Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases ...resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers.
All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR.
Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9-306) since LT and PMR was performed after 2.4 months (0-43.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50-365); median post-operative overall stay 5 days (2-11). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7-213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12-74), respectively, with a median OS of 51 months (95%CI 24-78).
Selected patients with isolated pulmonary HCC-recurrence after LT and with preserved hepatic function showed that a pulmonary metastasectomy could be efficacious in managing a PM-HCC and could give an opportunity for long-term survival.
This essay discusses the concept of discovery, intended as content discovery, and defines it in the new context of Open Science, with a focus on Social Sciences and Humanities (SSH). Starting from ...the example of Google Scholar, the authors argue that this well-established service does not address the current needs, practices, and variety of discovery. Alternatives in terms of technical choices, features, and governance, do however exist, offering richer and more open discovery. The paper presents, in particular, the implementations and research work of the H2020 project TRIPLE (Transforming Research through Innovative Practices for Linked Interdisciplinary Exploration). Dedicated to the building of a discovery platform for the SSH, the project is meant to address the specificities and evolution of discovery in this field. Prevailing scholarly resource platforms like Google Scholar limit discovery by focussing only on publications, and favouring through their algorithm well-cited papers, English content, and discipline-specific resources. A limitation in the context of cross-disciplinary and collaborative Open Science, such a service more specifically hinders discovery in the SSH. Characterized by a fragmented landscape, a variety of languages, data types, and outputs, research in the SSH requires services that fully exploit discovery potentialities. Moreover, a survey conducted within the TRIPLE project showed that most SSH researchers use Google Scholar as their starting point, and that they recognise the lack of control they have with this system. Beyond the extension of features and content, transparency is the other important criterion for the building of an open infrastructure serving the research community. In light of this, we present the GoTriple platform, which exploits today’s technological potential and incorporates the best known functionalities, in order to unveil more and innovative scholarly outputs and lead to international and interdisciplinary research project collaborations.
Background & Aims
Hepatitis C virus (HCV) re‐infection following liver transplant (LT) is associated with reduced graft and patient survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment ...prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF‐regimen from pre‐ to post‐transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 weeks of HCV‐RNA undetectability at the time of transplant.
Methods
From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/without hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One hundred patients were transplanted and 31 patients (31%) treated with SOF/R bridging therapy were studied.
Results
Liver transplant indication in bridge subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV‐genotype was 1/4 in 18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a median of 35 days before LT. At transplant time, 19 patients were still HCV‐RNA positive (median HCV‐RNA 58 IU/mL). One recipient had a virological breakthrough at week 4 post‐transplant; one died, on treatment, 1‐month post‐transplant for sepsis and 29/31 achieved a 12‐week sustained virological response (94%). Acute cellular rejection occurred in three recipients. On September 2016, 30 recipients (97%) were alive with a median follow‐up of 18 months (range 13‐25).
Conclusions
In patients with suboptimal virological response at LT, a bridging SOF/R regimen helps avoiding post‐transplant graft reinfection.
Background & Aims The success of pegylated-interferon (PegIFN)/ribavirin (Rbv) therapy of chronic hepatitis C is compromised by liver fibrosis. Whether fibrosis equally affects the two PegIFNα-based ...therapies is unknown. To assess the response to the two PegIFN regimens in patients with different degree of liver fibrosis. Methods A sub-analysis of the MIST study: 431 consecutive naïve patients randomly assigned, based on HCV genotype, to receive either (A) PegIFNα2a 180 μg/wk plus daily Rbv 800–1200 mg or (B) PegIFNα2b 1.5 μg/kg/week plus daily Rbv 800–1200 mg, were stratified according to Ishak staging (S) into mild (S0–S2) or moderate (S3, S4) fibrosis and cirrhosis (S5, S6). Results In A the sustained virological response (SVR) rates were not significantly influenced by fibrosis stage (71% in S0–S2, 66% in S3, S4, 53% in S5, S6, p = 0.12), compared to B where the SVR rates differed according to fibrosis stage (65%, 46%, and 38%, p = 0.004, respectively). This was even more so in HCV-1/4 patients treated with PegIFNα2b where the SVR rates were twice as many in S0–S2 vs. S ⩾3 (44% vs. 22%, p = 0.02), while in A the SVR rates were similar between the two fibrosis subgroups (S0–S2: 47% vs . S ⩾3: 48%, p = 0.8). By logistic regression analysis genotype 1/4 and lack of rapid virological response were independent predictors of treatment failure in both treatment groups, while S ⩾3 fibrosis was associated to PegIFNα2b treatment failure, only (OR 2.83, 95% CI 1.4–5.68, p = 0.004). Conclusions Liver fibrosis was an independent moderator of treatment outcome in patients receiving PegIFNα2b, not in those receiving PegIFNα2a.
A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating ...in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March-April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45-64 (8%) and 15-44 year olds (1%). No excess mortality was observed in 0-14 year olds.
