Management of hepatorenal syndrome and treatment-related adverse events.

Hepatorenal Syndrome is a critical complication of liver failure, mainly in cirrhotic patients and rarely in patients with acute liver disease. It is a complex spectrum of conditions that leads to renal dysfunction in the liver cirrhosis population; the pathophysiology is characterized by a specific triad: circulatory dysfunction, nitric oxide (NO) dysfunction and systemic inflammation but a specific kidney damage has never been demonstrated, in a clinicopathological study, kidney biopsies of patients with cirrhosis showed a wide spectrum of kidney damage. In addition, the absence of significant hematuria or proteinuria does not exclude renal damage. It is estimated that 40% of cirrhotic patients will develop hepatorenal syndrome with in-hospital mortality of about one-third of these patients. The burden of the problem is dramatic considering the worldwide prevalence of more than 10 million decompensated cirrhotic patients, and the age-standardized prevalence rate of decompensated cirrhosis has gone through a significant rise between 1990 and 2017. Given the syndrome's poor prognosis, the clinician must know how to manage early treatment and any complications. The widespread adoption of albumin and vasopressors has increased Hepatorenal syndrome-acute kidney injury reversal and may increase overall survival, as previously shown. Further research is needed to define whether the subclassification of patients may allow to find a personalized strategy to treat Hepatorenal Syndrome and to define the role of new molecules and extracorporeal treatment may allow better outcomes with a reduction in treatment-related adverse effects. This review aims to examine both pharmacological and non-pharmacological treatment of hepatorenal syndrome, with a particular focus on managing adverse events caused by treatment.

Intraoperative Monitoring of the Obese Patient Undergoing Surgery: A Narrative Review.

With the increasing prevalence of obesity in the population, anaesthetists must confidently manage both the pathophysiological and technical challenges presented in bariatric and non-bariatric surgery. The intraoperative period represents an important opportunity to optimise and mitigate risk. However, there is little formal guidance on what intraoperative monitoring techniques should be used in this population. This narrative review collates the existing evidence for intraoperative monitoring devices in the obese patients. Although a number of non-invasive blood pressure monitors have been tested, an invasive arterial line remains the most reliable monitor if accurate, continuous monitoring is required. Goal-directed fluid therapy is recommended by clinical practice guidelines, but the methods tested to assess this had guarded applicability to the obese population. Transcutaneous carbon dioxide (CO2) monitoring may offer additional benefit to standard capnography in this population. Individually titrated positive end expiratory pressure (PEEP) and recruitment manoeuvres improved intraoperative mechanics but yielded no benefit in the immediate postoperative period. Depth of anaesthesia monitoring appears to be beneficial in the perioperative period regarding recovery times and complications. Objective confirmation of reversal of neuromuscular blockade continues to be a central tenet of anaesthesia practice, particularly relevant to this group who have been characterised as an "at risk" extubation group. Where deep neuromuscular blockade is used, continuous neuromuscular blockade is suggested. Both obesity and the intraoperative context represent somewhat unstable search terms, as the clinical implications of the obesity phenotype are not uniform, and the type and urgency of surgery have significant impact on the intraoperative setting. This renders the generation of summary conclusions around what intraoperative monitoring techniques are suitable in this population highly challenging.

Nonalcoholic fatty liver disease prevalence in an Italian cohort of patients with hidradenitis suppurativa: A multi-center retrospective analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes two distinct conditions, with different histologic features and prognosis: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Furthermore, NASH is the more aggressive necro-inflammatory form, which may accumulate fibrosis and result in End stage liver disease (ESLD). NAFLD is also linked to systemic inflammatory conditions such as psoriasis. NAFLD is currently the most common cause of ESLD in Western countries, becoming a serious public health concern. Hidradenitis suppurativa (HS) is a systemic inflammatory/autoinflammatory disease of the terminal follicular epithelium of the apocrine gland with a prevalence of 0.05% to 4.10%. Due to its systemic inflammatory behavior several comorbidities were recently associated, however liver ones were scarcely assessed. AIM: To evaluate the prevalence and characteristics of NASH/NAFL in HS patients. METHODS: This retrospective study is a sub-analysis of a larger study carried out in 4 Italian dermatological centers. In this cohort, there were 83 patients: 51 patients with HS only, 20 patients with HS/NAFL and 12 with HS/NASH. RESULTS: Inflammatory comorbidities were present in 3.9% of HS only patients, 25% of HS/NAFL patients and 58.3% of HS/NASH patients (P < 0.001). Similarly, mean Autoinflammatory Disease Damage Index (ADDI) was significantly higher among patients with HS/NASH (5.3 ± 2.2, P < 0.001) compared to patients with HS/NAFL or HS only (2.8 ± 1.6 and 2.6 ± 1.4 respectively). Furthermore, ADDI correlates with IHS4 in HS, HS/NAFL and HS/NASH. Diabetic patients have higher Hurley score than not diabetic ones. Ultrasound examination was significantly different in the three groups. CONCLUSION: HS patients displayed a high prevalence of NASH/NAFLD and ultrasound examination should be particularly addressed to patients that display high ADDI scores.

