A look at the hepatic encephalopathy in cirrhosis

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome complicating acute and chronic liver failure and characterized by a wide range of manifestations, in absence of other brain disease. HE is very frequent in course of cirrhosis and even mild forms involve a great additional burden on patients, their families and health-care resources. Its onset affects subsequent survival of patients. Historically, pathophysiology of HE was connected to several substances (mostly ammonia) produced in the gut and normally metabolized by the liver, but more recently other factors such as inflammation, bacterial translocation and oxidative stress have shown a crucial role. Symptoms are often overt (confusion, asterixis, disorientation, ataxia or coma) but can also be subtle (sleep disturbances, cognitive impairment, mood alterations, impairment of executive decision-making, and psychomotor speed – Minimal HE); the West Haven Criteria are most often used to grade Overt HE (OHE), with grade ranging from 0 to 4 (4 corresponding to coma). Since both Minimal HE and grade 1 HE cannot be diagnosed by clinical examination and need for specific tests, it results practical to combine these entities and name them "Covert" HE (CHE) to aid clinical use. Diagnosis is based on evidence of neurological impairment in presence of liver cirrhosis, only after the exclusion of other brain diseases. Measurement of serum ammonia and electroencephalography are little specific, while brain magnetic resonance and search for portosystemic shunts are important in complex cases. Diagnosis of OHE is often just clinical, while that of CHE requires dedicated psychometric and neurophysiological tests. Although these tests are difficult to be performed in the clinical practice, detection and treatment of CHE are cost-effective and important; indeed, CHE affects patients' quality of life, socioeconomic status and driving skills, and increases the risk for falls, car accidents, development of OHE, and death. Management of HE includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, dehydration, hypotension, use of benzodiazepines, psychoactive drugs, and/or alcohol). Current treatment is based principally on reducing intestinal ammonia with nonabsorbable disaccharides (lactulose or lactitol); rifaximin, used solely or in addition, is also becoming a first-line treatment

The use of albumin in the complications of cirrhosis: evidence and future perspectives

The therapeutic use of albumin in cirrhosis dates back to the 50s, when hypoalbuminemia was thought to play a crucial role in the pathophysiology of ascites. Today, while its efficacy in the treatment of ascites is still under investigation, it has been proved that albumin is able to improve patient outcome and survival in some specific complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction and the treatment of spontaneous bacterial peritonitis and hepatorenal syndrome. Beside its oncotic power, albumin carries other biological properties, the so called non-oncotic properties, including transportation and detoxification of several molecules, free radical scavenging, modulation of vascular permeability, activity on the immune system and on the haemostatic balance. Some experimental evidences indicate that not only albumin concentration but also its function is reduced in patients with cirrhosis. However, the clinical implications of such functional abnormalities is still unclear. We here present the available evidence on the use of albumin in cirrhosis and future perspectives

A case of pneumonia and sepsis in cirrhosis as paradigm of the problems in the management of bacterial infections in cirrhosis and of the limitations of current knowledge

Bacterial infections are a major problem in the management of liver cirrhosis. They represent the first precipitating cause of death since patients with cirrhosis carry an increased risk of sepsis, sepsis-induced organ failure and death. Although the clinical presentation is often misleading, the presence of bacterial infection should always be actively searched and ruled out with certainty whenever a cirrhotic patient is admitted to the hospital with an acute clinical deterioration. Major changes in the epidemiology of bacterial infections have also occurred in the last decade making the choice of empirical antibiotic therapy a challenge. We report a paradigmatic case of a 54-year old man with hepatitis C-related cirrhosis admitted to the hospital for worsening of his ascites and onset of hepatic encephalopathy, an excellent example for the difficulties of management of sepsis in cirrhosis and the limits of current knowledge

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

A Case of Immune-Mediated Liver Injury Induced by Olaparib

Non presente