Assessment of HIV testing recommendations in Greek specialty guidelines: A missed opportunity and room for improvement for recommending testing.

HIV testing for individuals presenting with indicator conditions (ICs) including AIDS-defining conditions (ADCs) is explicitly recommended by European guidelines. We aimed to review specialty guidelines in Greece and assess if HIV was discussed and testing recommended. We reviewed European guidelines to produce a list of 25 ADCs and 48 ICs. We identified Greek guidelines for 11 of 25 (44%) ADCs and 30 of 48 (63%) ICs. In total, 47 guidelines were reviewed (range: 1-6 per condition); 11 (23%) for ADCs and 36 (77%) for ICs. Association with HIV was discussed in 7 of 11 (64%) ADC and 8 of 36 IC guidelines (22%), whereas HIV testing was appropriately recommended in two of 11 ADC (18%) and 10 of 36 IC guidelines (28%). Significant differences were found for the distribution of recommendations to test in both types of condition, with ICs having higher percentage of non-recommendation (50%, p < 0.05). No association was found between source of guideline or publication year and testing recommendation. Most guidelines for ICs and ADCs do not recommend testing. Specialists managing most ICs and ADCs may be unaware of the actual prevalence of undiagnosed HIV infection among their patients or the respective recommendations produced by HIV societies.

Fecal Microbiota Transplantation and Hydrocortisone Ameliorate Intestinal Barrier Dysfunction and Improve Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis.

INTRODUCTION: Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation, and survival, in a model of polymicrobial sepsis in rats. METHODS: Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP + HC (2.8 mg/kg, intraperitoneally single dose at 6 h) (group III), and CLP + FMT at 6 h (group IV). At 24 h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6, and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for 7 days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats. RESULTS: HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (µm, mean ±â€ŠSD: Group I: 620 ±â€Š35, Group II: 411 ±â€Š52, Group III: 622 ±â€Š19, Group IV: 617 ±â€Š44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas these increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean ±â€ŠSD: Group I: 1.6 ±â€Š0.5, Group II: 5.8 ±â€Š2.4, Group III: 3.6 ±â€Š0.9, Group IV: 2.3 ±â€Š0.6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92 ±â€Š8%) and claudin-1 (98 ±â€Š4%) and CLP reduced this expression to 34 ±â€Š12% for occludin and 35 ±â€Š7% for claudin-1. Administration of HC significantly increased occludin (51 ±â€Š17%) and claudin-1 (77 ±â€Š9%) expression. FMT exerted also a significant restoring effect in tight junction by increasing occludin (56 ±â€Š15%) and claudin-1 (84 ±â€Š7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/mL, mean ±â€ŠSD: Group I: 0.93 ±â€Š0.36, Group II: 2.14 ±â€Š1.74, Group III: 1.48 ±â€Š0.53, Group IV: 1.61 ±â€Š0.58), while FMT additionally decreased IL-6 and IL-10 levels. CONCLUSION: Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.

Patient-reported outcomes in HIV clinical trials evaluating antiretroviral treatment: a systematic review.

We aimed to assess patterns of patient-reported outcomes (PRO) instruments' utilization in HIV clinical trials in relation to antiretroviral therapy (ART). PubMed/MEDLINE, Scopus, and EMBASE were searched using the terms "Patient-Reported Outcomes" and "HIV/AIDS" or "Antiretroviral Treatment" or "ART" or "Antiretroviral Therapy" from 1 January 1990 until 1 December 2019. In total, 173 studies were identified and 26 were directly related to ART. Study population included treatment-naïve patients (n = 4), treatment-experienced (n = 20), or both (n = 2). Instruments were implemented to assess general experience with ART (n = 3), single-tablet regimens (STR) (n = 2), monotherapy (n = 4), regimen switch (n = 9), or regimen comparison (n = 8). The most commonly used instruments were Medical Outcomes Study-HIV Health Survey (MOS-HIV, n = 8), HIV Symptom Index (HIV-SI, n = 7) and unstructured self-reports (n = 5) followed by others. MOS-HIV was used mainly in comparative (n = 4) and monotherapy (n = 3) trials, HIV-SI in switch (n = 4) and STR (n = 2) trials, and self-reports in comparative trials (n = 3). Even though, the implementation of PRO tools is increasing with time, reporting of PRO in HIV clinical trials remains limited.

