Development and validation of a comprehensive model to predict complications after hepatectomy.

OBJECTIVE: Despite advances in perioperative care, hepatectomy remains associated with morbidity rates of up to 40%. Currently, available nomograms for predicting severe post-hepatectomy complications do not include early postoperative data. This retrospective observational study aimed to determine whether the parameters routinely measured in patients admitted to the Intensive Care Unit (ICU) after hepatectomy could represent risk factors for severe morbidity and to propose a nomogram scoring system to predict severe postoperative complications. PATIENTS AND METHODS: 411 adult patients who underwent elective hepatectomy at a high-volume tertiary care center for hepatic surgery from December 2016 to June 2022 were enrolled. The primary outcome was the assessment of predictors of 30-day severe postoperative complications following hepatectomy, defined as Clavien-Dindo grade 3a or higher. As a secondary outcome, we aimed to develop an easy-to-use scoring system to estimate the risk of severe postoperative complications. RESULTS: Severe complications occurred in 78 patients (19%). The final model included body mass index, preoperative bilirubin level, and ICU data (i.e., pH, lactate clearance, arterial lactate concentration 12 hours after ICU admission, need for packed red blood cell transfusions, and length of stay). Notably, the latter three variables were proven to be independent predictors of the outcomes. The model showed an overall good fit (C-index=0.754, corrected Dxy=0.692). A calibration plot using bootstrap internal validity resampling confirmed the stability of the model (mean absolute error=0.017, root mean square error of approximation=0.00051). CONCLUSIONS: We developed an accurate and practical scoring system based on preoperative and early postoperative data to predict poor outcomes after hepatectomy. Further external validation on larger series could lead to the integration of such a tool in the routine clinical practice to support patients' management and early warning during ICU stay. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-Abstract-NEW-2.pdf.

High intraoperative blood product requirements in liver transplantation: risk factors and impact on the outcome.

OBJECTIVE: Liver transplantation (LT) is associated with a significant bleeding and the high transfusion requirements (HTR) negatively affect the outcome of LT patients. Our primary aim was to identify potential predictors of intraoperative transfusion requirements. Secondarily, we investigated, the effect of transfusion requirements on different clinical outcomes, including short-term morbidity and mortality. PATIENTS AND METHODS: Data collected in 219 adult LT from a deceased donor, grouped according to HTR (defined as the need of 5 or more red blood cell units), were compared. RESULTS: We found that previous portal vein thromboses (p=0.0156), hemoglobin (Hb) (p<0.0001), International Normalized Ratio (INR) (p=0.0010) at transplant and veno-venous by-pass (p=0.0048) independently predicted HTR. HTR was always associated with poorer outcomes, including higher simplified acute physiology II score at Intensive Care Unit admission (p=0.0005), higher rates of pulmonary infections (p=0.0015) and early rejection (p=0.0176), longer requirement of mechanical ventilation, (p<0.0001), more frequent need for hemodialysis after transplantation (p=0.0036), overall survival (p=0.0010) and rate of day-90 survival (p=0.0016). CONCLUSIONS: This study identified specific risk factors for HTR and confirmed the negative impact exerted by HTR on clinical outcomes, including recipient survival. Prospective investigations are worth to assess whether correcting pre-transplant Hb and INR levels may effectively reduce blood product need and improve prognosis.

Use of an esophageal echo-Doppler device during liver transplantation: preliminary report.

Determination of cardiac output (CO) is crucial for perioperative monitoring of orthotopic liver transplant (OLT) recipients. A pulmonary artery catheter (PAC) has always been considered the "gold standard" of hemodynamic monitoring. The aim of this study was to evaluate the suitability of a transesophageal echo-Doppler device (ED) as a minimally invasive device to measure CO in OLT. ED was compared with the standard PAC technique taking into account the disease severity of OLT recipients as defined by the model for end-stage liver disease (MELD) score. We enrolled 42 cirrhotic patients scheduled for OLT 3 thermodilution CO measurements were taken by a PAC and the most recent ED measurement (CO(ED)) was also recorded. Paired measurements of CO were performed at standard times, unless there were additional clinical needs. Recipients were stratified into 3 groups according to MELD score: MELD score < or = 15 (14 patients); MELD score between 16 and 28 (17 patients); and MELD score > or = 29 (11 patients). We performed 495 paired measurements of CO. Mean bias was 0.34 +/- 0.9 L/min and limits of agreement were -1.46 and 2.14 L/min. In patients with MELD score <15, the bias was 0.12 +/- 0.55. The ED results were not interchangeable with PAC, because of the large limits of agreement. However, in cirrhotic patients with MELD scores <15, the precision of the new method was similar to that of PAC; therefore, in this subset of patients, it may represent a reliable alternative to PAC.

