. Conclusions EEG could serve as a useful tool to identify brain alterations at an early stage in sepsis, before clinical sings of encephalopathy can be detected. However, the presence of EEG abnormalities does not correlate with sepsis severity as measured by the commonly used prognostic sepsis scores SOFA, APACHE II or SAPS II. Because this was a small single center observational study, large multi-center studies are warranted to confirm these findings.

There is a plethora of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) serological tests based either on nucleocapsid phosphoprotein (N), S1-subunit of spike glycoprotein (S1) or receptor binding domain (RBD). Although these single-antigen based tests demonstrate high clinical performance, there is growing evidence regarding their limitations in epidemiological serosurveys. To address this, we developed a Luminex-based multiplex immunoassay that detects total antibodies (IgG/IgM/IgA) against the N, S1 and RBD antigens and used it to compare antibody responses in 1225 blood donors across Greece. Seroprevalence based on single-antigen readouts was strongly influenced by both the antigen type and cut-off value and ranged widely [0.8% (95% CI 0.4–1.5%)–7.5% (95% CI 6.0–8.9%)]. A multi-antigen approach requiring partial agreement between RBD and N or S1 readouts (RBD&N|S1 rule) was less affected by cut-off selection, resulting in robust seroprevalence estimation [0.6% (95% CI 0.3–1.1%)–1.2% (95% CI 0.7–2.0%)] and accurate identification of seroconverted individuals.

Background: There is an amenable need for clinically applicable biomarkers in patients with SARS-CoV-2 infection. Red Cell Distribution Width (RDW) has been recently suggested as a prognostic biomarker for COVID-19.Methods: This was an observational study enrolling patients between February 26 and May 15 2020. We aimed to validate the association of the previously published RDW threshold of 14.5% with markers of disease progression and mortality.Results: A total number of 193 hospitalized patients with COVID-19 were enrolled and analyzed. Median age was 61 years (95% CI: 58–64). Patients with baseline RDW ≥14.5% (n = 41, 19.2%) presented with more progressive disease compared to patients with baseline RDW n = 156, 80.8%) as indicated by significant differences in maximum FiO2% during hospitalization (median: 100, 95% CI: 45.2–100, vs. 35, 95% CI: 31–40, p = 0.0001, respectively). Values of RDW ≥14.5% were also strongly associated with increased risk of mortality (HR: 4.1, 95% CI: 0.88–19.23), (p = 0.02).Conclusion: Our study provides evidence to support reproducibility and validity of a specified cut-off threshold of RDW as biomarker of disease severity and mortality in patients with COVID-19.

More than 300 SARS-COV-2 serological tests have recently been developed using either the nucleocapsid phosphoprotein (N), the spike glycoprotein subunit (S1), and more recently the receptor binding domain (RBD). Most of the assays report very good clinical performance characteristics in well-controlled clinical settings. However, there is a growing belief that good performance characteristics that are obtained during clinical performance trials might not be sufficient to deliver good diagnostic results in population-wide screens that are usually characterized with low seroprevalence. In this paper, we developed a serological assay against N, S1 and RBD using a bead-based multiplex platform and a rules-based computational approach to assess the performance of single and multi-antigen readouts in well-defined clinical samples and in a population-wide serosurvey from blood donors. Even though assays based on single antigen readouts performed similarly well in the clinical samples, there was a striking difference between the antigens on the population-wide screen. Asymptomatic individuals with low antibody titers and sub-optimal assay specificity might contribute to the large discrepancies in population studies with low seroprevalence. A multi-antigen assay requiring partial agreement between RBD, N and S1 readouts exhibited enhanced specificity, less dependency on assay cut-off values and an overall more robust performance in both sample settings. Our data suggest that assays based on multiple antigen readouts combined with a rules-based computational consensus can provide a more robust platform for routine antibody screening.One Sentence SummaryClinical and Population-level performance of single and multiplex SARS-CoV-2 serological assays.

