Analysis of outcomes of emergency general and gastrointestinal surgery during the COVID-19 pandemic.

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.

Electromyographic activity of the jaw muscles and mandibular kinematics in young adults with theoretically ideal dental occlusion: Reference values.

BACKGROUND: A necessary step to use neuromuscular analysis as diagnostic tool is to establish normal reference values for the physiological range in a healthy population. Surface electromyographic (sEMG) activity of the jaw muscles and mandibular kinematics were measured in young adults with theoretically ideal dental occlusion to determine normal reference values during different tasks. Differences between the sexes were evaluated. MATERIAL AND METHODS: Forty young adults (20 men, 20 women; mean age 22.8 ± 3.9 years) with theoretically ideal dental occlusion were selected using very restrictive criteria. sEMG activity of the anterior temporalis (AT), posterior temporalis, masseter (MA), and suprahyoid muscles were evaluated in the rest position and during swallowing, mastication, and clenching. Mandibular kinematics in the rest position and during maximum excursions were assessed. Asymmetry, activity, and torque indices and MA/AT ratios were calculated. RESULTS: For all muscles, sEMG values were 1.01-3.57 µV at rest, 3.50-10.85 µV during swallowing, and 41.04-86.59 µV during mastication. During clenching, values were 230.08-243.55 µV for the AT and MA muscles. Mean total asymmetry, activity, and torque indices at rest were 20.34 %, -15.04 %, and 19.02 %, respectively; during clenching, these values were 6.14 %, -2.62 %, and 4.46 %. MA/AT ratios were near 1. Kinematic measurements during lateral excursion, protrusive and maximum opening were 7.54, 8.44, and 37.38 mm respectively; lateral mandibular shift was 1.41 mm; free way and lateral displacement at rest were 1.40 and 0.26 mm. Right MA activity during mastication and clenching was higher in men than women. CONCLUSIONS: Reference values for sEMG activity and mandibular kinematics were determined. Some muscular asymmetry and torque were observed.

The feasibility of masks and face shields designed by 3D printing makers; some considerations of their use against the COVID-19.

The use of mask and face shield has been established as one of the main preventive measures for the control of COVID 19 spread. In Mexico, as well as in other regions of the world, 3D printing has been employed for the design and production of masks and face shields as personal protective equipment (PPE). These models have been fabricated mainly by the makers, industries, and university communities; therefore, it is necessary to analyze the feasibility of the 3D printed PPE to understand its advantages and limitations. In this work, some characteristics of masks and face shields fabricated by additive manufacturing were studied to explore their viability as protection against flow fluids similar to human sneeze. In the present paper, the PPE was designed, and 3D printed utilizing three types of polylactic acid (PLA) as base material. The morphology and the surface elemental analyses of sectioned samples were analyzed by scanning electron microscopy (SEM) and energy dispersion x-ray spectroscopy (EDS). Showing spacing between printed layers, porous areas, and dispersed copper particles. On the other hand, a computational fluid dynamics (CFD) simulation was carried out, the results demonstrated the importance of using PPE for protection of a possible exposure to a "contaminated" aerosol and human sneeze. Based on the abovementioned results, it is possible to consider the commercial PLA as suitable material for the manufacturing of PPE due to its capability to be disinfected employing isopropanol, ethanol, or commercial disinfectants.

[Teaching and perception of urology by medical students at the end of the second cycle: an appraisal]. / Enseignement et perception de l'urologie à la fin du deuxième cycle des études médicales: état des lieux.

