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.

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.

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.

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.

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.

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.

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.

Unusual manifestation of brucellosis: liver abscess and pancytopenia caused by Brucella melitensis.

Brucellosis is a zoonosis with a worldwide distribution, and still endemic in Greece. Although hepatic involvement is common, cholecystitis and hepatic abscesses represent rare complications of the disease. Hematological manifestations of brucellosis include various abnormalities such as anemia and leucopenia, but the disease rarely presents with pancytopenia. We present a case of liver abscess and pancytopenia caused by Brucella melitensis in a 54-year-old worker who consumed unpasteurized dairy products. The patient was admitted twice to our hospital and finally diagnosed as suffering from a gallbladder empyema complicated by a liver abscess, for which he underwent surgery. Blood cultures drawn on his second admission isolated Brucella melitensis. Repeated serum agglutination testing for brucella turned out negative.

Stress-induced hyperglycemia in patients with severe sepsis: a compromising factor for survival.

OBJECTIVE: To study the clinical and laboratory characteristics of patients with severe sepsis and baseline hyperglycemia and investigate the impact of hyperglycemia on the final outcome. PATIENTS: A total of 265 patients admitted with severe sepsis in 3 major hospitals in South-Western Greece, during a 1-year period, were included in the study. Patients were divided in 3 groups according to their glycemic profile at admission: patients with stress hyperglycemia (group SH, n=47), with diabetes mellitus (group DM, n=65), and with normal glucose level (group NG, n=153). Hyperglycemia was defined as an admission or in-hospital fasting glucose level of >or=126 mg/dL or a random blood glucose level of >or=200 mg/dL on >or=2 determinations. RESULTS: A total of 42.2% of patients with severe sepsis had baseline hyperglycemia with 17.7% having sepsis-induced stress hyperglycemia. No family history was noted in the SH group. A higher percentage of septic patients with stress hyperglycemia died compared with patients with normal glucose levels (42.5% versus 13.7%) and diabetics (42.5% versus 24.6%). Group DM had also a poorer prognosis than group NG (24.6% versus 13.7%). A positive correlation was detected between the fasting blood glucose levels of group SH and the severity of sepsis indicated by sepsis-related organ failure assessment score. CONCLUSION: Baseline hyperglycemia, including stress-induced hyperglycemia, is common in patients with severe sepsis. Stress-induced hyperglycemia is related to a more severe disease and poorer prognosis.

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.

Red blood cell deformability in patients with sepsis: a marker for prognosis and monitoring of severity.

Sepsis in different states of severity (sepsis, severe sepsis, septic shock and adult respiratory distress syndrome (ARDS)) is associated with microcirculatory blood flow abnormalities leading to decreased red blood cell's (RBC's) deformability, impaired oxygen delivery to tissues and organs failure. The main goal of the present study, was to first determine the values of RBC's deformability, in the course of patients treated in an Intensive Care Unit (ICU) for basically sepsis and then deteriorated states and secondly to establish the prognostic efficiency of the test. For this purpose a filtration method and the hemorheometer, was used to determine experimentally the RBC's deformability, by measuring the RBC's Index of Rigidity (IR). Our results indicated that the IR was significantly increased in all patient groups and it was found to be approximately 51% higher in patients with sepsis, 229% in patients with severe sepsis, 1285% in patients with septic shock and 923% in patients with ARDS than in the healthy donors. The relationships between IR and Simplified Acute Physiology Score II (SAPS) and IR and Projected Mortality (PM) were found to be IR = 2.0237(SAPS) - 58.807 (r=0.731) and IR = 1.0671(PM) - 5.9829 (r=0.726) respectively. Our findings imply a significant impairment of the membrane's deformability possibly due to changes in its structure. It seems that the RBC's deformability is a useful mechanical parameter to estimate the prognosis and monitor patients suffering from different severity levels of sepsis.

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.

Prevalence of liver steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis.

OBJECTIVES: The clinical significance of hepatic steatosis in chronic hepatitis B virus patients is poorly understood. The purpose of this study was to determine risk factors for liver steatosis in chronic hepatitis B patients and its relationship with fibrosis. METHODS: We retrospectively evaluated liver biopsies from patients with chronic hepatitis B treated in our department. Patients co-infected with other viruses (hepatitis C virus, HIV) or suffering from liver disease of any other cause were excluded from the study, as well as patients consuming alcohol above 30 g/day for males or 20 g/day for females. Liver steatosis, necroinflammation and fibrosis were assessed. RESULTS: A total of 233 patients with chronic hepatitis B were included in the study. The mean age was 44.7+/-16.2 years. There were 164 men (70.4%) and 69 women (29.6%). The majority of patients were HbeAg-negative, 196/233 (84.1%). Thirty-seven patients had cirrhosis (15.9%). Steatosis was present in 42 patients (18%). Steatosis was independently associated with fasting glucose level (P=0.019) and being overweight (body mass index >or=25; P=0.021). No correlation was found with stage of fibrosis, grade of inflammation, alcohol use or other parameters. Ninety-four out of 233 patients (40.3%) had advanced fibrosis. Patients with advanced fibrosis were older than those with minimal or no fibrosis (47.6+/-17 versus 42.3+/-15.2 years, P=0.024) and more frequently had a higher grade of necroinflammation activity (57/94 (60.6%) versus 26/139 (18.7%), P<0.0001). There was no significant association between advanced fibrosis and the presence of steatosis or mild alcohol consumption. CONCLUSION: Hepatic steatosis is present in 18% of our patients with biopsy-proven chronic hepatitis B. Steatosis is independently associated only with body mass index and fasting glucose level, risk factors for metabolic steatohepatitis, and was not correlated with the degree of fibrosis.

