Primary Sclerosing Cholangitis: Gender Effects in Valencia's Low-Prevalence Region.

BACKGROUND AND AIMS: Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course. METHODS: Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables. RESULTS: Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9 years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men. CONCLUSION: In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study.

There is uncertainty regarding Wilson's disease (WD) management. OBJECTIVES: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. METHODS: Data on WD patients followed at 32 Spanish hospitals were collected. RESULTS: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. CONCLUSIONS: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

[Patient safety incidents reported before and after the start of the COVID-19 pandemic in Primary Care in Tarragona]. / Incidentes de seguridad del paciente notificados antes y después del inicio de la pandemia de COVID-19 en atención primaria en Tarragona.

OBJECTIVE: To analyse and compare the epidemiology of patient safety incidents reported in Primary Health Care, before and after the start of the COVID-19 pandemic. DESIGN AND SETTING: Analytical descriptive study comparing reported incidents from March 1st 2019 to February 28th 2020, and from March 1st 2020 to February 28th 2021, notified through the TPSC Cloud™ platform accessible from the Intranet corporative in 25 Primary Health Care centres from Tarragona district, in Catalonia (Spain). MEASUREMENTS: Data obtained from voluntary notifications, through electronic, standardized and anonymized forms. VARIABLES: Centre, professional, incident type, risk matrix, causal factors and contributing factors, and avoidability. STATISTICAL ANALYSIS: Every notification was included in descriptive analysis, and another one specifically for adverse events, comparing both periods. RESULTS: 2231 incidents were reported. Comparing both periods, during the pandemic a reduction in the number of reported incidents was observed (only represented 20% of the total). However, the percentage of reported notifications from health care professionals and adverse events that required observation were increased. Causal factors related to attendance and diagnosis were incremented whereas the causal factors related to medication were decreased. In addition, an increase in contributing factors related to the professional was observed. Avoidability was high (>95%) in both periods. CONCLUSIONS: During the pandemic, fewer patient safety incidents have been reported, but proportionally more adverse events, most of which are preventable. The professional himself becomes the main contributing factor.

Analysis of Patient Safety Incidents in Primary Care Reported in an Electronic Registry Application.

OBJECTIVES: (1) To describe the epidemiology of patient safety (PS) incidents registered in an electronic notification system in primary care (PC) health centres; (2) to define a risk map; and (3) to identify the critical areas where intervention is needed. DESIGN: Descriptive analytical study of incidents reported from 1 January to 31 December 2018, on the TPSC Cloud™ platform (The Patient Safety Company) accessible from the corporate website (Intranet) of the regional public health service. SETTING: 24 Catalan Institute of Health PC health centres of the Tarragona region (Spain). PARTICIPANTS: Professionals from the PC health centres and a Patient Safety Functional Unit. MEASUREMENTS: Data obtained from records voluntarily submitted to an electronic, standardised and anonymised form. Data recorded: healthcare unit, notifier, type of incident, risk matrix, causal and contributing factors, preventability, level of resolution and improvement actions. RESULTS: A total of 1544 reports were reviewed and 1129 PS incidents were analysed: 25.0% of incidents did not reach the patient; 66.5% reached the patient without causing harm, and 8.5% caused adverse events. Nurses provided half of the reports (48.5%), while doctors reported more adverse events (70.8%; p < 0.01). Of the 96 adverse events, 46.9% only required observation, 34.4% caused temporary damage that required treatment, 13.5% required (or prolonged) hospitalization, and 5.2% caused severe permanent damage and/or a situation close to death. Notably, 99.2% were considered preventable. The main critical areas were: communication (27.8%), clinical-administrative management (25.1%), care delivery (23.5%) and medicines (18.4%); few incidents were related to diagnosis (3.6%). CONCLUSIONS: PS incident notification applications are adequate for reporting incidents and adverse events associated with healthcare. Approximately 75% and 10% of incidents reach the patient and cause some damage, respectively, and most cases are considered preventable. Adequate and strengthened risk management of critical areas is required to improve PS.

Effectiveness of New Tools to Define an Up-to-Date Patient Safety Risk Map: A Primary Care Study Protocol.

