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Background: Genomic instability is a common feature in hepatocellular carcinoma. Deregulation of replication licensing factors has been shown to trigger DNA damage response contributing to genomic instability. Overexpression of DNA replication licensing factors chromatin licensing and DNA replication factor 1 (CDT1) and minichromosome maintenance complex component 7 (MCM7) has been previously reported in several human cancers. The aim of the present study was to evaluate the expression and prognostic significance of CDT1 and MCM7 in association with DNA damage response markers and p53 in patients with hepatocellular carcinoma.Methods: Expression of CDT1, MCM7, p-H2A histone family member X (H2AX), phospho-ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia rad3-related (ATR) substrate, and p53 was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded surgical specimens from 111 patients who underwent hepatectomy for hepatocellular carcinoma. Statistical analysis was performed to evaluate associations between the studied proteins, clinicopathological parameters, and patient survival.Results: CDT1 expression correlated with p-H2AX (p = 0.038), while MCM7 correlated with p-H2AX and phospho-ATM/ATR substrate (p < 0.001). Increased CDT1 expression was associated with higher tumor grade (p = 0.006) and tumor-node-metastasis (TNM) stage (p = 0.033). High CDT1 expression correlated significantly with reduced overall survival (60.8 and 26.5 % vs 82.8 and 53.0 %, for low CDT1 expression, at 2 and 5 years, respectively, p = 0.012) and was identified by multivariate analysis as an independent predictor of poor overall survival (p = 0.049).Conclusions: Overexpression of CDT1 and MCM7 in hepatocellular carcinoma correlates with DNA damage response, and CDT1 overexpression is a significant prognostic biomarker in hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Summary: Patients with liver cirrhosis are prone to serious complications by almost all systems, leading to high morbidity rates and even death. Although the functional and structural derangement of diverse vital organs developed in the course of advanced liver disease is the result of one entity (cirrhosis) there are various treatment modalities for each system’s complications, which are often ineffective. Identification of the link which connects the complications of cirrhosis from diverse systems might lead to a global, simple and more effective treatment approach for patients with cirrhosis. Accumulating evidence from experimental and clinical studies suggests that intestinal barrier dysfunction and subsequent gut-derived endotoxemia represent an important common pathogenetic mechanism in the development of diverse complications of cirrhosis. Intestinal oxidative stress seems to be a pivotal factor of gut barrier dysfunction in cirrhosis through promotion of enterocyte apoptosis, modulation of intestinal tight junctions and impairment of intestinal brush border function. In parallel, oxidative stress plays a fundamental role in the aggravation of liver injury and in the structural and/or functional derangements of diverse organs complicating the course of cirrhosis. Our hypothesis is that antioxidant treatments could prevent in a global way virtually all cirrhosis-related complications acting in two crucial levels in the pathophysiological cascade of events: (a) in a primary level, which is the gut–liver axis by ameliorating gut-derived endotoxemia, through prevention of intestinal oxidative stress and its associated gut barrier dysfunction, concurrently conferring direct antioxidant protection in the liver tissue and (b) in a secondary level, which refers to the diverse organs whose function is affected by liver cirrhosis, by preventing their oxidant-related structural and functional derangements. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To investigate whether stress hyperglycemia affects the production of the main pro- and anti-inflammatory cytokines and the 28-day hospital mortality in patients with severe sepsis. Methods: The study included 62 patients with severe sepsis, divided in three groups according to their glycemic profile within 24h after admission: patients with stress hyperglycemia (group SH, n =16), diabetes mellitus type II (group DM, n =27), and normal glucose levels (group NG, n =19). The serum levels of the cytokines TNF-alpha, IL-6, IL-10 and TGFbeta-1 were measured within 24h after admission. Results: A higher percentage of septic patients with stress hyperglycemia died compared to diabetic patients (43.7 vs. 14.8%) and group NG (43.7 vs. 5.2%). Group SH had higher SOFA score and levels of IL-6 and IL-10 than group DM and group NG. It also had higher levels of TNF-alpha than group DM but not group NG. There was no difference in the levels of TGFbeta-1 among the three groups. Non-survivors had higher levels of IL-10, no difference was detected for IL-6, TNF-alpha, IL-10/TNF-alpha ratio and TGFbeta-1. Interleukin-10 values, mean fasting glucose values and age were found as prognostic factors associated with outcome. Conclusions: Stress hyperglycemia is associated with increased cytokine production and an adverse clinical outcome in patients with severe sepsis. [Copyright &y& Elsevier]