OBJECTIVES: Our purpose was to determine how the medical students from the second cycle perceived urology and what their learning methods were. MATERIAL AND METHODS: An e-questionnaire was sent to 1600 students in 16 teaching faculties during the last year of their second cycle. RESULTS: Overall, we obtained 590 answers (36.8%). In our population, 70.2% of the students were women. Of them, 24.1% had been already enrolled in an academic urology unit. Urology was defined as a medical, surgical and medico-surgical discipline by 3.7%, 37.8% and 58% of the students, respectively. Urology was considered as very important, important, not very important and not important at all by 5.1%, 54.4%, 37.5% and 2.4% of the students. The teaching methods used to learn urology were duplicated-notes for ENC preparation (45.3%), conferences for ENC (French national ranking exam) preparation (43.7%), courses of the national urology college (38.6%) and courses of the faculty (32%). The best mastered items were lithiasis disease (86.3%), voiding dysfunction (76.3%) and urological cancers (56.7%). On the contrary, only 34.7% and 28% considered their knowledge sufficient on the erectile dysfunctions and on renal transplantation. Lastly, 7.3% intended to become urologists. Having a work experience in a urology unit was significantly associated to the feeling of being prepared to become an intern (p<0.001) and to the project of becoming a urologist (p<0.001). CONCLUSION: Urology was considered like an important discipline by half of the students at the end of the second cycle even though it is under-represented in the national teaching programme for ENC. A third of the students used courses from the faculty to learn urology and a quarter of them had a work experience in a urology unit during their second cycle.

[Evidence-based medicine and French medical students: an appraisal]. / Evidence-based medicine et étudiants en médecine français : état des lieux.

INTRODUCTION: Nowadays, evidence-based medicine (EBM) is essential to learn and to practice medicine. The aim of the current study was to investigate the baseline level of knowledge of French students regarding EBM. MATERIALS AND METHODS: Between April and May2008, a questionnaire was sent by e-mail to 900students in their last year of medical study. RESULTS: On 327 answers, 297 (91%), 94 (29%) and 85 (26%) students declared they read, write and speak medical English. Ninety (28%) read an article of a French medical review once a month and 43 (13%) read an article of an international medical review once a month. Three hundred and eleven (95%) knew the bases of medical research on the Internet and 219 (67%) used them. Twenty-four (7%) had already participated in a editorial staff of a medical article, 7 (2%) had been co-authors. Two hundred and seventy-two (83%) had made an oral presentation during a medical staff and 3 (1%) during a congress. Finally, 237 (73%) understood the interest of the critical analysis of an article at the ECN and 70 (21%) thought they were prepared. CONCLUSION: The incapacity of learning EBM is one of the limits of the French medical training system. The introduction of the reading critical of an article at the ECN is the concrete beginning of an answer to this problem.

Long-term efficacy of mupirocin in the prevention of infections with meticillin-resistant Staphylococcus aureus in a gastroenterology unit.

The long-term efficacy (55 months) of eradication of nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) by mupirocin was assessed for MRSA infections in a gastroenterology unit receiving patients for long hospital stays. In total, 2242 patients were included in the study; 92% had been hospitalized in another hospital before admission to the study department, 64% had chronic liver diseases (LD), 25% had miscellaneous medical conditions and 11% were admitted following gastroenterological surgery. Three consecutive periods were considered in the analysis. Nasal carriage at admission was similar in all three periods (10.9 vs 7.5 vs 8.6% in Periods 1, 2 and 3, respectively), while acquired nasal carriage decreased in the whole population (14.3 vs 16.2 vs 10.2% in Periods 1, 2 and 3, respectively, P=0.006) and in LD patients (15.8 vs 18.7 vs 11.9% in Periods 1, 2 and 3, respectively, P=0.018). The incidence of MRSA infections (N per total number of hospitalization-days) was 1.41 per 1000 in the year before initiation of eradication, 1.40 in Period 1, 0.74 in Period 2 and 0.59 in Period 3 (P=0.022). The incidence of MRSA infections among patients was 7.0% in Period 1, 3.7% in Period 2 and 3.1% in Period 3 in LD patients (P=0.0062). The corresponding figures were 5.5, 3.0 and 2.4% for the whole population (P=0.0024). The mortality caused by MRSA was 0.31, 0.19 and 0.13% (P=0.035) in Periods 1, 2 and 3, respectively. The numbers of resistant strains among those acquired during hospitalization were 12 in Period 1, four in Period 2 and six in Period 3. Long-term intranasal mupirocin treatment in MRSA carrier patients with long hospital stay is associated with a decrease in acquired carriage and MRSA infections, while resistance of the strains to mupirocin does not increase provided that colonized patients are only treated once.

