The Clinical Impact of Combining Neutrophil-to-Lymphocyte Ratio with Sarcopenia for Improved Discrimination of Progression-Free Survival in Patients with Colorectal Cancer

This study aimed to evaluate the clinical impact of combined sarcopenia and inflammation classification (CSIC) in patients with colorectal cancer (CRC). The skeletal muscle index (SMI) and neutrophil-to-lymphocyte ratio (NLR) were measured in 1270 patients who underwent surgery between January 2005 and April 2014. A Cox proportional hazards model was used to evaluate the correlation of sarcopenia, NLR, and CSIC, with progression-free survival (PFS). The integrated area under the curve (iAUC) was used to compare the discriminatory performance of each model. Using the cut-off values for SMI suggested by Martin et al. and for an NLR of 2.26, the CSIC was defined as follows: nonsarcopenia with low NLR (group 1), nonsarcopenia with high NLR (group 2), sarcopenia with low NLR (group 3), and sarcopenia with high NLR (group 4). Sarcopenia alone was not statistically significant. Multivariate analysis identified that CSIC (group 4 vs. group 1; hazard ratio (HR), 1.726; 95% CI, 1.130–2.634; p = 0.011) and NLR (HR, 1.600; 95% CI, 1.203–2.128; p = 0.001) were independently associated with PFS. The CSIC improved the prediction accuracy of PFS compared with NLR (iAUC mean difference = 0.011; 95% CI, 0.0018–0.028). In conclusion, the combination of sarcopenia and NLR could improve prognostic accuracy, and thus compensate for the limitation of sarcopenia.

Extra-Pulmonary Complications in SARS-CoV-2 Infection: A Comprehensive Multi Organ-System Review

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is typically presented with acute symptoms affecting upper and lower respiratory systems. As the current pandemic progresses, COVID-19 patients are experiencing a series of nonspecific or atypical extra-pulmonary complications such as systemic inflammation, hypercoagulability state, and dysregulation of the renin–angiotensin–aldosterone system (RAAS). These manifestations often delay testing, diagnosis, and the urge to seek effective treatment. Although the pathophysiology of these complications is not clearly understood, the incidence of COVID-19 increases with age and the presence of pre-existing conditions. This review article outlines the pathophysiology and clinical impact of SARS-CoV-2 infection on extra-pulmonary systems. Understanding the broad spectrum of atypical extra-pulmonary manifestations of COVID-19 should increase disease surveillance, restrict transmission, and most importantly prevent multiple organ-system complications.

Clinical impact of glycans in platelet and megakaryocyte biology

Humans produce and remove 1011 platelets daily to maintain a steady-state platelet count. The production of platelets by bone marrow megakaryocytes and their removal from the blood circulation are tightly regulated mechanisms, and abnormalities in both processes can result in thrombocytopenia (low platelet count) or thrombocytosis (high platelet count), often associated with the risk of bleeding or overt thrombus formation, respectively. This review focuses on the role of glycans, also known as carbohydrates or oligosaccharides, including N- and O-glycans, proteoglycans, and glycosaminoglycans, in human and mouse platelet and megakaryocyte physiology. Based on recent clinical observations and mouse models, we focused on the pathological aspects of glycan biosynthesis and degradation and its effects on platelet numbers and megakaryocyte function.

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer

Extracellular signal-regulated kinase 5 (ERK5) is a unique kinase among MAPKs family members, given its large structure characterized by the presence of a unique C-terminal domain. Despite increasing data demonstrating the relevance of the ERK5 pathway in the growth, survival, and differentiation of normal cells, ERK5 has recently attracted the attention of several research groups given its relevance in inflammatory disorders and cancer. Accumulating evidence reported its role in tumor initiation and progression. In this review, we explore the gene expression profile of ERK5 among cancers correlated with its clinical impact, as well as the prognostic value of ERK5 and pERK5 expression levels in tumors. We also summarize the importance of ERK5 in the maintenance of a cancer stem-like phenotype and explore the major known contributions of ERK5 in the tumor-associated microenvironment. Moreover, although several questions are still open concerning ERK5 molecular regulation, different ERK5 isoforms derived from the alternative splicing process are also described, highlighting the potential clinical relevance of targeting ERK5 pathways.

Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine

Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle mRNA vaccines for SARS-CoV-2 contain small amounts of PEG but it is not known if PEG antibodies are enhanced by vaccination and if there are any consequences. We studied plasma from 55 people receiving the Comirnaty (Pfizer-BioNTech) mRNA vaccine for PEG-specific antibodies. Anti-PEG IgG was commonly detected prior to vaccination and was boosted a mean of 1.78-fold (range 0.68 to 16.6) by vaccination. Anti-PEG IgM increased 2.64-fold (0.76 to 12.84) following vaccination. PEG antibodies did not impact the neutralizing antibody response to vaccination. Pre-existing levels of anti-PEG IgM correlated with increased reactogenicity. A rise in PEG antibodies following vaccination was associated with an increase in the association of PEG-based nanoparticles to blood immune cells ex vivo. We conclude that low level PEG-specific antibodies can be modestly boosted by a lipid nanoparticle mRNA-vaccine and that PEG-specific antibodies are associated with higher reactogenicity. The longer-term clinical impact of the increase in PEG-specific antibodies induced by lipid nanoparticle mRNA-vaccines should be monitored.

Clinical impact of subcutaneous treprostinil in trisomy 21 patient with pulmonary arterial hypertension associated with CHD

Subcutaneous treprostinil is commonly used to improve idiopathic pulmonary arterial hypertension in children. However, its effectiveness has not been reported in trisomy 21. We report the case of 9-year-old boy in trisomy 21 with CHD-pulmonary artery hypertension after surgical correction of CHD. Haemodynamics and exercise capacity dramatically improved with a transition from oral selexipag to subcutaneous treprostinil.