Molecular adsorbent recirculating system (Mars) in patients with primary nonfunction and other causes of graft dysfunction after liver transplantation in the era of extended criteria donor organs.

Liver dysfunction is an important cause of morbidity and mortality after orthotopic liver transplantation (OLT). The Molecular Adsorbent Recirculating System (MARS) is an albumin-based dialysis system designed to enhance the excretory function of a failing liver. MARS has been successfully used in patients affected by advanced liver disease and presenting with severe cholestasis. The aim of this study was to evaluate the safety and clinical efficacy of MARS in patients with liver dysfunction after OLT. Seven patients (primary nonfunction, 2 patients; graft dysfunction, 5 patients) fulfilled the inclusion criteria of serum bilirubin level >15 mg/dL and least 1 of the following clinical signs: hepatic encephalopathy (HE) > or = grade II, hepatorenal syndrome (HRS), and intractable pruritus. Graft and patient survival rates at 6 months were 42.8% and 57.1%, respectively. All patients tolerated MARS treatment, with no adverse event. In all patients, a decrease in serum bilirubin (P < .05), bile acids (P < .05), serum creatinine, and ammonia levels was observed after treatment with MARS. A considerable improvement of HE, as well as renal and synthetic liver functions, was observed in 4 of 5 patients with graft dysfunction, but not among those with primary nonfunction. The patients with intractable pruritus showed significant improvement of this symptom after MARS therapy. Thus, MARS is a safe, therapeutic option for the treatment of liver dysfunction after OLT. Further studies are necessary to confirm whether this treatment is able to improve both graft and patient survival.

Aggregation phenomena in a system of molecules with two internal states.

A model for the aggregation of molecules with two internal states is studied by kinetic Monte Carlo simulations. Molecules are represented by simple beads, discarding all stereochemical specificity. Monomers are placed in a three-dimensional lattice and diffusion processes are simulated, as well as internal state conversions of the molecules. The two internal states feature a stable (S) not assembly competent configuration, and an unstable assembly competent (A) configuration. Monomers in A state are given a higher energy if isolated, but they can reach the lowest energy level through short-range interactions between each other, so that their aggregation is promoted. Kinetics of cluster formation are examined, as well as the basic mechanisms ruling growth in our system. The simulations show that the aggregation process is preceded by a lag phase, which is followed by a fast growth phase. The duration of the lag phase is determined by the strength of the A-A interaction, whereas the time slope of the growth phase is mainly influenced by the conversion rate between internal states. The whole work has been inspired by the biological problem of amyloid aggregation, whose aggregation curves often present a sigmoidal behavior which is reproduced by the present model.

Molecular adsorbent recirculating system in liver transplantation: Safety and efficacy.

We assessed the safety and clinical efficacy of the Molecular Adsorbent Recirculating System (MARS) in liver failure patients admitted to our intensive care unit (ICU) from May 2000 to February 2006. Of 28 adult patients with bilirubin >15 mg/dL and hepatic encephalopathy (HE) grade > or =2 or hepato-renal syndrome, 22 patients were included in the study, because 6 patients were older than 65 years of age or showed recent alcohol abuse or extrahepatic malignancy. Patients were assigned to 2 groups according to whether MARS therapy was associated with a transplantation procedure: 11 patients received MARS therapy and liver transplantation (OLT group) and 11 patients received MARS therapy alone (non-OLT group). Five of 11 patients in the OLT group were listed for transplantation and 6 patients with graft failure for retransplantation. The patients in the OLT and non-OLT groups were similar in MELD, SOFA, and SAPS scores. All patients were stable and free from complications. MARS significantly reduced bilirubin, bile acids, and blood urea nitrogen (BUN) levels in both groups (P < .05), whereas a significant decrease in ammonia level was observed in the OLT group. Patient survival rates at 3 and 6 months in the OLT group were 91% and 73%, respectively, and in the non-OLT group, 9% and 9%, respectively (P < .001). MARS was safe and well tolerated, improving biochemical parameters, neurological function, and pruritus. In terms of survival, the use of MARS alone was not effective due to the high rate of multiple organ failure. Nevertheless, the association of MARS with a transplant/retransplantation procedure was highly effective.