Key Points Question Is the receipt of colchicine among patients hospitalized with symptomatic coronavirus disease 2019 associated with clinical benefit? Findings In this randomized clinical trial of 105 patients, the rate of the primary clinical end point (clinical deterioration) was higher in the control group than in the colchicine group, and the time to clinical deterioration was shorter in the control group than in the colchicine arm. No difference was observed in the primary biochemical end point (high-sensitivity troponin concentration), but patients in the colchicine group had a smaller increase in dimerized plasma fragment D compared with patients in the control group. Meaning The hypothesis-generating findings of this study suggest a role for colchicine in the treatment of patients with coronavirus disease 2019., This randomized clinical trial evaluates the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19)., Importance Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. Objective To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). Design, Setting, and Participants In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. Intervention Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. Main Outcomes and Measures Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. Results A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). Conclusions and Relevance In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. Trial Registration ClinicalTrials.gov Identifier: NCT04326790

Background No evidence is available on the natural history of grade 1 ascites and its progression to grade 2/3 in patients with liver cirrhosis. The aim of the current study was to address this issue, to assess the development of main comorbid disorders closely related to ascites progression, and to identify the predictive factors for survival in this setting. Methods Consecutive Caucasian cirrhotic patients with grade 1 ascites were retrospectively analyzed. None of patients was under treatment with diuretics at diagnosis. Control groups consisted of 145 cirrhotics with grade 2/3 ascites and 175 cirrhotics without ascites. Results Diuretics were initiated in 58 patients with grade 1 ascites at baseline by the attending physician. At the last follow up, 29 patients had no ascites, 33 patients had grade 1 and 38 patients had grade 2/3 ascites. No variable was found to be an independent predictor of grade 2/3 ascites. Seven patients developed spontaneous bacterial peritonitis while under treatment with diuretics; at that time only 1 patient had grade 1 ascites. The mortality rate was similar among all examined groups. Conclusions This study suggests that the presence of grade 1 ascites does not constitute a precursor of grade 2/3 ascites in patients with cirrhosis. Thus, patients with grade 1 ascites do not require specific treatment with diuretics.

Introduction. The neutrophil-to-lymphocyte ratio (NLR) as calculated from the white cell differential blood count is a marker that has been used as a prognostic index when assessing patients suffering from several clinical syndromes, including sepsis. The aim of this study was to evaluate the relationship between NLR and the commonly used severity scores of sepsis SOFA, APACHE II and SAPS II in a population of emergency admitted adult patients with sepsis in a tertiary center. Methods. A prospective observational study was conducted in the Emergency Department of the University Hospital of Patras, Greece, based on data extracted from 50 patients consecutively enrolled, suffering from sepsis of multiple origin. The study period was from May 01, 2017 until June 30, 2017. The NLR was calculated from the total white blood cell (WBC) count values measured from a peripheral venous blood specimen drawn on admission. C-reactive protein (CRP) was also measured. The sepsis severity prognostic scores APACHE II, SAPS II and SOFA were calculated for each patient. Results. NLR was positively correlated with the sepsis severity prognostic scores on admission (SOFA, rs = 0.497, p < 0.001; APACHE II, rs = 0.411, p = 0.003; SAPS II, rs = 0.445, p = 0.001). Total WBC was also significantly correlated with the scores (SOFA, rs = 0.342, p = 0.015; APACHE II, rs = 0.384, p = 0.006; SAPS II, rs = 0.287, p = 0.043). Serum CRP did not show any significant correlation either to NLR or to the sepsis severity scores on admission. Conclusions. NLR is an easily calculated, cost-efficient index that could be used as a tool for clinicians when assessing sepsis patients in the Emergency Department. Although NLR measurement is simple, and rapidly available, future and larger prospective studies are warranted to confirm its definite value as a prognostic index in sepsis patients.