BACKGROUND: Reducing incidents related to health care interventions to improve patient safety is a health policy priority. To strengthen a culture of safety, reporting incidents is essential. This study aims to define a patient safety risk map using the description and analysis of incidents within a primary care region with a prior patient safety improvement strategy organisationally developed and promoted. METHODS: The study will be conducted in two phases: (1) a cross-sectional descriptive observational study to describe reported incidents; and (2) a quasi-experimental study to compare reported incidents. The study will take place in the Camp de Tarragona Primary Care Management (Catalan Institute of Health). In Phase 1, all reactive notifications collected within one year (2018) will be analysed; during Phase 2, all proactive notifications of the second and third weeks of June 2019 will be analysed. Adverse events will also be assessed. Phases 1 and 2 will use a digital platform and the proactive tool proSP to notify and analyse incidents related to patient safety. EXPECTED RESULTS: To obtain an up-to-date, primary care patient safety risk map to prioritise strategies that result in safer practices.

Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry.

AIM: To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life. METHODS: Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16. RESULTS: A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1-0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3-0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1-0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3-1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events. CONCLUSIONS: Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure.

Cuff-assisted versus cap-assisted colonoscopy for adenoma detection: results of a randomized study.

BACKGROUND: The adenoma detection rate (ADR) is the most important marker of colonoscopy quality. Devices to improve adenoma detection have been developed, such as the Endocuff and transparent cap. The aim of the current study was to examine whether there was a difference in ADR between Endocuff-assisted (EAC) and cap-assisted colonoscopy (CAC). METHODS: A randomized prospective trial was conducted. Eligible patients included adults ≥ 18 years referred because of symptoms, surveillance, or colonoscopies as part of the Bowel Cancer Screening Programme (BCSP). The primary outcome measure was ADR. Secondary outcomes included mean number of adenomas, mean number of polyps, polyp detection rate, cecal intubation rate, and time to cecal intubation. Procedural measures, device removal rate, and adverse events were also recorded. RESULTS: A total of 711 patients (51.1 % men; median age 63 years) were included, of whom 357 patients were randomized to EAC and 354 patients to CAC. In the intention-to-treat analysis, the ADR was similar in both groups: EAC 50.4 % (95 % confidence interval [CI] 45.1 - 55.7) vs. CAC 50.6 % (95 %CI 45.2 - 55.9). Similar results were obtained in the per-protocol analysis: EAC 51.6 % (95 %CI 46.2 - 57) vs. CAC 51.4 % (95 %CI 46 - 56.8). There were no differences between the two devices in ADR according to the mean number of adenomas and polyps per procedure, polyp detection rate, cecal intubation rate, and time to cecal intubation. Device removal rate and adverse events were also similar. CONCLUSION: In this randomized study, no differences in ADR were found between Endocuff- and cap-assisted colonoscopy.

Accuracy for optical diagnosis of colorectal polyps in clinical practice.

BACKGROUND: Optical diagnostic involves predicting polyp histopathology from its endoscopic characteristics. It is only recommended for diminutive polyps ( < or = 5 mm) and for predictions made with high confidence. OBJECTIVES: To evaluate the accuracy of optical imaging in clinical practice and to assess if optical diagnosis is useful for predicting future colonoscopy surveillance intervals without waiting for histopathological analysis. METHODS: consecutive > 18 years patients were enrolled in this prospective study. Colonoscopies were performed by five expert endoscopists who previously participated in an ex-vivo training. Colonoscopes CF-H180AL and CF-Q180AL were used together with Exera II (Olympus Medical System, Tokyo, Japan) processors. Each polyp was characterized in real time using white light and Narrow Band Imaging. Accuracy of optical diagnosis (S, E, NPV, PPV) and correlation between surveillance interval based on optical diagnosis and histopathological analysis were calculated. RESULTS: 311 colon polyps < 10 mm (216 diminutive) in 195 patients were analyzed. Accuracy of optical diagnostics for predictions made with high confidence: Diminutive polyps(sensitivity 0.59, specificity 0.92, NPV 0.48); polyps < 10 mm (sensitivity 0.73, specificity 0.88, NPV 0.50). An optical diagnosis based surveillance recommendation was given to 90 patients. Concordance with histopathology based recommendation was 92.2% according to the European guideline and 93.3% according to the ESGE guideline. CONCLUSIONS: Optical diagnostics can be used to predict future surveillance intervals immediately after colonoscopy. However, in this study, based on clinical practice, the accuracy of optical imaging is below the recommended standards.