The decrease in cytokine concentration during albumin dialysis correlates with the prognosis of patients with acute on chronic liver failure.

BACKGROUND AND AIM: The clearance of plasma cytokines by means of albumin dialysis (MARS) has been demonstrated in various studies involving patients affected by either acute liver failure (ALF) or acute on chronic liver failure. The aim of the study was to measure the plasma levels of TNF-alpha, IL-6, and IL-1beta in patients with ALF after each MARS treatment to evaluate the relationship between variations in cytokines levels and patient prognosis. MATERIALS AND METHODS: Ten patients with ALF undergoing several MARS treatments were enrolled (group 1). Blood samples were collected before and after each MARS treatment to measure TNF-alpha, IL-6, and IL-1beta, and other hematochemical parameters. We also enrolled 10 patients with ALF who underwent standard therapy (group 2) as well as a control group of 10 healthy subjects matched for sex and age (group 3). RESULTS: MARS reduced total bilirubin levels, biliary acids, BUN, ammonia, TNF-alpha, IL-6, and IL-1beta (P < .05). Moreover, the reduction in inflammatory cytokines levels and improved prognosis were related. CONCLUSIONS: We confirmed the therapeutic efficacy of MARS treatment for ALF, which appeared to be related to removal of toxins and inflammatory cytokines determine that which patients prognosis.

Improvement of mitochondrial function evaluated by ketoisocaproic acid breath test in patients with HCV infection undergoing albumin dialysis.

BACKGROUND AND AIM: Oxidative injury occurs as a direct result of hepatitis C virus (HCV) core protein expression both in vitro and in vivo, and may be due to a direct effect on mitochondria. The ketoisocaproic acid (KICA) breath test is a simple, reliable, and noninvasive test to evaluate hepatic mitochondrial function. Albumin dialysis (MARS) is an effective bridge treatment for patients with acute failure superimposed on chronic liver disease. The aim of our study was to evaluate the improvement of mitochondrial function measured by KICA in patients undergoing MARS for acute-on-chronic HCV liver failure. MATERIALS AND METHODS: Five patients with HCV chronic infection undergoing MARS treatment for acute decompensation were enrolled. Before and after each MARS treatment, patients underwent blood testing for the main hematochemical parameters as well as for mitochondrial function by the KICA breath test and the arterial ketone bodies ratio (AKBR). RESULTS: MARS treatment effectively decreased the serum level of total bilirubin, bile acids, urea, and ammonium. Moreover, MARS treatment produced an increase in AKBR and in the cumulative percentage of (13)CO(2) recovered in exhaled air 2 hours after KICA ingestion. CONCLUSION: Liver mitochondrial function appears to be beneficially affected by MARS treatment.

Catholic university experience with molecular adsorbent recycling system in patients with severe liver failure.

BACKGROUND AND AIM: Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. MATERIALS: Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin > or =10 mg/dL and at least one of the following: hepatic encephalopathy (HE) > or =II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin > or =5 mg/dL and HE > or =I grade for acute patients. RESULTS: MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. CONCLUSIONS: Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.

Acute Liver Failure in an Adult, a Rare Complication of Alagille Syndrome: Case Report and Brief Review.

Alagille syndrome (AS) is an autosomal-dominant, multisystem disorder affecting the liver, heart, eyes, skeleton, and face. The manifestations are predominantly pediatric. Diagnosis is based on findings of a paucity of bile ducts on liver biopsy combined with ≥3 of 5 major clinical criteria. Orthotopic liver transplantation (OLT) is the only option for treating patients who developed liver failure, portal hypertension, severe itching, and xanthomatosis. It is difficult to establish clear criteria for OLT; indications are controversial because of the wide variety of clinical symptoms and the multisystem involvement. Generally, AS-associated liver disease is never an acute illness. We report the case of a 28-year-old woman with AS who underwent urgent OLT for acute liver failure. At 24 months posttransplant, the patient is in good clinical condition and with normal hepatic and renal function.

Advances in extracorporeal detoxification by MARS dialysis in patients with liver failure.