Increased risk of alteration of nutritional status in hospitalized elderly patients with advanced cancer.

Malnutrition is common in patients with advanced cancer and is associated with worse prognosis. The aim of this study was to follow-up the nutritional status of elderly patients with advanced cancer in comparison with that of younger ones, in the course of hospitalization. Eighty-eight (44 males and 44 females) patients with advanced cancer entered the study. Two groups were defined according to age : superior 70 y (n = 45) and < 70 y (n = 43). Nutritional status by means of anthropometric variables and daily intake were assessed on Day 0, Day 30 and Day 60. A blood sample was collected on Day 0 for determination of serum proteins. The two groups of patients did not differ in terms of anthropometry and biological variables on admission to our department ; only bicipital skinfold thickness and energy intake were lower in the elderly patients. After one month hospitalization, tricipital skinfold thickness and fat mass decreased in these patients. After two months, mid-arm circumference also decreased. Unlike the older group, the younger patients increased their daily energy and protein intakes. During hospitalization, older persons with advanced cancer cannot improve their energy intake and therefore, are at particular risk of aggravating their nutritional status.

Changes in nature and antibiotic resistance of bacteria causing peritonitis in cirrhotic patients over a 20 year period.

AIM: To assess all clinically and bacteriologically documented episodes of spontaneous bacterial peritonitis diagnosed in a single unit over a 20 year period, to identify changes in the nature and antibiotic resistance of the causative bacteria. SETTING: A specialist liver disease unit in a tertiary care centre. MATERIAL: Cultured ascitic fluid obtained in the course of 240 consecutive episodes of clinically and bacteriologically proven spontaneous bacterial peritonitis. Patient recruitment remained stable during the 20 year period in terms of the number of cirrhotic patients admitted and the severity of their condition. RESULTS: 78.7% of isolates were Enterobacteriaceae (Escherichia coli in 51%) and 19% were Gram positive cocci. Until 1979 all the Enterobacteriaceae had the wild phenotype, compared with only 50% at the end of the study period. Since 1993, 22% of Enterobacteriaceae have been resistant to third generation cephalosporins. Methicillin resistant staphylococci were only isolated after 1989. CONCLUSIONS: Changes in the epidemiology and antibiotic resistance of bacteria causing spontaneous bacterial peritonitis must be monitored for optimal treatment.

Prophylaxis of folate deficiency in acutely ill patients: results of a randomized clinical trial.

A trial was carried out of prophylaxis of folate deficiency in 105 acutely ill patients immediately following admission to an ICU with evaluation of folate status. These patients were fed either orally or by enteral or parenteral nutrition. Three groups were established regardless of the type of nutrition: - Group 1 received 5 mg/day parenteral folinic acid; - Group 2 received 50 mg/week parenteral folinic acid; - Group 3 received no parenteral folinic acid. Before treatment, 19% of the patients presented very low serum folate levels (less than 2.7 ng/ml). Two of them developed acute folate deficiency with severe hematological disturbances quite reversed with folinic acid. Folate levels were inversely correlated with the severity of the clinical status and were lower in septic and feverish patients. The effect of folinic acid administration was assessed after seven days of treatment: daily administration of 5 mg folinic acid appeared to be the best regimen with normalization of serum folate levels in all cases; results appeared to be better than with 50 mg once weekly. Oral and enteral administration of folate supplies considered to be physiological (300 micrograms/day folic acid) did not appear to be sufficient to normalize in all cases blood folate levels in these acutely ill patients.

Short-term changes in energy metabolism after 1 month of a regular oral diet in severely malnourished cirrhotic patients.