Factors related to the effectiveness of variable stiffness colonoscope: results of a multivariate analysis.

BACKGROUND: Various studies and two meta-analysis have shown that a variable stiffness colonoscope improves cecal intubation rate. However, there are few studies on how this colonoscope should be used. OBJECTIVE: The aim of this study was to identify factors related to the advancement of the colonoscope when the variable stiffness function is activated. METHODS: Prospective study enrolling consecutive patients referred for colonoscopy. The variable stiffness colonoscope (Olympus CF-H180DI/L®) was used. We performed univariate and multivariate analyses of factors associated with the success of the variable stiffness function. RESULTS: After the data inclusion period, 260 patients were analyzed. The variable stiffness function was used most in the proximal colon segments (ascending and transverse colon 85%; descending/sigmoid colon 15.2%). The body mass index was lower in patients in whom the endoscope advanced after activating the variable stiffness than those in which it could not be advanced (25.9 + or - 4.8 vs. 28.3 + or - 5.4 kg/m2, p = 0.009). The endoscope advanced less frequently when the stiffness function was activated in the ascending colon versus activation in other segments of the colon (25% vs. 64.5% ascending colon vs. other segments; p < 0.05). In the multivariate analysis, only the colon segment in which the variable stiffness was activated was an independent predictor of advancement of the colonoscope. CONCLUSIONS: The variable stiffness function is effective, allowing the colonoscope advancement especially when applied in the transverse colon, descending colon and sigmoid. However, when used in the ascending colon it has a lower effectiveness.

Quantification of Helicobacter pylori in gastric mucosa by real-time polymerase chain reaction: comparison with traditional diagnostic methods.

The aim of this study was to determine the main diagnostic validity parameters of a quantitative real-time polymerase chain reaction (PCR) system for detecting Helicobacter pylori in gastric biopsies. Prospective study. The real-time PCR has an internal control for eliminating the false negatives. Our system has a good diagnostic capacity compared with the gold standard and was superior in antral mucosa: area under the curve was 0.91 for antrum (95% confidence interval [CI] 0.87 to 0.96) and 0.83 for corpus (95% CI 0.77 to 0.9). The optimum cut-off point was 3.56 microorganisms/cell for antrum (sensitivity 83.5% [95% CI 74.2 to 89.9]; specificity 91.3% [95% CI 82.3 to 96.0]; positive predictive value 92.2%; negative predictive value 81.8%). The positive likelihood ratios were 9.61 and 8.52 for antrum and corpus, respectively. With the cut-off point that maximises the Youden index, 8.7% false positives were obtained. Our methodology is useful for diagnosing infection due to H. pylori and the false positives detected probably correspond to patients who were actually infected but the infection was not detected by traditional techniques. The clinical importance of these cases should be studied in greater detail since they may involve colonisations unrelated to the patient's digestive pathology.

Real-time PCR for diagnosing Helicobacter pylori infection in patients with upper gastrointestinal bleeding: comparison with other classical diagnostic methods.

The aim of this study was to determine the diagnostic usefulness of quantification of the H. pylori genome in detection of infection in patients with upper gastrointestinal bleeding (UGB). A total of 158 consecutive patients with digestive disorders, 80 of whom had clinical presentation of UGB, were studied. The number of microorganisms was quantified using a real-time PCR system which amplifies the urease gene with an internal control for eliminating the false negatives. A biopsy sample from the antrum and corpus of each patient was processed. The rapid urease test, culture, histological study, stool antigen test, and breath test were done. The gold standard was a positive culture or positive results in at least two of the other techniques. When a positive result was defined as any number of microorganisms/human cell, the sensitivity of real-time PCR was greater in bleeding patients, especially in the gastric corpus: 68.4% (95% confidence interval [CI], 52.3 to 84.5%) in non-UGB patients versus 91.5% (95% CI, 79.6 to 97.6%) in UGB patients. When a positive result was defined as a number of microorganisms/human cell above the optimal value that maximizes the Youden index (>3.56 microorganisms/human cell in the antrum and >2.69 in the corpus), the sensitivity and specificity in UGB patients were over 80% in both antrum and corpus. Our findings suggest that some bleeding patients with infection caused by H. pylori may not be correctly diagnosed by classical methods, and such patients could benefit from the improved diagnosis provided by real-time PCR. However, the clinical significance of a small number of microorganisms in patients with negative results in classical tests should be evaluated.