New antimicrobial options for the management of complicated intra-abdominal infections.

Complicated intra-abdominal infections (cIAIs) are a common cause of morbidity and mortality in surgical patients. Optimal management of cIAI requires early source control in combination with adequate antimicrobial treatment and aggressive fluid resuscitation. cIAIs are mainly caused by Gram-negative bacilli and anaerobes. Broad-spectrum single-agent or combination drug regimens against these microorganisms are the mainstay of therapy. However, development of antimicrobial resistance has become an increasingly large concern: multidrug-resistant organisms are associated with a higher rate of inadequate antimicrobial therapy, which in turn is associated with higher mortality rate, longer hospital stay, and increased cost compared to adequate antimicrobial therapy. In this mini-review, we discuss the effectiveness of several new antimicrobial agents, recently approved or in advanced phases of clinical development, for the treatment of cIAIs, including the new beta-lactam and beta-lactamase inhibitor combinations (ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, aztreonam/avibactam), siderophore cephalosporins (cefiderocol), aminoglycosides (plazomicin), and tetracyclines (eravacycline).

Extracellular ATP Regulates CD73 and ABCC6 Expression in HepG2 Cells.

The ATP-binding cassette sub-family C member 6 transporter (ABCC6) is an ATP dependent transporter mainly found in the basolateral plasma membrane of hepatic and kidney cells. Mutations in ABCC6 gene were associated to the Pseudoxanthoma elasticum (PXE), an autosomal recessive disease characterized by a progressive ectopic calcification of elastic fibers in dermal, ocular, and vascular tissues. It is reported that the over-expression of ABCC6 in HEK293 cells results in the cellular efflux of ATP and other nucleoside triphosphates, which in turn are rapidly converted into nucleoside monophosphates and pyrophosphate (PPi). Since PPi is an inhibitor of mineralization, it was proposed that the absence of circulating PPi in PXE patients results in the ectopic mineralization, a typical feature of PXE. In the extracellular environment, ATP is converted, not only into pyrophosphate, but also into AMP by an ectonucleosidase, which in turn is transformed into adenosine and phosphate. ABCC6 protein is thus involved in the production of extracellular adenosine and therefore it could have a role in the activation of the purinergic system. In the liver, purinergic signaling has been shown to regulate key basic cellular functions. Our previous studies showed that in ABCC6 knockdown HepG2 cells the expression of some genes, related with the calcification processes, is dysregulated. In this study, experiments have been carried out in order to verify if ABCC6, besides supplying the pyrophosphate required to prevent the mineralization of soft tissues, also plays a role in the activation of the purinergic system. For this purpose, the transport activity of ABCC6 was blocked with Probenecid and the expression of ABCC6 and NT5E was analyzed with real time PCR and western blotting. The results of this study showed that both proteins are downregulated in the presence of Probenecid and upregulated in the presence of adenosine or ATP.