Hepatocellular Carcinoma: An Uncommon Metastasis in the Orbit.

Hepatocellular carcinoma (HCC) represents the most common type of primary cancer of the liver and is associated with poor prognosis. It is the most common cause of death in cirrhotic patients and in different studies was shown as the third most common cause of cancer-related deaths worldwide. Each year, approximately half a million people are diagnosed with HCC. In recent decades, the prognosis of patients with HCC has improved because more cases are diagnosed and treated at early stages; high-risk patients (i.e., with chronic HBV or HCV infection) are followed more often for the possibility of HCC, and novel treatment options such as locoregional therapy are used with better overall results. The extrahepatic metastases represent a poor prognostic factor. The most common sites of metastasis in advanced hepatocellular carcinoma are the lung (44%), portal vein (35%), and portal lymph nodes (27%). Also, intra-abdominal lymph nodes and bones are common sites. Orbital metastases rarely occur, representing the 3-7% of orbital masses. These metastases are usually found in advanced tumor stages. The mechanism of metastasis to the orbit is difficult to determine. A hematogenous route, as for other primary neoplasms of the abdomen, may be suspected. Tumor cells may circulate through the vena cava, beyond the pulmonary filter to the heart, and finally be distributed to the orbital region through the arterial systemic circulation. We describe herein a case of an adult male with liver cirrhosis due to alcohol abuse who presented with concomitant diagnosis of HCC and orbit metastasis.

The Prognostic Value of Endotoxemia and Intestinal Barrier Biomarker ZO-1 in Bacteremic Sepsis.

BACKGROUND: Intestinal barrier dysfunction exerts a pivotal pathophysiological role in the development of multiple organ dysfunction in sepsis. The present study was undertaken to investigate the potential role of serum intestinal fatty acid-binding protein (I-FABP) and zonula occludens-1 (ZO-1) levels as biomarkers of intestinal barrier dysfunction in bacteremic sepsis. METHODS: Seventy-five patients with bacteremic sepsis of abdominal origin (n = 34) or nonabdominal origin (n = 41) and 12 healthy controls were retrospectively studied. Blood samples collected upon sepsis diagnosis were analyzed for serum ZO-1, I-FABP and endotoxin levels. Prognostic scores Sequential Organ Failure Assessment (SOFA), quickSOFA and Acute Physiology and Chronic Health Evaluation (APACHE-II) were determined over the first 24 hours after sepsis diagnosis and patients' outcome in terms of 28-day mortality was recorded. RESULTS: Serum ZO-1 levels were significantly higher in bacteremic septic patients as compared to controls with no difference between patients with abdominal or extra-abdominal source of infection. Serum I-FABP levels were significantly lower in septic patients as compared to control and this reduction was more evident in patients with bacteremic abdominal sepsis. Serum ZO-1 and endotoxin concentrations were found significantly higher in patients who did not survive from sepsis. In receiver operating characteristic curve analysis, both endotoxin and ZO-1 predicted 28-day mortality. In addition, ZO-1 and endotoxin were correlated with the prognostic scores of qSOFA, SOFA and APACHE II. CONCLUSIONS: The results of this study indicate that serum ZO-1 might be a reliable biomarker of gut barrier dysfunction in sepsis, not affected by the abdominal or extra-abdominal site of infection. ZO-1, measured early at sepsis diagnosis, might represent a valuable additional prognostic tool for patients' outcome.

Gut-origin sepsis in the critically ill patient: pathophysiology and treatment.

INTRODUCTION: Gut permeability is increased in critically ill patients, and associated with the development of the systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS). The pathogenetic link(s) and potential therapies are an area of intense research over the last decades. METHODS: We thoroughly reviewed the literature on gut-origin sepsis and MODS in critically ill patients, with emphasis on the implicated pathophysiological mechanisms and therapeutic interventions. FINDINGS: Intestinal barrier failure leading to systemic bacterial translocation associated with MODS was the predominant pathophysiological theory for several years. However, clinical studies with critically ill patients failed to provide the evidence of systemic spread of gut-derived bacteria and/or their products as a cause of MODS. Newer experimental data highlight the role of the mesenteric lymph as a carrier of gut-derived danger-associated molecular patterns (DAMPs) to the lung and the systemic circulation. These substances are recognized by pattern recognition receptor-bearing cells in diverse tissues and promote proinflammatory pathways and the development MODS. Therefore, the gut becomes a pivotal proinflammatory organ, driving the systemic inflammatory response through DAMPs release in mesenteric lymph, without the need for systemic bacterial translocation. CONCLUSIONS: There is an emerging need for application of sensitive non-invasive and easily measured biomarkers of early intestinal injury (e.g., citrulline, intestinal fatty acid protein, and zonulin) in our everyday clinical practice, guiding the early pharmacological intervention in critically ill patients to restore or prevent intestinal injury and improve their outcomes.