Although liver transplantation has become standard procedure for patients with liver failure, a number of issues in the management of these patients remains to be addressed. Alternative approaches have been tested, such as hepatocytes containing liver-support systems and filtration devices. However, the replacement of detoxification has been difficult, as the majority of toxins accumulating in liver failure is albumin-bound. Albumin dialysis (MARS system) is characterized by the specific removal of albumin-bound toxins through an innovative membrane transport. In particular, the albumin acts as a specific molecular adsorbent that is regenerated on line in a recycling system. Nowadays MARS represents the most frequently used liver support system. This treatment has been shown to remove albumin-bound molecules, such as bilirubin, bile acids, aromatic amino acids and copper. The removal of these toxins is clinically accompanied with an improvement of liver, cardiovascular and renal functions and hepatic encephalopathy. In several trials MARS was found to improve the clinical situation in patients with acute exacerbation of chronic liver failure and acute hepatic failure, but also in hepatorenal syndrome and primary graft non function or chronic rejection after liver transplantation. In summary, a critical analysis of the literature confirms that MARS device can be a safe therapeutic choice to achieve a better clinical outcome, and, sometimes, a survival advantage in patients with liver failure, even if a multi-center randomized trial is the only reliable way to enforce today's results. Further advances in the MARS components will definitively state whether albumin dialysis may represent the future in the field of artificial liver devices.

Magnetically guided orotracheal intubation.

OBJECTIVE: To describe a novel endotracheal intubation technique, magnetically guided intubation (MGI), and its rate of success in inexperienced medical students and interns using an airway mannequin model. METHODS: This was a prospective, descriptive study of 25 medical students and interns participating in an introductory course on emergency medicine without prior experience in human orotracheal intubation. Magnetically guided intubation consists of a strong external magnet placed over the cricothyroid membrane to guide the introduction of a standard endotracheal tube containing a stylet with a magnetized tip. An airway mannequin was placed in a rigid cervical spinal collar to increase the difficulty of the intubation, and each student performed two sequential intubation attempts using MGI. The proportions of successful intubations and the time to complete intubation were determined. Descriptive statistics were used to describe point estimates and 95% confidence intervals for means and proportions of continuous and categorical data, respectively. RESULTS: Of 25 participants, 19 were students and six were interns. Their mean age was 27 years, and 76% were male. The overall proportion of successful intubations using MGI was 80% (95% CI = 69% to 91%). Of 24 intubations, 48% were attempted without visualization of the vocal cords; 67% were successful (95% CI = 46% to 87%). The mean time required to complete intubation was 17.0 seconds (95% CI = 14.5 to 19.5 seconds). CONCLUSIONS: A novel method of orotracheal intubation using magnetic guidance is described as achieving a high rate of successful intubations when performed by inexperienced intubators.

Prediction of 6-month survival after liver transplantation using Cox regression.

BACKGROUND: The outcome of liver transplantation (LTx) has been correlated with several donor and recipient factors. METHODS: A database of 191 consecutive LTx cases was analyzed using Kaplan-Meier and Cox regression statistics based on 80 variables. To avoid additional effects of late events on patient survival, the chosen endpoint was 6 months. Data were evaluated using SPSS statistical software. RESULTS: Kaplan-Meier analysis revealed a difference in 1- to 6-month graft survival between patients transplanted with organs from donors older versus younger than 60 years (Breslow, P <.01). Differences in 1- to 6-month graft survivals were observed between patients listed as UNOS status 3, 2B, 2A, and 1: the outcomes for UNOS status 2B versus UNOS status 2A and UNOS status 2B versus status 1 were significant (P <.05). Differences in 1- to 6-month graft survival rates were found between patients with versus without sepsis (P <.05), and with versus without rejection episodes (P <.01). Cox regression analysis revealed only three of the variables to be independent prognostic predictors of graft failure: donor age; postoperative septic status; and rejection. The best mathematical multivariate Cox regression model linked donor age + donor Na + rejection + sepsis to 1- to 6-month graft survival (chi-square = 29.06, P <.001). CONCLUSION: Factors predictive of 1- to 6-month graft survival after liver transplantation include donor age; UNOS status; sepsis; and rejection.

Emergency therapeutical approach simulating ultrarapid opioid detoxification in methadone withdrawal precipitated by erroneous administration of naltrexone.

We report the case of a 30-year-old male, heroin dependent, receiving methadone treatment, who, while staying at home, ingested 50 mg of naltrexone. He immediately developed serious withdrawal symptoms and was admitted to the hospital. In the emergency department the drugs given to counteract the agitation were ineffective, and the patient developed respiratory distress. Anaesthesia with propofol was then started and the patient was intubated, ventilated and hospitalized in the intensive care unit. He was then sedated for 48 hours due to persistent withdrawal signs. When medically stable the patient was transferred to the medical ward where daily treatment with naltrexone and psychological support where started. After 4 days the patient was discharged. Afterwards he did not attend his scheduled outpatient follow-up visits. Treatment with propofol is effective in the case of a patient with a serious withdrawal syndrome secondary to naltrexone overdose during methadone therapy. Despite the actual possibility of getting through the withdrawal symptoms the patient failed to return for follow-up visits, which might be related to a lack of motivation.