Malnutrition in patients with liver cirrhosis is currently associated with abnormal fuel metabolism. The aim of this study was to evaluate changes in energy production and substrate oxidation rates in a group of 26 nonanorectic severely malnourished cirrhotic patients in stable clinical condition after 1 month of an oral diet. Child-Pugh score, nutritional status, energy expenditure, rates of nutrient oxidation, and plasma levels of intermediary metabolites in the postabsorptive phase were assessed before and after 1 month of oral nutrition. Upon entry onto the study, caloric and protein intakes were 40.1 +/- 2.0 kcal/kg and 1.44 +/- 0.8 g/kg, respectively. The Child-Pugh score did not change during the study, whereas nutritional status improved as shown by increased muscular midarm circumference, ([MMAC] P < .02), height-creatinine index (P < .05), triceps skinfold thickness ([TST] P < .01), and fat mass (P < .001). Inflammatory state improved during the study, as shown by the decrease of C-reactive protein ([CRP] P < .01) and orosomucoid (P < .001). The ratio of caloric intake to resting energy expenditure (REE) increased (1.53 +/- 0.06 v 1.66 +/- 0.07, P < .05), as well as the rate of glucose oxidation ([Gox] 73.6 +/- 9.9 v 128.1 +/- 10.3 mg/min, P < .001) and urine nitrogen excretion (6.69 +/- 0.47 v 7.96 +/- 0.48 g/d, P < .02). On the other hand, the rate of lipid oxidation (Lox) decreased (67.3 +/- 3.9 v 47.3 +/- 4.9 mg/min, P < .001) and was correlated with the decrease of free fatty acid (FFA) levels (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

The thermogenic and metabolic effects of food in liver cirrhosis: consequences on the storage of nutrients and the hormonal counterregulatory response.

The thermogenic effect of food and the rates of oxidation and storage of nutrients were evaluated by indirect calorimetry in 10 cirrhotic patients and seven normal controls for a 6-hour period, after they had consumed a standard meal supplying 15 kcal/kg body weight with 15%, 30%, and 55% protein, fat, and carbohydrate calories, respectively. Although the thermogenic response to food was not significantly lower in patients than in controls (51.6 +/- 13.5 v 72.2 +/- 8.8 kcal/6 h), patients exhibited a delayed and blunted increment of energy expenditure after the meal intake (P less than .025). The greater part of the glucose load was oxidized in patients (70.2 +/- 3.9% v 50.4 +/- 3.9% in controls; P less than .01), suggesting a defective glucose storage as glycogen. This result could be related to insulin resistance, which was evidenced by a large increase in glucose and insulin levels after the meal intake in patients (P +/- .001). Conversely, lipid oxidation was sharply reduced and de novo lipogenesis occurred in patients, so that the rate of lipid storage was increased. The profiles of circulating levels of catecholamines, thyroid hormones (free thyroxine [FT4] and triiodothyronine [T3]), and glucagon were assayed during the test. Norepinephrine and glucagon levels remained higher in patients throughout the test (P less than .001), whereas thyroid hormones stayed in the same range in the two groups. After an initial increase, glucose levels decreased sharply, inducing an activation of counterregulatory hormones, glucagon, and notably, epinephrine, for which the increment was correlated with the decrease of glucose (r = -.917; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal and metabolic changes during exercise in cirrhotic patients.

The metabolic response to exercise was compared in 10 cirrhotic patients (P) in a stable clinical condition and in 6 sedentary, age-matched, normal subjects (C) performing 32 minutes of treadmill exercise with the same constant workload corresponding to three to four times their resting oxygen uptake. Taking indirect calorimetry as reference, respiratory exchanges indicated that cirrhotic patients consumed carbohydrates almost exclusively, unlike the normal controls, who consumed lipids and glucids in about the same proportions (RQ: 0.98 +/- 0.04 v 0.87 +/- 0.04, P less than .0001). In the patients, this carbohydrate path of exercise metabolism lowered glycemia from the resting value of 5.23 +/- 0.16 mmol/L to 4.03 +/- 0.37 mmol/L (P less than .0001) and raised the plasma lactate concentration from 2.08 +/- 0.24 mmol/L at rest to 3.48 +/- 0.32 mmol/L at the eighth minute of exercise (P less than .001), thus suggesting defective liver glyconeogenesis. Fatty free acids and glycerol remained almost constant during exercise, whereas catecholamines increased. Insulin levels were high in patients at rest (67.1 +/- 14.5 U/mL v 15.1 +/- 3.5 U/mL); they declined sharply at the onset of exercise but nevertheless remained high compared to those observed in the controls (P less than .0001). Glucagon increased in exercising patients from 88.3 +/- 21.3 pg/mL to 127.4 +/- 30.6 pg/mL (NS). Esterified plasma carnitine declined in the patients from 13.0 +/- 2.2 mumol/L to 8.6 +/- 1.5 mumol/L (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

A clinical trial of mupirocin in the eradication of methicillin-resistant Staphylococcus aureus nasal carriage in a digestive disease unit.