Presents a case of Salmonella sepsis syndrome with bacteremia and vertebral osteomyelitis (VO) in an immunocompetent patient. Signs and symptoms; Treatment; Pathogenesis of Salmonella VO.

Caring for the elderly has always been challenging for the intensive care unit (ICU) physician. Concerns like frailty, comorbidities, polypharmacy and advanced directives come up even before admission into the unit. The COVID-19 pandemic has put forward a variety of issues concerning elderly populations, making the topic more relevant than ever. Admittance to the ICU, an unequivocally multifactorial decision, requires special consideration from the side of the physician when caring for an elderly person. Patients' wishes are to be respected and thus given priority. Triage assessment must also account for age-related physiological alterations and functional status. Once in the ICU, special attention should be given to age-related specificities, such as therapeutic interventions' controversial role, infection susceptibility, and post-operative care, that could potentially alter the course of hospitalization and affect outcomes. Following ICU discharge, ensuring proper rehabilitation for both survivors and their caregivers can improve long-term outcomes and subsequent quality of life. The pandemic and its implications may limit the standard of care for the elderly requiring ICU support. Socioeconomic factors that further perplex the situation must be addressed. Elderly patients currently represent a vast expanding population in ICU. Tailoring safe treatment plans to match patients' wishes, and personalized needs will guide critical care for the elderly from this time forward. • Age-related specificities impact ICU care on multiple levels. • Incorporating patient's wishes into the therapeutic plan is of paramount importance. • Frailty assessment is crucial for patient selection and disease prognosis. • Comorbidities and immunosenescence influence decision-making and outcomes in the ICU. • Structuring individualized treatment plans for the elderly is essential. [ABSTRACT FROM AUTHOR]

Highlights: [•] Among patients with sepsis, endotoxemia is greater after community-acquired pneumonia and primary bacteremia. [•] Circulating LPS decrease within the first 48h in survivors. [•] Circulating monocytes from patients with significant endotoxemia become hyporesponsive to ex vivo stimulation. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to look for factors that affect attitudes to antibiotic use in Greek urban settings. By using a questionnaire-based survey, we conducted 323 face-to-face interviews (173 adults, 150 carers of children). In the adult group, 74.6% admitted using non-prescribed antibiotics, while only 22.7% of parents had administered non-prescribed antibiotics to their children. Around 50% of adults discontinued therapy earlier, more than 10% did not follow the correct dosage instructions and about 55% admitted using leftover antibiotics. Of the parents, 18.7% discontinued therapy earlier and 7.3% admitted keeping leftover antibiotics. Our results showed that adults were likely to show unsatisfactory compliance and to use non-prescribed antibiotics, while parents were less likely to use non-prescribed antibiotics for their children and were more compliant. [Copyright &y& Elsevier]