Does the use of a variable stiffness colonoscope offer advantages during colonoscopy under deep sedation? Results of a randomized trial.

INTRODUCTION: Variable stiffness colonoscope may be useful in performing colonoscopies in nonsedated patients or under endoscopist-controlled sedation. The objective of this study is to evaluate whether this instrument facilitates colonoscopy in patients under deep sedation monitored by an anaesthesiologist. METHODS: Prospective and randomized study enroling consecutive patients referred for colonoscopy under deep sedation monitored by an anaesthesiologist. In group I, a variable stiffness colonoscope was used, whereas in group II, a standard colonoscope was used. The main variable was the need to change the position of the patient during the endoscopy. RESULTS: Fifty-six patients were included in group I (variable stiffness colonoscope) and 54 in group II (standard colonoscope). The caecum was reached in 92.9% of patients in group I and in 90.7% of group II (P=0.7). The time required to reach the caecum was significantly less in group I (6.14±3.5 vs. 7.7±3.8; P=0.035). The variable stiffness colonoscope was effective in 66.7% of cases. Changing the position of the patient was necessary in 12.5% of cases in group I compared with 33.3% of cases in group II (P=0.01). CONCLUSION: The variable stiffness colonoscope avoids the need to change the patient's position and reduces caecal intubation time in patients undergoing colonoscopy under deep sedation controlled by an anaesthesiologist.

Factors associated with non-attendance at outpatient endoscopy.

OBJECTIVE: Non-attendance at endoscopy procedures leads to wasted resources and increased costs. The purpose of this study was to investigate the factors associated with non-attendance. MATERIAL AND METHODS: All patients who attended the outpatient clinic for gastroscopy or colonoscopy examinations were included in the study. Patients who missed their appointment were identified and their data were collected prospectively. Patients who kept their appointment in the same period of time served as controls. RESULTS: Between August 2002 and February 2003, 1051 gastroscopies and 756 colonoscopies were scheduled. A total of 265 patients (14.7%) missed their appointment. No significant differences were found between attendees and non-attendees for mean age, gender, type of examination and day of the week on which the examination was scheduled. The time on the waiting list was longer in patients who did not keep their appointment than in those who did. Fewer appointments were missed in patients with a preferent referral, and among patients referred by their general practitioner a higher percentage failed to keep their appointment compared with those referred by a specialist. In the multivariate analysis, length of time on the waiting list and the source of referral were the only two independent predictive factors for non-attendance. CONCLUSIONS: A longer time on the waiting list and referral by a general practitioner are factors associated with patients failing to keep their endoscopy appointment.

Successful treatment of severe gastrointestinal bleeding secondary to Crohn disease with recombinant factor VIIa.

A 58-year-old man diagnosed with ileocolonic Crohn disease was admitted to the emergency room with massive lower gastrointestinal hemorrhage and hypovolemic shock. Treatment was started with methylprednisolone, metronidazole and omeprazole. Within the next 24 hours, he received a total of 9 U of red blood cell concentrate and 2 U of fresh frozen plasma. Because of persistence of bleeding, hypovolemic shock and life-threatening situation, we started therapy with rFVIIa. One dose of 120 microg/kg and another dose of 120 microg/kg three hours after the first dose were administered as compassionate use, with resolution of bleeding in the next 12 hours. On day 4 the patient was stabilized. We performed a total colonoscopy and intubation of the ileocecal valve that showed patchy deep ulcerations in the rectum with bleeding inflammatory pseudopolyps. Acute gastrointestinal bleeding is an unusual complication in Crohn disease. In this case, the use of recombinant activated factor VIIa controlled the massive gastrointestinal bleeding secondary to Crohn disease and without clinically significant adverse effect. There are few case reports documenting the use of recombinant activated factor VIIa for this type of off-label indication. Clinical trials should be carried out to define the dosage and dose interval schedule of rFVIIa in the treatment of uncontrolled massive gastrointestinal bleeding secondary to Crohn disease.

Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis.

Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL+HD. The BDL+HD rats were made hyperammonemic via an ammonia-containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL+HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL+HD rats showed activation of the inflammatory system. BDL+HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo-inositol, and a significant increase in the level of brain water. In coordination tests, BDL+HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances.