Propranolol reduces systemic oxidative stress and endotoxemia in cirrhotic patients with esophageal varices.

BACKGROUND: The aim of the study was to investigate the effect of propranolol on systemic oxidative stress and endotoxemia in patients with liver cirrhosis and clinically significant portal hypertension evidenced by the presence of esophageal varices. METHODS: Fourteen patients with liver cirrhosis and esophageal varices, not previously been treated with non-selective beta-blockers (NSBB), were prospectively started on propranolol and followed up for three months. Serum early and late lipid peroxidation products (lipid hydroperoxides [LOOH] and malondialdehyde [MDA], respectively), and endotoxin concentrations in peripheral blood were measured. Fourteen age- and sex-matched healthy individuals were used as controls. RESULTS: Patients with liver cirrhosis presented significantly higher systemic oxidative stress and endotoxin concentrations compared to healthy controls (P<0.001). Propranolol treatment for one month significantly reduced serum MDA (P<0.05), LOOH (P<0.01), and endotoxin levels (P<0.01) compared to pre-treatment values, whilst LOOH reached control levels. At three months of propranolol treatment, serum LOOH did not differ significantly from the one-month values, whilst serum endotoxin and MDA levels were further reduced between 3- and 1-month period (P<0.05 and P<0.01, respectively), with the latter reaching control levels. Amelioration of systemic endotoxemia at the one- and three-month follow-up intervals (compared to pre-treatment values) was not correlated with the respective reductions in serum MDA and LOOH. CONCLUSIONS: This is the first study to show that NSBB treatment in liver cirrhosis exerts a significant systemic antioxidant action. This effect seems to be, at least partly, independent of their beneficial effects on intestinal barrier function and endotoxemia.

How well does qSOFA correspond to underlying systemic inflammatory response?

Need for prompt recognition and management of sepsis recently led to the introduction of qSOFA score. However, its association with underlying host inflammatory response remains unclear, while previous studies have challenged its performance in non - intensive care unit (ICU) patients comparing to previously used systemic inflammatory response syndrome (SIRS) criteria. Between June 2016 and April 2017, we performed a prospective observational study in the medical ward of a tertiary hospital to explore the relation of qSOFA ≥ 2 and <2 to underlying inflammatory response, as this is mirrored in levels of serum pro- and anti-inflammatory mediators i.e. IL-6, IL-10 and TNF-α. A total of 100 consecutive patients were finally included in this study. Comparable levels [(pg/ml) median (IQR)] of IL-6 [200 (53-200) vs 65.1 (17.3-200)], IL-10 [ 7 (2.3-170.6) vs 2.3 (2.3-27.7)], and TNF-α [4 (4-46.1) vs 46.06 (4-227.2)] were noted between group of patients with qSOFA ≥ 2 or <2. Nevertheless, prognosis was worse in patients with qSOFA ≥ 2 showing longer length of stay [10 (7-25) vs 5 (3-7) days, p = .03] and lower recovery rates (41 vs 93%, p < .0001). Our results underline the need for prompt management of critically ill patients in presence of systemic inflammatory response regardless of qSOFA score, partly reflecting its low sensitivity comparing to previously used SIRS criteria.

Platelet reactivity in sepsis syndrome: results from the PRESS study.