We assessed the incidence of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) on admission, the rate of acquisition during the hospital stay and the relationship with subsequent infection in a digestive disease unit. The efficacy of a program of nasal carriage eradication with mupirocin was evaluated simultaneously. Over one year 484 patients were studied prospectively on admission for nasal and stool carriage of MRSA, then every week for nasal carriage. Nearly 70% (68.8%) of patients had chronic liver diseases. Nasal carriers were assigned to a five-day course of intranasal mupirocin ointment. One hundred and seventeen (24.2%) patients were MRSA positive, 57 (11.8%) of which were carriers on admission and 60 (12.4%) acquired carriage. Of these, 86 were treated with mupirocin with a success rate of 98.8% and 25.9% of them recolonized. Fourteen patients were retreated, to allow eradication in 71.4% of cases. Seventy percent of these became carriers again. One high-level mupirocin-resistant strain was isolated before treatment and seven during or after treatment. Hospital stay and stool carriage were independently associated with reacquisition (P = 0.0105 and P = 0.0462, respectively). Molecular analysis showed identity between the strains isolated from infection samples and from nasal swabs during the same week. For every patient who became recolonized, nasal strains isolated before and after eradication were the same in 70% of cases. Mortality during hospital stay was independently associated with age (P = 0.0081), MRSA nasal carriage (P = 0.02631), MRSA infection (P < 0.0001) and liver disease (P = 0.0017). This study did not show a change in the prevalence rate of infection in the unit during treatment with mupirocin. This treatment should only be attempted once due to the risk of emergence of high-level resistant strains.

Serum levels of insulin-like growth factor-1 in the three months following surgery for a hip fracture in elderly: relationship with nutritional status and inflammatory reaction.

BACKGROUND AND AIMS: Serum IGF-1 level declines with advancing age and is a reliable index of protein-energy undernutrition in elderly patients in a metabolically stable condition. We have examined the value of IGF-1 as an indicator of malnutrition in elderly patients during recovery within 1 month after surgery for a hip fracture and we have studied the relationship between changes in IGF-1 levels, nutritional status and inflammatory reaction during 2 month follow up. STUDY DESIGN: Forty elderly patients (mean age 84.0+/-1.9) were nutritionally assessed upon admission to our rehabilitation unit (D0) then monthly (D30-D60) by measurement of anthropometric and biological parameters. Two groups of patients were defined on the basis of mid-arm circumference (MAC) and tricipital skinfold thickness (TST) measurement at D0: group 1, undernourished (n=13) and group 2, normally nourished (n=27). Changes in anthropometric and biological parameters during the study were compared between these two groups of patients. RESULTS: IGF-1 level was significantly lower in group 1 (79.5+/-9.1 vs 108+/-8.6 ng/ml, P<0.05) while usual serum protein levels were in the same range in the two groups. Orosomucoid level significantly decreased during 2 month follow-up in group 2 (P<0.01), CRP level decreased but not significantly. TST and MAC decreased in group 2 (respectively P<0.02 and P<0.05) while anthropometric parameters tended to slightly increase in group 1 in relation with an increase in caloric intake (P<0.05). IGF-1 level increased significantly during the study in group 2 (P<0.05) and was significantly lower in patients with complications occurring between D0 and D30 in comparison with patients without complications (respectively P<0.05 at D0, P<0.02 at D30). IGF-1 level correlated with body mass index, MAC, TST, muscle midarm circumference, albumin and transthyretin levels. Changes in IGF-1 levels positively correlated with those in transthyretin levels and negatively with those in orosomucoid levels. CONCLUSION: IGF-1 level seems a reliable index of protein-energy under-nutrition in elderly patients in the recovery period after surgery for a hip fracture. This marker is influenced by the inflammatory reaction. Decline of inflammatory reaction, rather than change in nutritional status, is responsible for the variation in IGF-1 level during a 2 month follow-up.

