Diagnostic Circulating miRNAs in Sporadic Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the neurodegeneration of motoneurons. About 10% of ALS is hereditary and involves mutation in 25 different genes, while 90% of the cases are sporadic forms of ALS (sALS). The diagnosis of ALS includes the detection of early symptoms and, as disease progresses, muscle twitching and then atrophy spreads from hands to other parts of the body. The disease causes high disability and has a high mortality rate; moreover, the therapeutic approaches for the pathology are not effective. miRNAs are small non-coding RNAs, whose activity has a major impact on the expression levels of coding mRNA. The literature identifies several miRNAs with diagnostic abilities on sALS, but a unique diagnostic profile is not defined. As miRNAs could be secreted, the identification of specific blood miRNAs with diagnostic ability for sALS could be helpful in the identification of the patients. In the view of personalized medicine, we performed a meta-analysis of the literature in order to select specific circulating miRNAs with diagnostic properties and, by bioinformatics approaches, we identified a panel of 10 miRNAs (miR-193b, miR-3911, miR-139-5p, miR-193b-1, miR-338-5p, miR-3911-1, miR-455-3p, miR-4687-5p, miR-4745-5p, and miR-4763-3p) able to classify sALS patients by blood analysis. Among them, the analysis of expression levels of the couple of blood miR-193b/miR-4745-5p could be translated in clinical practice for the diagnosis of sALS.

Extubation score in the operating room after liver transplantation.

BACKGROUND: Early extubation after liver transplantation (LT) is an increasingly applied safe practice. The aim of the present study was to provide a simple extubation rule for accelerated weaning in the operating room (OR). METHODS: Data of 597 patients transplanted at the LT center of Turin (Italy) were retrospectively analyzed. Fifty-two nonextubated patients (excluding those with a scheduled early reoperation) were compared with 545 successfully extubated patients (not in need of reintubation within the first 48 h). Significant variables at univariate analysis were entered into a logistic regression model and the regression coefficients of independent predictors were used to yield a prognostic score called the safe operating room extubation after liver transplantation (SORELT) score. RESULTS: Two major and three minor criteria were found. The major ones were blood transfusions (higher than/or equal to 7 U of packed red blood cells) and end of surgery lactate (higher than/or equal to 3.4 mmol/l). The minor ones were status before LT (home vs. hospitalized patient), duration of surgery (longer than/or equal to 5 h), vasoactive drugs at the end of surgery (dopamine higher than 5 microg/kg/min or norepinephrine higher than 0.05 microg/kg/min). Patients who fulfill the SORELT score-derived criteria (fewer than two major/one major plus two minor/three minor criteria) can be considered for OR extubation. CONCLUSION: Early extubation after LT requires a very careful assessment of the pre-operative, intraoperative, graft and post-operative care data available. The SORELT score helps as a simple and objective aid in considering such a decision.

Neurological complications of liver cirrhosis and orthotopic liver transplant.

Neurological complications are common in cirrhotic patients with end-stage liver failure. They comprise a wide array of etiologies, which may originate before, during, or after liver transplantation. The objective of this study was to describe the nature of the main neurological complications in patients with end-stage liver failure. Several toxins including ammonia, manganese, benzodiazepine-like substances, gamma-aminobutyric acid-like substances, and impaired dopaminergic neurotransmission are at the top of the list of candidates for hepatic encephalopathy, subclinical encephalopathy, and extrapyramidal signs before liver transplantation. Central pontine myelinolysis, cerebrovascular autoregulation impairment, and paradoxical cerebral embolism are probably responsible for the neurological complications during liver transplantation. Neurological complications represented by alterations of mental status, seizures, and focal motor deficits have been described after liver transplantation. These complications have been attributed to several pathogenetic factors, such as a poorly functioning graft, an intracranial hemorrhage, a cerebral infarction, an infection, or the toxicity of immunosuppressants.

Invasive Candida infections in low risk liver transplant patients given no antifungal prophylaxis in the post-operative period.

