The threat of carbapenem resistance in Eastern Europe in patients with decompensated cirrhosis admitted to intensive care unit.

BACKGROUND: Multidrug-resistant organisms are an increasing concern in patients with decompensated cirrhosis. AIM: We aimed to evaluate the prevalence of infections with carbapenem-resistant Enterobacteriaceae in patients with decompensated cirrhosis. METHODS: Patients with decompensated cirrhosis admitted to ICU were included. The isolated Enterobacteriaceae strains were tested for carbapenemase-producing genes using the Roche LightMix® Modular VIM/IMP/NDM/GES/KPC/OXA48-carbapenemase detection kit. RESULTS: 48 culture-positive infections were registered in 75 patients with acutely decompensated cirrhosis. Thirty patients contracted a second infection. 46% of bacteria isolated at admission and 60% of bacteria responsible for infections identified during ICU-stay were multiresistant. ESBL+ Enterobacteriaceae were predominant at admission, while carbapenem-resistance was dominant in both Enterobacteriaceae and Non-Fermenting-Gram-Negative Bacteria responsible for infections diagnosed during hospitalisation. OXA 48 or KPC type carbapenemases were present in 30% of the analyzed Enterobacteriaceae and in 40% of the phenotypically carbapenem-resistant Klebsiella pneumoniae strains. The length of ICU stay was a risk-factor for a second infection (p=0.04). Previous carbapenem usage was associated with occurence of infections with carbapenem-resistant Gram-negative bacteria during hospitalization (p=0.03). CONCLUSION: The prevalence of infections with carbapenem-resistant Enterobacteriaceae is high in patients with decompensated cirrhosis admitted to ICU. Carbapenemase-producing genes in Enterobacteriaceae in our center are blaOXA-48 and blaKPC.

Acute Intermittent Porphyria - an Unexpected Association in a Patient with Newly Diagnosed Crohn's Disease.

The association of Crohn's disease (CD) with acute intermittent porphyria (AIP), both without a family or personal pathological history, is a very rare clinical possibility. We present the case of a 23-year-old male diagnosed on the same admission with ileal CD and with an AIP crisis. The diagnosis was challenging as the symptoms overlapped. Crohn's disease was complicated with intestinal occlusion and sepsis; the inflammatory, metabolic and septic changes represented the trigger factor for the first AIP seizure. The neurological symptoms were the key element for AIP diagnosis. The presence of atypical extra-intestinal manifestations in CD patients should raise also the possibility of AIP.

Are presepsin and resistin better markers for bacterial infection in patients with decompensated liver cirrhosis?

BACKGROUND: Bacterial infections impair prognosis in patients with cirrhosis. Presepsin and, more recently, resistin are promising markers of infection and sepsis in patients without cirrhosis. AIMS: The aim of our study was to assess the performance of presepsin and resistin as early markers of infection compared with C reactive protein (CRP) and procalcitonin (PCT), and their prognostic relevance in patients with decompensated cirrhosis. METHODS: One hundred and fourteen consecutive patients with decompensated cirrhosis were enrolled and followed-up for 28 days. Diagnostic performances of CRP, PCT, presepsin and resistin were assessed. RESULTS: Fifty-three (46.5%) patients had bacterial infections of which 30 (56%) had sepsis. Presepsin and resistin had similar performance as CRP and PCT for the diagnosis of infection (best cut-off of 1444 pg/ml and 20 ng/ml, respectively) and sepsis. Presepsin (HR = 5.5; 95%CI: 2.36-13.21, p < 0.0001) and the ≥500 pg/ml increase of presepsin at 48 h (HR = 9.24; 95%CI: 3.66-23.27, p < 0.008) were independently associated with 28-day mortality. CONCLUSIONS: Presepsin and resistin have similar diagnostic performances to CRP and PCT for bacterial infection in decompensated cirrhosis. Presepsin and Δ presepsin ≥500 pg/ml have also a prognostic relevance for 28-day mortality.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Carcinomatosis: Our Initial Experience.