Platelet activation mediates systemic inflammatory response during infection. However, data on platelet reactivity (PR) varies among different settings. We assessed PR along different stages of sepsis and tried to predict for determinants of its variance. In parallel, we evaluated it as an early bedside diagnostic biomarker. This was an observational prospective cohort study. Incoming patients were assorted to distinct groups of uncomplicated infection, sepsis, and severe sepsis/septic shock. A control group of healthy volunteers was used as comparison. PR was assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU) alongside with levels of major inflammatory markers and whole blood parameters. A total of 101 patients and 27 healthy volunteers were enrolled. PR significantly and reversibly increases during sepsis compared to uncomplicated infection and healthy controls (244 ± 66.7 vs 187.33 ± 60.98, p < 0.001 and 192.17 ± 47.51, p < 0.001, respectively). In severe sepsis, PR did not significantly differ compared to other groups. Sepsis stage uniquely accounts for 15.5% of PR in a linear regression prediction model accounting for 30% of the variance of PR (F = 8.836, p < 0.001). PRU >253 had specificity of 91.2% and sensitivity of 40.8% in discriminating septic from non-septic patients. The addition of PRU to SOFA and qSOFA scores significantly increased their c-statistic (AUC SOFA + PRU, 0.867 vs SOFA, 0.824, p < 0.003 and AUC qSOFA + PRU, 0.842 vs qSOFA, 0.739, p < 0.001), making them comparable (AUC SOFA + PRU vs qSOFA + PRU, p = 0.4). PR significantly and reversibly increases early in sepsis, but seems to exhaust while disease progresses. Bedside assessment of PR can provide robust discriminative accuracy in the early diagnosis of septic patients.

Effect of Immediate Initiation of Antiretroviral Treatment in HIV-Positive Individuals Aged 50 Years or Older.

BACKGROUND: Clinical guidelines recommend immediate initiation of combined antiretroviral therapy for all HIV-positive individuals. However, those guidelines are based on trials of relatively young participants. METHODS: We included HIV-positive antiretroviral therapy-naive, AIDS-free individuals aged 50-70 years after 2004 in the HIV-CAUSAL Collaboration. We used the parametric g-formula to estimate the 5-year risk of all-cause and non-AIDS mortality under (1) immediate initiation at baseline and initiation at CD4 count, (2) <500 cells/mm, and (3) <350 cells/mm. Results were presented separately for the general HIV population and for a US Veterans cohort with high mortality. RESULTS: The study included 9596 individuals (28% US Veterans) with median (interquantile range) age of 55 (52-60) years and CD4 count of 336 (182-513) at baseline. The 5-year risk of all-cause mortality was 0.40% (95% confidence interval (CI): 0.10 to 0.71) lower for the general HIV population and 1.61% (95% CI: 0.79 to 2.67) lower for US Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm. The 5-year risk of non-AIDS mortality was 0.17% (95% CI: -0.07 to 0.43) lower for the general HIV population and 1% (95% CI: 0.31 to 2.00) lower for US Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm. CONCLUSIONS: Immediate initiation seems to reduce all-cause and non-AIDS mortality in patients aged 50-70 years.

HIV-1 subtype characteristics of infected persons living in southwestern Greece.

BACKGROUND: The rapid replication rate of HIV-1, coupled with a high mutation rate and recombination, is the underlying force driving its genetic diversity. In the infected individual, a population of highly related but nonidentical strains exists. At the population level, multiple subtypes often cocirculate, leading to the generation of intersubtype recombinant forms. As a result, the geographic distribution of subtypes and recombinant forms is complex and uneven. Genetic subtyping of HIV-1 isolates has been shown to be helpful for understanding the genetic evolution, the worldwide spread of the virus, and the evaluation of drug resistance. MATERIALS AND METHODS: We determined the genetic heterogeneity of HIV-1 group M in southwestern Greece. Protease and partial reverse-transcriptase sequences were generated from 150 HIV-1-infected individuals attending the Division of Infectious Diseases of Patras University Hospital, Greece, from 2006 to 2012, and analyzed using online subtyping tools and phylogenetic methods. RESULTS: The majority of the infected individuals were male (77%). HIV-1 subtype A1 was responsible for 51.3% of infections, followed by subtypes B (34%), G (4%), F1 (2%), and the circulating recombinant forms 02_AG (2.7%), 14_BG (1.3%), 35_AD (1.3%), and 01_AE (0.7%). Additionally, we identified three cases with a recombinant B/CRF02_AG strain (2%) and one with a recombinant G/GRF_AG strain. Sexual transmission was responsible for 96.3% of cases. Heterosexual transmission was responsible for 70.2% of subtype-A1 infections, whereas subtype B was transmitted by men who have sex with men in 75.5% of cases. Protease substitutions I13V, E35D, M36I, R57K, H69K, and L89M, which serve as drug-resistance support mutations in subtype B, were present in the majority of subtype-A1 sequences of the population. CONCLUSION: HIV-1 infection in southwestern Greece is sexually transmitted and highly heterogeneous. Subtype A1 has surpassed subtype B, and is the most prevalent strain. In the population studied, subtype A1 exhibited certain polymorphisms in the protease region, which may serve as drug-resistance support mutations in subtype B.