Are third-generation cephalosporins still the empirical antibiotic treatment of community-acquired spontaneous bacterial peritonitis? A systematic review and meta-analysis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a common complication among cirrhotic patients. Guidelines recommend third-generation cephalosporins (3GCs) as empiric antibiotic therapy (EAT) of SBP. Recently, a broad-spectrum EAT was shown to be more effective than cephalosporins in the treatment of nosocomial spontaneous bacterial peritonitis (N-SBP); however, the prevalence of 3GCs-resistant bacteria is high in the nosocomial setting and broad-spectrum EAT cannot be used in all cases of SBP. AIM: The aim of this study was to evaluate the 3GCs resistance distribution between N-SBP and community-acquired spontaneous bacterial peritonitis (CA-SBP) to clarify whether 3GCs are still an effective therapeutic intervention for CA-SBP. METHODS: We searched for studies that reported the aetiology of SBP and the resistance profile of both gram-positive and gram-negative bacteria in MEDLINE and Google Scholar databases (since 1 January 2000 to 30 April 2017). A meta-analysis was carried out to estimate the risk difference [relative risk (RR) and 95% confidence intervals (CIs)] for 3GCs resistance in N-SBP and CA-SBP. Heterogeneity was assessed using the I-test. RESULTS: A total of eight studies were included, including 1074 positive cultures of ascitic fluid in cirrhotic patients; 462 positive cultures were from N-SBP and, among these, 251 (54.3%) were 3GCs resistant. Six hundred and twelve positive cultures were from CA-SBP and, among these, 207 (33.8%) were 3GCs-resistant SBP. A pooled RR of 3GCs resistance in N-SBP compared with CA-SBP showed a significant difference (RR=1.67, 95% CI: 1.14-2.44; P=0.008). We carried out two subgroup analyses: the first according to the median year of study observation (before vs. since 2008) and the second according to the country of the study (China vs. others). The studies carried out before 2008 (327 SBP-positive culture) showed a significantly higher risk for 3GCs-resistant strains in N-SBP compared with CA-SBP (RR=2.36, 95% CI: 1.39-3.99; P=0.001), whereas this was not found in SBP acquired after 2008 (RR=1.24, 95% CI: 0.83-1.84; P=0.29). N-SBP occurring in China had no significantly higher risk for 3GCs-resistant strains compared with CA-SBP (RR=1.44, 95% CI: 0.87-2.37; P=0.16). CONCLUSION: Our findings suggest that although the pooled RR of 3GCs resistance in N-SBP compared with CA-SBP show that 3GCs are still an effective option for the treatment of CA-SBP, the subanalysis of studies that enroled patients in the last decade did not show a significant higher RR of 3GCs resistance in N-SBP compared with CA-SBP. Therefore, in centres where local patterns of antimicrobial susceptibility (with low rates of 3GCs resistance) are not available, 3GCs should not be used initially for CA-SBP treatment. Future studies are needed to confirm this trend of 3GCs resistance.

Perioperative pain management in cardiac surgery: a systematic review.

BACKGROUND: Every year, more than 1.5 million patients, who undergo cardiac surgery worldwide, are exposed to a series of factors that can trigger acute postoperative pain associated with hemodynamic instability, respiratory complications, and psychological disorders. Through an evaluation of literature data about postoperative pain in cardiac surgery we define unmet needs and potential objectives for future research on this often-underestimated problem. METHODS: Following PRISMA Guidelines, a systematic literature search was carried out by two independent researchers on Scopus, CINAHL, the Cochrane Library, and PubMed using the key words: (perioperative OR postoperative) analgesia AND "cardiac surgery." Papers concerning children, or published prior to 2000, were considered ineligible, as well as abstracts, animal studies, and studies written in languages other than English. RESULTS: Fifty-four papers were selected and subsequently divided into two main categories: systemic analgesic drugs and regional anesthesia techniques. CONCLUSIONS: Over the past 17 years, opioids are still the most extensively used therapy, whereas we found only few trials investigating other drugs (e.g. paracetamol). Regional anesthesia techniques, especially thoracic epidural analgesia and intrathecal morphine administration, can effectively treat pain, but have not yet showed any significant impact on major clinical outcomes, with several concerns related to their potential complications. To date multimodal analgesia with implementation of regional analgesia seems to be the best choice. In the future, better-designed studies should consider other drugs stratifying groups according to comorbidities and risk factors, as well as using standardized units of measurement.

Risk of spontaneous fungal peritonitis in hospitalized cirrhotic patients with ascites: a systematic review of observational studies and meta-analysis.

INTRODUCTION: Spontaneous fungal peritonitis (SFP) is an infection of ascitic fluid occurring in cirrhotic patients. SFP prevalence varies from 0% to 41% of patients with spontaneous peritonitis (SP) and a positive ascitic fluid culture. Cirrhotic patients with SFP who fail to show improvement with empirical antibiotic therapy, before the identification of the fungal pathogen, have high mortality (89.5-100%). Although the weight of the disease is so dramatic, more recent guidelines on infections in cirrhosis do not consider SFP management. The aim of this meta-analysis was to investigate the association between hospitalization (at least 48-72 hours after admission) and risk of SFP. EVIDENCE ACQUISITION: A literature search was performed on PubMed, Scopus and Web of Science to identify relevant studies published up to March 2, 2017. Only observational studies that specify the etiology of SP were included. Data were pooled using risk difference as a summary measure and corresponding 95% confidence interval (CI). EVIDENCE SYNTHESIS: Thirteen cohort studies were included in the meta-analysis (12 retrospective and one prospective). A pooled risk difference, using a random effects model, of nosocomial versus non-nosocomial SFP was 2.9% (95% CI, 0.4% to 5.3%, P=0.024) with a no significant heterogeneity among studies (P=0.090, I²=37%). CONCLUSIONS: This meta-analysis suggests that hospitalization is related to a significant increase of SFP risk.