Introduction: Peritoneal carcinomatosis represents an advanced stage of tumor dissemination of abdominal cancers in general and colorectal cancer in particular. The only therapeutic methods currently available for the treatment of this pathology are systemic chemotherapy (palliative character) and cytoreductive surgery (CR) with intraperitoneal chemotherapy. After evaluation of evidence-based medical literature and current guide lines we can state that CR + HIPEC procedure is considered to be the treatment of choice in case of patients with peritoneal carcinomatosis of colorectal, ovarian and mucinous appendicular origin. Material and method: In the present study we prospectively analyzed the immediate postoperative results obtained in the first 50 patients that were treated by our team for peritoneal carcinomatosis of different origin. We described the protocol of selection, the patients characteristics that were included in our CR+HIPEC program and analyzed the complications and death rate. Results: From January 2015 till Dec 2018 we evaluated 98 patients with peritoneal carcinomatosis. From them, 51 received radical CR+HIPEC treatment, 33 were not suitable for surgery because of the exclusion criteria's and 15 had only exploratory laparotomies. In regard with the histopathological diagnosis, 30 patients had ovarian cancer and 19 had colorectal cancer or peritoneal pseudomixoma of appendicular origin. There was no 30 days postoperative mortality. The incidence of significant postoperative complications was 15%. Conclusions: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy is a complex technique accompanied by an acceptable rate of complications and postoperative deaths, the results being optimized by a standardized perioperative management and patient selection. The initial results obtained by our team emphasize the feasibility of this procedure, with immediate good results, as a result of a standardization protocol of patient selection and perioperative care.

The Use of Endotoxin Adsorption in Extracorporeal Blood Purification Techniques. A Case Report.

Sepsis and septic shock are major healthcare problems, resulting in high morbidity and mortality. The Surviving Sepsis Campaign (SSC), which standardised the approach to sepsis, was recently updated. Strategies to decrease the systemic inflammatory response have been proposed to modulate organ dysfunctions. Endotoxin, derived from the membrane of Gram-negative bacteria, is considered a major factor in the pathogenesis of sepsis. Endotoxin adsorption, if effective, has the potential to reduce the biological cascade of Gram-negative sepsis. We present a case of a 64-year-old man with severe Gram-negative sepsis, following purulent peritonitis secondary to rectosigmoid adenocarcinoma. To reduce the amplitude of the general effects of endotoxins we used a novel device, the Alteco® LPS Adsorber (Alteco Medical AB, Lund, Sweden), for lipopolysaccharide (LPS) adsorption. The efficacy markers were: the overall haemodynamic profile, translated into decreased vasopressor requirements, the normalisation of the cardiac index, the systemic vascular resistance index combined with the lactate level and the reduction in procalcitonin (PCT) levels. A decrease in the sequential organ failure assessment (SOFA) score at twenty-four hours was demonstrated. The clinical course following treatment was favourable for the days immediately following the treatment.This was attributed to the removal of endotoxin from the systemic circulation. The patient died one week after the endotoxin removal session, developing an ischemic bowel perforation with subsequent multiple organ failures.

The efficacy of oblique subcostal transversus abdominis plane block in laparoscopic cholecystectomy - a prospective, placebo controlled study.

INTRODUCTION: Pain control after a laparoscopic cholecystectomy can represent a challenge, considering the side effects due to standard analgesia methods. Recently the transversus abdominis plane block (TAP Block) has been used as a part of multimodal analgesia with promising results. The subcostal approach (OSTAP Block), a variant on the TAP block, produces reliable unilateral supraumbilical analgesia. This study evaluated the efficacy of the OSTAP block with bupivacaine in laparoscopic cholecystectomy compared with the placebo OSTAP block. MATERIAL AND METHODS: Sixty ASA I/II adult patients listed for elective laparoscopic cholecystectomy were randomly allocated in one of two groups: Group A (OSTAP placebo) received preoperatively bilateral OSTAP block with sterile normal saline and Group B (OSTAP bupivacaine) received bilateral preoperatively OSTAP block with the same volumes of 0.25% bupivacaine. Twenty-four hours postoperative opioid consumption, the dose of opioid required during surgery, opioid dose in the recovery unit (PACU) and PACU length of stay were evaluated. The quality of analgesia was assessed by the Visual Analogue Scale (VAS) at specific interval hours during 24 h, at rest and with movement. RESULTS: The mean intraoperative opioid consumption showed a significant difference between the two groups, (385 ± 72.52 mg in group A vs 173.67 ± 48.60 mg in group B, p < 0.001). The mean 24 h opioid consumption showed a statistically significant difference between groups (32 ± 26.05 mg vs 79 ± 16.68 mg, p < 0.001). PACU length of stay was significantly lower for group B patients compared with group A patients (20.67 ± 11.27 min vs 41.67 ± 12.41 min, p < 0.001). The OSTAP bupivacaine group had a statistically significant lower pain score than the OSTAP placebo group at 0, 2, 4, 6, 12, 24 h, both at rest and with movement. No signs or symptoms of local anaesthetic systemic toxicity or other complications were detected. CONCLUSION: OSTAP block with bupivacaine 0.25% can provide effective analgesia up to 24 hours after laparoscopic cholecystectomy when combined with conventional multimodal analgesia regimen.