Assessment of Oxidative Stress in Septic and Obese Patients Using Markers of Oxidation-reduction Potential.

BACKGROUND/AIM: The novel static (sORP) and capacity (cORP) oxidation-reduction potential markers were examined for assessing oxidative stress in plasma of patients with sepsis. Moreover, the possible effect of obesity-induced oxidative stress on patients with sepsis was investigated. MATERIALS AND METHODS: sORP and cORP markers, as well as the conventional oxidative stress biomarkers total antioxidant capacity (TAC), thiobarbituric acid-reactive substances (TBARS) and protein carbonyls (CARB), were assessed in plasma. RESULTS: sORP marker was increased significantly in the sepsis group, while cORP was significantly lower compared to the control group, indicating oxidative stress. Furthermore, in patients with sepsis, TAC was significantly lower compared to control group. However, obesity had no effect on sORP, cORP and TAC in patients with sepsis, although it increased levels of CARB and TBARS. CONCLUSION: The present results suggest, for the first time, that ORP markers could be used for assessing oxidative stress in patients with sepsis.

Serum lipid profile, cytokine production, and clinical outcome in patients with severe sepsis.

PURPOSE: The purpose of the study is to evaluate the prevalence and clinical significance of hypolipidemia and the relationship to cytokine concentrations and outcomes in septic patients. MATERIALS AND METHODS: A prospective study was undertaken including 50 patients with severe sepsis due to community-acquired infections. Serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein as well as tumor necrosis factor α (TNF-α), interleukin (IL) 6, IL-8, IL-10, and transforming growth factor (TGF) ß1 were determined on admission and days 3 and 10 during hospitalization. RESULTS: Of the 50 patients enrolled, 28 survived, whereas 22 died during their hospital stay. Sepsis survivors had significantly higher HDL-C concentrations than nonsurvivors, whereas all patients with HDL-C values greater than 25 mg/dL survived. Baseline levels of TGF-ß1 were significantly higher in survivors. High-density lipoprotein levels correlated inversely with TNF-α, IL-6, and IL-10 concentrations and positively with baseline TGF-ß1 levels. Independent risk factors of mortality were IL-10 levels on day 3, whereas HDL-C concentration on admission was related to survival. CONCLUSIONS: Low cholesterol and lipoprotein concentrations are detected in septic patients, especially in individuals with poor outcome. High-density lipoprotein cholesterol concentration seems to be an early independent predictive marker of survival in severe sepsis.

Serum cytokine profile in patients with hepatitis B e antigen-negative chronic active hepatitis B and inactive hepatitis B virus carriers.

An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection. We have previously demonstrated no differences of T-lymphocyte subsets in blood between inactive hepatitis B s antigen (HBsAg) carriers and patients with HBeAg-negative chronic active hepatitis B. This study investigated the peripheral blood cytokine profile in patients with HBeAg-negative chronic active hepatitis B infection (Group A, n = 21) and inactive HBsAg carriers (Group B, n = 13). Serum cytokines [interferon (IFN)-γ, tumor necrosis factor-α, interleukin (IL)-1b, IL-4, IL-12, IL-10, IL-2, IL-5, IL-8] were analyzed by using flow cytometry. Patients with chronic active disease presented with significantly decreased levels of IFN-γ and IL-10 compared to inactive carriers (P = 0.048 and P = 0.008, respectively). In HBeAg-negative chronic active hepatitis B patients, a significant negative correlation of IFN-γ levels with serum hepatitis B viral load was noted (P = 0.021). In conclusion, patients with HBeAg-negative chronic active hepatitis B and HBsAg inactive carriers display a different cytokine profile. Decreased Th1 response observed in patients with chronic active hepatitis B could be implicated in the persistence of virus replication and ongoing progression of liver disease.

Alterations in T-lymphocyte subpopulations in patients with complicated liver cirrhosis.