Diabetic foot ulcers (DFUs) are a very common cause of mortality and morbidity. The distinction between infected and non-infected DFU remains a very challenging task for clinicians in everyday practice. Even when infection is documented, the spectrum of diabetic foot infection is wide, ranging from cellulitis and soft tissue infection to osteomyelitis. Procalcitonin (PCT), a well-established sepsis biomarker, has been used in the diagnosis of several infections including osteomyelitis in patients with diabetes mellitus. This review gathers and presents all the relevant data, up until now, regarding the use of PCT as an assessment tool in diabetic patients with foot infection. Current evidence suggests that PCT levels could aid clinicians in distinguishing infected from non-infected DFUs as well as in the distinction between soft tissue infection and bone involvement, but further and larger studies are warranted to confirm these findings.

How circulating inflammatory mediators change upon sepsis progression has not been studied. We studied the follow-up changes of circulating vasoactive peptides and cytokines until the improvement or the worsening of a patient and progression into specific organ dysfunctions. In a prospective study, concentrations of tumor necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), endocan and angiopoietin-2 (Ang-2) were measured in serum by an enzyme immunoassay in 175 patients at baseline; this was repeated within 24 h upon progression into new organ dysfunction (n = 141) or improvement (n = 34). Endocan and Ang-2 were the only parameters that were significantly increased among patients who worsened. Any increase of endocan was associated with worsening with odds ratio 16.65 (p

Background: Acute abdominal pain (AAP) is a common symptom in the emergency department (ED). Because abdominal pain can be caused by a wide spectrum of underlying pathology, evaluation of abdominal pain in the ED requires a comprehensive approach, based on patient history, physical examination, laboratory tests and imaging studies. The aim of this study was to investigate predictive factors for admission to the hospital in patients who presented to the ED with AAP as the main symptom. Methods: This prospective observational study enrolled 125 patients who presented with AAP in the ED of the Patras University Hospital in western Greece. The sample of patients who enrolled in the study was representative of patients who receive care in this academic institution. All patients underwent clinical examination, laboratory testing and radiological assessment. Clinical and laboratory data were analyzed in an attempt to identify clinical or laboratory factors predicting hospital admission. Results: Based on clinical, laboratory and radiologic evaluation, 37.6% of patients enrolled in the study were admitted to the hospital, whereas 62.4% were not admitted. Compared to patients who were not admitted, patients admitted to the hospital had higher age and significantly higher inflammatory markers, white blood count and C-reactive protein (CRP). Binary logistic regression analysis showed that abnormal imaging findings (odds ratio (OR) = 6.47, 95% confidence interval (CI): 2.11 - 19.77, P < 0.001) and elevated serum CRP levels (OR = 6.24, 95% CI: 2.16 - 18.03, P < 0.001) were significant predictive factors for hospital admission. Conclusions: Assessment of AAP remains a challenging problem in the ED. Comprehensive history combined with detailed clinical examination, appropriate laboratory testing and radiologic imaging facilitates effective assessment of patients who present in the ED with AAP and guides the decision to admit patients to the hospital for further care. J Clin Med Res. 2017;9(12):987-993 doi: https://doi.org/10.14740/jocmr3206w

Meningococcal meningitis is a well established potential fatal infection characterized by fever, headache, petechial rash, and vomiting in the majority of cases. However, protean manifestations including abdominal pain, sore throat, diarrhea and cough, even though rare, should not be overlooked. Similarly, although disseminated infection could potentially involve various organ-targets, secondary immune related complications including joints or pericardium should be dealt with caution, since they remain unresponsive to appropriate antibiotic regimens. We hereby report the rare case of an otherwise healthy adult female, presenting with acute abdominal pain masking Neisseria meningitidis serotype B meningitis, later complicated with recurrent reactive pericarditis despite appropriate antibiotic treatment. There follows a review of current literature. Keywords: Reactive pericarditis, Neisseria meningitidis, Meningococcal meningitis