Total Intravenous Versus Inhalation Anesthesia in Patients Undergoing Laparoscopic Cholecystectomies. Effects on Two Proinflammatory Cytokines Serum Levels: Il-32 and TNF-Alfa.

INTRODUCTION: It has been reported that as compared with total intravenous anesthesia (TIVA), inhalation anesthesia is increasing the postoperative level of proinflammatory interleukins.The aim of the study is to investigate if there is an in-vivo relationship between proinflammatory cytokines, Interleukin-32 (IL-32) and Tumour necrosis factor - α (TNF-α), in patients undergoing laparoscopic cholecystectomies with two different anesthetic techniques, TIVA or inhalation anesthesia. MATERIAL AND METHODS: Twenty two consecutive patients undergoing laparoscopic cholecystectomies were prospectively randomized into two groups: Group 1: TIVA with target-controlled infusion (TIVA-TCI) (n=11) and Group 2: isoflurane anesthesia (ISO) (n=11). IL-32 and TNF-α were determined before the induction of anesthesia (T1), before incision (T2) and at 2h (T3) and 24h (T4) postoperatively. Our primary outcome was to compare plasma levels of IL-32 and TNF-α concentrations (expressed as area-under-the-curve) over 24 hours between study groups. Our secondary outcome was to establish whether there is a correlation between plasma levels of IL-32 and of TNF-α at each time point between the two groups. RESULTS: Area-under-the-curve (AUC) of IL-32 plasma concentration was 7.53 in Group 1 (TIVA) versus 3.80 in Group 2 (ISO), p= 1. For TNF-α, AUC of plasma concentration was 733.9 in Group 1 (TIVA) and 668.7 in Group 2 (ISO), p=0.066. There were no significant differences in plasma concentrations of both IL-32 and TNF-α between the groups. CONCLUSIONS: IL-32 expression in response to minor surgery is very low. There were no significant difference between plasma levels of TNF-α and IL-32 after TIVA versus inhalation anesthesia during the first 24 hours postoperatively. Further studies are needed on larger groups to investigate whether there can be a correlation between these interleukins after 2 different anesthetic techniques and the impact of this correlation on postoperative outcome.

The influence of a prophylactic dose of dexamethasone for postoperative nausea and vomiting on plasma interleukin concentrations after laparoscopic cholecystectomy: a randomised trial.

BACKGROUND: Little is known about the effects of small doses of dexamethasone used for the prophylaxis of postoperative nausea and vomiting on the innate host response. OBJECTIVES: We studied the influence of dexamethasone 4 mg on the perioperative plasma concentrations of interleukins after laparoscopic cholecystectomy. We hypothesised that there would be differences in pro-inflammatory interleukin concentrations in patients who received dexamethasone. DESIGN: A randomised controlled study. SETTING: University hospital. PATIENTS: Forty-six patients undergoing laparoscopic cholecystectomy under total intravenous anaesthesia were allocated randomly into one of two study groups; 42 patients completed the study. INTERVENTIONS: Patients in group 1 (dexamethasone, n = 22) received dexamethasone 4 mg and group 2 (n = 20) acted as controls. MAIN OUTCOME MEASURES: Plasma levels of tumour necrosis factor alpha and interleukins 1ß, 6, 8, 10 and 13 were measured before anaesthesia, before surgery and 2 and 24 h after surgery. The frequency and number of episodes of postoperative nausea and vomiting were recorded. RESULTS: Areas under the curve of the percentage variation of interleukins 6 and 8 were significantly lower in the dexamethasone group. There were no significant differences between groups in the areas under the curve for tumour necrosis factor alpha and interleukins 1ß, 10 and 13. The greatest variation in interleukin concentrations was 2 h postoperatively, when the concentration of interleukin 6 was greater in the control group, whereas the concentration of interleukin 10 was higher in the dexamethasone group. Twenty-four hours after surgery, only the concentration of interleukin 6 remained significantly increased in both groups (P = 0.001 and P = 0.002, respectively). There were no significant differences between groups in respect of postoperative nausea and vomiting. CONCLUSION: Prophylactic dexamethasone given before laparoscopic cholecystectomy produced a significant decrease in concentrations of interleukins 6 and 8. Further studies are needed to investigate the clinical implications of these findings.