Value of body mass index in the detection of severe malnutrition: influence of the pathology and changes in anthropometric parameters.

BACKGROUND & AIMS: We have estimated the prevalence of severe malnutrition in groups of patients hospitalized for different medical causes and assessed the sensitivity of BMI in the diagnosis of severe malnutrition. DESIGN: A prospective study enrolled 1052 patients: 396 patients with liver cirrhosis including 165 non-ascitic patients (NAP), 124 patients with mild ascites (MAP), 107 patients with tense ascites (TAP), 251 patients after cardiac surgery (SCP), 81 patients with cardiac diseases (MCP), 85 patients with stroke (SP), 36 patients with degenerative neurological diseases (DNP), 68 patients after surgery of a hip fracture (HFP), 91 patients with palliative care for cancer (CP) and 44 elderly patients with medical affections (EP). BMI, mid-arm muscular circumference (MAMC) and triceps skinfold thickness (TST) were measured within 48 h after admission. Patients with MAMC and TST below the 5th percentile of a reference population when aged < or = 74 or the 10th percentile when aged > or = 75 were defined as severely malnourished. Sensitivity of BMI < 20 to detect malnutrition was assessed. RESULTS: The prevalence of severe malnutrition was the highest in TAP (39.1%) HFP (25.6%) and MAP (24.3%) and the lowest in SCP (4%), SP (4.8%), DNP (5.7%) and MCP (7.4%) (P < 10(-4)). In multivariate analysis, low TST was associated with female gender (P < 10(-4)) mild and tense ascites (P = 0.038, P = 0.0004), low MAMC with male gender (P < 10(-4)), low BMI with female gender (P = 0.0082), hip fracture (P = 0.0407) and cancer (P = 0.0059). The sensitivity of BMI to detect severe malnutrition was the highest in HFP, CP and EP (100%, 80% and 100% respectively) and the lowest in TAP, MCP and SP (40%, 33.3% and 50% respectively). After exclusion of TAP, sensitivity of BMI to detect malnutrition correlated significantly with the coefficient of correlation between MAMC and TST observed in each group (r = 0.821, P = 0.0066). CONCLUSION: Ascitic cirrhotic patients and elderly patients after surgery of hip fracture had the highest prevalence of severe malnutrition. BMI had the highest sensitivity when both TST and MAMC were damaged to the same extent. BMI < 20 has a high sensitivity in the diagnosis of severe malnutrition in elderly and cancer patients but not in cirrhotic patients with tense ascites, cardiovascular and neurological patients.

Intestinal permeability in liver cirrhosis: relationship with severe septic complications.

OBJECTIVES: Patients with liver cirrhosis are at high risk of severe septic complications such as spontaneous bacterial peritonitis (SBP) and bacteraemia. The aims of this study were to assess intestinal permeability in patients with liver cirrhosis and to search for a relationship between an impaired intestinal permeability and the occurrence of severe septic complications. METHODS: Intestinal permeability was assessed in a group of 80 cirrhotic patients (Child A, n = 13; Child B, n = 26; Child C, n = 41) and 28 healthy control subjects. A severe septic complication (bacteraemia and/or SBP) occurred in 16 patients, within 10 days before (n = 8 cases) or after (n = 8 cases) the test was performed. Lactulose (LAC) 10 g was given orally together with mannitol (MAN) 5 g, and urinary excretion rates were determined. RESULTS: Urinary mannitol excretion (MAN%) was lower while the LAC/MAN ratio was higher in patients than in control subjects (P < 0.001); these abnormalities were more marked in Child C patients (Child C patients vs control subjects: MAN%, 8.20 +/- 0.79 vs 14.59 +/- 0.58, P < 0.001; LAC/MAN, 0.066 +/- 0.026 vs 0.017 +/- 0.001, P < 0.02). When compared with non-infected patients, septic patients had a lower MAN% and an increased LAC/ MAN ratio (5.45 +/- 1.12 vs 9.83 +/- 0.87, P < 0.02; 0.130 +/- 0.063 vs 0.029 +/- 0.005, P < 0.02). CONCLUSION: Although the main mechanism involved in the decrease in MAN% is likely a reduction in area of the intestinal absorptive surface, these results argue in favour of an increased intestinal permeability in liver cirrhosis, especially in patients with severe infectious complications. The impairment of intestinal function barrier may contribute to severe septic complications in these patients.