The objective of this study is to assess the prognostic value regarding 28-day outcome of the quick sequential organ failure assessment (qSOFA) score and the combined score calculated from blood lactate levels + qSOFA (LqSOFA) score in elderly patients initially treated in the Emergency Department (ED) for sepsis due to pneumonia or other chest infections. This is a prospective observational study, conducted at the ED in a Greek University Hospital. Forty-one patients with sepsis due to chest infection were enrolled in the study. All patients were treated in the Resuscitation Room of the ED according to the international treatment protocols for sepsis. The qSOFA score was calculated on admission for all patients, and one point was added in the calculation of the LqSOFA score in patients with blood lactate levels >2 mmol/L. Both the qSOFA and the LqSOFA scores had high sensitivity and specificity in predicting unfavorable outcome in elderly patients with chest infection and sepsis. In the ongoing debate of early diagnosis of sepsis and identification of prognostic indexes of the syndrome, qSOFA score alone or in combination with lactate levels could serve as a reliable predictor of outcome. Large prospective studies are needed to further evaluate the role and prognostic validity of these scores in the ED.

Introduction Current pathogenetic aspects on HIV infection highlight the importance of a chronic immune activation ultimately leading to T lymphocyte homeostasis disruption and immune deregulation associated with disease manifestations and progression. It is widely accepted that this continuous immune activation in HIV infection is principally driven by the phenomenon of pathological microbial translocation (MT).

Thymomas can present with a variety of paraneoplastic manifestations, mostly of autoimmune origin, including Good's syndrome when there is associated hypogammaglobulinemia. Although pure red cell aplasia is a recognised complication of thymoma, selective white cell aplasia is very rare, particularly in Good's syndrome. Lethal opportunistic infections are a feature of Good's syndrome, usually occurring in those patients with associated severe T lymphocyte defects. Although the cryptococcus is a recognised fungal pathogen in patients with other causes of CD4+ T cell lymphopenia, surprisingly this complication has not been reported in patients with Good's syndrome. We now describe a 70 year old man with Good's syndrome and pure white cell aplasia who presented with disseminated cryptococcosis, and provide an up-to-date review of the relevant literature. Despite meningeal involvement our patient recovered after combined treatment with intravenous globulin, granulocyte stimulating growth, corticosteroids and antifungal therapy.

Background Thalassemic patients demonstrate an increased rate of extracardiac vascular complications and increased carotid wall intima-media thickness (cIMT), but very low prevalence of coronary artery disease (CAD). We investigated the atheroma burden by assessing the coronary artery calcium (CAC) and cIMT in these patients. Methods We examined 37 patients with β-thalassemia and 150 healthy control volunteers with multi-detector computer tomography (CT) and ultrasonography to determine CAC score and cIMT, respectively. Results Propensity score matching (C-statistic: 0.88; 95% CI: 0.83–0.93) resulted in 27 pairs of patients; severe CAC was observed in 2 (7.4%) and 0 of β-thalassemia patients and healthy volunteers respectively (P = 0.5). Median calcium score was 0 (0–0) in β-thalassemia patients and 0 (0–4) in healthy volunteers (P = 0.8). Median intima-media thickness was higher in β-thalassemia patients compared to control group [0.45 (0.06–0.65) vs. 0.062 (0.054–0.086); P = 0.04]. Conclusions Patients with β–thalassemia in comparison with healthy control subjects exhibit similar CAC score and increased cIMT. Our findings indicate a disparate rate of progression of atherosclerosis between coronary and extracardiac arteries in these patients lending support to the epidemiological evidence.

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26–0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT0.12 ng/mL [P0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission.

Septic thrombophlebitis is characterized by venous thrombosis, inflammation and bacteremia, that can lead to fatal complications such as sepsis, septic emboli and even death. Though most commonly caused by indwelling catheters, it is also related to intravenous drug users (IVDU) especially those who attempt to inject drugs into more proximal and central veins. Lemierre’s syndrome, also referred to as post-anginal sepsis or necrobacillosis, is a suppurative thrombophlebitis of the internal jugular vein. Primary infection is associated with oropharyngeal and dental infections and the most common causative organism isFusobacterium necrophorum. We report a case of Lemierre’s syndrome in an IVDU, caused byFusobacterium necrophorum, which was inoculated at the site of injection, without a history of sore throat or pharyngitis.