Aims: We sought to determine whether primary outcomes differ between non-ICU septic patients with and without type 2 diabetes (T2D).Methods: This study utilized the Hellenic Sepsis Study Group Registry, collecting nationwide data for sepsis patients since 2006, and classified patients upon presence or absence of T2D. Patients were perfectly matched for a) Sepsis 3 definition criteria (including septic shock) b) gender, c) age, d) APACHE II score and e) Charlson's comorbidity index (CCI). Independent sample t-test and chi-square t-test was used to compare prognostic indices and primary outcomes.Results: Of 4320 initially included non-ICU sepsis patients, 812 were finally analysed, following match on criteria. Baseline characteristics were age 76 [±10.3] years, 46% male, APACHE II 15.5 [±6], CCI 5.1 [±1.8], 24% infection, 63.8% sepsis and 12.2% septic shock. No significant difference was noted between two groups in qSOFA, SOFA, or suPAR1 levels (p = 0.7, 0.1 & 0.3) respectively. Primary sepsis syndrome resolved in 70.9% of cases (p = 0.9), while mortality was 24% in 28-days time. Cause of death was similar between patients with and without T2D (sepsis 17.8% vs 15.8%, heart event 3.7% vs 3.2%, CNS event 0.5% vs 0.5%, malignancy 0.7% vs 2% respectively, p = 0.6).Conclusions: DM does not appear to negatively affect outcomes in septic patients not requiring ICU. [ABSTRACT FROM AUTHOR]

• Twenty-eight-day outcomes of patients with pneumonia were analysed retrospectively. • All patients had sepsis according to the 2016 definition. • Intake of clarithromycin with one β-lactam was associated with survival benefit. • Superiority over azithromycin intake and quinolone monotherapy was found. Although analysis of retrospective studies has documented survival benefit from the addition of a macrolide to the treatment regimen for community-acquired pneumonia (CAP), no data are available to determine if there is differential efficacy between members of the macrolide family. In order to investigate this, an analysis was undertaken of data from 1174 patients with CAP who met the new Sepsis-3 definitions and were enrolled prospectively in the data registry of the Hellenic Sepsis Study Group. Four well-matched treatment groups were identified with 130 patients per group: clarithromycin and β-lactam; azithromycin and β-lactam; respiratory fluoroquinolone and β-lactam monotherapy. The primary endpoint was comparison of the effects of clarithromycin with β-lactam monotherapy on 28-day mortality. The secondary endpoint was resolution of CAP. Mortality rates for the clarithromycin, azithromycin, respiratory fluoroquinolone and β-lactam groups were 20.8%, 33.8% (P =0.026 vs clarithromycin), 32.3% (P =0.049 vs clarithromycin) and 36.2% (P =0.009 vs clarithromycin), respectively. After stepwise Cox regression analysis among all groups, clarithromycin was the only treatment modality associated with a favourable outcome (hazard ratio 0.61; P =0.021). CAP resolved in 73.1%, 65.9% (P =0.226 vs clarithromycin), 58.5% (P =0.009 vs clarithromycin) and 61.5% (P =0.046 vs clarithromycin) of patients, respectively. It is concluded that the addition of clarithromycin to the treatment regimen of patients with severe CAP leads to better survival rates. [ABSTRACT FROM AUTHOR]

Summary: Background: The Crimean-Congo hemorrhagic fever virus (CCHFV) presents a wide distribution, with the Balkan Peninsula being among the endemic regions. To date, only one CCHF case has been reported in Greece; however, based on seroprevalence data, there is evidence that CCHFV circulates in the country. Achaia is a prefecture in western Greece that has not previously been studied for CCHFV. Objectives: The aim of this study was to estimate the seroprevalence of CCHFV in humans in Achaia Prefecture, Greece, and to assess possible factors playing a role in seropositivity. Methods: A total of 207 serum samples from people of all age groups, from both urban and rural areas, were prospectively collected and tested for IgG antibodies against CCHFV. Results: The overall seroprevalence was 3.4%, with significant differences among municipalities. An agro-pastoral occupation, contact with sheep and goats, former tick bite, increasing age, and living at an altitude of ≥400 m, on specific land cover types, were significantly associated with CCHFV seropositivity. Conclusions: A relatively high seroprevalence was detected in a previously unstudied region of Greece, where CCHFV infection seems to occur mainly through tick bites. Further investigations are needed to identify the circulating CCHFV strains in Greece, in order to gain a better understanding of CCHFV ecology and epidemiology in the country. [ABSTRACT FROM AUTHOR]