[Mortality according to the birthplace in a Turin longitudinal study]. / La mortalità secondo il luogo di nascita nello studio longitudinale torinese.

Mortality 1981-85 in the Turin Longitudinal Study population, 25-74 years old, was analyzed according to selected geographic areas of birth and socioeconomic status. People born in the Southern Regions and in the Isles, when compared with people ever resident in Turin, have low mortality from malignancies and accidents and in general from all causes of death but respiratory diseases. People born in the North-Eastern Regions have high mortality, mainly due to malignancies, and respiratory and digestive diseases. Such differences are stronger among men in low socio-economic status and tend to weaken with time from migration.

Dexmedetomidine use in general anaesthesia.

Dexmedetomidine is a potent and highly selective alpha(2)-adrenoreceptor agonist currently utilized for continuous infusion for sedation/analgesia in the intensive care unit (ICU). Dexmedetomidine offers remarkable pharmacological properties including sedation, anxiolysis, and analgesia with the unique characteristic to cause no respiratory depression. In addition it posses sympatholytic and antinociceptive effects that allow hemodynamic stability during surgical stimulation. Different from most of clinically used anesthetics, dexmedetomidine brings about not only a sedative-hypnotic effect via an action on a single type of receptors, but also an analgesic effect and an autonomic blockade that is beneficial in cardiac risk situations. Several studies have demonstrated its safety, although bradycardia and hypotension are the most predictable and frequent side effects. Dexmedetomidine has shown to consistently reduce opioids, propofol, and benzodiazepines requirements. In the last years it has emerged as an affective therapeutic drug in a wide range of anesthetic management, promising large benefits in the perioperative use. In particular this review focuses on dexmedetomidine utilization in premedication, general surgery, neurosurgery, cardiac surgery, bariatric surgery, and for procedural sedation and awake fiberoptic intubation. In all these fields dexmedetomidine has demonstrated to be an efficacious and safe adjuvant to other sedative and anesthetic medications.

A normal response to Synachten test does not rule out corticosteroid effectiveness in weaning from catecholamine after septic shock.

Corticosteroids may improve haemodynamics and facilitate weaning from catecholamines in septic shock. According to some authors, such effects are only accomplished in the presence of absolute or relative adrenal insufficiency. Consequently, corticosteroids are usually given only to patients that present low blood cortisol values or show an inadequate response to cosyntropin (Synachten test). We report the case of a woman affected by septic shock secondary to pneumonia and dependent on norepinephrine infusion for 26 days, who was weaned from catecholamines with hydrocortisone, 100 mg/day i.v. She exhibited a normal response to Synachten, but corticosteroid therapy was continued because haemodynamics improved promptly. A pharmacological effect was hypothesized; the contemporary increase of platelet, decrease of white blood cells, and decrease of plasma fibrinogen supported this hypothesis.

Unusual presentation of leptospirosis in the late stage of pregnancy.

Here we report a case of leptospirosis without fever during the late stage of pregnancy in which the initial clinical presentation was more suggestive of a pregnancy-related liver dysfunction rather than an infectious disease. A 32-year-old primipara at 37 week of gestation was hospitalised with a 10-day history of nausea, vomiting, and abdominal pain without fever. Initial routine blood tests showed hyperbilirubinemia, a moderate increase in transaminase levels, severe coagulopathy and an increased creatinine level. On clinical suspicion of pregnancy-related liver dysfunction such as HELLP syndrome (hemolysis, elevated liver enzyme levels, low platelet count) or acute fatty liver of pregnancy (AFLP), emergency caesarean section was performed and a healthy baby was delivered. Postoperatively, the patient was stable, but 5 days later she developed clouding of consciousness, severe jaundice and respiratory failure. At this time, an infectious disease was considered and leptospirosis was confirmed by serological tests. In conjunction with intensive care management, antibiotic therapy was given; the patient was discharged in good condition and her baby did not develop signs of active leptospirosis. While leptospirosis is rare in pregnancy, this is the first report of acute infection without fever mimicking the clinical pattern of HELLP syndrome or AFLP