Choice of anesthetic technique on plasma concentrations of interleukins and cell adhesion molecules.

BACKGROUND: Whether inflammatory responses to surgery are comparably activated during total intravenous anesthesia (TIVA) and during volatile anesthesia remains unclear. We thus compared the perioperative effects of TIVA and isoflurane anesthesia on plasma concentrations of proinflammatory and anti-inflammatory interleukins and cell adhesion molecules. METHODS: Patients having laparoscopic cholecystectomies were randomly allocated to two groups: 44 were assigned to TIVA and 44 to isoflurane anesthesia. IL-1ß, IL-6, IL-8, IL-10, IL-13, and the cellular adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were determined preoperatively, before incision, and at 2 and 24 hours postoperatively. Our primary outcomes were area-under-the-curve cytokine and adhesion molecule concentrations over 24 postoperative hours. RESULTS: The only statistically significant difference in area-under-the-curve concentrations was for IL-6, which was greater in patients given isoflurane:78 (95% confidence interval (CI): 52 to 109) pg/ml versus 33 (22 to 50) pg/ml, P= 0.006. Two hours after surgery, IL-6 was significantly greater than baseline in patients assigned to isoflurane: 47 (95% CI: 4 to 216, P<0.001) pg/ml versus 18 (95%CI: 4 to 374, P<0.001) pg/ml in the TIVA group. In contrast, IL-10 was significantly greater in patients assigned to TIVA: 20 (95% CI: 2 to 140, P<0.001) pg/ml versus 12 (95% CI: 3 to 126, P<0.001) pg/ml. By 24 hours after surgery, concentrations were generally similar between study groups and similar to baseline values. CONCLUSION: The only biomarker whose postoperative area-under-the-curve concentrations differed significantly as a function of anesthetic management was IL-6. Two hours after surgery, IL-6 concentrations were significantly greater in patients given isoflurane than TIVA. However, the differences were modest and seem unlikely to prove clinically important. Further studies are needed.

The effects of a small dose of dexamethasone on cell adhesion molecules during laparoscopic cholecystectomy.

BACKGROUND AND OBJECTIVE: There are only a few publications on the effects of dexamethasone on the plasma levels of cell adhesion molecules (CAMs). The goal of this study was to investigate the effects of dexamethasone 4 mg on the perioperative plasma levels of CAMs (soluble intercellular adhesion molecules [sICAM-1] and soluble vascular cell adhesion molecules [sVCAM-1]) during laparoscopic cholecystectomy. METHODS: Forty-two patients undergoing laparoscopic cholecystectomy under total intravenous anesthesia were enrolled and randomly divided into two groups: the first group received dexamethasone 4 mg (DEX group, n = 21) and the second group were controls (C group, n = 21). Plasma levels of sICAM-1 and sVCAM-1 were assessed before anesthesia, after induction (before surgery), and at 2 and 24 hours after surgery, respectively. Comparisons were performed for area under the plasma concentration-time curve (AUC) and within-group values. RESULTS: AUC comparison for sICAM-1 showed significantly increased levels in the C group (p = 0.036), while there was no significant difference for sVCAM-1 (p = 0.052). Within-group analysis showed increased levels for both sICAM-1 and sVCAM-1 in the C group at 24 hours postoperatively (p = 0.35 and p = 0.025, respectively). CONCLUSIONS: In our study, dexamethasone 4 mg given before laparoscopic cholecystectomy determined a significant decrease in plasma levels of sICAM-1. Both sICAM-1 and sVCAM-1 remained increased compared with baseline at 24 hours in the C group. This may partially explain the postoperative anti-inflammatory effects of dexamethasone. Further studies are needed.