Objective: The aim of this study was to determine prognostic factors for outcome in patients with lower respiratory tract infections (LRTI). LRTI are an heterogeneous group of disorders, including acute bronchitis, pneumonia, superinfection of chronic bronchitis and influenza. Methodology: A total of 616 patients with LRTI were retrospectively reviewed with regard to epidemiological, clinical, laboratory and radiographical data. Prognostic analysis included a univariate as well as a multivariate approach, in order to identify parameters associated with death. Results: The parameters found to be significantly different between survivors and non-survivors in the univariate analysis, were respiratory rate, Pao2, heart rate, systolic and diastolic blood pressure, platelet count, urea, creatinine, previous admission to the hospital in the last year and cavitations visible on the chest radiograph. Conclusions: LRTI remain a widespread problem and have a significant impact on primary healthcare resources. The great variability seen in rates of hospital admission and lengths of stay in part reflects uncertainty among physicians in assessing the severity of the illness. According to our data, Pao2 and heart rate were most closely associated with patient death and are readily defined and available at presentation.

We have read with great interest the recent article by Leclerc et al. [1] assessing rituximab therapy in hairy cell leukemia, following recent guidelines upon its usage in combination with or without purine analogs in relapsed/refractory disease [2, 3]. The authors [1] make an important statement concerning the scarce data upon the use of frontline rituximab as monotherapy, in patients unable to receive other agents due to associated cytopenias, progressive disease, patients who are very elderly, and/or have a poor performance status. Of note in the latter group, attending physicians are not uncommonlymet with patients with second malignancy including the solid organ, skin, and lymphoid neoplasms, as shown in large epidemiological studies [4]. We hereby would like to report our recent experience with a 70year-old male patient admitted to our department with shortness of breath in the context of a newly diagnosed pleural effusion (Fig. 1a) for further evaluation. Initial investigation revealed mild pancytopenia (WBC, 2.20 K/μl; poly, 46 %; lymph, 52 %; mono, 2 %; PLT, 135.00 K/μl; Hb, 11.5 g/dl) in the presence of hairy cells in peripheral blood smear, along with several nodular lesions of nonspecific characteristics, approximately ~1 cm at the top and posterior segments of the right and left lungs (Fig. 1b). Bone marrow trephine biopsy confirmed 40–50 % lymphocyte infiltration (Fig. 1c, d), the great majority being strongly positive for CD20 (Fig. 1e) and less for CD79a, while 15 % of cells were positive for DBA44 (Fig. 1f). Immunophenotypic analysis of peripheral blood revealed a small CD103(+) population, supporting the diagnosis of B hairy cell leukemia. However, fine needle biopsy staining of pulmonary lesions was positive for TTF-1 and surfactant apoprotein, leading to the diagnosis of synchronous adenocarcinoma of the lung. A PET-CT scan confirmed lesions in the right and left upper lung fields, together with abnormal signal along the right pleura, spleen, and right scapula, along with a newly identified right axillary lymph node. Due to the second malignancy and existing cytopenias, we decided to treat this patient with rituximab alone. He received a weekly course of rituximab (375 mg/m) for 4 weeks, followed by five monthly courses. Marked increase and complete normalization of blood count were noted after the first 4 cycles and the end of therapy, respectively. A month following the end of the last course, bone marrow trephine biopsy confirmed complete remission of hairy cell leukemia; hence, the patient went on to receive chemotherapy for his lung cancer. Including ours, 12 cases of frontline rituximab monotherapy, the majority of which due to existing neutropenia have been recorded in the literature [1, 5–7] receiving approximately 4–8 weekly infusions. Forty-two percent of patients (5/12) achieved some response [5–7], while in 58 % (7/12) of patients, complete remission was noted ranging from 1 to K. Akinosoglou (*) : C. Papakonstantinou :C. A. Gogos : E. E. Solomou Department of Internal Medicine, University General Hospital of Patras, 5th Floor, 265 04 Rio, Greece e-mail: akin@upatras.gr

The aim of the present study was to evaluate the prognostic value of HLA-DR antigen expression in monocytes, in patients with community-acquired infections presenting with fever, as possible markers for the patients' final outcome.