AIM: To investigate possible alterations of T-lymphocyte subpopulations in patients with cirrhosis complicated with infection and variceal bleeding, and to evaluate the relationship between T-lymphocyte subpopulations and outcome. PATIENTS AND METHODS: This was a prospective study on 99 patients with liver cirrhosis, who were admitted to a university hospital over a period of 18 months. Twenty-six patients (37.6%, group A) were admitted for reasons other than infection or bleeding, 24 (34.7%, group B) presented with sepsis, and 19 (27.5%, group C) were admitted with variceal bleeding. A group of 30 healthy individuals admitted to the hospital without cirrhosis and served as the control group. We evaluated T-cell subsets CD3, CD4, CD5, CD8, CD56, and CD20 as well as CD14 and CD64 subsets of monocytes and neutrophils by using flow cytometry. Measurements for group A were taken only on admission, while for patients of group B and C measurements were repeated on the third and the last hospital day. RESULTS: T-cell subsets (CD3, CD4, CD5, CD8, CD56, and CD20 as well as CD14 and CD64 subsets of monocytes and neutrophils) were reduced in septic cirrhotics, but this reduction was not statistically significant compared to the other groups. A significant decrease was observed in T helper cells between cirrhotic patients with and without variceal bleeding (day 3: CD4: 293 ± 214 versus 442 ± 277 [P < 0.049]; discharge day: CD4:178 ± 113 versus 442 ± 277 [P < 0.003]). Concerning phagocytic potential as detected by CD14 and/or CD64 expression on monocytes and neutrophils, a significant decrease was noted in septic versus nonseptic cirrhotics (day 1: 61.66 ± 40.16 versus 252 ± 73 [P < 0.039]; day 3: 66.99 ± 34.64 versus 252 ± 73 [P < 0.042]). CONCLUSIONS: Our study showed that the T helper cells and phagocytic potential of monocytes and neutrophils are decreased in patients with liver cirrhosis complicated by sepsis and variceal bleeding. Particularly, these abnormalities seem to be more pronounced in cirrhosis with variceal bleeding. To our knowledge, this is the first study to show these T-cell abnormalities in patients with cirrhosis. Further studies are needed to confirm these findings.

Bacteraemia due to Cedecea davisae in a patient with sigmoid colon cancer: a case report and brief review of the literature.

Cedecea spp. represent a new member of the Enterobacteriaceae family, and although they are commonly described, they have rarely been reported as causes of invasive infection. The species' inherent resistance to antibiotics makes their management extremely challenging, especially in the context of immunocompromise when infections occur. We hereby report a rare case of Cedecea davisae bacteraemia in a patient with stage IV sigmoid colon cancer followed by a brief review of the literature.

Malaria: a haematological disease.

Plasmodium falciparum malaria remains a major cause of mortality throughout the tropical world. Haematological abnormalities are considered a hallmark of malaria, bearing an impact on final outcome and representing indices of prognostic and follow-up value. These include severe anaemia, coagulation disturbances, leukocyte numerical or functional changes and spleen involvement. Anaemia involves red blood cell lysis due to parasite invasion, as well as mechanisms of intravascular haemolysis and decreased erythropoiesis. Exchange or blood transfusion is mainly recommended in the management of these patients. Haemorrhagic complications in severe malaria are relatively rare despite prominent thrombocytopenia and dysfunction in the coagulation pathway. Numerical, as well as functional changes in the white blood cell are less dramatic than other blood cell series, but still, remain a significant index of disease progression and ultimate prognosis. Finally, the role of the spleen in severe malaria is multifactorial. Care and vigilance should be taken against splenic rupture which is fatal and can occur despite appropriate antimalarial prophylaxis and treatment.

Right-sided infective endocarditis: surgical management.

Right-sided infective endocarditis (RSIE) accounts for 5-10% of all cases of infective endocarditis and is predominantly encountered among injecting drug users (IDUs). RSIE diagnosis requires a high index of suspicion as respiratory symptoms predominate. Prognosis of isolated RSIE is favourable, and most cases (70-80%) resolve following antibiotic administration. Surgical intervention is indicated in patients with persistent infection that does not respond to antibiotic therapy, recurrent pulmonary emboli, intractable heart failure and if the size of a vegetation increases or persists at >1 cm. Techniques can be divided into 'prosthetic' (valve replacement or prosthetic annular implantation) or 'non-prosthetic' ones (Kay's or De Vega's annuloplasty, bicuspidalization or valvectomy). In IDUs who run a high risk of complications, vegetectomy and valve repair, avoiding artificial material should be considered as the first line of surgical management as is associated with better late survival.