Acenocoumarol-induced Henoch-Schönlein purpura.

OBJECTIVE: To report a probable case of Henoch-Schönlein purpura associated with acenocoumarol therapy. CASE SUMMARY: A 76-year-old white woman was prescribed acenocoumarol for chronic atrial fibrillation. Two months after starting therapy, the patient came to our hospital's emergency department because of abdominal pain associated with vomiting. Physical examination revealed multiple round, confluent, purpuric lesions with some vesicles and an area of residual pigmentation. Lesions were present predominantly on the legs and gluteus, and also on the abdomen and arms. Skin biopsy of the lesions was compatible with leukocytoclastic vasculitis with deposition of immunoglobulin A. An upper intestinal endoscopy was done and identified purpuric mucosal lesions in the fundus, body, and antrum of the stomach and the duodenal bulb. Renal function was not affected, although proteinuria (1.26 g/day) was found and microscopic hematuria was observed. DISCUSSION: The most likely cause of the Henoch-Schönlein purpura in this case was considered to be acenocoumarol because of the close temporal relationship between exposure to the drug and onset of symptoms, as well as the rapid resolution of the symptoms and signs after acenocoumarol was discontinued. The oral anticoagulant was the only identifiable precipitant that the patient encountered before the Henoch-Schönlein purpura developed. An objective causality assessment revealed that the adverse drug event was probable. CONCLUSIONS: This case report illustrates a probable association between Henoch-Schönlein purpura and acenocoumarol. As of December 2003, this reaction had not been previously reported. Clinicians should be aware of this potential adverse effect of a widely used drug.

Intestinal permeability is increased in patients with advanced cirrhosis.

BACKGROUND/AIMS: The dysfunction of the intestinal barrier is a factor that has been related to bacterial translocation from lumen to extra-intestinal sites and consequently to the development of spontaneous bacterial peritonitis. The aim of this study was to investigate if the alterations of the intestinal barrier in cirrhosis are related with the degree of liver failure and associated with other clinical complications. METHODOLOGY: Intestinal permeability was assessed by means of the lactulose/mannitol test in 79 cirrhotic and 25 controls subjects. They received 10 g of lactulose and 5 g of mannitol. Lactulose and mannitol were measured in a five-hour urinary volume. RESULTS: Lactulose/mannitol ratio was significantly higher in cirrhotic patients than in controls (p = 0.03). This was more evident in end-stage cirrhosis. Patients with ascites, or encephalopathy showed a statistically significant increase in lactulose/mannitol ratio when compared to patients without these complications. CONCLUSIONS: The increased intestinal permeability is related to the progression of the liver disease and is more relevant with overt clinical complications. This is due to an increased absorption of lactulose. However, as liver disease progresses, mannitol absorption is progressively reduced, probably due to a reduced surface of absorption, and these events are more relevant in patients with overt clinical complications.

Minimal hepatic encephalopathy and extrapyramidal signs in patients with cirrhosis.

OBJECTIVE: Two types of neurological dysfunction can occur in compensated cirrhosis: 1) extrapyramidal signs related to the accumulation of manganese in the basal ganglia and 2) milder degrees of cognitive impairment known as minimal hepatic encephalopathy (mHE). We assessed whether there was any relationship between both disorders in 42 patients with compensated cirrhosis. METHODS: Minimal hepatic encephalopathy was diagnosed using a battery of manual neuropsychological tests. Cognitive functioning was assessed by the Mini-Mental State Examination. Extrapyramidal signs were evaluated by the Columbia scale. RESULTS: Minimal hepatic encephalopathy was diagnosed in 15 (35.7%) patients. A total of 52.4% of patients showed significant extrapyramidal signs. Scores for the Columbia scale were higher in the presence of mHE (mean +/- SD, 16.0 +/- 10.9 vs 5.3 +/- 7.1, p = 0.0004). In the bivariate analysis, mHE, Child-Pugh score, and Mini-Mental State Examination score were significantly associated with extrapyramidal signs, whereas in the multivariate analysis, mHE was the only independent variable related to extrapyramidal signs. CONCLUSIONS: There was a link between extrapyramidal signs and diagnosis of mHE based on manual neuropsychological testing. This finding may be explained by the influence of extrapyramidal manifestations on test performance or by a real pathophysiological relationship between both disorders. Further studies are necessary to resolve this question.