Notes

Studying SARS-CoV-2 infectivity and also therapeutic answers together with complicated organoids.
Ibrutinib (IMBRUVICA®), a small molecule inhibitor of Bruton's tyrosine kinase (BTK) developed by Pharmacyclics, Inc. and Janssen Pharmaceutical, is well established as a treatment for B-cell malignancies and is also approved in the USA in adult patients with chronic graft-versus-host disease (cGVHD) and in Japan in adults and adolescents aged ≥ 12 years with cGVHD. Ibrutinib was approved in August 2022 in the USA for use in pediatric patients with cGVHD after failure of one or more lines of systemic therapy and is the first treatment approved for use in this group of patients aged less then  12 years (ibrutinib is now indicated for the treatment of adult and pediatric patients aged 1 year and older with cGVHD after failure of one or more lines of systemic therapy). This article summarizes the milestones in the development of ibrutinib leading to this pediatric first approval for the treatment of patients with cGVHD.
The antiinflammatory and antioxidative effects of melatonin have been established in recent years. Several studies indicate that oxidative stress and inflammation are key drivers of post-coronary artery bypass graft (CABG) surgery complications. In the present study, we aimed to investigate the effects of melatonin on cardiac injury and inflammatory biomarkers in CABG candidates.

Embase, Medline/PubMed, Web of Science, Scopus, and the Cochrane library were searched up to 5 June 2022. All randomized controlled trials examining cardiac injury and inflammatory biomarkers of CABG patients who received melatonin were included. The random-effects model was utilized to perform the analysis.

A total of 947 citations were retrieved through database searches. Finally, five articles (six trials with 342 patients) were included after the screening. Melatonin supplementation led to a significant reduction in cardiac troponin I (CTnI) [weighted mean difference(WMD) -2.28ng/ml; 95% CI -2.87, -1.69; P < 0.01; I
91.25%] and high sensitivity-C reactive protein (hs-CRP) levels (WMD -0.62mg/L; 95% CI -0.73, -0.5; P < 0.01; I
99.98%) in patients undergoing CABG surgery. We found a nonsignificant decrease in creatine kinase isoenzyme muscle/brain (CK-MB) levels (WMD -2.87ng/ml; 95% CI -5.97, 0.23; P = 0.07; I
99.98%) after melatonin supplementation. No publication bias was found according to Egger's test.

Melatonin supplementation may be useful in reducing cardiac injury and inflammatory biomarkers in CABG candidates. Future studies should investigate the clinical significance of these findings.
Melatonin supplementation may be useful in reducing cardiac injury and inflammatory biomarkers in CABG candidates. Future studies should investigate the clinical significance of these findings.
The subsequent waves of the COVID-19 pandemic in Italy had a major impact on cardiac care.

A survey to evaluate the dynamic changes in arrhythmia care during the first five waves of COVID-19 in Italy (first March-May 2020; second October 2020-January 2021; third February-May 2021; fourth June-October 2021; fifth November 2021-February 2022) was launched.

A total of 127 physicians from arrhythmia centers (34% of Italian centers) took part in the survey. As compared to 2019, a reduction in 40% of elective pacemaker (PM), defibrillators (ICD), and cardiac resynchronization devices (CRT) implantations, with a 70% reduction for ablations, was reported during the first wave, with a progressive and gradual return to pre-pandemic volumes, generally during the third-fourth waves, slower for ablations. For emergency procedures (PM, ICD, CRT, and ablations), recovery from the initial 10% decline occurred in most cases during the second wave, with some variability. However, acute care for atrial fibrillation, electrical cardioversions, and evaluations for syncope showed a prolonged reduction of activity. The number of patients with devices which started remote monitoring increased by 40% during the first wave, but then the adoption of remote monitoring declined.

The dramatic and profound derangement in arrhythmia management that characterized the first wave of the COVID-19 pandemic was followed by a progressive return to the volume of activities of the pre-pandemic periods, even if with different temporal dynamics and some heterogeneity. Remote monitoring was largely implemented during the first wave, but full implementation is needed.
The dramatic and profound derangement in arrhythmia management that characterized the first wave of the COVID-19 pandemic was followed by a progressive return to the volume of activities of the pre-pandemic periods, even if with different temporal dynamics and some heterogeneity. Remote monitoring was largely implemented during the first wave, but full implementation is needed.Insects represent a valuable and environmentally friendly protein alternative in food and feed. The Farm to Fork strategy encouraged the reintroduction of animal by-products in feed production to optimise recycling and to valorise under-used resources. In order to grant safe and valuable feed products, this study investigated the black soldier fly (BSF) (Hermetia illucens) chemical risk. Samples collected in different steps of production (8 samples of substrate for culturing, 7 samples of larvae, 15 samples of protein meal, 18 samples of spent substrate) were analysed for microessential elements (chromium, copper, iron, nickel, selenium and zinc) and inorganic contaminants (aluminium, arsenic, cadmium, lead, tin and vanadium) by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). Microessential elements were found in the following order Fe > Zn > Cu > Ni > Se > Cr (mg kg-1). Non-essential element concentrations were found lower than the set limits according to the European Union Regulations. The growing demand for alternative protein sources for feed production could be partially compensated by black soldier fly (BSF) (Hermetia illucens) meal, as it appears a good source for high-quality proteins and microessential elements which play a pivotal role in animal growth. In the foreseeable future the current legislation and the official monitoring plans may be implemented and broaden, to focus and assess limits for upcoming matrices, and to ensure feed and food safety.
To examine sex-specific differences in renal cell carcinoma (RCC) in relation to abdominal fat accumulation, psoas muscle density, tumor size, pathology, and survival, and to evaluate possible associations with RCC characteristics and outcome.