Postprandial de novo lipogenesis in alcoholic liver cirrhosis: relationship with fuel homeostasis and nutritional status.

The prevalence and nutritional consequences of postprandial de novo lipogenesis were evaluated in 24 stable alcoholic cirrhotic patients. Energy expenditure and the rates of nutrient oxidation were assessed by indirect calorimetry after an overnight fast and 2 h after a standard meal supplying 15 kcal/kg (63 kJ/kg) of body weight. Postprandially, net lipogenesis occurred in 16 patients (group L+) as shown by a respiratory quotient clearly above 1.00 (P < 0.01). The rate of lipid oxidation remained positive in 8 patients (group L-). The main mechanism involved in this metabolic pathway appeared to be a sharp postprandial hyperinsulinaemia. When compared to group L+, patient group L- showed an impaired thermic effect of food (P < 0.05), a lower rate of glucose oxidation (P < 0.05) and a mild hyperketonaemia (P < 0.05) at fasting levels. Muscular and fat masses were lower (respectively P < 0.05 and P = 0.05) and the severity of the disease as assessed by the Child-Pugh classification was more pronounced in this group (P < 0.02). The occurrence of postprandial lipogenesis in stable cirrhotic patients is related to better nutritional status. Such a metabolic pathway may explain the nutritional heterogeneity of cirrhotics and is likely to have an effect on the benefits of refeeding.

Serum leptin levels in alcoholic liver cirrhosis: relationship with gender, nutritional status, liver function and energy metabolism.

OBJECTIVE: To determine serum leptin levels in alcoholic liver cirrhosis and the relationship with gender, nutritional status, liver function, energy metabolism, inflammatory state and refeeding. SUBJECTS: Thirty-seven hospitalized alcoholic cirrhotic patients (M/F: 24/13), 27 hospitalized patients at risk of malnutrition but with normal liver function (M/F: 15/12) as control patients, and 31 healthy control subjects (M/F: 17/14) participated. DESIGN: Liver function was assessed from Child-Pugh classification; anthropometric parameters and resting energy expenditure (REE) were measured; caloric intake was evaluated over 5 days; and serum leptin and insulin were assayed. The same protocol was performed after 1 month refeeding in 22 patients. Healthy subjects were studied as controls for anthropometric parameters and serum leptin levels. RESULTS: Serum leptin levels were higher in male cirrhotic patients than in the other two male groups (P=0.0079) and in the same range in the female groups. They were higher in female than in male subjects in the three groups. In female cirrhotic patients, logarithmically transformed serum leptin levels correlated significantly with fat mass (P=0.0043), insulin levels (P=0.0072), REE (P=0.0133), bilirubin levels (P<0.0001), prothrombin time (P=0.0003) and Pugh score (P=0.0266) in simple regression analysis and with insulin levels (P=0.0137), but not with fat mass (P=0.0761), Pugh score (P=0.4472) and REE (P=0.4576) in multiple regression analysis. In the male cirrhotic and control patients, log (leptin) levels correlated with CRP (C reactive protein) (r=0.365, P=0.0223). Log (leptin) levels did not correlate with caloric intake in any of the groups. Leptin levels (P<0.05) and fat mass (P<0.02) increased with refeeding while liver function improved (P<0.01). CONCLUSION: There is a gender difference in regulation of serum leptin level in alcoholic liver cirrhosis. Insulin level is the best determinant of leptin level in female patients while inflammatory state related to alcoholic hepatitis seems to have a greater influence in male patients. Although leptin levels positively correlated with REE in female patients, there is no evidence that leptin reduces caloric intake and fat stores in these patients.