Background: Heat waves and air pollution are both associated with increased mortality. Their joint effects are less well understood. Methods: We explored the role of air pollution in modifying the ...effects of heat waves on mortality, within the EuroHEAT project. Daily mortality, meteorologic, and air pollution data from nine European cities for the years 1990–2004 were assembled. We defined heat waves by taking both intensity and duration into account. The city-specific effects of heat wave episodes were estimated using generalized estimating equation models, adjusting for potential confounders with and without inclusion of air pollutants (particles, ozone, nitrogen dioxide, sulphur dioxide, carbon monoxide). To investigate effect modification, we introduced an interaction term between heat waves and each single pollutant in the models. Random effects meta-analysis was used to summarize the city-specific results. Results: The increase in the number of daily deaths during heat wave episodes was 54% higher on high ozone days compared with low, among people age 75–84 years. The heat wave effect on high PM10 days was increased by 36% and 106% in the 75–84 year and 85+ year age groups, respectively. A similar pattern was observed for effects on cardiovascular mortality. Effect modification was less evident for respiratory mortality, although the heat wave effect itself was greater for this cause of death. The heat wave effect was smaller (15–30%) after adjustment for ozone or PM10. Conclusions: The heat wave effect on mortality was larger during high ozone or high PM10 days. When assessing the effect of heat waves on mortality, lack of adjustment for ozone and especially PM10 overestimates effect parameters. This bias has implications for public health policy.
Heat and cold are established environmental risk factors for human health. However, mapping the related health burden is a difficult task due to the complexity of the associations and the differences ...in vulnerability and demographic distributions. In this study, we did a comprehensive mortality impact assessment due to heat and cold in European urban areas, considering geographical differences and age-specific risks.
We included urban areas across Europe between Jan 1, 2000, and Dec 12, 2019, using the Urban Audit dataset of Eurostat and adults aged 20 years and older living in these areas. Data were extracted from Eurostat, the Multi-country Multi-city Collaborative Research Network, Moderate Resolution Imaging Spectroradiometer, and Copernicus. We applied a three-stage method to estimate risks of temperature continuously across the age and space dimensions, identifying patterns of vulnerability on the basis of city-specific characteristics and demographic structures. These risks were used to derive minimum mortality temperatures and related percentiles and raw and standardised excess mortality rates for heat and cold aggregated at various geographical levels.
Across the 854 urban areas in Europe, we estimated an annual excess of 130 228 (empirical 95% CI 115 893–143 929) deaths attributed to cold and 13 589 (11 530–15 475)) attributed to heat. These corresponded to age-standardised rates of 83 (empirical 95% CI 74–92) and 9 (7–10) deaths per 100 000 person-years. Results differed across Europe and age groups, with the highest effects in eastern European cities for both cold and heat.
Maps of mortality risks and excess deaths indicate geographical differences, such as a north–south gradient and increased vulnerability in eastern Europe, as well as local variations due to urban characteristics. The modelling framework and results are crucial for the design of national and local health and climate policies and for projecting the effects of cold and heat under future climatic and socioeconomic scenarios.
Medical Research Council of UK, the Natural Environment Research Council UK, the EU's Horizon 2020, and the EU's Joint Research Center.
Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated.
We performed a national survey to ...investigate the listing criteria, comorbidities, and outcomes.
In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years.
From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence).
Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death.
High temperatures have been associated with increased mortality, with evidence reported predominately in large cities and for total cardiovascular or respiratory deaths. This case-crossover study ...examined heat-related cause-specific cardiopulmonary mortality and vulnerability factors using small-area data from Germany.
We analyzed daily counts of cause-specific cardiopulmonary deaths from 380 German districts (2000–2016) and daily mean temperatures estimated by spatial–temporal models. We applied conditional quasi-Poisson regression using distributed lag nonlinear models to examine heat effects during May–September in each district and random-effects meta-analysis to pool the district-specific estimates. Potential individual- and district-level vulnerability factors were examined by subgroup analyses and meta-regressions, respectively.
Heat was associated with increased mortality risks for all cardiopulmonary sub-causes. The relative risk (RR) of total cardiovascular and respiratory mortality for a temperature increment from the 75th to the 99th percentile was 1.24 (95% confidence interval: 1.23, 1.26) and 1.34 (1.30, 1.38), respectively. The RRs of cardiovascular sub-causes ranged from 1.16 (1.13, 1.19) for myocardial infarction to 1.32 (1.29, 1.36) for heart failure. For respiratory sub-causes, the RR was 1.27 (1.22, 1.31) for COPD and 1.49 (1.42, 1.57) for pneumonia. We observed greater susceptibility related to several individual- and district-level characteristics, e.g., among females or in highly urbanized districts. Heat vulnerability factors remained consistent between urban and rural areas.
Our study highlights heat-related increases in cause-specific cardiopulmonary mortality across Germany and identifies key vulnerability factors, offering insights for improving public health practices to mitigate heat-related health impacts.
European Union's Horizon 2020 research and innovation program; Helmholtz Associations Initiative and Networking Fund.
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