In the present study the effect of ciprofloxacin versus ceftazidime on concentrations of pro- and anti-inflammatory cytokines in the sera of patients with severe sepsis was evaluated. The study included 58 previously healthy patients suffering from severe sepsis caused by gram-negative bacteria, treated with either ciprofloxacin or ceftazidime after thorough clinical and microbiological evaluation and followed up for clinical outcome. Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1b (IL-1b), IL-6, and IL-8 and of the anti-inflammatory cytokine IL-10, as well as of IL-1 receptor antagonist and soluble TNF receptors I and II, in serum were measured at baseline and 24 and 48 h after the first antimicrobial dose. Mean SAPS-II scores, development of septic shock, and mortality rates were similar in the two groups (43.2 ± 9.2, 21.4%, and 14.3% in the ceftazidime group versus 49.8 ± 11.3, 20%, and 13.3% in the ciprofloxacin group). Serum TNF-α and IL-6 levels at 24 and 48 h were significantly lower in the ciprofloxacin group, while the IL-10/TNF-α ratio was significantly higher, than those for the ceftazidime group. Among patients with high baseline TNF-α levels, there were significant increases in the IL-10/TNF-α ratio at both 24 and 48 h over that at admission for the ciprofloxacin group, while no differences were noted in the ceftazidime group. These results indicate that ciprofloxacin may have an immunomodulatory effect on septic patients by attenuating the proinflammatory response, while there is no evidence that differences in the cytokines measured have any impact on the final outcome.

In this randomized, non-blinded study, the efficacy and safety of a 5-day course of moxifloxacin (one 400 mg tablet daily) was compared with that of co-amoxiclav (one 625 mg tablet every 8h) for 7 days, for the treatment of acute exacerbations of chronic bronchitis (AECB). A total of 162 patients with clear signs of an acute exacerbation of chronic bronchitis were enrolled. Of these, 153 could be studied. Seventy-nine patients were randomized in the moxifloxacin arm and 74 in the co-amoxiclav arm of the study. The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and ronchi. The success rate in the moxifloxacin group was 88.6% (70 of 79) and that for co-amoxiclav group was 89.2% (66 of 74). At follow-up (28-35 days post-treatment), the continued clinical cure rates were 90.0% (63 of 70) for moxifloxacin and 89.4% (59 of 66) for co-amoxiclav. No significant differences were detected between the two groups. A total of 78 pathogenic bacteria were isolated from the sputum samples of the patients, with Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently isolated pathogens. The eradication rate at 14 days in the valid patients was similar for both groups, 90.9% (20 of 22) for the moxifloxacin group and 90.0% (18 of 20) for the co-amoxiclav group. Both drugs were well tolerated with no differences in the drug-related adverse effects or the patients withdrawing because of an adverse event. These results and the good spectrum of antibacterial activity make moxifloxacin a promising and also safe alternative for the empirical treatment of AECB.

