Cumulative exposure to tacrolimus and incidence of cancer after liver transplantation.

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case-control nested study aimed to evaluate the effect of maintenance immunosuppression on post-LT malignancy. The eligible cohort included 2495 LT patients who received tacrolimus-based immunosuppression. After 13 922 person/years follow-up, 425 patients (19.7%) developed malignancy (cases) and were matched with 425 controls by propensity score based on age, gender, smoking habit, etiology of liver disease, and hepatocellular carcinoma (HCC) before LT. The independent predictors of post-LT malignancy were older age (HR = 1.06 [95% CI 1.05-1.07]; p < .001), male sex (HR = 1.50 [95% CI 1.14-1.99]), smoking habit (HR = 1.96 [95% CI 1.42-2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19-1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT.

Paroxysmal nocturnal hemoglobinuria and liver transplantation, a new paradigm.

Paroxysmal nocturnal hemoglobinuria (PNH) is a type of hemolytic anemia acquired by the PIG-A gene mutation. This causes a deficiency of a complement regulatory protein, CD59, which results in hemolysis, hemoglobinuria and thrombosis (due to the release of procoagulant factors). Budd-Chiari syndrome is characteristic in these patients and has classically been considered as a contraindication for liver transplantation (LT) due to post-transplant recurrence. Since the approval of eculizumab for the treatment of PHN, disease control is possible and therefore the post-transplant recurrence of thrombotic phenomena involving the liver is avoided.

Influence of demographic and clinical features of the patient on transit times and impact the on the diagnostic yield of capsule endoscopy.

BACKGROUND: transit times in the gastric cavity and the small bowel can be easily calculated using capsule endoscopy software. The factors that can influence these times and impact on diagnostic yield have not been completely assessed. AIMS: to analyze the influence of demographic and clinical features on transit times and the impact on diagnostic yield. METHODS: a retrospective, single-center study of examinations between January 2013 and November 2017 was performed. The analyzed features included gender, age, body mass index, diabetes, thyroid disease and indications. The association and correlation between the variables were assessed, as well as the presence of positive and significant findings. RESULTS: six hundred and thirty-one patients were included in the study. Gastric and small bowel transit times were 36.10 ± 48.50 and 251.82 ± 116.42 minutes, respectively. Gastric time was not affected by any of the variables. Small bowel time was longer in males, patients over 60 years of age and diabetics. Prolonged small bowel time, male gender and older age were associated with a higher diagnostic yield. Age over 60 years was the only factor independently associated with positive findings (OR: 1.550 [1.369-1.754]; p: 0.007). CONCLUSIONS: patients over 60 years have a longer small bowel transit time and higher probability of having small bowel lesions. Males and diabetic patients also seem more likely to have longer transit times and higher rates of positive findings.

Lung Ultrasound as a First-Line Test in the Evaluation of Post-COVID-19 Pulmonary Sequelae.

Background: Interstitial lung sequelae are increasingly being reported in survivors of COVID-19 pneumonia. An early detection of these lesions may help prevent the development of irreversible lung fibrosis. Lung ultrasound (LUS) has shown high diagnostic accuracy in interstitial lung disease (ILD) and could likely be used as a first-line test for post-COVID-19 lung sequelae. Methods: Single-center observational prospective study. Follow-up assessments of consecutive patients hospitalized for COVID-19 pneumonia were conducted 2-5 months after the hospitalization. All patients underwent pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and LUS. Radiological alterations in HRCT were quantified using the Warrick score. The LUS score was obtained by evaluating the presence of pathological B-lines in 12 thoracic areas (range, 0-12). The correlation between the LUS and Warrick scores was analyzed. Results: Three hundred and fifty-two patients who recovered from COVID-19 pneumonia were recruited between July and September 2020. At follow-up, dyspnea was the most frequent symptom (69.3%). FVC and DLCO alterations were present in 79 (22.4%) and 234 (66.5%) patients, respectively. HRCT showed relevant interstitial lung sequelae (RILS) in 154 (43.8%) patients (Warrick score ≥ 7). The LUS score was strongly correlated with the HRCT Warrick score (r = 0.77) and showed a moderate inverse correlation with DLCO (r = -0.55). The ROC curve analysis revealed that a LUS score ≥ 3 indicated an excellent ability to discriminate patients with RILS (sensitivity, 94.2%; specificity, 81.8%; negative predictive value, 94.7%). Conclusions: LUS could be implemented as a first-line procedure in the evaluation of Post-COVID-19 interstitial lung sequelae. A normal LUS examination rules out the presence of these sequelae in COVID-19 survivors, avoiding the need for additional diagnostic tests such as HRCT.

Use of biomarkers in inflammatory bowel disease. / Marcadores de actividad en la enfermedad inflamatoria intestinal.

There are many useful biomarkers for initial diagnosis and the management of inflammatory bowel disease. Serologic biomarkers have been traditionally used because they are widely disposable, but recently faecal biomarkers, especially faecal calprotectin, have acquired great importance as they have shown to be more precise when establishing suspicion of the disease and also as predictors of mucosal healing or persistence of inflammatory activity. Faecal calprotectin is a good tool for predicting abnormal endoscopic studies, but has limited specificity because its levels can be altered in many digestive diseases presenting with similar symptoms. The precision of faecal calprotectin is higher when associated with other altered parameters, especially with C-reactive protein, or with clinical scores of inflammatory activity. Finally, there are many new generation serologic and faecal biomarkers. Despite there not being much evidence about these yet, some of them have shown promising results in different studies.