Observable frequency shifts via spin-rotation coupling

The phase perturbation arising from spin-rotation coupling is developed as a natural extension of the celebrated Sagnac effect. Experimental evidence in support of this phase shift, however, has yet to be realized due to the exceptional sensitivity required. We draw attention to the relevance of a series of experiments establishing that circularly polarized light, upon passing through a rotating half-wave plate, is changed in frequency by twice the rotation rate. These experiments may be interpreted as demonstrating the role of spin-rotation coupling in inducing this frequency shift, thus providing direct empirical verification of the coupling of the photon helicity to rotation. A neutron interferometry experiment is proposed which would be sensitive to an analogous frequency shift for fermions. In this arrangement, polarized neutrons enter an interferometer containing two spin flippers, one of which is rotating while the other is held stationary. An observable beating in the transmitted neutron beam intensity is predicted.Comment: LaTeX, 15 pages with 4 PostScript figures, submitted to Phys. Lett.

Glucocorticoids and Antivirals for HBV Reactivation in Onco-Hematologic Patients.

Patients with inactive or occult hepatitis B virus infection and onco-hematological malignancies are at risk of hepatitis flare, hepatic failure and death due to chemotherapy-mediated reactivation. Nucleot(s)ide analogues can reduce reactivation risks and/or hepatitis. However, immuno-mediated phenomena combine to determine liver damage and clinical outcome. We describe in this report two patients with onco-hematological malignancies and hepatitis B reactivation after chemotherapy in whom glucocorticoids were added to nucleot(s)ide. Antiviral therapy was effective on replication, while glucocorticoids managed hyperergic response. One patient without underlying liver disease survived, while the second died and the autopsy demonstrated cirrhosis undetected before death. This clinical trial suggests that in patients with onco-hematological malignancies and altered liver function tests in spite of effective antiviral response, glucocorticoids could control the effects of immune response. However prognosis and survival are related to the underlying liver status

Risk factors for liver decompensation and hcc in hcv-cirrhotic patients after daas: A multicenter prospective study

Background: Prospective studies on predictors of liver-related events in cirrhotic subjects achieving SVR after DAAs are lacking. Methods: We prospectively enrolled HCV cirrhotic patients in four Italian centers between November 2015 and October 2017. SVR and no-SVR cases were compared according to the presence or absence of liver-related events during a 24-month follow-up. Independent predictors of liver-related events were evaluated by Cox regression analysis. Results: A total of 706 subjects started DAAs therapy. SVR was confirmed in 687 (97.3%). A total of 61 subjects (8.9%) in the SVR group and 5 (26.3%) in the no-SVR group had liver-related events (p < 0.03). The incidence rate x 100 p/y was 1.6 for HCC, 1.7 for any liver decompensation, and 0.5 for hepatic death. Baseline liver stiffness (LSM) ≥ 20 kPa (HR 4.0; 95% CI 1.1–14.1) and genotype different from 1 (HR 7.5; 95% CI 2.1–27.3) were both independent predictors of liver decompensation. Baseline LSM > 20 KPa (HR 7.2; 95% CI 1.9–26.7) was the sole independent predictor of HCC. A decrease in liver stiffness (Delta LSM) by at least 20% at the end of follow-up was not associated with a decreased risk of liver-related events. Conclusion: Baseline LSM ≥ 20 kPa identifies HCV cirrhotic subjects at higher risk of liver-related events after SVR

Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment

Background: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and solid tumours. Objective: Analyse the influence of sarcopenia on survival and treatment duration in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods: We conducted a multicentre, retrospective study on 96 patients with advanced HCC treated with sorafenib, all with available abdominal computed tomography (CT) scan within 30 days from treatment start. Anthropometric, laboratory, treatment and follow-up data were collected. Sarcopenia was defined by reduced skeletal muscle index calculated from an L3 section CT image. Results: Sarcopenia was present in 49% of patients. Patients were divided into two groups according to sarcopenia: age was significantly higher in the sarcopenic group (SG) (66 years (31–87) versus 72 years (30–84), p = 0.04], with no difference in other baseline characteristics. The SG showed shorter overall survival (OS) (39 (95% confidence interval (CI) 26–50) versus 61 (95% CI 47–77) weeks (p = 0,01)) and shorter time on treatment (12.3 (95% CI 8–19) versus 25.9 (95% CI 15–33) weeks (p = 0.0044)). At multivariate analysis, sarcopenia was independently associated to reduced OS (p = 0.03) and reduced time on treatment (p = 0.001). Conclusion: Sarcopenia is present in almost half of patients with advanced HCC, and is associated with reduced survival and reduced duration of oral chemotherapy

Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment

Background: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and solid tumours. Objective: Analyse the influence of sarcopenia on survival and treatment duration in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods: We conducted a multicentre, retrospective study on 96 patients with advanced HCC treated with sorafenib, all with available abdominal computed tomography (CT) scan within 30 days from treatment start. Anthropometric, laboratory, treatment and follow-up data were collected. Sarcopenia was defined by reduced skeletal muscle index calculated from an L3 section CT image. Results: Sarcopenia was present in 49% of patients. Patients were divided into two groups according to sarcopenia: age was significantly higher in the sarcopenic group (SG) (66 years (31\u201387) versus 72 years (30\u201384), p = 0.04], with no difference in other baseline characteristics. The SG showed shorter overall survival (OS) (39 (95% confidence interval (CI) 26\u201350) versus 61 (95% CI 47\u201377) weeks (p = 0,01)) and shorter time on treatment (12.3 (95% CI 8\u201319) versus 25.9 (95% CI 15\u201333) weeks (p = 0.0044)). At multivariate analysis, sarcopenia was independently associated to reduced OS (p = 0.03) and reduced time on treatment (p = 0.001). Conclusion: Sarcopenia is present in almost half of patients with advanced HCC, and is associated with reduced survival and reduced duration of oral chemotherapy

Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world

Background & Aims: Several studies have assessed the short-term effectiveness and safety of obeticholic acid (OCA) in the real-world setting. We aimed to extend knowledge on the real-world effectiveness and safety of OCA treatment by expanding sample size and follow-up, and by exploring changes in liver stiffness measurement (LSM) over time. Methods: The RECAPITULATE project involves centres belonging to the “Italian PBC registry” and/or the “Club Epatologi Ospedalieri” PBC working group. Effectiveness was evaluated as biochemical response according to POISE and normal range (NR) criteria (normal alkaline phosphatase/alanine aminotransferase/bilirubin). Safety was assessed as the incidence of de novo/worsening pruritus and discontinuation rate/causes. Available LSMs were also captured. Results: We included 747 patients from 66 Italian centres: mean age 58 years; female/male 88%/14%; median follow-up 24 months [IQR 12-42]; 28% with cirrhosis, and 14% with autoimmune hepatitis (AIH)/PBC overlap syndrome. Probabilities of POISE and NR response increased from baseline to 57% and 20%, respectively, by the 42nd month. The probabilities of response were lower in patients with cirrhosis (p = 0.02 and p = 0.004 for POISE and NR), but not different between patients with AIH/PBC and pure PBC (p = 0.8). Overall, 130 patients (17%) discontinued treatment, mainly due to pruritus (36.9%), while 28.5% did so after developing hepatic events. The discontinuation rate was higher in patients with cirrhosis (p <0.001). LSM was available in 573 patients (∼77%), of whom 255 had multiple measurements. LSM variation over time differed based on the attainment of POISE biochemical response (expected mean annual variation -0.48 [-0.78, -0.19] in responders vs. +0.33 [-0.07, 0.73] in non-responders, respectively, p <0.001). Conclusions: Our findings confirm the effectiveness and safety profiles of OCA in the medium/long term and demonstrate that biochemical response is associated with the change in LSM over time. Impact and Implications: After the conditional approval of OCA for the treatment of PBC, the main confirmatory study failed to demonstrate OCA's ability to reduce liver-related events, leading the EMA to revoke the drug's marketing authorization. The ensuing scientific debate highlights an urgent need for further evidence from real-world practice. In the largest real-world series of patients treated with OCA to date, we confirm that the drug's effectiveness and safety profiles are maintained over a medium-to-long follow-up period. Valuable data for the management of the drug in relevant subgroups of patients, such as those with cirrhosis and autoimmune hepatitis/PBC overlap syndrome, are also provided. Our original results on liver stiffness measurement variation over time suggest a favourable impact of OCA on fibrosis progression, particularly in patients achieving a biochemical response to the drug. Overall, these data provide important insights for clinicians managing patients with PBC and contribute to the ongoing scientific debate about the effectiveness/safety profile of this drug

Lean body mass wasting and toxicity in early breast cancer patients receiving anthracyclines

peer reviewe

La presenza di Sarcopenia predice una ridotta sopravvivenza nei pazienti con epatocarcinoma alla prima diagnosi

Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. Aim. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Material and methods. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. Results. Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). Conclusions. This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population

Hematological Malignancies and HBV Reactivation Risk: Suggestions for Clinical Management

It is well known that hepatitis B virus reactivation (HBVr) can occur among patients undergoing treatment for hematological malignancies (HM). The evaluation of HBVr risk in patients undergoing immunosuppressive treatments is a multidimensional process, which includes conducting an accurate clinical history and physical examination, consideration of the virological categories, of the medication chosen to treat these hematological malignancies and the degree of immunosuppression induced. Once the risk of reactivation has been defined, it is crucial to adopt adequate management strategies (should reactivation occur). The purpose of treatment is to prevent dire clinical consequences of HBVr such as acute/fulminant hepatitis, and liver failure. Treatment will be instituted according to the indications and evidence provided by current international recommendations and to prevent interruption of lifesaving anti-neoplastic treatments. In this paper, we will present the available data regarding the risk of HBVr in this special population of immunosuppressed patients and explore the relevance of effective prevention and management of this potentially life-threatening event. A computerized literature search was performed using appropriate terms to discover relevant articles. Current evidence supports the policy of universal HBV testing of patients scheduled to undergo treatment for hematological malignancies, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and classes of immunosuppressive drugs

Hematological Malignancies and HBV Reactivation: Suggestions for Clinical Management

It is well known that the event of hepatitis B virus reactivation can occur among patients undergoing treatment for hematological malignancies. In this paper we will present the available data regarding the risk of hepatitis B virus reactivation in this special population of immunosuppressed patients and explore the relevance of an accurate prevention and management of this condition. A computerized literature search was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. The evaluation of hepatitis B reactivation risk is a multidimensional process, which includes conducting an accurate clinical and physical history, considering the virological categories, the knowledge of the medication chosen to treat these hematological malignancies and the induced grade of immunosuppression. Adopting adequate preventive strategies and surveillance according to the current international recommendations is crucial to prevent HBVr and its dire clinical consequences (hepatitis, liver failure, interruption of lifesaving anti-neoplastic treatments). Universal HBV screening of patients scheduled to undergo treatment for hematological malignancies should be the chosen policy, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and the classes of immunosuppressive drugs.</jats:p