been more encouraging. The trial should therefore not be regarded as a definitive dismissal of the promise of these or related agents. 3 Theoretically, depression in bipolar disorder is a more heterogeneous construct than mania, which is more monothematically biological in its causation. Depression is driven by a far wider array and admixture of biological factors, consequences of behaviours while manic, losses in domains such as educational and vocational horizons, relationships, personality, finances, guilt, stigma, and self-stigma, among others. Therefore, it is arguably ambitious at the outset to expect a singular biological therapy targeting one biological marker of the disorder to address all phenotypes of this heterogeneous clinical presentation. The complexity of bipolar depression might be an explanation more broadly for the relatively common failure of singular treatment approaches. These failures suggest that polyvalent and personalised therapies predicated on individualised profiles are needed to select from the diverse pharmacological, neurostimulatory, nutraceutical, lifestyle, and psychological approaches that are available. 10 In sum, this might not be the last word on the potential role of anti-inflammatory drugs in the treatment of bipolar depression, but notwithstanding the methodological issues that accompany any clinical trial, the promise of targeting the inflammation pathway in the management of this challenging condition is today somewhat weaker.

Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis. (Hepatology 2018).

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Background. The Coronavirus disease 2019 (COVID-19) pandemic is an unprecedented traumatic event influencing the healthcare, economic, and social welfare systems worldwide. In order to slow the infection rates, lockdown has been implemented almost everywhere. Italy, one of the countries most severely affected, entered the "lockdown" on March 8, 2020. Methods. The COvid Mental hEalth Trial (COMET) network includes 10 Italian university sites and the National Institute of Health. The whole study has three different phases. The first phase includes an online survey conducted between March and May 2020 in the Italian population. Recruitment took place through email invitation letters, social media, mailing lists of universities, national medical associations, and associations of stakeholders (e.g., associations of users/ carers). In order to evaluate the impact of lockdown on depressive, anxiety and stress symptoms, multivariate linear regression models were performed, weighted for the propensity score. Results. The final sample consisted of 20,720 participants. Among them, 12.4% of respondents (N = 2,555) reported severe or extremely severe levels of depressive symptoms, 17.6% (N = 3,627) of anxiety symptoms and 41.6% (N = 8,619) reported to feel at least moderately stressed by the situation at the DASS-21. According to the multivariate regression models, the depressive, anxiety and stress symptoms significantly worsened from the week April 9-15 to the week April 30 to May 4 (p < 0.0001). Moreover, female respondents and people with pre-existing mental health problems were at higher risk of developing severe depression and anxiety symptoms (p < 0.0001). Conclusions. Although physical isolation and lockdown represent essential public health measures for containing the spread of the COVID-19 pandemic, they are a serious threat for mental health and well-being of the general population. As an integral part of COVID-19 response, mental health needs should be addressed.

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