A total of 470 patients with RCC who underwent nephrectomy between 2006 and 2019 were included in this retrospective study. Specific characteristics of RCC patients were collected, including sex, height, tumor size, grade, and data on patient survival, if available. Abdominal fat measurements and psoas muscle area were determined at the level of L3 (cm
).

Women had a higher subcutaneous (p < 0.001) and men had a higher visceral fat area, relative proportion of visceral fat area (p < 0.001), and psoas muscle index (p < 0.001). Logistic regression analysis showed an association between higher psoas muscle index and lower grade tumors [women odds ratio (OR) 0.94, 95% confidence interval (CI) 0.89-0.99, p = 0.011; men OR 0.97 (95% CI, 0.95-0.99, p = 0.012]. than in men.
An accurate recurrence risk assessment system and surveillance strategy for hepatoid adenocarcinoma of the stomach (HAS) remain poorly defined. This study aimed to develop a nomogram to predict postoperative recurrence of HAS and guide individually tailored surveillance strategies.

The study enrolled all patients with primary HAS who had undergone curative-intent resection at 14 institutions from 2004 to 2019. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram to build a recurrence predictive model.

The nomogram of recurrence-free survival (RFS) based on independent prognostic factors, including age, preoperative carcinoembryonic antigen, number of examined lymph nodes, perineural invasion, and lymph node ratio, achieved a C-index of 0.723 (95% confidence interval [CI], 0.674-0.772) in the whole cohort, which was significantly higher than those of the eighth American Joint Committed on Cancer (AJCC) staging system (C-index, 0.62sk patients, more active surveillance and targeted examination methods should be adopted within 36 months after the operation, particularly for liver and multiple metastases.Hepatitis C virus (HCV) infection causes a substantial economic burden, not only in terms of healthcare costs, but also in labour productivity losses. The main objective of this study is to provide objective and comparable information about the trend in labour productivity losses caused by premature HCV-associated deaths in Spain in recent years (2009-2018). We used nationwide data from several official sources to create a simulation model based on the human capital approach and to estimate the flows in labour productivity losses due to deaths identified in the period considered. Based on a pessimistic scenario, the annual number of deaths due to HCV infections decreased by 19.7% between 2009 and 2018. The years of potential labour productive life lost (YPLPLL) decreased by 38.1%. That reduction led to a decrease in annual labour productivity losses from €236 million in 2009 to €156 million in 2018 (-33.8%). The aggregate HCV-related labour productivity losses between 2009 and 2018 ranged from €1742 million (optimistic scenario) to €1949 million (pessimistic scenario), with an intermediate estimation of €1846 million (moderately optimistic scenario). These results show a substantial reduction in annual deaths, working-age deaths, YPLPLL, and labour productivity losses associated with HCV infection over this period.Fibrinogen plays an important role in tumor progression. Here, we explored the role of fibrinogen in gallbladder cancer (GBC) metastasis. The plasma fibrinogen level in M1 GBC patients was higher than in M0 GBC patients, indicating that fibrinogen may participate in GBC metastasis. Treatment of GBC cell lines with fibrinogen promoted metastasis and induced the expression of intercellular adhesion molecule 1 (ICAM1). ICAM1 overexpression promoted metastasis and knockdown inhibited it. The cell adhesion and transendothelial migration of GBC cells were enhanced by fibrinogen treatment and ICAM1 overexpression. In addition, the medium of fibrinogen-treated and overexpression-ICAM1 NOZ cells exhibited enhanced macrophages recruitment. This may work in concert to promote angiogenesis. Immunohistochemistry results on clinical specimens showed that higher fibrinogen levels, higher ICAM1 expression, higher blood vessel density, and higher macrophage levels were present simultaneously. Collectively, this study indicates fibrinogen promotes metastasis and extravasation by inducing ICAM1 expression to enhance tumor cell migration, cell adhesion, transendothelial migration and promote angiogenesis and increase vascular endothelial permeability.Young men who have sex with men (YMSM) face the highest risk of HIV infection among adolescents, yet effective sexual health interventions for this population are limited. Parents and Adolescents Talking about Healthy Sexuality (PATHS) is an online intervention for parents designed to improve communication about HIV and increase behaviors supportive of YMSM sexual health. We conducted an RCT of PATHS with sixty-one parent-son dyads recruited online (sons were cisgender, gay or bisexual, ages 14-22). RBN-2397 cell line Assessments were completed at baseline, immediate post-intervention, and over the next 3 months. Per parent and son report, in the 3 months following the intervention, parents assigned to PATHS engaged in more HIV discussion, condom instruction, and facilitation of HIV testing. Parents also reported significant pre- to immediate-post intervention changes in attitudes, skills, and behavioral intentions relevant to engaging with their sons about sexual health. Parents are an untapped but promising resource in preventing HIV among YMSM.
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