Liver steatosis is an independent risk factor for treatment failure in patients with chronic hepatitis C.

OBJECTIVES: Hepatic steatosis is a common feature of chronic hepatitis C. The purpose of this study was to determine factors related to the presence of steatosis and to define the role of steatosis in the response to antiviral treatment in chronic hepatitis C patients. METHODS: We retrospectively analysed all patients with chronic hepatitis C treated in a 5 year period in our department. Patients were included in the study only if a pretreatment liver biopsy specimen was available for evaluation. All patients treated either with interferon in combination with ribavirin, or with pegylated interferon in combination with ribavirin were included irrespectively of their response (early, end of treatment and/or sustained) to antiviral therapy. RESULTS: A total of 116 patients with chronic hepatitis C were included in the study with a mean age of 45.5 +/- 14.1 years. Steatosis was present in 52 patients (44.8%). On univariate analysis age, P = 0.04 and body mass index > or = 25, P = 0.004 were correlated with the presence of steatosis and on multivariate analysis only body mass index > or = 25, P = 0.032. Advanced fibrosis was not found associated with steatosis. Sixty patients out of 116 (51.7%) had sustained virological response (SVR). In particular 42 out of 64 patients with no steatosis (65.6%) had SVR compared to 20 out of 52 patients (38.4%) with any degree of steatosis (P = 0.009). Patients with genotype 2 or 3 had a more favourable outcome compared to patients with 1 or 4 genotypes, 63.2% vs 49.2%, P = 0.032. Also increased age (P = 0.0001), gamma glutamyltransferase (GGT) (P = 0.029), no history of intravenous drugs use (P = 0.001) and advanced fibrosis on pretreatment biopsy (P = 0.046) were correlated with treatment failure. On multivariate analysis significant independent association with SVR was found with the presence of steatosis on pretreatment biopsy (P = 0.004), increased GGT (P = 0.005) and genotype (P = 0.017). CONCLUSION: Steatosis in the liver biopsy performed before the beginning of antiviral treatment was found to be associated only to the body mass index of the patients and to be a strong independent factor for treatment failure.

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.

Viraemia, cryoglobulins and autoantibodies in haemodialysis patients infected with hepatitis C virus.

OBJECTIVES: The clinical features of hepatitis C virus (HCV) infection depend on the immune and autoimmune reactions induced by the virus. Chronic renal failure might alter the pattern of these reactions. The aim of this study was to determine the prevalence of cryoglobulinaemia, the frequency of autoantibodies and HCV viral load in HCV infected Greek patients on chronic haemodialysis. METHODS: Seventy-three HCV Ab(+) patients on maintenance haemodialysis and 87 otherwise normal patients with chronic HCV infection were evaluated for the presence of cryoglobulins, autoantibodies and viral markers. RESULTS: Cryoglobulins were detected in 22/73 (30.1%) haemodialysis patients and in 23/87 (26.4%) patients with normal renal function (NS). The mean cryocrit value was significantly lower in the haemodialysis group ( = 0.002). Haemodialysis patients had significantly higher levels of C4 component of complement and lower incidence of rheumatoid factor than those of patients with normal renal function. Serum HCV RNA levels were found significantly lower in the haemodialysis group (median, 2.20 Meq/ml; range, 119.9 Meq/ml) than in the group with normal renal function (median, 4.50 Meq/ml; range, 114.9 Meq/ml; = 0.046). The distribution of genotypes was not different between the two groups. CONCLUSIONS: There are subtle differences in autoimmune features of HCV infection if the patients are also haemodialysed for renal failure. HCV viral load is lower in haemodialysis patients, with no difference in the HCV genotype prevalence. The clinical significance of these findings is unknown.

Clinical prognostic markers in patients with severe sepsis: a prospective analysis of 139 consecutive cases.

OBJECTIVES: To analyze the clinical characteristics and determine predictive factors of mortality in previously healthy individuals suffering from severe sepsis. METHODS: The study included 139 patients with severe sepsis, admitted to the Department of Medicine over a two years period. Data recorded on admission included demographic information, blood pressure, core temperature, white blood count, hepatic and renal function tests, coagulation factors, blood gases, serum lactic acid levels, simplified acute physiology score (SAPS-II) and Glasgow Coma Scale (GCS). RESULTS: On admission, 62 patients were hypotensive, 52 had signs of diffuse intravascular coagulation (DIC), 72 had renal and 27 hepatic dysfunction. The overall mortality rate was 27.3%. Twenty-nine patients had septic shock on admission with a mortality rate of 62.07%. Hypoxemia, metabolic acidosis and the presence of DIC were more frequent in non-survivors, who also had significantly higher SAPS-II on admission and days 3 and 7. Independent factors associated with mortality were older age, septic shock, DIC and acute renal failure on admission, as well as SAPS-II at all time points and lactic acid levels on day 7. CONCLUSIONS: Septic patients with advanced age, septic shock, renal failure, DIC and metabolic acidosis on admission are at increased risk of mortality. The sustained presence of high SAPS-II and lactacidemia one week after admission are also important risk factors of poor outcome.