The Diagnostic and Prognostic Role of Vascular Endothelial Growth Factor C in Sepsis and Septic Shock.

INTRODUCTION: Variations in the expression of vascular endothelial growth factor (VEGF) could be used as a biomarker in critically ill patients with sepsis and septic shock. Inflammation potently upregulates VEGF-C expression via macrophages with an unpredictable response. This study aimed to assess one of the newer biomarkers (VEGF-C) in patients with sepsis or septic shock and its clinical value as a diagnostic and prognostic tool. MATERIAL AND METHODS: The study involved 142 persons divided into three groups. Group A consisted of fifty-eight patients with sepsis; Group B consisted of forty-nine patients diagnosed as having septic shock according to the Sepsis -3 criteria. A control group of thirty-five healthy volunteers comprised Group C. Severity scores, prognostic score and organ dysfunction score, were recorded at the time of enrolment in the study. The analysis included specificity and sensitivity of plasma VEGF-C for diagnosis of septic shock. Circulating plasma VEGF-C levels were correlated with the APACHE II, MODS and severity scores and mortality. RESULTS: The mean (SD) plasma VEGF-C levels in septic shock patients (1374(789) pg./m), on vasopressors at the time of admission to the ICU, were significantly higher 1374(789)pg./mL, compared the mean (SD) plasma VEGF-C levels in sepsis patients (934(468) pg./mL); (p = 0.0005, Student's t-test.) Plasma VEGF-C levels in groups A and B were shown to be significantly correlated with the APACHE II (r = 0.21, p = 0.02; r = 0.45, p = 0.0009) and MODS score (r = 0.29, p = 0.03; r = 0.4, p = 0.003). There was no association between plasma VEGF-C levels and mortality [p = 0.1]. The cut-off value for septic shock was 1010 pg./ml. CONCLUSIONS: VEGF-C may be used as a prognostic marker in sepsis and septic shock due to its correlation with APACHE II values and as an early marker to determine the likelihood of developing MODS. It could be used as an early biomarker for diagnosing patients with septic shock.

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression.

BACKGROUND: The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. METHODS: We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. RESULTS: TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. CONCLUSIONS: TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

The role of interleukin-6 as an early predictor of sepsis in a murine sepsis model.

AIM: Evaluating the role of interleukin-6 (IL-6) as an early predictor of sepsis in a murine model. MATERIALS AND METHODS: The study divided 26 Wistar rats into two experimental groups in which sepsis was induced through the intraperitoneal injection of different Escherichia coli cultures [Group 1: Extended-spectrum beta-lactamase (ESBL)-producing culture and Group 2: Standardized ATCC35218 culture] and a control group. IL-6 levels were determined at 5 and 24 hours post-inoculation and immunohistochemistry (IHC) was performed on tissue samples from the sacrificed animals. RESULTS: Mean plasma IL-6 levels in Group 1 peaked at 5 hours [37.4 pg∕mL; standard deviation (SD) = 2.4 pg∕mL] and decreased at 24 hours (34 pg∕mL; SD=3.2 pg∕mL) after inoculation. IL-6 levels in Group 1 were elevated compared to Group 2, at 5 hours (33.7 pg∕mL; SD=3.3 pg∕mL; p=0.019) and non-significantly so at 24 hours (32.5 pg∕mL; SD=2.4 pg∕mL; p=0.233). The results did not show an increase over control levels at either 5 hours (37.6 pg∕mL; SD=3.4 pg∕mL) or 24 hours (40.8 pg∕mL; SD=2.9 pg∕mL) after inoculation. The IHC shows a varying degree of IL-6 expression across all organ types studied. No statistically significant correlations were found between the tissue level quantification of IL-6 and serum values at 24 hours in either group. CONCLUSIONS: For an early stage of infection/inflammation, serum levels of IL-6 are not correlated with tissue-level inflammation disproving a potential role of IL-6 as a very precocious diagnostic and predictor test. Accumulation of IL-6 in lung, kidney and spleen tissue can be observed from the beginning of inflammation.

