H3 Propranolol serum levels following lidocaine administration in rats with CCL4 induced liver damage.

Liver disease alters the pharmacokinetic and pharmacodynamic properties of hepatically eliminated drugs. The main factors influenced are plasma albumin levels, enzyme balance (induction & inhibition) and drug binding to tissue proteins. The influence of lidocaine on serum, heart and liver propranolol levels in Wistar rats after liver injury induced by carbon tetrachloride CCl4 0.4 ml/kg x 2/wkl, was investigated. 40 male Wistar rats were divided into four groups (I, II, III, IV; n=10), Group I animals received only propranolol (labelled + cold substance) 40 mg/kg/12 h p.o., group II propranolol plus lidocaine in a single dose of 4mg/kg s.c., group III was treated with CCl4 for 6 weeks and received propranolol x2 at the same dosage as group I, while group VI was treated with CCl4 and the same drug dosage as group II. The simultaneous administration of H3-propranolol and lidocaine increased propranolol levels in the serum and tissues. The liver in damaged animals showed an increase of propranolol level under lidocaine co-administration, probably due to CCl4 induced liver enzyme activity, resulting in a rapid propranolol metabolism or to competition between both drug protein binding sites. The increased propranolol levels in the heart after lidocaine administration were probably due to attributed to its high affinity for heart tissue. Consequently, as regards the therapeutic approach for patients with liver disease receiving propranolol their propranolol dosage should be reduced when lidocaine is co-administered.     

Binge-eating disorder is associated with an unfavorable body mass composition in patients with non-alcoholic fatty liver disease

The interaction between eating disorders and non-alcoholic fatty liver disease (NAFLD) remains unexplored, especially with regards to binge-eating disorder (BED). Our team conducted a service evaluation project in order to assess risk factors for the presence of BED among patients with NAFLD and the impact of BED on body mass composition. The overall prevalence of patients screening positive to BED Screener-7 (BEDS-7) was 28.4%, while a previous diagnosis of depression and marital status (as single or separated) were independently associated with positive BED. Furthermore, patients with positive BEDS-7 had higher BMI, with greater visceral component and overall lower muscle mass. There was no difference in terms of liver disease severity as assessed by noninvasive markers of fibrosis. However, as body mass composition and sarcopenia have been shown to be associated to disease progression in patients with NAFLD, further studies are required to ascertain the long-term impact of BED in these patients. Moreover, further work is warranted to identify to implement multidisciplinary approach within clinical psychology for the management of patients with BED, who may be particularly challenging in terms of achieving lifestyle modifications. As a hepatology community, we should address NAFLD with a more holistic approach.     

Cutaneous perforators of the peroneal artery: Cadaveric study with implications in the design of the osteocutaneous free fibular flap

Bilateral dissection of 15 formalin embalmed cadaver legs was performed in order to study the anatomic pattern of the peroneal artery (PA) and its cutaneous perforating vessels (CB). The total number of CB from the PA was 125 or an average of 4.17 branches per leg. CB were distributed in the superoinferior axis between 18.25 and 84.25% of the length of the fibula and their average length was 5 ± 1.8 cm. 86/125 (68.8%) of the CB were classified as myocutaneous branches (MC) that penetrated muscle before reaching the skin, whereas 39/125 (31.2%) were septocutaneous branches (SC) that passed through the intermuscular septum. The mean distance between the posterior border of the fibula and the site where the perforators emerged was 1.88 ± 0.79 cm for the SC and 1.21 ± 0.87 cm for the MC. These anatomic findings should encourage the surgeon to design the skin paddle in the boundary between the middle and the distal third of the fibular length about 2 cm behind the posterior fibular border on the posterolateral leg, where the number of CB is maximal. Clin. Anat. 22:826–833, 2009. © 2009 Wiley‐Liss, Inc.     

Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review

In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.     

Anti-cardiolipin and Anti-β2-glycoprotein I Antibodies in Patients with Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD)frequently suffer from thromboembolic events.Anti-cardiolipin (aCL) antibodies have been shown to beassociated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor₂-glycoprotein I(a₂GPI) have been found with higherspecificity for thrombosis. The presence of theseantibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 withCrohn's disease (CD)] and 100 healthy controls (blooddonors). Patients with UC and CD had a significantlyhigher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBDpatients (8.6%) but no HC had a₂GPI.None of the IBD patients with a history of thrombosishad aCL and only one of them (a UC patient with deepvein thrombosis of the right leg) had a high titer of IgGa₂GPI. In conclusion, these data showthat both aCL and a₂GPI aresignificantly associated with IBD but further studiesare needed to determine the significance of our findings.     

The association of diabetic microvascular and macrovascular disease with cutaneous circulation in patients with type 2 diabetes mellitus

Aims

To study the impact of diabetic neuropathy, both peripheral sensorimotor (DPN) and cardiac autonomic neuropathy (CAN), on transcutaneous oxygen tension (TcPO₂) in patients with type 2 diabetes mellitus (T2DM).

Liver collagen proportionate area predicts decompensation in patients with recurrent hepatitis C virus cirrhosis after liver transplantation

Background and Aims: Current histological scoring systems do not subclassify cirrhosis. Computer‐assisted digital image analysis (DIA) of Sirius Red‐stained sections measures fibrosis morphologically producing a fibrosis ratio (collagen proportionate area [CPA]). CPA could have prognostic value within a disease stage, such as cirrhosis. The aim of the present study was to evaluate CPA in patients with recurrent hepatitis C virus (HCV) allograft cirrhosis and assess its relationship with hepatic venous pressure gradient (HVPG). Methods: In 121 consecutively‐transplanted HCV patients with HVPG, measured contemporaneously with transjugular liver biopsies, 65 had Ishak stage 5 or 6 disease (43 with HVPG measurement). Biopsies were stained with Sirius Red for DIA, and the collagen content was expressed as a CPA. In three cases, a tissue for Sirius Red staining was not obtained, and the patients were excluded. Results: Sixty‐two patients were analyzed. The median HVPG was 8 mmHg (interquartile range [IQR]: 5–10). Portal hypertension (HVPG ≥ 6 < 10 mmHg) was present in 30 (69.8%), and HVPG ≥ 10 mmHg in 13 (30.2%). The median CPA was 16% (IQR 10.75–23.25). Median Child–Pugh score and HVPG were not significantly different between Ishak fibrosis stage 5 or 6, whereas CPA was statistically different: 13% in stage 5 (IQR 8.3–12.4) versus 23% in stage 6 (IQR 17–33.7, P < 0.001). In the multivariate analysis, CPA was the only variable significantly associated with clinically‐significant portal hypertension (HVPG ≥ 10 mmHg, odds ratio: 1.085, confidence interval: 1.004–1.172, P = 0.040). A CPA of 14% was the best cut‐off value for clinically‐significant portal hypertension (CSPH) and liver decompensation, which occurred in 24 patients. Event‐free survival was significantly shorter in patients with CSPH or with a CPA value ≥ 14%, or with a combination of both. Conclusion: In Ishak stages 5 and 6, CPA correlated with HVPG, but had a wider range of values, suggesting a greater sensitivity for distinguishing “early” from “late” severe fibrosis/cirrhosis. CPA was a unique, independent predictor of HVPG ≥ 10 mmHg. CPA can be used to subclassify cirrhosis and for prognostic stratification.