Influence of liver failure, ascites, and energy expenditure on the response to oral nutrition in alcoholic liver cirrhosis.

The influence of liver failure, ascites, and energy expenditure on the response to oral nutrition was assessed in a group of 55 alcoholic cirrhotic patients. Caloric intake, nutritional status, resting energy expenditure (REE), and Child-Pugh score were evaluated before and after 1 mo of oral nutrition. Patients were severely malnourished, 73% had muscular midarm circumference (MMAC) below the 5th percentile of a reference population, 51% had triceps skinfold thickness below the 25th percentile. Eleven patients were in class A of Child, 19 in class B, and 25 in class C. Twenty-six patients were nonascitic, whereas ascites was resolved in 10 ascitic patients by the end of the study and 19 patients had refractory ascites. Liver damage was more pronounced and did not improve during the study in patients with refractory ascites. Caloric intake was approximately 40 kcal/kg of body weight and was in the same range in the three groups according to Child classification. Fat mass (FM) increased, respectively, from 17.4% +/- 1.7% to 19.5% +/- 1.4%, P < 0.01, in Child A patients; from 17.1% +/- 1.4% to 19.3% +/- 1.4%, P < 0.001, in Child B patients; and from 17.6% +/- 1.5% to 18.8% +/- 1.5%, P < 0.05, in Child C patients. The increase in FM was comparable in the three groups, whereas MMAC and the creatinine/height ratio did not change significantly. FM was lower and did not increase in patients with refractory ascites. Child C patients were characterized by an increase in the rate of glucose oxidation (P < 0.02) and a decrease in the rate of lipid oxidation (P < 0.05). High-density lipoprotein cholesterol and apolipoprotein (Apo) A1 were reliable indices of improvement of liver function in patients with severe liver failure, ApoA1 was also a marker of improvement of metabolic impairment. With respect to the measured REE/predicted REE ratio calculated according to Harris-Benedict equation (r), 19 patients were considered hypermetabolic (r < 1.1), 30 normometabolic (0.9 < r < 1.1), and 6 hypometabolic (r < 0.9). An increase in FM correlated with r (P < 0.01) and was more marked in hypermetabolic patients. In contrast to the other two groups, Child-Pugh score and nutritional status remained unchanged in the hypometabolic patients. These results show that severe liver failure did not preclude improvement of nutritional status provided caloric intake was high. In Child C patients, improvement of nutritional status paralleled improvement of liver function and normalization of oxidative metabolism. Refractory ascites had negative effects on changes in nutritional status and liver function. Despite adequate caloric intake to energy requirements, hypometabolism has a poor prognosis regarding both nutritional status and liver function.

Nutritional and metabolic consequences of basal hyperinsulinemia in alcoholic liver cirrhosis: relationship with postprandial changes in erythrocyte insulin-receptor affinity.

The nutritional and metabolic consequences of basal hyperinsulinemia were investigated in a group of 13 alcoholic cirrhotic patients; 7 healthy subjects were studied as a control group. Two groups of patients were defined on the basis of fasting insulin level: group 1 (n = 7) displayed acute hyperinsulinemia (> mean of control group + 2SD), and group 2 (n = 6) had lower insulin levels. Nutrition status was assessed by means of anthropometric parameters; the rates of nutrient oxidation were measured after an overnight fast and 2 h after a standard meal intake. Group 1 had better nutrition status in terms of fat mass than group 2 (p < 0.05). Although the basal rates of nutrient oxidation were in the same range in the three groups, postprandially, the rate of lipid oxidation was significantly different (p < 0.01). Moreover, group 1 showed greater inhibition of postprandial lipid oxidation than the control group (p < 0.05), whereas there was no difference between group 2 and the control group. In the postprandial phase, erythrocyte insulin-receptor binding and affinity increased paradoxically in group 1, whereas they decreased in group 2 and healthy subjects (changes in binding, p < 0.025; changes in affinity, p < 0.01). In conclusion, basal hyperinsulinemia in alcoholic liver cirrhosis is related to more marked inhibition of postprandial lipid oxidation and better-preserved nutrition status and may lead to a paradoxical postprandial increase in insulin-receptor affinity.