Background/Objectives: Sepsis is one of the most important causes of mortality in the developed world, where almost two-thirds of the population suffer from obesity. Therefore, the coexistence of both conditions has become frequent in clinical practice and a growing number of clinical studies attempts to examine the potential effect of obesity on sepsis with controversial results up to now. The present study investigates how obesity influences the immune response of septic patients, by assessing the number and activation state of adipose tissue macrophages, serum and adipose tissue tumor necrosis factor-alpha (TNFα) levels and plasma oxidative stress markers. Subjects/methods: The study included 106 patients, divided into four groups (control n=26, obesity n=27, sepsis n=27 and sepsis and obesity n=26). The number of macrophages in subcutaneous and visceral adipose tissue (SAT and VAT) and their subtypes (M1 and M2) were defined with immunohistochemical staining techniques under light microscopy. TNFα mRNA levels were determined in SAT and VAT using real-time reverse transcription-PCR. Serum levels of TNFα were determined with sandwich enzyme-linked immunosorbent assay. Plasma oxidative stress was evaluated using selective biomarkers (thiobarbituric acid-reactive substances (TBARS), protein carbonyls and total antioxidant capacity (TAC)). Results: Sepsis increased the total number of macrophages and their M2 subtype in (VAT), whereas obesity did not seem to affect the concentration of macrophages in fat. Obesity increased TNFα mRNA levels (PPP Conclusions: Obesity is associated with elevated TNFα adipose tissue production and increased oxidative stress biomarkers, promoting the proinflammatory response in septic patients.

Aim: To determine the pattern of cytokine synthesis in the ascitic fluid (AF) of cirrhotic patients, with or without spontaneous bacterial peritonitis (SBP). Patients and methods: We

Eight patients with brain abscesses who refused prolonged hospitalisation were treated with a short course (6-12 days) of intravenous antibiotics followed by prolonged treatment (15-19 weeks) with an oral antibiotic regimen consisting of metronidazole, ciprofloxacin and amoxicillin. All patients responded favourably as shown clinically and in imaging studies. No severe adverse events or sequelae were noted. On admission all patients had a normal or mildly impaired mental status, abscesses less than 3 cm in diameter and no serious predisposing factors. Although combined surgical/medical treatment remains the standard approach in management of these patients, the findings suggest that oral antibiotic therapy only subsequent to a short course of intravenous antibiotics may be an acceptable alternative in selected cases.

Three cases of deep venous thrombosis following varicella infection are described which were successfully treated with bed rest and anticoagulants. Two of these patients had severe pulmonary manifestations of varicella and the third was complicated by pulmonary embolism. Deep vein thrombosis is an uncommon systemic manifestation of varicella, possibly associated with vascular endothelium wall damage caused by varicella zoster virus infection.

In the present study we investigated the early prognostic value of the serum levels of the main proinflammatory and anti-inflammatory cytokines and soluble cytokine inhibitors for mortality and late complications such as sepsis and multiorgan failure (MOF) in a well-defined population of patients with severe trauma.

Abscess formation at the injection site is an unusual infectious complication of interferon-alpha (IFN-alpha) treatment of chronic hepatitis C virus (HCV) infection, but remote abscess formation during IFN-alpha therapy is very rare. In the present communication, we report three cases of remote abscess formation detected among 68 patients with chronic viral hepatitis treated with IFN-alpha, and review the pertinent English literature. We believe that, as fever and constitutional symptoms are common side effects of IFN-alpha treatment, a high index of suspicion is indicated to exclude abscess formation in cases of unexplained fever during IFN-alpha therapy.

Introduction A rare complication of chronic pancreatitis is the formation of single or multiple mediastinal pseudocysts, which are fueled from the pancreas through anatomical openings of the diaphragm. We present a rare case with a difficult diagnosis, treatment and potentially catastrophic complications. Case presentation A 53-year-old Caucasian man was referred to our hospital for further investigation and treatment of a large heterogeneous mass situated in the posterior mediastinum, and bilateral pleural effusions which had developed after recent multiple episodes of pancreatitis. He had a history of chronic alcoholism. Laboratory and imaging modalities established the diagnosis of a pancreatic mediastinal pseudocyst. Conclusions Despite successful initial conservative treatment, our patient had a relapse and underwent emergency surgical intervention due to internal hemorrhage. We present his diagnostic and imaging workup, along with the multidisciplinary intervention, and a literature review referring to the diagnosis and treatment of mediastinal pancreatic pseudocysts.