Abdominal Sepsis: An Update.

Despite the significant development and advancement in antibiotic therapy, life-threatening complication of infective diseases cause hundreds of thousands of deaths world. This paper updates some of the issues regarding the etiology and treatment of abdominal sepsis and summaries the latest guidelines as recommended by the Intra-abdominal Infection (IAI) Consensus (2017). Prognostic scores are currently used to assess the course of peritonitis. Irrespective of the initial cause, there are several measures universally accepted as contributing to an improved survival rate, with the early recognition of IAI being the critical matter in this respect. Immediate correction of fluid balance should be undertaken with the use of vasoactive agents being prescribed, if necessary, to augment and assist fluid resuscitation. The WISS study showed that mortality was significantly affected by sepsis irrespective of any medical and surgical measures. A significant issue is the prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae in the clinical setting, and the reported prevalence of ESBLs intra-abdominal infections has steadily increased in Asia. Europe, Latin America, Middle East, North America, and South Pacific. Abdominal cavity pathology is second only to sepsis occurring in a pulmonary site. Following IAI (2017) guidelines, antibiotic therapy should be initiated as soon as possible after a diagnosis has been verified.

The value of histopathological diagnosis in the elderly patients with granulomatous dermatoses. Case series.

Granulomatous inflammations are a particular type of chronic septic or aseptic inflammation, in which infectious or non-infectious agents are difficult to eliminate by the immune system. These are type IV hypersensitivity reactions mediated by pre-sensitized T-lymphocytes cells CD4+ and CD8+ lymphocytes. Disorders included in this category are: tuberculosis, leprosy, syphilis, sarcoidosis, type I diabetes, multiple sclerosis, Crohn's disease and rheumatoid arthritis. At cutaneous level, this pattern of granulomatous reaction is characterized by a chronic inflammation with formation of granulomas consisting of a variable number of histiocytes, multinucleated giant cells and lymphocytes. Granulomatous dermatoses should be differentiated from other primary or secondary lesions affecting the skin such as inflammation or tumors. Often granulomatous dermatoses can be confused with other skin disorders, both clinically and histological. Histopathology examination can add important information and clarify the diagnosis. This paper presents a series of three clinical cases of granulomatous skin occurring in the elderly patients confirmed at histology examination. Clinical and histology criteria were analyzed, along with specific differential diagnosis, based on data from the literature.

An Evaluation of Serum Procalcitonin and C-Reactive Protein Levels as Diagnostic and Prognostic Biomarkers of Severe Sepsis.

BACKGROUND: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR), urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT) is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP) is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body. The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis. MATERIAL AND METHOD: Sixty patients, diagnosed as being "septic", were admitted to the intensive care unit (ICU). Based on laboratory results and clinical findings a diagnosis of "severe sepsis" was made, and correlated with PCT and CRP values. The APACHE II, SAPS II and SOFA severity scores were calculated, analyzed and correlated with PCT and CRP. RESULTS: Fifty two patients (86.67%) presented with criteria for severe sepsis. Multivariate correlation analysis indicated a significant positive association between procalcitonin and all severity scores (APACHEII p<0.0001, SOFA p<0.0001, SAPS II p<0.0001). CRP proved to be significantly correlated only with the SAPS II score (p=0.0145). Mortality rate was high, with 48 patients (80%) dying. There was no significant correlation between the levels of the PCT and CRP biomarkers and severe sepsis (p=0.2059 for PCT, p=0.6059 for CRP). CONCLUSIONS: The procalcitonin levels are highly correlated with the severity scores (APACHE II, SAPS II, SOFA) regularly used in ICUs and therefore can be used for determining the severity of the septic process. Quantitive procalcitonin and C-reactive protein analysis was not shown to be useful in diagnosing severe sepsis. However, PCT and CRP can be used to predict the fatal progression of the septic patient.