BACKGROUND: In recent years the incidence of invasive fungal infections (IFIs) in post liver transplant (LT) has reduced to about 5%, however the majority of IFIs develops early in the post-transplant course. Candida species are the most frequent causative pathogens followed by Aspergillus species. Mortality for invasive candidiasis is still 40-50%. For this reason universal prophylaxis is still considered useful and is adopted by different LT centers, although it is not justified by available data. The aim of study is to evaluate Candida infection incidence and mortality in low risk patients and therefore not subjected to antifungal prophylaxis in the immediate post-LT. METHODS: The patient is defined low risk if without any risk factor for IFIs as reported in literature and according to our center protocol described below. We analyzed retrospectively the records (with 90 days follow-up) of all adult patients underwent to LT at our center in 2011-2012. RESULTS: At our center between 2011 and 2012, 247 LT in 232 adult patients were performed: 137 patients (59%) received prophylaxis with Amphotericin B lipid complex or liposomal Amphotericin B, 95 patients (41%) didn't receive any prophylaxis. In these latter patients was observed only one case of Candida oesophagitis at the second month post-LT. The incidence of invasive candidiasis was 0%, and there wasn't mortality ascribed to Candida infection. CONCLUSIONS: It is possible to identify low risk patients for IFIs post-LT and the no prophylaxis policy in the early LT course appears safe and feasible.

Extracorporeal membrane oxygenation rescue therapy in a case of portopulmonary hypertension during liver transplantation: a case report.

Portopulmonary hypertension has been reported in 2% to 9% of candidates for liver transplantation (OLT). If it is moderate to severe, it represents a contraindication to the procedure until pulmonary vasodilatative therapy has been optimized. We report the case of a 43-year-old man, scheduled for OLT due to alcoholic cirrhosis with hemosiderosis. His Model for End-Stage Liver Disease was 25 at that time. The preoperative evaluation showed a severe alteration of diffusion (pO2 68 mm Hg), without hepatopulmonary syndrome or portopulmonary hypertension (PPH) upon basal and dobutamine stress echocardiography. At the beginning of the OLT the hemodynamic profile showed mean pulmonary artery pressure (mPAP) 38 mm Hg, wedge pressure (WP) 19 mm Hg, cardiac output (CO) 9.1 L/min, pulmonary vascular resistance (PVR) 166 dyne s/cm(5), transpulmonary gradient (TPG) 19 mm Hg, which lead us to promptly initiate inhaled nitric oxide (iNO) and intravenous epoprostenol 2 to 5 ng/kg/min. Upon graft reperfusion the hemodynamic profile was: mPAP 47 mm Hg, WP 23 mm Hg, CO 14.2 L/min, PVR 135 dyne s/cm(5), TPG 24 mm Hg, and at the end of surgery, mPAP 39 mm Hg, WP 20 mm Hg, CO 10.6 L/min, PVR 123 dyne s/cm(5), TPG 19 mm Hg. On postoperative day (POD) 3, we observed severe worsening of PPH: mPAP 60 mm Hg, WP 10 mm Hg, CO 9.8 L/min, PVR 395 dyne s/cm(5), TPG 50 mm Hg even with maximal pulmonary vasodilatatory therapy (ambrisentan 5 mg, intravenous sildenafil 20 mg × 3 and epoprostenol 22 ng/kg/min, iNO). Severe acute respiratory distress syndrome (ARDS) was presents. Therefore we decided to begin veno-venous extracorporeal membrane oxygenation (v-v ECMO) to correct the hypoxic vasoconstriction. Subsequent weaning from inotropic support with iNO and epoprostenol was possible on POD 7 due to mPAP 42 mm Hg, WP 15 mm Hg, CO 7.9 L/min, PVR 273 dyne s/cm(5), and TPG 27 mm Hg. On POD 11 he was weaned from ECMO due to: mPAP 40 mm Hg, WP 16 mm Hg, CO 6.5 L/min, PVR 295 dyne s/cm(5) and TPG 24 mm Hg. The patient was extubated on POD 17. The cardiac catheterization 1 month after OLT showed: mPAP 28 mm Hg, WP 13 mm Hg, CO 5.4 L/min, PVR 220 dyne s/cm(5) and TPG 15 mm Hg. ECMO rescue therapy in this "extreme" case allowed us to correct hypoxemia responsible for worsening of pulmonary hypertension allowing time to reach the goal of vasodilatatory therapy.

[A case of Veratrum poisoning]. / Un caso di avvelenamento da Veratro.

A poisoning from a Veratrum album infusion mistaken for Gentiana lutea is described. Confusion between these two plants can easily occur because they are very similar, although flowers and disposition of leaves allow their botanic determinat: V. album leaves are alternate and flowers are white, while G. lutea leaves are opposite and flowers yellow. The poisoning involves gastrointestinal (pyrosis, vomiting) and cardiocirculatory systems (bradyarrhy-thmias, A-V dissociation, vasodilatation) Atropine is the drug of choice.