Efficacy and Safety of Obinutuzumab-chemotherapy Combinations in Front-line Treatment of Follicular Non-Hodgkin Lymphoma During the COVID-19 Pandemic: A Study of KROHEM, the Croatian Cooperative Group for Hematologic Diseases.

Obinutuzumab (G) has become part of front-line treatment of follicular lymphoma (FL) based on results of a large randomized study. Data on patients treated outside of clinical trials are lacking. We have retrospectively investigated efficacy and safety of G-based immunochemotherapy regimens in 114 patients treated in a real-life setting during a period of 2 years, largely coinciding with the COVID-19 pandemic. The response rate was 93.8%; 18-months overall (OS) and progression-free survival (PFS) were 88% and 84%, respectively. Patients treated with G-cyclophosphamide, vincristine and glucocorticoid + doxorubicine (CHOP) had statistically significantly superior OS and PFS compared to patients treated with G-bendamustine (G-B) (P = 0.002 and P = 0.006, respectively) due to an increase in lethal infections, most notably COVID-19, in the latter group. A total of 12 patients died during follow-up; 9 of 61 treated with G-B, 1 of 49 treated with G-CHOP and 2 of 4 treated with G-cyclophosphamide, vincristine and glucocorticoid (CVP). SARS-CoV-2 infection was diagnosed in 20 (17.5%) patients. All of the 7 treated with G-CHOP recovered, while 4 of 12 treated with G-B died. Immunoglobulin levels and severity of neutropenia were similar between the groups. In multivariate analysis, G-B in comparison to G-CHOP was an independent prognostic factor (P = 0.044, hazard ratio = 9.81) after adjustment for age, sex and Follicular Lymphoma International Prognostic Index (FLIPI). Based on our experience G has excellent antilymphoma activity in patients receiving front-line treatment for FL in real-life setting, but during the COVID-19 pandemic, it should be preferentially combined with CHOP, at least in patients younger than 65.

Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand?

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis (laboratory tests and ultrasonography) or cannot be applied as a screening procedure (liver biopsy). Among the non-invasive tests, transient elastography (FibroScan(®), TE) with controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.

Factors associated with significant liver steatosis and fibrosis as assessed by transient elastography in patients with one or more components of the metabolic syndrome.

BACKGROUND/AIMS: We examined the relationship between controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), as assessed by transient elastography (TE), and different clinical and biochemical parameters in patients with one or more components of the metabolic syndrome (MetS). The hypothesis of the study was that LSM and CAP values correlate with the number of MetS components. METHODS: In this cross-sectional study a total of 648 consecutive patients were recruited during the years 2013-2015. Significant liver steatosis was defined as a CAP value≥238dB/m, whereas significant fibrosis was defined as an LSM value>7.0 kPa. RESULTS: The prevalences of patients with CAP≥238dB/m and LSM>7.0 kPa were 88.3% and 16.5%, respectively. Patients with CAP≥238dB/m (n=572) had a markedly higher prevalence of the MetS and all its individual components, as well as higher levels of serum liver enzymes and uric acid compared with those with normal CAP. Moreover, CAP measurements increased progressively with the number of MetS components. Similarly, among patients with CAP≥238dB/m, those with LSM>7.0 kPa (n=103) had higher serum liver enzymes and a greater prevalence of the MetS and its individual components than those with LSM≤7.0 kPa. In multivariable regression analysis the factors independently associated with elevated CAP were the presence of the MetS (or its individual components), insulin resistance (defined by HOMA-IR score), increased serum uric acid and LSM>7 kPa. Similarly, the MetS (or its individual components), insulin resistance and increased serum uric acid levels were also independently associated with LSM>7.0 kPa. CONCLUSIONS: Patients with one or more MetS components have a high prevalence of NAFLD and advanced liver fibrosis. LSM and CAP correlate with the number of MetS components.

Stomach--key player in the regulation of metabolism.

Although the stomach is often perceived as a crude, food-grinding, muscular bag, scientific breakthroughs have shown us that in the case of the stomach there is more than meets the eye. The endocrine function of the stomach is mainly exerted through the actions of ghrelin, an acylated peptide hormone that is the first known and so far most extensively studied endogenous orexigenic substance. The satiety-hunger balance is kept in check by many anorexigenic gut hormones among which is the deacylated form of ghrelin--desacyl ghrelin. The interplay of gut hormones affects the brain directly, as most gut hormones cross the blood-brain barrier and bind to their respective receptors in the central nervous system. Other hormones like obestatin and nesfatin are secreted from the stomach along with ghrelin, yet their physiological function is to be elucidated. The importance of the satiety-hunger balance can be seen in its most typical derangement--obesity. Some studies imply that ghrelin, along with other gut hormones, plays an important part in the pathophysiology of obesity. More importantly, it seems that the mechanisms by which bariatric surgery procedures induce weight loss are primarily based on changing the gut hormone levels, including ghrelin. If proven, ghrelin antagonists could be the renaissance of pharmacological obesity treatment.

[Place of biologic therapy in the treatment of inflammatory bowel diseases and assessment of its efficacy]. / Mjesto bioloske terapije u lijecenju upalnih bolesti crijeva i procjena njene djelotvornosti.

Biological therapy (infliximab and adalimumab) in inflammatory bowel diseases is based on the IgG1 anti-TNF monoclonal antibodies with potent anti-inflammatory effects whose main mechanism of action is thought to be the induction of inflammatory cell apoptosis. Unquestionably, which arises from the most recent studies and meta-analysis, anti-TNF angents are an effective therapy primarily for the treatment of Crohn's disease, but also ulcerative colitis, in different clinical situations. Infliximab has the most extensive clinical trial data, but other biological agents, such as adalimumab and certolizumab pegol appear to have similar benefits. In terms of future research, more long-term data are needed for both certolizumab pegol in Crohn's disease and adalimumab in ulcerative colitis. Important role in the application of biological therapy is assessing its effectiveness and cost-benefit relationships that are estimated by regular follow-up. In the absence of response (primary and secondary) therapeutical options are dose increase, giving the drug in shorter intervals and substitution with other biological drug.